Butrans (buprenorphine)

WARNING

ADDICTION, ABUSE and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS

Addiction, Abuse, and Misuse

Butrans 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 Butrans, and monitor all patients regularly for the development of these behaviors and conditions.

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of Butrans. Monitor for respiratory depression, especially during initiation of Butrans or following a dose increase. Misuse or abuse of Butrans by chewing, swallowing, snorting or injecting buprenorphine extracted from the transdermal system will result in the uncontrolled delivery of buprenorphine and pose a significant risk of overdose and death.

Accidental Exposure

Accidental exposure to even one dose of Butrans, especially in children, can result in a fatal overdose of buprenorphine.

Neonatal Opioid Withdrawal Syndrome

Prolonged use of Butrans 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 Butrans 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.

Butrans may cause serious side effects including:

• weak or shallow breathing,
• deep sighs,
• snoring that is new or unusual,
• breathing that stops during sleep,
• chest pain,
• fast heart rate,
• seizure,
• lightheadedness,
• blisters, swelling, severe irritation where the patch was worn,
• nausea,
• vomiting,
• loss of appetite,
• dizziness,
• feeling weak or tired,
• upper stomach pain,
• dark urine,
• clay-colored stools,
• yellowing of the skin or eyes (jaundice),
• agitation,
• hallucination,
• fever,
• sweating,
• shivering,
• muscle stiffness,
• twitching,
• loss of coordination, and
• diarrhea

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Butrans include:

• constipation,
• nausea,
• vomiting,
• headache,
• dizziness,
• drowsiness,
• tiredness, and
• redness, itching, or rash where the patch was worn

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Butrans. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Controlled Substance

• Butrans contains buprenorphine, a Schedule III controlled substance.

Abuse

• Butrans contains buprenorphine, a Schedule III controlled substance with an abuse potential similar to other Schedule III opioids. Butrans can be abused and is subject to misuse, addiction and criminal diversion. The high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse.
• All patients treated with opioids, including Butrans, require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
• Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.
• Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
• “Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare providers(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.
• Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.
• Butrans, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
• Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific To The Abuse Of Butrans

• Butrans is intended for transdermal use only.
• Abuse of Butrans poses a risk of overdose and death. This risk is increased with concurrent abuse of Butrans with alcohol and other substances including other opioids and benzodiazepines.
•  Intentional compromise of the transdermal delivery system will result in the uncontrolled delivery of buprenorphine and pose a significant risk to the abuser that could result in overdose and death.
• Abuse may occur by applying the transdermal system in the absence of legitimate purpose, or by chewing, swallowing, snorting, or injecting buprenorphine extracted from the transdermal system. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Dependence

• Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.
• Physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug.
• Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), or mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine).
• Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.
• Do not abruptly discontinue Butrans in a patient physically dependent on opioids.
• Rapid tapering of Butrans in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide.
• Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.
• When discontinuing Butrans, gradually taper the dosage using a patient-specific plan that considers the following: the dose of Butrans the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient.
• To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper.
• Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs.

Important Dosage And Administration Information

Butrans should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Butrans doses of 7.5, 10, 15, and 20 mcg/hour are only for use in patients who are opioid experienced and in whom tolerance to an opioid of comparable potency has been established. Patients who are opioid-experienced are those receiving, for one week or longer, daily opioid doses up to 80 mg/day of oral morphine or an equianalgesic dose of another opioid.

• Use the lowest effective dosage for the shortest duration consistent with individual patients treatment goals.
• Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse.
• Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with Butrans.
• Instruct patients not to use Butrans if the pouch seal is broken or the patch is cut, damaged, or changed in any way and not to cut Butrans.
• Instruct patients to avoid exposing Butrans to external heat sources, hot water, or prolonged direct sunlight.

Butrans is for transdermal use (on intact skin) only. Each Butrans patch is intended to be worn for 7 days.

Table 5 Includes clinically significant drug interactions with Butrans.

Table 5: Significant Drug Interactions with Butrans

• Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome.
• Available data with Butrans in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.
• Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Butrans.