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Buprenorphine Hydrochloride

Pronunciation: BUE-pre-NOR-feen HYE-droe-KLOR-ide
Class: Opioid agonist-antagonist analgesic

Trade Names

- Injection, solution 0.3 mg/mL

- Patch, transdermal 5 mcg/hour
- Patch, transdermal 10 mcg/hour
- Patch, transdermal 20 mcg/hour

- Tablets, sublingual 2 mg
- Tablets, sublingual 8 mg


Analgesic effect caused by binding to opiate receptors in the CNS. Antagonist effects decrease abuse potential.



C max is approximately 5.47 ng/mL and AUC is approximately 32.63 h•ng/mL (16 mg SL dose). The absolute bioavailability following a 7-day transdermal application is approximately 15%.


Approximately 96% protein bound, primarily to alpha and beta globulin. Vd is approximately 430 L (IV).


Undergoes CYP3A4-mediated N-dealkylation to norbuprenorphine (active) and glucuronidation.


30% is excreted in the urine and 69% in the feces. The mean elimination half-life is 37 h (oral) and 2.2 h (IV). Total Cl is 55 L/h.


15 min (IM).


1 h (IM).


At least 6 h (IM).

Special Populations

Renal Function Impairment

No differences in pharmacokinetics were observed between dialysis-dependent and healthy patients following IV administration.

Hepatic Function Impairment

The effect of hepatic impairment on the pharmacokinetics is unknown. Because it is extensively metabolized, plasma levels are expected to be higher in patients with moderate and severe hepatic impairment.


The pharmacokinetics are similar between younger adults and elderly, although elderly patients showed a trend toward higher plasma concentrations immediately after transdermal system removal.


Cl may be higher in children compared with adults after IV administration.


No differences in C max and AUC or body weight–normalized C max and AUC were observed between men and women treated with the transdermal system.

Indications and Usage

Treatment of opioid dependence (tablet); for the relief of moderate to severe pain (injection); management of moderate to severe chronic pain in patients requiring a continuous, around-the-clock opioid analgesic for an extended period of time (patch).


Known hypersensitivity to the drug or any of the product components.


Significant respiratory depression; severe bronchial asthma; paralytic ileus or suspected paralytic ileus; management of acute pain or in patients who require opioid analgesia for a short period of time; management of postoperative pain, including use after outpatient or day surgeries; management of mild pain; management of intermittent pain (ie, use on an as-needed basis).

Dosage and Administration

Moderate to Severe Pain
Injection Adults and children 13 y of age and older

IM/IV 0.3 mg deep IM or slow IV (over at least 2 min) injection at up to 6 h intervals, as needed. May repeat once (up to 0.3 mg) 30 to 60 min after initial dosage, if required. Single doses of up to 0.6 mg IM may occasionally be necessary and should only be given to adults not in a high-risk category.

Children 2 to 12 y of age

IM/IV 2 to 6 mcg/kg of body weight IM or slow IV (over at least 2 min) given every 4 to 6 h.

High-risk patients

IM/IV Reduce the dose by approximately one-half in high-risk patients, such as elderly or debilitated patients.

Patch Adults

Transdermal Initiate with 5 mcg/h in opioid-naive patients. Dose may be titrated to the next higher level (max, 20 mcg/h) after a minimum of 72 h. For nonopioid-naive patients whose daily dose was less than morphine 30 mg orally or equivalent, initiate treatment with 5 mcg/h. For patients whose daily dose was between 30 and 80 mg of morphine equivalents, initiate treatment with 10 mcg/h. Buprenorphine 20 mcg/h may not provide adequate analgesia for patients requiring more than 80 mg/day of oral morphine equivalents. Each patch is intended to be worn for 7 days.

Opioid Dependence
Tablets Adults (16 y of age and older)

SL 8 mg on day 1, followed by 16 mg on day 2; from day 3 onward, patients should receive buprenorphine/naloxone at the same buprenorphine dose as day 2. Usual maintenance dosage is buprenorphine 12 to 16 mg/day. Treatment should begin at least 4 hours after last use of heroin or short-acting opioid, preferably when first signs of withdrawal appear. Titrate dose to clinical effectiveness as rapidly as possible to prevent unnecessary withdrawal symptoms and patient drop out during induction period.

General Advice

  • Injection
  • For deep IM or slow IV (over at least 2 min) administration only.
  • Tablets
  • For SL use only. Place tablets under the tongue until they are dissolved. Swallowing tablets reduces effectiveness.
  • Do not initiate therapy until objective signs of opioid withdrawal are evident.
  • For doses requiring more than 2 tablets, place all tablets under the tongue and allow to dissolve. If patient cannot fit more than 2 tablets under the tongue at one time, then place 2 tablets under the tongue at a time.
  • Prior to induction, consider the type of opioid dependence, the time since last opioid use, and the degree of opioid dependence.
  • Transdermal
  • For transdermal use only. Apply immediately after removal from the individually sealed pouch. Do not cut patch.
  • Apply patch to a hairless or nearly hairless site on the upper outer arm, upper chest, upper back, or the side of the chest. Do not apply to irritated skin. Rotate patch among skin sites. After removal, wait a minimum of 21 days before reapplying to the same skin site.
  • If the application site must be cleaned, clean the site with water only. Do not use soaps, alcohol, oils, lotions, or abrasive devices. Allow the skin to dry before applying patch.
  • If the patch falls off during the 7-day dosing interval, dispose of the transdermal system properly and place a new patch at a different skin site.
  • If the buprenorphine-containing adhesive matrix accidentally contacts the skin, wash the area with water.
  • When changing the system, remove the patch, fold it over on itself, and flush it down the toilet. Alternatively, it can be sealed in the patch-disposal unit provided and then disposed of in the trash.
  • When discontinuing therapy, taper the dose gradually to prevent signs and symptoms of withdrawal in the physically dependent patient; consider introduction of an appropriate immediate-release opioid medication.


