BUPRENORPHINE HYDROCHLORIDE

BUPRENORPHINE HYDROCHLORIDE (byoo-pre-nor'feen) Buprenex, Subutex Classifications: analgesic; narcotic (opiate) agonist-antagonist; Therapeutic: narcotic analgesic; opiate Prototype: Pentazocine Pregnancy Category: C Controlled Substance: Schedule III

Availability

0.3 mg (base)/mL injection; 2 mg, 8 mg sublingual tablets

Action

Opiate agonist-antagonist with agonist activity approximately 30 times that of morphine and antagonist activity equal to or up to 3 times that of naloxone. Respiratory depression occurs infrequently, probably due to drug's opiate antagonist activity. Has a low level of physical dependence.

Therapeutic Effect

Dose-related analgesia results from a high affinity of buprenorphine for mu-opioid receptors and an antagonist at the kappa-opiate receptors in the CNS. Naloxone is an antagonist at the mu-opioid receptor.

Uses

Injectable used for moderate to severe pain. Sublingual tablets used for treatment of opioid dependence.

Unlabeled Uses

Injectable to reverse fentanyl-induced anesthesia. Sublingual tablets may be used to ease cocaine withdrawal.

Contraindications

Hypersensitivity to buprenorphine or hypersensitivity to naloxone; pregnancy (category C), lactation, children <2 y.

Cautious Use

Patient with history of opiate use; compromised respiratory function [e.g., chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression]; concomitant use of other respiratory depressants; hypothyroidism, myxedema, Addison's disease; severe renal or hepatic impairment; geriatric or debilitated patients; acute alcoholism, delirium tremens; prostatic hypertrophy, urethral stricture; comatose patient; patients with CNS depression, head injury, or intracranial lesion; biliary tract dysfunction.

Route & Dosage

Postoperative Pain Adult/Adolescent (>12 y): IV/IM 0.3 mg q6h up to 0.6 mg q4h or 25–50 mcg/h by IV infusion Geriatric: IV/IM 0.15 mg q6h Child (2–12 y): IV/IM 2–6 mcg/kg q4–6h prn Opioid Dependence/Cocaine Withdrawal Adult: SL Initiate with 8 mg q.d. Subutex on day 1 at least 4 h after last opioid dose, 16 mg q.d. Subutex on day 2, then switch to Suboxone for maintenance therapy at the same buprenorphine dose as day 2 (e.g., 16 mg q.d.). Adjust dose daily until opiate withdrawal effects are suppressed. Maintenance dose range 4–24 mg/d buprenorphine.

Administration

Sublingual

• Place SUBONONE and SUBUTEX tablets under tongue until dissolved. For doses requiring more than two tablets, place all tablets at once under tongue, or if patient cannot accommodate all tablets, place two tablets at a time under tongue.
• Instruct to hold the tablets under tongue until dissolved; advise not to swallow.

Intramuscular

• Give undiluted, deep IM into a large muscle.

Intravenous PREPARE: Direct/IV Infusion: May be given undiluted direct IV or further dilute each 1 mL (0.3 mg) ampule in 50 mL of D5W, NS, D5NS, or RL to yield 6 mcg/mL for infusion. Do not use if discolored or contains particulate matter.   ADMINISTER: Direct: ??Give slowly at a rate of 0.3 mg over 2 min to a patient in a recumbent position. IV Infusion: Give by slow infusion over 3 min or longer depending on volume of IV solution.   INCOMPATIBILITIES Solution/Additive: Diltiazem, floxacillin, furosemide, lorazepam. Y-site: Amphotericin B cholesteryl sulfate complex, doxorubicin liposome, lansoprazole.

• Store at 15°–30° C (59°–86° F); avoid freezing.

Adverse Effects (≥1%)

CNS: Sedation, drowsiness, dizziness, vertigo, headache, amnesia, euphoria, asthenia, insomnia, pain (when used for withdrawal), withdrawal symptoms. CV: Hypotension, vasodilation. Special Senses: Miosis. GI: Nausea, vomiting, diarrhea, constipation. Respiratory: Respiratory depression, hyperventilation. Skin: Pruritus, injection site reactions, sweating.

Interactions

Drug: Alcohol, opiates, other cns depressants, benzodiazepines augment CNS depression; diazepam may cause respiratory or cardiovascular collapse; azole antifungals (e.g., fluconazole), macrolide antibiotics (e.g., erythromycin), and protease inhibitors (e.g., saquinavir) may increase buprenorphine levels.

Pharmacokinetics

Absorption: Widely variable sublingual absorption. Onset: 10–30 min IM/IV. Peak: 1 h IM/IV; 2–6 h SL. Duration: 6–10 h. Metabolism: Extensively in liver by CYP3A4 to active metabolite norbuprenorphine. Elimination: 70% in feces, 30% in urine in 7 d. Half-Life: 2.2 h IM/IV; 37 h SL.

Nursing Implications

Assessment & Drug Effects

• Monitor respiratory status during therapy. Buprenorphine-induced respiratory depression is about equal to that produced by 10 mg morphine, but onset is slower, and if it occurs, it lasts longer.
• Note: Respiratory depression in the healthy adult plateaus or may even decrease in severity with doses more than 1.2 mg because of antagonist activity of the drug.
• Use lower dosing of buprenorphine with a concurrent NSAID or other nonnarcotic analgesic due to additive analgesic effect.
• Monitor I&O ratio and pattern during buprenorphine therapy; urinary retention is a potential adverse effect.
• Lab tests: Baseline liver function, renal function, alkaline phosphatase, and PSA.
• Supervise ambulation; drowsiness occurs in 66% of patients taking this drug.

Patient & Family Education

• Do not drive or engage in other potentially hazardous activities until response to drug is known.
• Do not use alcohol or other CNS depressing drugs without consulting physician. An additive effect exists between buprenorphine hydrochloride and other CNS depressants including alcohol.

---

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug