COLL Collegium Pharmaceutical Inc.

18.49
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Previous Close 18.49
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Drug Pipeline

Drug Stage Notes
Xtampza ER (oxycodone)
Severe pain
Approved
Approved
Approval announced November 7, 2017.
Xtampza ER (oxycodone)
Severe pain
Approved
Approved
Approved April 26 2016

Latest News

  1. STOUGHTON, Mass., Sept. 25, 2020 (GLOBE NEWSWIRE) -- Collegium Pharmaceutical, Inc. (NASDAQ:COLL), a specialty pharmaceutical company committed to being the leader in responsible pain management, today announced the appointment of Rita Balice-Gordon to its Board of Directors, effective September 24, 2020.

    "Collegium is honored to welcome Rita to our Board of Directors," said Mike Heffernan, Founder and Chairman of the Board of Collegium. "Rita's impressive scientific expertise and industry experience will be incredibly valuable for the Company. We are confident that she will make meaningful contributions to our Board of Directors and that Collegium will benefit from her insights as we continue our commitment to leadership in responsible pain…

    STOUGHTON, Mass., Sept. 25, 2020 (GLOBE NEWSWIRE) -- Collegium Pharmaceutical, Inc. (NASDAQ:COLL), a specialty pharmaceutical company committed to being the leader in responsible pain management, today announced the appointment of Rita Balice-Gordon to its Board of Directors, effective September 24, 2020.

    "Collegium is honored to welcome Rita to our Board of Directors," said Mike Heffernan, Founder and Chairman of the Board of Collegium. "Rita's impressive scientific expertise and industry experience will be incredibly valuable for the Company. We are confident that she will make meaningful contributions to our Board of Directors and that Collegium will benefit from her insights as we continue our commitment to leadership in responsible pain management."

    "I am excited for the opportunity to join Collegium's Board during this important time in the Company's evolution, and I look forward to working with the Board and the management team to make a positive difference in the lives of people suffering from pain," said Dr. Balice-Gordon.

    About Rita Balice-Gordon

    Rita Balice-Gordon, Ph.D., has served as the Chief Scientific Officer of Muna Therapeutics, a newly formed biotech company focused on developing novel therapeutics for patients with neurodegenerative diseases, since May 2020, and is an entrepreneur-in-residence at Novo Seeds since August 2020. Previously, Dr. Balice-Gordon served in scientific roles of increasing responsibility at Sanofi, Inc., most recently as Global Head of Rare and Neurological Diseases. Prior to joining Sanofi, Dr. Balice-Gordon led the psychiatry and pain drug discovery portfolios as Vice President in the Neuroscience and Pain Research Unit at Pfizer, Inc. Earlier in her career, Dr. Balice-Gordon was Professor of Neuroscience and Chair of the Neuroscience Graduate Group at the University of Pennsylvania Perelman School of Medicine, where she currently holds an appointment as Adjunct Professor in the Department of Neuroscience.

    Dr. Balice-Gordon has authored more than 100 scientific papers, received numerous accolades for her work in the field of neuroscience and has chaired or served on many NIH, national and international committees. She received her B.A. degree in Biological Sciences from Northwestern University and her Ph.D. in Neurobiology from the University of Texas at Austin.

    About Collegium Pharmaceutical, Inc.

    Collegium is a specialty pharmaceutical company committed to being the leader in responsible pain management. Collegium's headquarters are located in Stoughton, Massachusetts. For more information, please visit the company's website at www.collegiumpharma.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as "predicts," "forecasts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the impact of the COVID-19 pandemic on our ability to conduct our business, reach our customers, and supply the market with our products. This and other risks are described under the heading "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and other filings with the SEC. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

    Contact:

    Alex Dasalla

     

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  2. STOUGHTON, Mass., Sept. 14, 2020 (GLOBE NEWSWIRE) -- Collegium Pharmaceutical, Inc. (NASDAQ:COLL), a specialty pharmaceutical company committed to being the leader in responsible pain management, today announced that five poster presentations highlighting data regarding its product portfolio were presented at the 14th Annual PAINWeek National Conference which took place virtually September 11-13th.

    "Pursuant to Collegium's commitment to leading with science, we were pleased to support five posters regarding our product portfolio that were presented at PAINWeek this past weekend," said Richard Malamut, M.D., Executive Vice President and Chief Medical Officer of Collegium. "This year's virtual scientific program provided a timely opportunity…

    STOUGHTON, Mass., Sept. 14, 2020 (GLOBE NEWSWIRE) -- Collegium Pharmaceutical, Inc. (NASDAQ:COLL), a specialty pharmaceutical company committed to being the leader in responsible pain management, today announced that five poster presentations highlighting data regarding its product portfolio were presented at the 14th Annual PAINWeek National Conference which took place virtually September 11-13th.

    "Pursuant to Collegium's commitment to leading with science, we were pleased to support five posters regarding our product portfolio that were presented at PAINWeek this past weekend," said Richard Malamut, M.D., Executive Vice President and Chief Medical Officer of Collegium. "This year's virtual scientific program provided a timely opportunity to share encouraging data around certain real-world evidence related to abuse, misuse and diversion of our product portfolio." 

    Poster Presentations

    Poster # 1:Nonmedical Use of Xtampza® ER versus Other Oxycodone-Containing Products
    Authors:Jody L. Green, PhD; Rebekkah Robbins, MPH; Taryn Dailey-Govoni, MPH, Stephen F. Butler, PhD
      
    Poster # 2:Perception of XTAMPZA® ER and Other Abuse-deterrent Opioid Formulations on the Internet
    Authors:Joshua C. Black, Zachary R. Margolin, Janetta L. Iwanicki, Richard C. Dart
      
    Poster # 3:The Diversion and Street Price of XTAMPZA® ER Relative to Other Prescription Opioids
    Authors:Stevan Geoffrey Severtson, Zachary R. Margolin, Kevin May, Janetta L. Iwanicki, Richard C. Dart
      
    Poster # 4:Abuse of XTAMPZA® ER Relative to Other Opioid Analgesics
    Authors:Stevan Geoffrey Severtson, Heather Olsen, Janetta L. Iwanicki, Richard C. Dart
      
    Poster # 5:Abuse of Tapentadol Among Individuals Entering Treatment for Opioid Use Disorder
    Authors:Stevan Geoffrey Severtson, Heather Olsen, Janetta L. Iwanicki, Richard C. Dart

    Xtampza® ER (oxycodone) extended-release tablets, CII, Nucynta® ER (tapentadol) extended-release tablets, CII, and Nucynta® (tapentadol) tablets, CII, can be abused or misused, and carry a risk of addiction. These products are intended for use only in appropriate pain patients and only when other treatment alternatives are inadequate. Use of Xtampza® ER, Nucynta® ER and Nucynta® can result in serious, life-threatening or fatal respiratory depression, even when used exactly as prescribed.  See Important Safety Information including Boxed Warning on addiction, abuse, and misuse and other serious risks regarding each of these three products at the end of this press release. 

    For more information on PAINWeek 2020, visit https://www.painweek.org/.

    About Collegium Pharmaceutical, Inc.

    Collegium is a specialty pharmaceutical company committed to being the leader in responsible pain management. Collegium's headquarters are located in Stoughton, Massachusetts. For more information, please visit the company's website at www.collegiumpharma.com.

    About Xtampza® ER

    Xtampza® ER is Collegium's first product utilizing the DETERx technology platform. Xtampza ER is an abuse-deterrent, extended-release, oral formulation of oxycodone approved by the FDA for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

    INDICATIONS AND USAGE

    Xtampza® ER (oxycodone) is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

    Limitations of Use

    • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve Xtampza ER for use in patients for whom alternative treatment options (eg, non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
    • Xtampza ER is not indicated as an as-needed (prn) analgesic

    IMPORTANT SAFETY INFORMATION

    WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
     
    Addiction, Abuse, and Misuse
    Xtampza ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing Xtampza ER and monitor all patients regularly for the development of these behaviors or conditions.
     
    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to
    • complete a REMS-compliant education program,
    • counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
    • emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
    • consider other tools to improve patient, household, and community safety.
    Life-Threatening Respiratory Depression
    Serious, life-threatening, or fatal respiratory depression may occur with use of Xtampza ER. Monitor for respiratory depression, especially during initiation of Xtampza ER or following a dose increase.
     
    Accidental Ingestion

    Accidental ingestion of even one dose of Xtampza ER, especially by children, can result in a fatal overdose of oxycodone.
     
    Neonatal Opioid Withdrawal Syndrome
    Prolonged use of Xtampza ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
     
    Cytochrome P450 3A4 Interaction
    The concomitant use of Xtampza ER with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving Xtampza ER and any CYP3A4 inhibitor or inducer.
     
    Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants
    Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
    • Reserve concomitant prescribing of Xtampza ER and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
    • Limit dosages and durations to the minimum required.
    • Follow patients for signs and symptoms of respiratory depression and sedation.

    CONTRAINDICATIONS:

    • Xtampza ER is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment, known or suspected gastrointestinal obstruction, including paralytic ileus, and hypersensitivity (eg, anaphylaxis) to oxycodone

    WARNINGS AND PRECAUTIONS:

    Addiction, Abuse, and Misuse

    Xtampza ER contains oxycodone, a Schedule II controlled substance. As an opioid, Xtampza ER exposes users to the risks of addiction, abuse, and misuse. As extended-release products such as Xtampza ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of oxycodone present.



    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:

    • Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain
    • Discuss with patients and/or their caregivers, with every prescription, the safe use, serious risks, and proper storage and disposal of these products. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG
    • Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist
    • Consider other tools to improve patient, household, and community safety such as patient-prescriber agreements that reinforce patient-prescriber responsibilities

    For further information on the REMS and a list of accredited REMS CME/CE, call 1-800-503-0784, or visit www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

    Life-Threatening Respiratory Depression

    • Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids
    • Opioids can cause sleep-related breathing disorders, including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper

    Neonatal Opioid Withdrawal Syndrome

    • Prolonged use of Xtampza ER during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome, and ensure that appropriate treatment will be available

    Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers

    • Concomitant use of Xtampza ER with a CYP3A4 inhibitor, such as macrolide antibiotics (eg, erythromycin), azole-antifungal agents (eg, ketoconazole), and protease inhibitors (eg, ritonavir), may increase plasma concentrations of oxycodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of Xtampza ER is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in Xtampza ER-treated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions. When using Xtampza ER with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in Xtampza ER-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of Xtampza ER until stable drug effects are achieved
    • Concomitant use of Xtampza ER with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone. When using Xtampza ER with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur

    Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants

    • Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Xtampza ER with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate
    • Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics

    Risk of Life-Threatening Respiratory Depression in Patients With Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

    The use of Xtampza ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

    Patients with Chronic Pulmonary Disease: Xtampza ER-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive, including apnea, even at recommended dosages of Xtampza ER.

    Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.

    Monitor such patients closely, particularly when initiating and titrating Xtampza ER and when Xtampza ER is given concomitantly with other drugs that depress respiration. Alternatively, consider the use of non-opioid analgesics in these patients. Use an alternative analgesic for patients who require a dose of Xtampza ER less than 9 mg.

    Adrenal Insufficiency

    • Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs, including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover, and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency

    Severe Hypotension

    • Xtampza ER may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dosage of Xtampza ER. In patients with circulatory shock, Xtampza ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of Xtampza ER in patients with circulatory shock

    Risks of Use in Patients With Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

    • In patients who may be susceptible to the intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors), Xtampza ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with Xtampza ER
    • Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of Xtampza ER in patients with impaired consciousness or coma

    Risks of Use in Patients With Gastrointestinal Conditions

    • Xtampza ER is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus
    • The oxycodone in Xtampza ER may cause spasm of the sphincter of Oddi. Opioids may cause increases in the serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

    Risk of Use in Patients With Seizure Disorders

    • The oxycodone in Xtampza ER may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during Xtampza ER therapy

    Withdrawal

    • Do not abruptly discontinue Xtampza ER in a patient physically dependent on opioids. When discontinuing Xtampza ER in a physically dependent patient, gradually taper the dosage. Rapid tapering of oxycodone in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain
    • Additionally, avoid the use of mixed agonist/antagonist (eg, pentazocine, nalbuphine, and butorphanol) or partial agonist (eg, buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including Xtampza ER.  In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms

    Risks of Driving and Operating Machinery

    • Xtampza ER may impair the mental or physical abilities needed to perform potentially hazardous activities, such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of Xtampza ER and know how they will react to the medication

    Laboratory Monitoring

    • Not every urine drug test for "opioids" or "opiates" detects oxycodone reliably, especially those designed for in-office use. Further, many laboratories will report urine drug concentrations below a specified "cut-off" value as "negative." Therefore, if urine testing for oxycodone is considered in the clinical management of an individual patient, ensure that the sensitivity and specificity of the assay is appropriate, and consider the limitations of the testing used when interpreting results

    ADMINISTRATION WITH FOOD:

    • Instruct patients to always take Xtampza ER capsules with food and with approximately the same amount of food in order to ensure consistent plasma levels are achieved. For patients who have difficulty swallowing, Xtampza ER can also be taken as a sprinkle on soft foods or sprinkled into a cup and administered directly into the mouth, or through a nasogastric or gastric feeding tube

    ADVERSE REACTIONS:

    • The most common adverse reactions (>5%) reported by patients in the Phase 3 clinical trial comparing Xtampza ER with placebo were nausea, headache, constipation, somnolence, pruritus, vomiting, and dizziness

    Please see full Prescribing Information, including Boxed Warning at xtampzaer.com.

    NUCYNTA® ER (tapentadol) INDICATIONS AND USAGE

    NUCYNTA ER (tapentadol) is indicated for the management of:

    • Pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate
    • Neuropathic pain associated with diabetic peripheral neuropathy (DPN) severe enough to require daily, around-the-clock, long- term opioid treatment and for which alternative treatment options are inadequate

    Limitations of Use

    • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve NUCYNTA ER for use in patients for whom alternative treatment options (eg, non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
    • NUCYNTA ER is not indicated as an as-needed (prn) analgesic
    WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
     
    Addiction, Abuse, and Misuse
    NUCYNTA ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing NUCYNTA ER, and monitor all patients regularly for the development of these behaviors and conditions.
     
    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to
    • complete a REMS-compliant education program,
    • counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
    • emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
    • consider other tools to improve patient, household, and community safety.
    Life-Threatening Respiratory Depression
    Serious, life-threatening, or fatal respiratory depression may occur with use of NUCYNTA ER. Monitor for respiratory depression, especially during initiation of NUCYNTA ER or following a dose increase. Instruct patients to swallow NUCYNTA ER tablets whole; crushing, chewing, or dissolving NUCYNTA ER tablets can cause rapid release and absorption of a potentially fatal dose of tapentadol.
     
    Accidental Ingestion
    Accidental ingestion of even one dose of NUCYNTA ER, especially by children, can result in a fatal overdose of tapentadol.
     
    Neonatal Opioid Withdrawal Syndrome
    Prolonged use of NUCYNTA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life- threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
     
    Interaction With Alcohol
    Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while taking NUCYNTA ER. The co-ingestion of alcohol with NUCYNTA ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol.
     
    Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants
    Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
    • Reserve concomitant prescribing of NUCYNTA ER and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
    • Limit dosages and durations to the minimum required.
    • Follow patients for signs and symptoms of respiratory depression and sedation

    CONTRAINDICATIONS:

    NUCYNTA ER is contraindicated in patients with:

    • Significant respiratory depression
    • Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment
    • Known or suspected gastrointestinal obstruction, including paralytic ileus
    • Hypersensitivity (eg, anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product
    • Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days

    WARNINGS AND PRECAUTIONS:

    Addiction, Abuse, and Misuse

    NUCYNTA ER contains tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA ER exposes users to the risks of addiction, abuse, and misuse. Because extended-release products such as NUCYNTA ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of tapentadol present.

    Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NUCYNTA ER. Addiction can occur at recommended doses and if the drug is misused or abused.

    Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA ER, and monitor all patients receiving NUCYNTA ER for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). The potential for these risks should not, however, prevent the prescribing of NUCYNTA ER for the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as NUCYNTA ER, but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA ER along with intensive monitoring for signs of addiction, abuse, and misuse.

    Abuse or misuse of NUCYNTA ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of tapentadol and can result in overdose and death.

    Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA ER. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug. Contact the local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:

    • Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain
    • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG
    • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
    • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities

    To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

    Life-Threatening Respiratory Depression

    Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

    While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA ER, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression especially within the first 24-72 hours of initiating therapy with and following dosage increases of NUCYNTA ER.

    To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA ER are essential. Overestimating the NUCYNTA ER dosage when converting patients from another opioid product can result in fatal overdose with the first dose.

    Accidental ingestion of even one dose of NUCYNTA ER, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

    Opioids can cause sleep-related breathing disorders, including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.

    Neonatal Opioid Withdrawal Syndrome

    Prolonged use of NUCYNTA ER during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to  protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

    Risk From Concomitant Use With Benzodiazepines or Other CNS Depressants

    Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on NUCYNTA ER therapy. The co-ingestion of alcohol with NUCYNTA ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol.

    Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA ER with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

    Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics.

    If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

    Advise both patients and caregivers about the risks of respiratory depression and sedation when NUCYNTA ER is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressants have been determined. Screen patients for risk of  substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs.

    Risk of Life-Threatening Respiratory Depression in Patients With Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

    The use of NUCYNTA ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

    Patients with Chronic Pulmonary Disease: NUCYNTA ER-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NUCYNTA ER.

    Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Alternatively, consider the use of non-opioid analgesics in these patients.

    Monitor such patients closely, particularly when initiating and titrating NUCYNTA ER and when NUCYNTA ER is given concomitantly with other drugs that depress respiration.

    Serotonin Syndrome With Concomitant Use of Serotonergic Drugs

    Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of tapentadol with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (eg, mirtazapine, trazodone, tramadol), certain muscle relaxants (ie, cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). This may occur within the recommended dosage range.

    Serotonin syndrome symptoms may include mental status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue NUCYNTA ER if serotonin syndrome is suspected.

    Adrenal Insufficiency

    Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

    Severe Hypotension

    NUCYNTA ER may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dosage of NUCYNTA ER. In patients with circulatory shock, NUCYNTA ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA ER in patients with circulatory shock.

    Risks of Use in Patients With Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

    In patients who may be susceptible to the intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors), NUCYNTA ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA ER.

    Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NUCYNTA ER in patients with impaired consciousness or coma.

    Risks of Use in Patients With Gastrointestinal Conditions

    NUCYNTA ER is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

    The tapentadol in NUCYNTA ER may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

    Increased Risk of Seizures in Patients With Seizure Disorders

    The tapentadol in NUCYNTA ER may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA ER therapy.

    Withdrawal

    Do not abruptly discontinue NUCYNTA ER in a patient physically dependent on opioids. When discontinuing NUCYNTA ER in a physically dependent patient, gradually taper the dosage. Rapid tapering of tapentadol in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain.

    Additionally, avoid the use of mixed agonist/antagonist (eg, pentazocine, nalbuphine, and butorphanol) or partial agonist (eg, buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including NUCYNTA ER.  In these patients, mixed agonists/antagonists and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.

    Risks of Driving and Operating Machinery

    NUCYNTA ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA ER and know how they will react to the medication.

    Risk of Toxicity in Patients With Hepatic Impairment

    A study with an immediate-release formulation of tapentadol in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA ER in patients with severe hepatic impairment. Reduce the dose of NUCYNTA ER in patients with moderate hepatic impairment. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when initiating and titrating NUCYNTA ER.

    Risk of Toxicity in Patients With Renal Impairment

    Use of NUCYNTA ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

    ADVERSE REACTIONS:

    In clinical studies, the most common (≥10%) adverse reactions were nausea, constipation, dizziness, headache, and somnolence.

    Please see full Prescribing Information, including Boxed Warning.

    NUCYNTA® (tapentadol) INDICATIONS AND USAGE

    NUCYNTA (tapentadol) tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate in adults.

    Limitations of Use

    Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve NUCYNTA tablets for use in patients for whom alternative treatment options (eg, non-opioid analgesics or opioid combination products):

    • Have not been tolerated, or are not expected to be tolerated
    • Have not provided adequate analgesia, or are not expected to provide adequate analgesia

    IMPORTANT SAFETY INFORMATION

    WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
     
    Addiction, Abuse, and Misuse
    NUCYNTA tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing NUCYNTA tablets, and monitor all patients regularly for the development of these behaviors and conditions.
     
    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to
    • complete a REMS-compliant education program,
    • counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
    • emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
    • consider other tools to improve patient, household, and community safety.
    Life-Threatening Respiratory Depression
    Serious, life-threatening, or fatal respiratory depression may occur with use of NUCYNTA tablets. Monitor for respiratory depression, especially during initiation of NUCYNTA tablets or following a dose increase.
     
    Accidental Ingestion
    Accidental ingestion of even one dose of NUCYNTA tablets, especially by children, can result in a fatal overdose of tapentadol.
     
    Neonatal Opioid Withdrawal Syndrome
    Prolonged use of NUCYNTA tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
     
    Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants
    Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
    • Reserve concomitant prescribing of NUCYNTA tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
    • Limit dosages and durations to the minimum required.
    • Follow patients for signs and symptoms of respiratory depression and sedation.

    CONTRAINDICATIONS:

    NUCYNTA tablets are contraindicated in patients with:

    • Significant respiratory depression
    • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
    • Known or suspected gastrointestinal obstruction, including suspected paralytic ileus
    • Hypersensitivity to tapentadol (eg, anaphylaxis, angioedema) or to any other ingredients of the product
    • Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days

    WARNINGS AND PRECAUTIONS:

    Addiction, Abuse, and Misuse

    NUCYNTA tablets contain tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA tablets expose users to the risks of addiction, abuse, and misuse.

    Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NUCYNTA tablets. Addiction can occur at recommended dosages and if the drug is misused or abused.

    Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA tablets and monitor all patients receiving NUCYNTA tablets for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as NUCYNTA tablets, but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA tablets along with intensive monitoring for signs of addiction, abuse, and misuse.

    Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:

    • Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain
    • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG
    • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
    • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient- prescriber responsibilities

    To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

    Life-Threatening Respiratory Depression

    Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

    While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA tablets, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of NUCYNTA tablets.

    To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA tablets are essential. Overestimating the NUCYNTA tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.

    Accidental ingestion of even one dose of NUCYNTA tablets, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

    Opioids can cause sleep-related breathing disorders, including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.

    Neonatal Opioid Withdrawal Syndrome

    Prolonged use of NUCYNTA tablets during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

    Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants

    Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA tablets with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

    Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics.

    If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

    Advise both patients and caregivers about the risks of respiratory depression and sedation when NUCYNTA tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs.

    Life-Threatening Respiratory Depression in Patients With Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

    The use of NUCYNTA tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

    Patients with Chronic Pulmonary Disease: NUCYNTA tablets-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NUCYNTA tablets.

    Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.

    Monitor such patients closely, particularly when initiating and titrating NUCYNTA tablets and when NUCYNTA tablets are given concomitantly with other drugs that depress respiration. Alternatively, consider the use of non-opioid analgesics in these patients.

    Serotonin Syndrome With Concomitant Use of Serotonergic Drugs

    Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concurrent use of tapentadol with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (eg, mirtazapine, trazodone, tramadol), certain muscle relaxants (ie, cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). This may occur within the recommended dosage range.

    Serotonin syndrome symptoms may include mental-status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination) and/or

    gastrointestinal symptoms (eg, nausea, vomiting, diarrhea) and can be fatal. The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue NUCYNTA tablets if serotonin syndrome is suspected.

    Adrenal Insufficiency

    Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

    Severe Hypotension

    NUCYNTA tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dosage of NUCYNTA tablets. In patients with circulatory shock, NUCYNTA tablets may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA tablets in patients with circulatory shock.

    Risks of Use in Patients With Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

    In patients who may be susceptible to the intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors), NUCYNTA tablets may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA tablets.

    Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NUCYNTA tablets in patients with impaired consciousness or coma.

    Risks of Use in Patients With Gastrointestinal Conditions

    NUCYNTA tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

    The tapentadol in NUCYNTA tablets may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.

    Increased Risk of Seizures in Patients With Seizure Disorders

    The tapentadol in NUCYNTA tablets may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA tablets therapy.

    Withdrawal

    Do not abruptly discontinue NUCYNTA tablets in a patient physically dependent on opioids. When discontinuing NUCYNTA tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of tapentadol in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain.

    Additionally, avoid the use of mixed agonist/antagonist (eg, pentazocine, nalbuphine, and butorphanol) or partial agonist (eg, buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including NUCYNTA tablets. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms.

    Risks of Driving and Operating Machinery

    NUCYNTA tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA tablets and know how they will react to the medication.

    Interactions With Alcohol, Other Opioids, and Drugs of Abuse

    Due to its mu-opioid agonist activity, NUCYNTA tablets may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression, respiratory depression, hypotension, and profound sedation, coma or death. Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol, other opioids, or drugs of abuse while on NUCYNTA tablets therapy.

    Risk of Toxicity in Patients With Hepatic Impairment

    A study with NUCYNTA tablets in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA tablets in patients with severe hepatic impairment. Reduce the dose of NUCYNTA tablets in patients with moderate hepatic impairment. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when receiving NUCYNTA tablets.

    Risk of Toxicity in Patients With Renal Impairment

    Use of NUCYNTA tablets in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

    ADVERSE REACTIONS:

    In clinical studies, the most common (≥10%) adverse reactions were nausea, dizziness, vomiting, and somnolence.

    Please see full Prescribing Information, including Boxed Warning.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as "predicts," "forecasts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Examples of forward-looking statements contained in this press release include, among others, statements regarding financial guidance for Xtampza ER and Nucynta Franchise revenues, total operating expenses, current and future market opportunities for our products and our assumptions related thereto. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results, performance, or achievements to differ materially from the company's current expectations. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the impact of the COVID-19 pandemic on our ability to conduct our business, reach our customers, and supply the market with our products; our ability to commercialize and grow sales of our products; our ability to manage our relationships with licensors; the success of competing products that are or become available; our ability to obtain and maintain regulatory approval of our products and any product candidates, and any related restrictions, limitations, and/or warnings in the label of an approved product; the size of the markets for our products and product candidates, and our ability to service those markets; our ability to obtain reimbursement and third-party payor contracts for our products; the rate and degree of market acceptance of our products and product candidates; the costs of commercialization activities, including marketing, sales and distribution; changing market conditions for our products; the outcome of any patent infringement, opioid-related or other litigation that may be brought by or against us, including litigation with Purdue Pharma, L.P. and Teva Pharmaceuticals USA, Inc.; the outcome of any governmental investigation related to the manufacture, marketing and sale of opioid medications; our ability to secure adequate supplies of active pharmaceutical ingredient for each of our products and manufacture adequate supplies of commercially saleable inventory; our ability to obtain funding for our operations and business development; regulatory developments in the U.S.; our expectations regarding our ability to obtain and maintain sufficient intellectual property protection for our products; our ability to comply with stringent U.S. and foreign government regulation in the manufacture of pharmaceutical products, including U.S. Drug Enforcement Agency, or DEA, compliance; our customer concentration; and the accuracy of our estimates regarding expenses, revenue, capital requirements and need for additional financing. These and other risks are described under the heading "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and other filings with the SEC. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

    Contact:

    Alex Dasalla

    Primary Logo

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  3. STOUGHTON, Mass., Sept. 09, 2020 (GLOBE NEWSWIRE) -- Collegium Pharmaceutical, Inc. (NASDAQ:COLL), a specialty pharmaceutical company committed to being the leader in responsible pain management, today announced that five poster presentations highlighting data regarding its product portfolio will be presented at the 14th Annual PAINWeek National Conference taking place virtually September 11-13th.

    Poster Presentations

    Poster # 1:Nonmedical Use of Xtampza® ER versus Other Oxycodone-Containing Products
    Authors:Jody L. Green, PhD; Rebekkah Robbins, MPH; Taryn Dailey-Govoni, MPH, Stephen F. Butler, PhD
      
    Poster # 2:Perception of XTAMPZA® ER and Other Abuse-deterrent Opioid Formulations on the Internet
    Authors:Joshua C. Black, Zachary R. Margolin,

    STOUGHTON, Mass., Sept. 09, 2020 (GLOBE NEWSWIRE) -- Collegium Pharmaceutical, Inc. (NASDAQ:COLL), a specialty pharmaceutical company committed to being the leader in responsible pain management, today announced that five poster presentations highlighting data regarding its product portfolio will be presented at the 14th Annual PAINWeek National Conference taking place virtually September 11-13th.

    Poster Presentations

    Poster # 1:Nonmedical Use of Xtampza® ER versus Other Oxycodone-Containing Products
    Authors:Jody L. Green, PhD; Rebekkah Robbins, MPH; Taryn Dailey-Govoni, MPH, Stephen F. Butler, PhD
      
    Poster # 2:Perception of XTAMPZA® ER and Other Abuse-deterrent Opioid Formulations on the Internet
    Authors:Joshua C. Black, Zachary R. Margolin, Janetta L. Iwanicki, Richard C. Dart
      
    Poster # 3:The Diversion and Street Price of XTAMPZA® ER Relative to Other Prescription Opioids
    Authors:Stevan Geoffrey Severtson, Zachary R. Margolin, Kevin May, Janetta L. Iwanicki, Richard C. Dart
      
    Poster # 4:Abuse of XTAMPZA® ER Relative to Other Opioid Analgesics
    Authors:Stevan Geoffrey Severtson, Heather Olsen, Janetta L. Iwanicki, Richard C. Dart
      
    Poster # 5:Abuse of Tapentadol Among Individuals Entering Treatment for Opioid Use Disorder
    Authors:Stevan Geoffrey Severtson, Heather Olsen, Janetta L. Iwanicki, Richard C. Dart

    Xtampza® ER, Nucynta® ER and Nucynta® can be abused or misused, and carry a risk of addiction. These products are intended for use only in appropriate pain patients and only when other treatment alternatives are inadequate. Use of Xtampza® ER, Nucynta® ER and Nucynta® can result in serious, life-threatening or fatal respiratory depression, even when used exactly as prescribed.  See Important Safety Information including Boxed Warning on addiction, abuse, and misuse and other serious risks regarding each of these three products at the end of this press release. 

    For more information on PAINWeek 2020, visit https://www.painweek.org/.

    About Collegium Pharmaceutical, Inc.

    Collegium is a specialty pharmaceutical company committed to being the leader in responsible pain management. Collegium's headquarters are located in Stoughton, Massachusetts. For more information, please visit the company's website at www.collegiumpharma.com.

    About Xtampza® ER

    Xtampza® ER is Collegium's first product utilizing the DETERx technology platform. Xtampza ER is an abuse-deterrent, extended-release, oral formulation of oxycodone approved by the FDA for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

    INDICATIONS AND USAGE

    Xtampza® ER (oxycodone) is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.



    Limitations of Use

    • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve Xtampza ER for use in patients for whom alternative treatment options (eg, non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
    • Xtampza ER is not indicated as an as-needed (prn) analgesic

    IMPORTANT SAFETY INFORMATION

    WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
     
    Addiction, Abuse, and Misuse
    Xtampza ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing Xtampza ER and monitor all patients regularly for the development of these behaviors or conditions.
     
    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to
    • complete a REMS-compliant education program,
    • counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
    • emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
    • consider other tools to improve patient, household, and community safety.
    Life-Threatening Respiratory Depression
    Serious, life-threatening, or fatal respiratory depression may occur with use of Xtampza ER. Monitor for respiratory depression, especially during initiation of Xtampza ER or following a dose increase.
     
    Accidental Ingestion

    Accidental ingestion of even one dose of Xtampza ER, especially by children, can result in a fatal overdose of oxycodone.
     
    Neonatal Opioid Withdrawal Syndrome
    Prolonged use of Xtampza ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
     
    Cytochrome P450 3A4 Interaction
    The concomitant use of Xtampza ER with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving Xtampza ER and any CYP3A4 inhibitor or inducer.
     
    Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants
    Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
    • Reserve concomitant prescribing of Xtampza ER and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
    • Limit dosages and durations to the minimum required.
    • Follow patients for signs and symptoms of respiratory depression and sedation.

    CONTRAINDICATIONS:

    • Xtampza ER is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment, known or suspected gastrointestinal obstruction, including paralytic ileus, and hypersensitivity (eg, anaphylaxis) to oxycodone

    WARNINGS AND PRECAUTIONS:

    Addiction, Abuse, and Misuse

    Xtampza ER contains oxycodone, a Schedule II controlled substance. As an opioid, Xtampza ER exposes users to the risks of addiction, abuse, and misuse. As extended-release products such as Xtampza ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of oxycodone present.



    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:

    • Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain
    • Discuss with patients and/or their caregivers, with every prescription, the safe use, serious risks, and proper storage and disposal of these products. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG
    • Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist
    • Consider other tools to improve patient, household, and community safety such as patient-prescriber agreements that reinforce patient-prescriber responsibilities

    For further information on the REMS and a list of accredited REMS CME/CE, call 1-800-503-0784, or visit www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

    Life-Threatening Respiratory Depression

    • Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids

    • Opioids can cause sleep-related breathing disorders, including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper

    Neonatal Opioid Withdrawal Syndrome

    • Prolonged use of Xtampza ER during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome, and ensure that appropriate treatment will be available

    Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers

    • Concomitant use of Xtampza ER with a CYP3A4 inhibitor, such as macrolide antibiotics (eg, erythromycin), azole-antifungal agents (eg, ketoconazole), and protease inhibitors (eg, ritonavir), may increase plasma concentrations of oxycodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of Xtampza ER is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in Xtampza ER-treated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions. When using Xtampza ER with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in Xtampza ER-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of Xtampza ER until stable drug effects are achieved

    • Concomitant use of Xtampza ER with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone. When using Xtampza ER with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur

    Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants

    • Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Xtampza ER with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate

    • Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics

    Risk of Life-Threatening Respiratory Depression in Patients With Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

    The use of Xtampza ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

    Patients with Chronic Pulmonary Disease: Xtampza ER-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive, including apnea, even at recommended dosages of Xtampza ER.

    Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.

    Monitor such patients closely, particularly when initiating and titrating Xtampza ER and when Xtampza ER is given concomitantly with other drugs that depress respiration. Alternatively, consider the use of non-opioid analgesics in these patients. Use an alternative analgesic for patients who require a dose of Xtampza ER less than 9 mg.

    Adrenal Insufficiency

    • Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs, including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover, and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency

    Severe Hypotension

    • Xtampza ER may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dosage of Xtampza ER. In patients with circulatory shock, Xtampza ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of Xtampza ER in patients with circulatory shock

    Risks of Use in Patients With Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

    • In patients who may be susceptible to the intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors), Xtampza ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with Xtampza ER
    • Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of Xtampza ER in patients with impaired consciousness or coma

    Risks of Use in Patients With Gastrointestinal Conditions

    • Xtampza ER is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus
    • The oxycodone in Xtampza ER may cause spasm of the sphincter of Oddi. Opioids may cause increases in the serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

    Risk of Use in Patients With Seizure Disorders

    • The oxycodone in Xtampza ER may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during Xtampza ER therapy

    Withdrawal

    • Do not abruptly discontinue Xtampza ER in a patient physically dependent on opioids. When discontinuing Xtampza ER in a physically dependent patient, gradually taper the dosage. Rapid tapering of oxycodone in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain
    • Additionally, avoid the use of mixed agonist/antagonist (eg, pentazocine, nalbuphine, and butorphanol) or partial agonist (eg, buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including Xtampza ER.  In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms

    Risks of Driving and Operating Machinery

    • Xtampza ER may impair the mental or physical abilities needed to perform potentially hazardous activities, such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of Xtampza ER and know how they will react to the medication

    Laboratory Monitoring

    • Not every urine drug test for "opioids" or "opiates" detects oxycodone reliably, especially those designed for in-office use. Further, many laboratories will report urine drug concentrations below a specified "cut-off" value as "negative." Therefore, if urine testing for oxycodone is considered in the clinical management of an individual patient, ensure that the sensitivity and specificity of the assay is appropriate, and consider the limitations of the testing used when interpreting results

    ADMINISTRATION WITH FOOD:

    • Instruct patients to always take Xtampza ER capsules with food and with approximately the same amount of food in order to ensure consistent plasma levels are achieved. For patients who have difficulty swallowing, Xtampza ER can also be taken as a sprinkle on soft foods or sprinkled into a cup and administered directly into the mouth, or through a nasogastric or gastric feeding tube   

    ADVERSE REACTIONS:

    • The most common adverse reactions (>5%) reported by patients in the Phase 3 clinical trial comparing Xtampza ER with placebo were nausea, headache, constipation, somnolence, pruritus, vomiting, and dizziness

    Please see full Prescribing Information, including Boxed Warning at xtampzaer.com.

    NUCYNTA® ER (tapentadol) INDICATIONS AND USAGE

    NUCYNTA ER (tapentadol) is indicated for the management of:

    • Pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate
    • Neuropathic pain associated with diabetic peripheral neuropathy (DPN) severe enough to require daily, around-the-clock, long- term opioid treatment and for which alternative treatment options are inadequate

    Limitations of Use

    • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve NUCYNTA ER for use in patients for whom alternative treatment options (eg, non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
    • NUCYNTA ER is not indicated as an as-needed (prn) analgesic
    WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
     
    Addiction, Abuse, and Misuse
    NUCYNTA ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing NUCYNTA ER, and monitor all patients regularly for the development of these behaviors and conditions.
     
    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to
    • complete a REMS-compliant education program,
    • counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
    • emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
    • consider other tools to improve patient, household, and community safety.
    Life-Threatening Respiratory Depression
    Serious, life-threatening, or fatal respiratory depression may occur with use of NUCYNTA ER. Monitor for respiratory depression, especially during initiation of NUCYNTA ER or following a dose increase. Instruct patients to swallow NUCYNTA ER tablets whole; crushing, chewing, or dissolving NUCYNTA ER tablets can cause rapid release and absorption of a potentially fatal dose of tapentadol.
     
    Accidental Ingestion
    Accidental ingestion of even one dose of NUCYNTA ER, especially by children, can result in a fatal overdose of tapentadol.
     
    Neonatal Opioid Withdrawal Syndrome
    Prolonged use of NUCYNTA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life- threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
     
    Interaction With Alcohol
    Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while taking NUCYNTA ER. The co-ingestion of alcohol with NUCYNTA ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol.
     
    Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants
    Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
    • Reserve concomitant prescribing of NUCYNTA ER and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
    • Limit dosages and durations to the minimum required.
    • Follow patients for signs and symptoms of respiratory depression and sedation



    CONTRAINDICATIONS:


    NUCYNTA ER is contraindicated in patients with:

    • Significant respiratory depression
    • Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment
    • Known or suspected gastrointestinal obstruction, including paralytic ileus
    • Hypersensitivity (eg, anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product
    • Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days

    WARNINGS AND PRECAUTIONS:

    Addiction, Abuse, and Misuse

    NUCYNTA ER contains tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA ER exposes users to the risks of addiction, abuse, and misuse. Because extended-release products such as NUCYNTA ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of tapentadol present.

    Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NUCYNTA ER. Addiction can occur at recommended doses and if the drug is misused or abused.

    Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA ER, and monitor all patients receiving NUCYNTA ER for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). The potential for these risks should not, however, prevent the prescribing of NUCYNTA ER for the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as NUCYNTA ER, but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA ER along with intensive monitoring for signs of addiction, abuse, and misuse.

    Abuse or misuse of NUCYNTA ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of tapentadol and can result in overdose and death.

    Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA ER. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug. Contact the local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:

    • Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain
    • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG
    • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
    • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities

    To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

    Life-Threatening Respiratory Depression

    Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

    While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA ER, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression especially within the first 24-72 hours of initiating therapy with and following dosage increases of NUCYNTA ER.

    To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA ER are essential. Overestimating the NUCYNTA ER dosage when converting patients from another opioid product can result in fatal overdose with the first dose.

    Accidental ingestion of even one dose of NUCYNTA ER, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

    Opioids can cause sleep-related breathing disorders, including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.

    Neonatal Opioid Withdrawal Syndrome

    Prolonged use of NUCYNTA ER during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to  protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

    Risk From Concomitant Use With Benzodiazepines or Other CNS Depressants

    Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on NUCYNTA ER therapy. The co-ingestion of alcohol with NUCYNTA ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol.

    Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA ER with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

    Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics.

    If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

    Advise both patients and caregivers about the risks of respiratory depression and sedation when NUCYNTA ER is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressants have been determined. Screen patients for risk of  substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs.

    Risk of Life-Threatening Respiratory Depression in Patients With Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

    The use of NUCYNTA ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

    Patients with Chronic Pulmonary Disease: NUCYNTA ER-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NUCYNTA ER.

    Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Alternatively, consider the use of non-opioid analgesics in these patients.

    Monitor such patients closely, particularly when initiating and titrating NUCYNTA ER and when NUCYNTA ER is given concomitantly with other drugs that depress respiration.

    Serotonin Syndrome With Concomitant Use of Serotonergic Drugs

    Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of tapentadol with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (eg, mirtazapine, trazodone, tramadol), certain muscle relaxants (ie, cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). This may occur within the recommended dosage range.

    Serotonin syndrome symptoms may include mental status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue NUCYNTA ER if serotonin syndrome is suspected.

    Adrenal Insufficiency

    Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

    Severe Hypotension

    NUCYNTA ER may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dosage of NUCYNTA ER. In patients with circulatory shock, NUCYNTA ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA ER in patients with circulatory shock.

    Risks of Use in Patients With Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

    In patients who may be susceptible to the intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors), NUCYNTA ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA ER.

    Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NUCYNTA ER in patients with impaired consciousness or coma.

    Risks of Use in Patients With Gastrointestinal Conditions

    NUCYNTA ER is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

    The tapentadol in NUCYNTA ER may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

    Increased Risk of Seizures in Patients With Seizure Disorders

    The tapentadol in NUCYNTA ER may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA ER therapy.

    Withdrawal

    Do not abruptly discontinue NUCYNTA ER in a patient physically dependent on opioids. When discontinuing NUCYNTA ER in a physically dependent patient, gradually taper the dosage. Rapid tapering of tapentadol in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain.

    Additionally, avoid the use of mixed agonist/antagonist (eg, pentazocine, nalbuphine, and butorphanol) or partial agonist (eg, buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including NUCYNTA ER.  In these patients, mixed agonists/antagonists and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.

    Risks of Driving and Operating Machinery

    NUCYNTA ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA ER and know how they will react to the medication.

    Risk of Toxicity in Patients With Hepatic Impairment

    A study with an immediate-release formulation of tapentadol in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA ER in patients with severe hepatic impairment. Reduce the dose of NUCYNTA ER in patients with moderate hepatic impairment. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when initiating and titrating NUCYNTA ER.

    Risk of Toxicity in Patients With Renal Impairment

    Use of NUCYNTA ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

    ADVERSE REACTIONS:

    In clinical studies, the most common (≥10%) adverse reactions were nausea, constipation, dizziness, headache, and somnolence.

    Please see full Prescribing Information, including Boxed Warning.

    NUCYNTA® (tapentadol) INDICATIONS AND USAGE

    NUCYNTA (tapentadol) tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate in adults.

    Limitations of Use

    Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve NUCYNTA tablets for use in patients for whom alternative treatment options (eg, non-opioid analgesics or opioid combination products):

    • Have not been tolerated, or are not expected to be tolerated
    • Have not provided adequate analgesia, or are not expected to provide adequate analgesia

    IMPORTANT SAFETY INFORMATION

    WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
     
    Addiction, Abuse, and Misuse
    NUCYNTA tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing NUCYNTA tablets, and monitor all patients regularly for the development of these behaviors and conditions.
     
    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to
    • complete a REMS-compliant education program,
    • counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
    • emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
    • consider other tools to improve patient, household, and community safety.
    Life-Threatening Respiratory Depression
    Serious, life-threatening, or fatal respiratory depression may occur with use of NUCYNTA tablets. Monitor for respiratory depression, especially during initiation of NUCYNTA tablets or following a dose increase.
     
    Accidental Ingestion
    Accidental ingestion of even one dose of NUCYNTA tablets, especially by children, can result in a fatal overdose of tapentadol.
     
    Neonatal Opioid Withdrawal Syndrome
    Prolonged use of NUCYNTA tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
     
    Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants
    Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
    • Reserve concomitant prescribing of NUCYNTA tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
    • Limit dosages and durations to the minimum required.
    • Follow patients for signs and symptoms of respiratory depression and sedation.

    CONTRAINDICATIONS:

    NUCYNTA tablets are contraindicated in patients with:

    • Significant respiratory depression
    • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
    • Known or suspected gastrointestinal obstruction, including suspected paralytic ileus
    • Hypersensitivity to tapentadol (eg, anaphylaxis, angioedema) or to any other ingredients of the product
    • Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days

    WARNINGS AND PRECAUTIONS:

    Addiction, Abuse, and Misuse

    NUCYNTA tablets contain tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA tablets expose users to the risks of addiction, abuse, and misuse.

    Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NUCYNTA tablets. Addiction can occur at recommended dosages and if the drug is misused or abused.

    Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA tablets and monitor all patients receiving NUCYNTA tablets for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as NUCYNTA tablets, but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA tablets along with intensive monitoring for signs of addiction, abuse, and misuse.

    Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

    Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

    To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:

    • Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain
    • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG
    • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
    • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient- prescriber responsibilities

    To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

    Life-Threatening Respiratory Depression

    Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

    While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA tablets, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of NUCYNTA tablets.

    To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA tablets are essential. Overestimating the NUCYNTA tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.

    Accidental ingestion of even one dose of NUCYNTA tablets, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

    Opioids can cause sleep-related breathing disorders, including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.

    Neonatal Opioid Withdrawal Syndrome

    Prolonged use of NUCYNTA tablets during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

    Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants

    Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA tablets with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

    Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics.

    If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower

    initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

    Advise both patients and caregivers about the risks of respiratory depression and sedation when NUCYNTA tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs.

    Life-Threatening Respiratory Depression in Patients With Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

    The use of NUCYNTA tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

    Patients with Chronic Pulmonary Disease: NUCYNTA tablets-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NUCYNTA tablets.

    Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.

    Monitor such patients closely, particularly when initiating and titrating NUCYNTA tablets and when NUCYNTA tablets are given concomitantly with other drugs that depress respiration. Alternatively, consider the use of non-opioid analgesics in these patients.

    Serotonin Syndrome With Concomitant Use of Serotonergic Drugs

    Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concurrent use of tapentadol with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (eg, mirtazapine, trazodone, tramadol), certain muscle relaxants (ie, cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). This may occur within the recommended dosage range.

    Serotonin syndrome symptoms may include mental-status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination) and/or

    gastrointestinal symptoms (eg, nausea, vomiting, diarrhea) and can be fatal. The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue NUCYNTA tablets if serotonin syndrome is suspected.

    Adrenal Insufficiency

    Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

    Severe Hypotension

    NUCYNTA tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dosage of NUCYNTA tablets. In patients with circulatory shock, NUCYNTA tablets may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA tablets in patients with circulatory shock.

    Risks of Use in Patients With Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

    In patients who may be susceptible to the intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors), NUCYNTA tablets may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA tablets.

    Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NUCYNTA tablets in patients with impaired consciousness or coma.

    Risks of Use in Patients With Gastrointestinal Conditions

    NUCYNTA tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

    The tapentadol in NUCYNTA tablets may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.

    Increased Risk of Seizures in Patients With Seizure Disorders

    The tapentadol in NUCYNTA tablets may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA tablets therapy.

    Withdrawal

    Do not abruptly discontinue NUCYNTA tablets in a patient physically dependent on opioids. When discontinuing NUCYNTA tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of tapentadol in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain.

    Additionally, avoid the use of mixed agonist/antagonist (eg, pentazocine, nalbuphine, and butorphanol) or partial agonist (eg, buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including NUCYNTA tablets. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms.

    Risks of Driving and Operating Machinery

    NUCYNTA tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA tablets and know how they will react to the medication.

    Interactions With Alcohol, Other Opioids, and Drugs of Abuse

    Due to its mu-opioid agonist activity, NUCYNTA tablets may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression, respiratory depression, hypotension, and profound sedation, coma or death. Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol, other opioids, or drugs of abuse while on NUCYNTA tablets therapy.

    Risk of Toxicity in Patients With Hepatic Impairment

    A study with NUCYNTA tablets in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA tablets in patients with severe hepatic impairment. Reduce the dose of NUCYNTA tablets in patients with moderate hepatic impairment. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when receiving NUCYNTA tablets.

    Risk of Toxicity in Patients With Renal Impairment

    Use of NUCYNTA tablets in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

    ADVERSE REACTIONS:

    In clinical studies, the most common (≥10%) adverse reactions were nausea, dizziness, vomiting, and somnolence.

    Please see full Prescribing Information, including Boxed Warning.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as "predicts," "forecasts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Examples of forward-looking statements contained in this press release include, among others, statements regarding financial guidance for Xtampza ER and Nucynta Franchise revenues, total operating expenses, current and future market opportunities for our products and our assumptions related thereto. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results, performance, or achievements to differ materially from the company's current expectations. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the impact of the COVID-19 pandemic on our ability to conduct our business, reach our customers, and supply the market with our products; our ability to commercialize and grow sales of our products; our ability to manage our relationships with licensors; the success of competing products that are or become available; our ability to obtain and maintain regulatory approval of our products and any product candidates, and any related restrictions, limitations, and/or warnings in the label of an approved product; the size of the markets for our products and product candidates, and our ability to service those markets; our ability to obtain reimbursement and third-party payor contracts for our products; the rate and degree of market acceptance of our products and product candidates; the costs of commercialization activities, including marketing, sales and distribution; changing market conditions for our products; the outcome of any patent infringement, opioid-related or other litigation that may be brought by or against us, including litigation with Purdue Pharma, L.P. and Teva Pharmaceuticals USA, Inc.; the outcome of any governmental investigation related to the manufacture, marketing and sale of opioid medications; our ability to secure adequate supplies of active pharmaceutical ingredient for each of our products and manufacture adequate supplies of commercially saleable inventory; our ability to obtain funding for our operations and business development; regulatory developments in the U.S.; our expectations regarding our ability to obtain and maintain sufficient intellectual property protection for our products; our ability to comply with stringent U.S. and foreign government regulation in the manufacture of pharmaceutical products, including U.S. Drug Enforcement Agency, or DEA, compliance; our customer concentration; and the accuracy of our estimates regarding expenses, revenue, capital requirements and need for additional financing. These and other risks are described under the heading "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and other filings with the SEC. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

    Contact:

    Alex Dasalla

    Primary Logo

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  4. – Non-GAAP Net Income of $33.2 Million in the Second Quarter of 2020 –

    – Generated $43.9 Million in Cash from Operating Activities in the Second Quarter of 2020 –

    – Xtampza ® ER Net Revenue Increased 29% over the Prior Year Period –

    – Conference Call Scheduled for Today at 4:30 p.m. ET –

    STOUGHTON, Mass., Aug. 05, 2020 (GLOBE NEWSWIRE) --  Collegium Pharmaceutical, Inc. (NASDAQ:COLL), a specialty pharmaceutical company committed to being the leader in responsible pain management, today reported its financial results for the second quarter ended June 30, 2020 and provided a corporate update.

    "Collegium delivered strong financial results in the second quarter of 2020, which is a testament to the resilience and adaptability of…

    – Non-GAAP Net Income of $33.2 Million in the Second Quarter of 2020 –

    – Generated $43.9 Million in Cash from Operating Activities in the Second Quarter of 2020 –

    – Xtampza ® ER Net Revenue Increased 29% over the Prior Year Period –

    – Conference Call Scheduled for Today at 4:30 p.m. ET –

    STOUGHTON, Mass., Aug. 05, 2020 (GLOBE NEWSWIRE) --  Collegium Pharmaceutical, Inc. (NASDAQ:COLL), a specialty pharmaceutical company committed to being the leader in responsible pain management, today reported its financial results for the second quarter ended June 30, 2020 and provided a corporate update.

    "Collegium delivered strong financial results in the second quarter of 2020, which is a testament to the resilience and adaptability of our people and operations," said Joe Ciaffoni, President and Chief Executive Officer of Collegium. "We made progress towards achieving each of our key business objectives, while prioritizing the health and safety of our people, customers and communities. Xtampza ER revenue growth and the impact of the Nucynta acquisition generated meaningful cashflow from operations, enabling us to begin to pay down debt, and setting the stage for 2020 to be a financially transformative year for Collegium."

    Recent Business Highlights

    • Xtampza ER total prescriptions grew to 141,678 for the quarter ended June 30, 2020 (the "2020 Quarter"), representing a 22% increase over the quarter ended June 30, 2019 (the "2019 Quarter") and a 4% increase over the first quarter of 2020.



    • Xtampza ER market share of the oxycodone extended-release market was 23.5% in the 2020 Quarter, up from 21.8% in the first quarter of 2020.



    • In the 2020 Quarter, two new formulation patents covering Xtampza ER were added to the FDA Orange Book, one with an expiry in 2030 and one with an expiry in 2036. With these recent additions to the patent estate, Xtampza ER is now covered by 19 Orange Book-listed patents.



    • A manuscript describing certain real-world evidence with respect to abuse, misuse, and diversion of Xtampza ER was recently accepted for publication in Pain Medicine, the Journal of the American Academy of Pain Medicine.



    • Nucynta® ER market share of the branded extended-release market grew to 6.2% in the 2020 Quarter, up from 6.1% in the first quarter of 2020. This represents five consecutive quarters in which market share was stable or growing.

    Financial Results for Quarter Ended June 30, 2020

    • Xtampza ER net product revenues were $33.6 million for the 2020 Quarter, compared to $26.0 million for the 2019 Quarter and $31.5 million for the quarter ended March 31, 2020, representing an increase of 29% and 7%, respectively.



    • Nucynta franchise net product revenues were $44.5 million in the 2020 Quarter, compared to $49.0 million for the 2019 Quarter and $45.0 million for the quarter ended March 31, 2020, representing a decrease of 9% and 1%, respectively.



    • Operating expenses were $31.8 million for the 2020 Quarter, compared to $31.4 million for the 2019 Quarter.



    • Net income for the 2020 Quarter was $8.1 million, or $0.23 per share (basic and diluted), compared to net loss of $4.7 million, or $0.14 loss per share (basic and diluted), for the 2019 Quarter.



    • Non-GAAP adjusted income for the 2020 Quarter was $33.2 million, compared to a non-GAAP adjusted income of $3.1 million for the 2019 Quarter.

    Conference Call Information

    The Company will host a conference call and live audio webcast on Wednesday, August 5, 2020 at 4:30 p.m. Eastern Time. To access the conference call, please dial (877) 407-8037 (U.S.) or (201) 689-8037 (International) and reference the "Collegium Q2 Earnings Call." An audio webcast will be accessible from the Investors section of the Company's website: www.collegiumpharma.com. The webcast will be available for replay on the Company's website approximately two hours after the event.

    About Collegium Pharmaceutical, Inc.

    Collegium is a specialty pharmaceutical company committed to being the leader in responsible pain management. Collegium's headquarters are located in Stoughton, Massachusetts. For more information, please visit the company's website at www.collegiumpharma.com.

    Non-GAAP Financial Measures

    To supplement our financial results presented on a GAAP basis, we have included information about non-GAAP adjusted income. We use this non-GAAP financial measure to understand, manage and evaluate the Company as we believe it represents the performance of our core business. Because this non-GAAP financial measure is an important internal measure for the Company, we believe that the presentation of the non-GAAP financial measure provides analysts, investors and lenders insight into management's view and assessment of the Company's ongoing operating performance. In addition, we believe that the presentation of this non-GAAP financial measure, when viewed with our results under GAAP and the accompanying reconciliation, provides supplementary information that may be useful to analysts, investors, lenders, and other third parties in assessing the Company's performance and results from period to period. We report this non-GAAP financial measure in order to portray the results of our major operations prior to considering certain income statement elements. This non-GAAP financial measure should be considered in addition to, and not a substitute for, or superior to, net income or other financial measures calculated in accordance with GAAP.