Store tablets and patch at 59° to 86°F. For injection, avoid excessive heat greater than 104°F and protect from prolonged exposure to light.

Drug Interactions

Antiarrhythmic agents, class IA (eg, disopyramide, procainamide, quinidine) or class III (eg, amiodarone, dofetilide, sotalol)

Avoid coadministration of these agents with transdermal buprenorphine.

Barbiturate 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.

Benzodiazepines (eg, diazepam)

Coma and death have been associated with misuse of buprenorphine and benzodiazepines. Use with caution. Warn patients of the potential danger of self-administration of benzodiazepines while receiving treatment with buprenorphine.


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.

CNS depressants (eg, alcohol, phenothiazines, sedative-hypnotics)

Hypotension, profound sedation, coma, or respiratory depression may occur. Use with caution. Consider giving a lower initial dose of CNS depressant.

CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin)

May reduce buprenorphine plasma levels, decreasing the efficacy. Closely monitor the patient and adjust the buprenorphine dose as needed.

CYP3A4 inhibitors (eg, erythromycin, indinavir, ketoconazole, ritonavir, voriconazole)

May elevate buprenorphine plasma levels, increasing the risk of adverse effects. Closely monitor the patient. Buprenorphine dosage adjustment may be required. Transdermal buprenorphine pharmacokinetics do not appear to be affected by CYP3A4 inhibitors.

MAOIs (eg, phenelzine)

Buprenorphine is not recommended for use in patients who have received MAOIs within 14 days.


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 may decrease or attenuate the pharmacologic effects of buprenorphine. Precipitation of withdrawal symptoms may occur. 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 ER injection requiring emergency pain management with opioids.

Nondepolarizing muscle relaxants (eg, tubocurarine)

Concurrent use may enhance neuromuscular blocking action and increase respiratory depression. If coadministration cannot be avoided, monitor respiratory function and be prepared to provide life support if needed.

Sodium oxybate

Concurrent use may result in increased sleep duration and CNS depression because of additive pharmacologic activity. Coadministration of sodium oxybate is contraindicated with other sedative-hypnotics.

Adverse Reactions


Hypotension (1% to 5%); hypertension (1% to less than 5%).


Sedation (67%); headache (34%); insomnia (28%); asthenia, dizziness (16%); anxiety, somnolence (14%); depression (13%); dizziness/vertigo (5% to 10%); chills (8%); nervousness (7%); fatigue (5%); migraine (1% to less than 5%); hypoesthesia, paresthesia, tremor (2%).


Sweating (13%); hyperhidrosis, pruritus (4%); rash (2%).


Runny eyes (7%); pharyngitis (5%); miosis (1% to 5%); nasopharyngitis, pharyngolaryngeal pain (1% to less than 5%).


Nausea (23%); constipation (14%); abdominal pain (12%); vomiting (11%); diarrhea (10%); dry mouth (7%); dyspepsia (6%); nausea/vomiting (1% to 5%); upper abdominal pain (1% to less than 5%); stomach discomfort (2%).


Application-site pruritus (15%); application-site erythema (10%); application-site rash (9%); application-site irritation (5%).


Peripheral edema (7%); anorexia (2%).


Back pain (16%); arthralgia, muscle spasms, musculoskeletal pain, myalgia, neck pain (1% to less than 5%); joint swelling, pain in extremity (3%).


Rhinitis (15%); increased cough (6%); hypoventilation (1% to 5%); bronchitis, cough, sinusitis, upper respiratory tract infection (1% to less than 5%); dyspnea (3%).


Pain (26%); withdrawal syndrome (24%); infection (22%); flu syndrome (10%); fever (6%); abscess (5%); chest pain, influenza, urinary tract infection (1% to less than 5%); fall (4%).



Patient selection

The transdermal formulation is indicated for the management of moderate to severe chronic pain in patients requiring a continuous, around-the-clock opioid analgesic for an extended period of time.

Potential for abuse

Buprenorphine is a Schedule III controlled substance and can be abused in a manner similar to other opioid agonists, legal or illicit.

Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). Assess patients for their clinical risks for opioid abuse or addiction prior to being prescribed opioids.

Limitations of use

Do not exceed a dose of one buprenorphine 20 mcg/h system because of the risk of QTc interval prolongation.

