Buprenorphine

Buprenorphine is indicated for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate. Buprenorphine is available under the following different brand names: Buprenex.

Limitations of Use

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses reserve buprenorphine for use in patients for whom alternative treatment options [e.g., 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

Adult and Pediatric Dosage Forms and Strengths

Injectable solution: Schedule III (Buprenex

• 0.3 mg/mL

Tablet, sublingual: Schedule III (generic)

• 2 mg
• 8 mg

Dosage Considerations – Should be Given as Follows:

Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death

• 0.25 mg orally every 12 hours initially; may increase to 1 mg/day after 3 days (up to 4 mg/day in some patients)

Moderate-to-Severe Pain

• Adult: 0.3 mg intravenous/intramuscular (IV/IM) every 6 hours; for IV, administered slowly over 2 minutes; maybe repeated once (up to 0.3 mg) if required 30-60 minutes after the initial dose
• Children under 2 years: Safety and efficacy not established
• Children 2-12 years: 2-6 mcg/kg slow IV/IM every 4-6 hours as needed
• Children over 12 years: As in adults
• Geriatric: 0.15 mg IV/IM every 6 hours; for IV, administered slowly over 2 minutes

Opioid Dependence

Induction (sublingual tablet)

• 8 mg sublingually (SL) on day 1, then 16 mg SL on day 2; continued over 3-4 days

Maintenance (buprenorphine-naloxone combination)

• Switch to buprenorphine/naloxone combination for unsupervised maintenance
• For dosing, see drug monograph for buprenorphine/naloxone

Children under 16 years: Not recommended

Children 16 years and older: As in adults

Dosage Modifications

• Renal impairment: Use with caution; dosage adjustments recommended
• Hepatic impairment
  • Mild: No dose adjustment is needed
  • Moderate: No dose adjustment is necessary, closely monitor patients for signs and symptoms of toxicity or overdose
  • Severe: Reducing the starting and titration incremental dose by half, and monitor for signs and symptoms of toxicity or overdose

• Renal impairment: Supplemental dose in hemodialysis not necessary

Dosing Considerations

• For prescriber qualifications, see prescribing information
• Also given in combination with naloxone
• Decrease dose with hepatic or renal impairment, respiratory disease, geriatric or debilitated patients

Side effects associated with the use of Buprenorphine, include the following:

• Sedation
• Dizziness
• Headache
• Low blood pressure (hypotension)
• Slow breathing
• Constricted pupils
• Nausea
• Spinning sensation (vertigo)
• Sweating
• Vomiting

Less common side effects of buprenorphine include:

• Abdominal cramps
• Blurred vision
• Coma
• Confusion
• Conjunctivitis
• Constipation
• Cyanosis
• Depersonalization
• Dilated pupils
• Double vision
• Dreaming
• Dry mouth
• Electrocardiographic (ECG) abnormalities
• Euphoria
• Fast heart rate
• Fatigue
• Feeling unwell (malaise)
• Gas (flatulence)
• Hallucinations
• High blood pressure (hypertension)
• Hives
• Indigestion
• Injection-site reactions
• Itching
• Lazy eye
• Mental depression
• Nervousness
• Numbness and tingling
• Pauses in breathing, especially during sleep (apnea)
• Psychosis
• Respiratory depression
• Shortness of breath
• Slow heart rate
• Slurred speech

Postmarketing side effects of buprenorphine reported include:

• Adrenal Insufficiency
• Serotonin syndrome
• Liver damage

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Severe interactions of buprenorphine include:
  • alvimopan
• Buprenorphine has serious interactions with at least 42 different drugs.
• Buprenorphine has moderate interactions with at least 195 different drugs.
• Mild Interactions of buprenorphine include:
  • brimonidine
  • dextroamphetamine
  • elvitegravir
  • eucalyptus
  • lidocaine
  • sage
  • ziconotide

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns, or for more information about this medicine.

Warnings

Addiction, abuse, and misuse:

• Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
• Assess each patient's risk before prescribing and monitor all patients regularly for the development of these behaviors or conditions

Life-threatening respiratory depression:

• Serious, life-threatening, or fatal respiratory depression may occur
• Monitor for respiratory depression, especially during initiation or following a dose increase

Accidental exposure:

• Accidental exposure of even 1 dose, especially by children, can result in a fatal overdose

Neonatal Opioid Withdrawal Syndrome:

• Prolonged use 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
• Syndrome presents as irritability, hyperactivity, and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight
• Onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn
• 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 systems (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required, and follow patients for signs and symptoms of respiratory depression and sedation

This medication contains buprenorphine. Do not take Buprenex if you are allergic to buprenorphine or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity
• Significant respiratory depression
• Acute or severe bronchial asthma in an unmonitored setting or the absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus

Effects of Drug Abuse

Addiction, abuse, and misuse

• Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
• Assess each patient's risk before prescribing and monitor all patients regularly for the development of these behaviors or conditions

Short-Term Effects

• Accidental exposure of even 1 dose, especially by children, can result in a fatal overdose
• See "What Are Side Effects Associated with Using Buprenorphine?"