    Non-GAAP adjusted income is not based on any standardized methodology prescribed by GAAP and represents GAAP net income adjusted to exclude stock-based compensation expense, amortization expense, non-cash interest expense, certain royalty costs recognized in connection with the Nucynta Commercialization Agreement and the provision for income taxes. Any non-GAAP financial measures used by us may be calculated differently from, and therefore may not be comparable to, a non-GAAP measure used by other companies. Please see the section of this press release titled "Reconciliation of GAAP to Non-GAAP Financial Information" for a reconciliation of non-GAAP adjusted income to its most directly comparable GAAP measure.

    The Company has not provided a reconciliation of its full-year 2020 guidance for non-GAAP adjusted income to the most directly comparable forward-looking GAAP measure because it is unable to predict, without unreasonable efforts, the timing and amount of items that would be included such a reconciliation. These items are uncertain and depend on various factors that could have a material impact on GAAP net income for the guidance period.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as "predicts," "forecasts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Examples of forward-looking statements contained in this press release include, among others, statements regarding financial guidance for Xtampza ER and Nucynta Franchise revenues, total operating expenses, current and future market opportunities for our products and our assumptions related thereto. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results, performance, or achievements to differ materially from the company's current expectations. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the impact of the COVID-19 pandemic on our ability to conduct our business, reach our customers, and supply the market with our products; our ability to commercialize and grow sales of our products; our ability to manage our relationships with licensors; the success of competing products that are or become available; our ability to obtain and maintain regulatory approval of our products and any product candidates, and any related restrictions, limitations, and/or warnings in the label of an approved product; the size of the markets for our products and product candidates, and our ability to service those markets; our ability to obtain reimbursement and third-party payor contracts for our products; the rate and degree of market acceptance of our products and product candidates; the costs of commercialization activities, including marketing, sales and distribution; changing market conditions for our products; the outcome of any patent infringement, opioid-related or other litigation that may be brought by or against us, including litigation with Purdue Pharma, L.P. and Teva Pharmaceuticals USA, Inc.; the outcome of any governmental investigation related to the manufacture, marketing and sale of opioid medications; our ability to secure adequate supplies of active pharmaceutical ingredient for each of our products and manufacture adequate supplies of commercially saleable inventory; our ability to obtain funding for our operations and business development; regulatory developments in the U.S.; our expectations regarding our ability to obtain and maintain sufficient intellectual property protection for our products; our ability to comply with stringent U.S. and foreign government regulation in the manufacture of pharmaceutical products, including U.S. Drug Enforcement Agency, or DEA, compliance; our customer concentration; and the accuracy of our estimates regarding expenses, revenue, capital requirements and need for additional financing. These and other risks are described under the heading "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and other filings with the SEC. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

    Contact:

    Alex Dasalla



    Collegium Pharmaceutical, Inc.

    Unaudited Selected Consolidated Balance Sheet Information

    (in thousands)

           
      June 30,  December 31, 
      2020 2019
    Cash and cash equivalents $145,678  170,019
    Accounts receivable  81,195  72,953
    Inventory  18,815  9,643
    Prepaid expenses and other current assets  5,125  3,105
    Property and equipment, net  15,156  11,854
    Operating lease assets  8,697  9,047
    Intangible asset, net  369,494  29,503
    Restricted cash  2,547  
    Other noncurrent assets  163  178
    Total assets $646,870 $306,302
           
    Accounts payable and accrued expenses  33,293  39,727
    Accrued rebates, returns and discounts  171,053  157,549
    Term notes payable  180,931  11,500
    Convertible senior notes  96,046  
    Operating lease liabilities  9,780  10,094
    Stockholders' equity  155,767  87,432
    Total liabilities and stockholders' equity $646,870 $306,302
           



    Collegium Pharmaceutical, Inc.

    Unaudited Condensed Statements of Operations

    (in thousands, except share and per share amounts)

     Three months ended June 30,  Six months ended June 30, 
     2020  2019  2020  2019 
    Product revenues, net$78,058  $75,040  $154,569  $149,556 
    Cost of product revenues           
    Cost of product revenues (excluding intangible asset amortization) 12,899   44,966   40,128   90,442 
    Intangible asset amortization 16,795   3,688   27,090   7,376 
    Total cost of products revenues 29,694   48,654   67,218   97,818 
    Gross profit 48,364   26,386   87,351   51,738 
    Operating expenses           
    Research and development 2,493   2,459   5,159   5,451 
    Selling, general and administrative 29,322   28,935   60,582   61,287 
    Total operating expenses 31,815   31,394   65,741   66,738 
    Income (loss) from operations 16,549   (5,008)  21,610   (15,000)
    Interest expense (8,259)  (236)  (13,082)  (470)
    Interest income 14   532   226   1,058 
    Income (loss) before income taxes 8,304   (4,712)  8,754   (14,412)
    Provision for income taxes 246      246    
    Net income (loss)$8,058  $(4,712) $8,508  $(14,412)
                
    Earnings (loss) per share — basic$0.23  $(0.14) $0.25  $(0.43)
    Weighted-average shares — basic 34,395,266   33,397,709   34,247,977   33,338,243 
                
    Earnings (loss) per share — diluted$0.23  $(0.14) $0.24  $(0.43)
    Weighted-average shares — diluted 35,091,906   33,397,709   35,089,740   33,338,243 
                    



    Collegium Pharmaceutical, Inc.

    Reconciliation of GAAP to Non-GAAP Financial Information

    (in thousands, except per share amounts)

    (unaudited)

     Three months ended Six Months Ended
     June 30,  June 30, 
     2020 2019  2020 2019 
    GAAP net income (loss)$8,058 $(4,712) $8,508 $(14,412)
    Non-GAAP adjustments:           
    Stock-based compensation expense(1) 5,584  4,162   10,535  8,425 
    Intangible asset amortization(2) 16,795  3,688   27,090  7,376 
    Non-cash interest expense(3) 2,524     3,860   
    Nucynta royalty adjustment (4)      14,216   
    Provision for income taxes (5) 246     246   
    Total non-GAAP adjustments$25,149 $7,850  $55,947 $15,801 
    Non-GAAP adjusted income$33,207 $3,138  $64,455 $1,389 
                  

    (1) Represents stock-based compensation expense associated with our stock option, restricted stock unit and performance stock unit grants and our employee share purchase plan.

    (2) Represents amortization expense from the Nucynta Intangible Asset.

    (3) Represents non-cash interest expense recognized related to the accretion of debt discount and amortization of debt issuance costs.

    (4) Represents non-recurring adjustment for royalty expense recognized in 2020 prior to the closing of the Nucynta Asset Purchase Agreement in February 2020. The royalty expense was included as a reduction to the base purchase price for the Nucynta Asset Purchase Agreement and, upon closing, the Company was discharged of any unpaid royalties due to Assertio.

    (5) Represents current provision for estimated income taxes.

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  5. STOUGHTON, Mass., July 21, 2020 (GLOBE NEWSWIRE) -- Collegium Pharmaceutical, Inc. (NASDAQ:COLL) announced today that the Company will host a conference call and live audio webcast on Wednesday, August 5, 2020 at 4:30 p.m. Eastern Time. The Company will discuss its financial results and provide a corporate update.

    Conference Call Information: 

    To access the conference call, please dial (877) 407-8037 (U.S.) or (201) 689-8037 (International) and reference the "Collegium Q2 Earnings Call." An audio webcast will be accessible from the Investors section of the Company's website: www.collegiumpharma.com. The webcast will be available for replay on the Company's website approximately two hours after the event.

    About Collegium Pharmaceutical,

    STOUGHTON, Mass., July 21, 2020 (GLOBE NEWSWIRE) -- Collegium Pharmaceutical, Inc. (NASDAQ:COLL) announced today that the Company will host a conference call and live audio webcast on Wednesday, August 5, 2020 at 4:30 p.m. Eastern Time. The Company will discuss its financial results and provide a corporate update.

    Conference Call Information: 

    To access the conference call, please dial (877) 407-8037 (U.S.) or (201) 689-8037 (International) and reference the "Collegium Q2 Earnings Call." An audio webcast will be accessible from the Investors section of the Company's website: www.collegiumpharma.com. The webcast will be available for replay on the Company's website approximately two hours after the event.

    About Collegium Pharmaceutical, Inc.

    Collegium is a specialty pharmaceutical company committed to being the leader in responsible pain management. Collegium's headquarters are located in Stoughton, Massachusetts. For more information, please visit the company's website at www.collegiumpharma.com.

    Contact:

    Alex Dasalla

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