Avoid exposing the transdermal system application site and surrounding area to direct external heat sources. Temperature-dependent increases in buprenorphine release from the system may result in overdose and death.


Ensure that liver enzymes and hepatic function are evaluated prior to starting therapy and periodically during treatment. Document type of opioid dependence (eg, long-, short-acting), time since last opioid use, and degree of opioid dependence prior to starting SL tablets. Monitor patient for respiratory depression. Monitor patient for narcotic withdrawal symptoms, CNS, GI, and general body adverse effects. Routinely monitor all patients receiving opioids for signs of misuse, abuse, and addiction.


Category C . Neonatal withdrawal has been reported in infants of women treated with buprenorphine during pregnancy.


Excreted in breast milk. Breast-feeding is not advised in mothers treated with buprenorphine.


Safety and efficacy not established in children younger than 2 y of age (injection), younger than 16 y of age (oral), or younger than 18 y of age (patch).


Use with caution.


Cases of acute and chronic hypersensitivity, including anaphylactic shock, angioneurotic edema, and bronchospasm have been reported.

Renal Function

Use with caution in patients with severe renal impairment.

Hepatic Function

Dosage should be adjusted and patients should be observed for symptoms of precipitated opioid withdrawal when taken orally; use with caution in severe hepatic impairment when used IV or transdermally.

Special Risk Patients

Use with caution in the following debilitated patients: patients with severely impaired pulmonary function; 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; biliary tract dysfunction; biliary tract disease, including acute pancreatitis; and in patients at risk of developing ileus.

Application-site reaction

Signs of marked inflammation, including burn, discharge, and vesicles, have occurred with patch use.

Drug abuse and dependence

Has abuse potential. Psychological and physical dependence as well as tolerance may occur.

GI conditions

May obscure diagnosis or clinical course of patients with acute abdominal conditions. May cause spasm of the sphincter of Oddi.

Hazardous tasks

May impair the mental or physical abilities required for the performance of potentially dangerous tasks. Administer with caution to ambulatory patients.

Head injury or increased intracranial pressure

Use with caution; drug can increase CSF pressure.

Hepatic effects

Cases of cytolytic hepatitis and hepatitis with jaundice, hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy have been reported.

Hypotensive effects

Buprenorphine may cause severe orthostatic hypotension, sometimes severe.

Narcotic-dependent patients

Use in physically dependent individuals may result in withdrawal effects.

Patients with fever

Patients using buprenorphine patch who develop fever or increased core body temperature due to strenuous exertion should be monitored for opioid adverse effects and the dose should be adjusted accordingly.

QT prolongation

May occur. Use with caution in patients with hypokalemia or clinically unstable cardiac disease.

Respiratory suppression

Significant respiratory depression has occurred, particularly by the IV route. If noted, re-establish adequate ventilation with mechanical assistance. Naloxone may not be effective in reversing respiratory depression caused by this drug. Use with caution in patients with compromised respiratory function.


May aggravate seizure disorders or lower seizure threshold, and therefore may induce seizures.



Atypical snoring, bradycardia, cold and clammy skin, death, hypotension, partial or complete airway obstruction, pinpoint pupils, respiratory depression, sedation, skeletal muscle flaccidity, somnolence progressing to stupor or coma.

Patient Information

  • Caution patient to avoid alcoholic beverages and other CNS depressants (eg, narcotics, benzodiazepines) while taking this drug. Combined use may result in a serious overdose and possibly death.
  • 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 they experience dizziness or light-headedness when standing.
  • Advise patient to contact health care provider if experiencing the following adverse effects: headache, insomnia, nausea, vomiting, or abdominal pain.
  • Advise women who become pregnant or plan to become pregnant to ask their health care provider about the effects that the drug may have on their pregnancy.
  • Inform patients that buprenorphine is a drug that some people may abuse and that they should use buprenorphine only as directed.
  • Injection
  • Advise patient, family, or caregiver that medication is used to control pain and will be prepared and administered by a health care provider in a medical setting.
  • SL tablets
  • Advise patient to take the prescribed dose 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 one time, then advise patient to place 2 tablets at a time under the tongue and repeat until entire dose has been taken.
  • Caution patient that swallowing tablets reduces effectiveness.
  • Advise patient to not change the dose or stop taking unless advised by the health care provider.
  • 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.
  • Transdermal
  • Advise patient to apply transdermal system to a hairless or nearly hairless skin site (eg, upper outer arm, upper chest, upper back, side of the chest) for 7 days.
  • Instruct patients that each week the transdermal system must be applied to a different site, with a minimum of 3 wk between applications to a previously used site.
  • Inform patients that if the application site must be cleaned, to use clear water only. Soaps, alcohol, oils, lotions, or abrasive devices should not be used.
  • Caution patients to avoid exposing the transdermal system site to external heat sources (eg, heating pads, electric blankets, heat lamps, sauna, hot tubs) because an increase in absorption of the drug may occur that could lead to an overdose or death.
  • Instruct patients to promptly report the development of severe application-site reactions (eg, inflammation, discharge) and to discontinue therapy.
  • Advise patients who develop a fever or an increase in body temperature due to strenuous exertion that they may need to have their dose adjusted.

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