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Buprenorphine Hydrochloride / Naloxone Hydrochloride
Pronunciation: BUE-pre-NOR-feen HYE-droe-KLOR-ide/nal-OX-one HYE-droe-KLOR-ide
Class: Opioid agonist-antagonist analgesic
- Film, sublingual buprenorphine 2 mg/naloxone 0.5 mg
- Film, sublingual buprenorphine 8 mg/naloxone 2 mg
- Tablets, sublingual buprenorphine 2 mg/naloxone 0.5 mg
- Tablets, sublingual buprenorphine 8 mg/naloxone 2 mg
Partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor.Naloxone
Potent antagonist at mu-opioid receptors.
Indications and Usage
For the maintenance treatment of opioid dependence.
Hypersensitivity to buprenorphine or naloxone.
Dosage and AdministrationSublingual Film
SL Target dosage is buprenorphine 16 mg/naloxone 4 mg as a single daily dose. Adjust the dose in increments/decrements of buprenorphine 2 or 4 mg to a level that holds the patient in treatment and suppresses opioid withdrawal effects. This is likely to range between buprenorphine 4 and 24 mg/day.Sublingual Tablets
Adults and children 16 y and older
SL Single daily dose in the range of buprenorphine 12 to 16 mg. The dose should be adjusted in increments/decrements of buprenorphine 2 or 4 mg to a level that holds the patient in treatment and suppresses opioid withdrawal effects. This is likely to range between buprenorphine 4 and 24 mg/day.
- For sublingual administration only. Do not chew, crush, or swallow the film or tablets. Place film or tablet under the tongue until completely dissolved. Swallowing the film or tablets reduces effectiveness.
- Patients being switched between sublingual tablets and sublingual film should be started on the same dosage as the previously administered product. However, dosage adjustments may be necessary when switching between products. Because of the potentially greater relative bioavailability of sublingual film compared with sublingual tablets, patients switching from sublingual tablets to sublingual film should be monitored for overmedication. Those switching from sublingual film to sublingual tablets should be monitored for withdrawal or other indications of underdosing.
- Make the decision to discontinue therapy with buprenorphine/naloxone after a period of maintenance or brief stabilization as part of a comprehensive treatment plan. Gradual and abrupt discontinuation has been used, but no controlled trials have been undertaken to determine the best method of dose taper at the end of treatment.
Store between 59° and 86°F.
Drug InteractionsBarbiturate anesthetics (eg, thiopental)
May have additive effects with buprenorphine, increasing the respiratory and CNS effects. Monitor the patient and adjust the buprenorphine dose as needed.Cimetidine
The risk of buprenorphine CNS toxicity may be increased. Monitor the patient. If excessive CNS or respiratory depression occurs, discontinue both drugs. Give a narcotic antagonist (eg, naloxone) if needed.Clonidine
Sudden elevation of BP may occur when naloxone is administered to patients receiving clonidine. Closely monitor BP and adjust treatment as needed.CNS depressants (eg, alcohol, benzodiazepines [eg, diazepam], general anesthetics, opioid analgesics, phenothiazines, sedative/hypnotics)
Increased CNS and respiratory depression may occur. Death has been reported. Use with caution. Consider dose reduction of CNS depressants. Warn patients of the associated dangers of coadministration.CYP3A4 inducers (eg, carbamazepine, efavirenz, etravirine, nevirapine, phenobarbital, phenytoin, rifampin)
May reduce buprenorphine plasma levels, decreasing the efficacy. Monitor patients for signs and symptoms of opioid withdrawal.CYP3A4 inhibitors (eg, azole antifungal agents [eg, ketoconazole], delavirdine, macrolide antibiotics [eg, erythromycin], protease inhibitors [eg, atazanavir])
May elevate buprenorphine plasma levels, increasing the risk of adverse effects. Closely monitor the clinical response. A dose reduction in one or both agents may be needed.Methadone
Buprenorphine may decrease or attenuate the pharmacologic effects of methadone. Precipitation of withdrawal symptoms may occur. Closely monitor for signs of opioid withdrawal or reduced opioid efficacy. Buprenorphine should not be administered to patients with dependence on methadone.Naltrexone
Naltrexone may decrease or attenuate the pharmacologic effects of buprenorphine. Closely monitor for signs of buprenorphine withdrawal or reduced efficacy. Buprenorphine-dependent patients should be detoxified before treatment with naltrexone. If there is any question of occult buprenorphine dependence, a naltrexone challenge test should be performed and treatment deferred until the naltrexone challenge is negative. Cardiopulmonary resuscitation staff and equipment should be available for patients receiving naltrexone who require emergency pain management with opioids.Opioid analgesics
The analgesic effects of opioids may be decreased. Opioid withdrawal symptoms in opioid-dependent patients may occur. Avoid indiscriminate use of buprenorphine. To avoid precipitating withdrawal in opioid-dependent patients, undertake induction with buprenorphine only when objective and clear signs of withdrawal are evident.Sodium oxybate
Concurrent use may result in increased sleep duration and CNS depression. Coadministration is contraindicated.