Long-Term Effects

• Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; 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
• Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; unknown whether effects on fertility are reversible
• Abrupt withdrawal, particularly in patients on long-term, high-dose therapy, may precipitate status epilepticus; when discontinuing buprenorphine, gradual withdrawal is essential; while being gradually withdrawn, the simultaneous substitution of another anticonvulsant may be indicated.
• See "What Are Side Effects Associated with Using Buprenorphine?”

Cautions

• Partial agonist at the mu-opioid receptor and a schedule III controlled opioid exposes users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids owing to the larger amount of active opioids present
• Serious, life-threatening, or fatal respiratory depression reported; may occur more frequently in elderly or debilitated patients, or conditions associated with hypoxia or hypercapnia (even moderate therapeutic doses)
• Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy
• Accidental exposure was reported, including fatalities
• Interactions with CNS depressants (e.g., alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase the risk for respiratory depression, profound sedation, and hypotension
• Risk of apnea in patients with chronic pulmonary disease; closely monitor these patients, when initiating and titrating therapy; alternatively, consider the use of alternative non-opioid analgesics in these patients
• QTc prolongation observed in healthy individuals at 40 mcg/hour; avoid in patients with a history of long QT syndrome or co-administration with class IA (e.g., quinidine, procainamide, disopyramide) or class III (e.g., sotalol, amiodarone, dofetilide) antiarrhythmics
• Respiratory depressant effects of opioids may include carbon dioxide retention and lead to elevated cerebrospinal fluid (CSF) pressure
• Can cause severe hypotension; caution with depleted blood volume or co-administration of drugs that affect vasomotor tone (e.g., phenothiazines), vasodilators, or antihypertensives
• Hypothyroidism, myxedema, adrenocortical insufficiency, alcohol intoxication, alcohol withdrawal syndrome, coma, geriatric or debilitated patients, delirium tremens, toxic psychoses, kyphoscoliosis, prostatic hypertrophy, urethral stricture, central nervous system (CNS) depression, biliary tract dysfunction, head injury, intracranial lesions, intracranial hypertension or conditions in which intracranial pressure may be increased
• Cases of cytolytic hepatitis and hepatitis with jaundice observed in individuals receiving buprenorphine SL for opioid dependence treatment; increased risk for overdose with moderate or severe hepatic impairment
• Anaphylactic reactions reported
• Caution in severe renal impairment
• Severe hepatic impairment can cause increased buprenorphine plasma levels and prolonged half-life, but not in subjects with mild hepatic impairment; dose adjustment recommended in patients with moderate or severe hepatic; consider reducing the dose by half and closely monitor for signs and symptoms of toxicity and overdose
• May cause sphincter of Oddi spasm and aggravate abdominal conditions, including ileus
• Respiratory sedation (dose-dependent; usual doses may depress respiration to the same degree as 10 mg of parenteral morphine)
• Similar to other opioids, may aggravate seizure disorders by lowering the seizure threshold
• Patients with cancer who have oral mucositis may absorb buprenorphine more rapidly than intended and have higher plasma levels of buprenorphine
• Special risk groups may experience increased adverse reactions; caution with alcoholism, delirium tremens, adrenocortical insufficiency, CNS depression, debilitation, kyphoscoliosis associated with respiratory compromise, myxedema or hypothyroidism, prostatic hypertrophy or urethral stricture, severe impairment of hepatic, pulmonary or renal function, and toxic psychosis
• Prescribers should discuss with patients the importance and benefits of management of opioid addiction throughout pregnancy
• Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; 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
• Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; unknown whether effects on fertility are reversible

Pregnancy and Lactation

• Opioids such as buprenorphine cross the placenta and may produce respiratory depression and psychophysiological effects in neonates; buprenorphine is not recommended for use in women immediately before and during labor when the use of shorter-acting analgesics or other analgesic techniques are more appropriate
• Neonates whose mothers have been taking opioids long term may also exhibit withdrawal signs, either at birth and/or in the nursery because they have developed physical dependence; neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts
• Caution should be exercised when buprenorphine therapy is administered to nursing women; the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for therapy and any potential adverse effects on the breastfed child from the drug or from an underlying maternal condition