Vasodilation (9%); palpitations.
Headache (36%); insomnia (14%); asthenia (7%); disturbance in attention.
Rhinitis (5%); oral hypoesthesia (more than 1%); blurred vision; glossodynia; oral mucosal erythema.
Nausea (15%); constipation (12%); abdominal pain (11%); vomiting (8%); diarrhea (4%).
Withdrawal syndrome (25%); pain (22%); sweating (14%); chills (8%); infection (6%); back pain (4%); intoxication; peripheral edema (postmarketing).
Ensure that liver enzymes and hepatic function are evaluated prior to starting therapy and periodically during treatment. Monitor patient for respiratory depression. Monitor patient for narcotic withdrawal symptoms.
Category C . Neonatal withdrawal syndrome has been reported in pregnant women treated with buprenorphine.
Buprenorphine is excreted in breast milk. Breast-feeding is not advised.
Safety and efficacy not established in children (sublingual film) or in children younger than 16 y (sublingual tablet).
Use with caution.
Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported.
Use caution in patients with severe renal impairment.
Use caution in patients with severe hepatic impairment. Adjust dosage and watch for signs and symptoms of precipitated opioid withdrawal in patients with moderate to severe hepatic impairment.
Special Risk Patients
Use with caution in debilitated patients; use with caution in myxedema or hypothyroidism, adrenal cortical insufficiency (eg, Addison disease), CNS depression or coma, toxic psychoses, prostatic hypertrophy or urethral stricture, acute alcoholism, delirium tremens, or kyphoscoliosis.
Acute abdominal conditions
May obscure the diagnosis or clinical course of patients with acute abdominal conditions.
Buprenorphine/naloxone is not appropriate as an analgesic.
Biliary tract dysfunction
May increase intracholedochal pressure; use with caution in patients with dysfunction of the biliary tract.
Buprenorphine has abuse potential. Psychological and physical dependence as well as tolerance may occur.
Head injury or increased IOP
Use with caution; drug can increase CSF pressure.
Cases of cytolytic hepatitis and hepatitis with jaundice have occurred.
May occur, especially when taken in combination with benzodiazepines or other CNS depressants (eg, alcohol). Use with caution in patients with compromised respiratory function (eg, COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, preexisting respiratory depression).
Marked and intense withdrawal symptoms are likely to occur if misused parenterally by individuals dependent on opioid agonists; sublingual use may cause opioid withdrawal symptoms if administered before the agonist effects of the opioid have subsided.
Death, hypotension, pinpoint pupils, respiratory depression, sedation.
- Advise patient to take prescribed dose of tablets once daily by placing tablet under the tongue until dissolved. For dose requiring more than 2 tablets, advise patient to place all tablets under the tongue and allow to dissolve. If patient cannot fit more than 2 tablets under the tongue at 1 time, then advise patient to place 2 tablets under the tongue at a time and repeat until entire dose has been taken.
- Instruct patients not to chew or swallow films or tablets. Caution patient that swallowing tablets reduces effectiveness.
- Advise patient to not change the dose or stop taking unless advised by the health care provider.
- Caution patient to avoid alcoholic beverages and other CNS depressants (eg, narcotics, benzodiazepines) while taking this drug. Combined use may result in a serious toxicity and possibly death.
- Advise patient to inform family members that, in the event of an emergency, the treating emergency personnel should be informed that the patient is physically dependent on narcotics and is being treated with buprenorphine.
- Advise patient that drug may impair mental or physical abilities required for the performance of potentially hazardous tasks and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
- Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
- Instruct patient to lie or sit down if experiencing dizziness or light-headedness when standing.
- Advise patient to contact their health care provider if they experience the following adverse effects: headache, insomnia, nausea, vomiting, abdominal pain.
- Inform breast-feeding women that buprenorphine passes into breast milk and breast-feeding is not advised in women treated with buprenorphine products.
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