Buprenex - Drug Monograph

Introduction

Buprenex (buprenorphine hydrochloride) is a semi-synthetic opioid analgesic medication that combines potent analgesic properties with a unique pharmacological profile. As a partial mu-opioid receptor agonist and kappa-opioid receptor antagonist, it occupies a distinctive position in pain management and medication-assisted treatment for opioid use disorder. Originally approved by the FDA in 1981, Buprenex is available as an injectable formulation for intramuscular or intravenous administration.

Mechanism of Action

Buprenorphine exerts its analgesic effects primarily through partial agonism at the mu-opioid receptor. Unlike full opioid agonists, it demonstrates a ceiling effect for respiratory depression while maintaining effective analgesia. Additionally, buprenorphine acts as an antagonist at the kappa-opioid receptor, which may contribute to its antidepressant properties and lower abuse potential. The drug displays high receptor affinity and slow dissociation from opioid receptors, resulting in prolonged duration of action and milder withdrawal symptoms compared to full agonists.

Indications

• Management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate

• Medication-assisted treatment for opioid use disorder (typically using sublingual formulations)
• Post-operative pain management
• Chronic pain conditions requiring long-term opioid therapy

Dosage and Administration

• Initial dose: 0.3 mg IM or slow IV injection (over at least 2 minutes)
• Repeat every 6-8 hours as needed for pain
• Dose titration: May increase to 0.6 mg per dose if necessary

• Hepatic impairment: Use with caution; consider dose reduction
• Renal impairment: No dosage adjustment typically required
• Elderly: Initiate with lower doses (0.15 mg)
• Pediatric: Safety and effectiveness not established for children under 2 years

• IV administration must be slow (over at least 2 minutes)
• IM injection should be into large muscle masses
• Rotate injection sites for repeated administration

Pharmacokinetics

Contraindications

• Hypersensitivity to buprenorphine or any component of the formulation
• Significant respiratory depression
• Acute or severe bronchial asthma in an unmonitored setting or without resuscitation equipment
• Known or suspected paralytic ileus
• Concurrent use with benzodiazepines or other CNS depressants (unless closely monitored)

Warnings and Precautions

• Serious, life-threatening, or fatal respiratory depression may occur
• Accidental exposure to Buprenex, especially in children, can result in fatal overdose
• Potential for abuse and dependence exists

• Risk of QT prolongation at higher doses
• Use with caution in patients with head injury, increased intracranial pressure, or brain tumors
• May cause severe hypotension in volume-depleted patients
• Hepatic impairment may reduce metabolism and increase exposure
• Risk of adrenal insufficiency with long-term use
• May obscure diagnosis or clinical course of acute abdominal conditions

Drug Interactions

• Benzodiazepines and other CNS depressants: Increased risk of respiratory depression, hypotension, and sedation
• CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin): Increased buprenorphine levels
• CYP3A4 inducers (rifampin, carbamazepine, phenytoin): Decreased buprenorphine efficacy
• MAO inhibitors: Risk of serotonin syndrome and enhanced opioid effects
• Other opioid analgesics: May precipitate withdrawal in opioid-dependent patients

• Anticholinergic agents: Increased risk of urinary retention and constipation
• Serotonergic drugs: Potential serotonin syndrome risk

Adverse Effects

• Sedation/drowsiness
• Nausea and vomiting
• Dizziness
• Headache
• Sweating
• Constipation

• Hypotension
• Respiratory depression
• Pruritus
• Dry mouth
• Miosis

• Respiratory depression and arrest
• QT prolongation and torsades de pointes
• Adrenal insufficiency
• Severe hypotension
• Anaphylaxis
• Seizures
• Withdrawal symptoms upon discontinuation

Monitoring Parameters

• Respiratory rate, depth, and rhythm (especially during initiation and dose increases)
• Blood pressure and heart rate
• Pain intensity and relief scores
• Signs of misuse or abuse
• Bowel function (constipation management)
• Mental status changes
• Liver function tests (periodically with long-term use)
• ECG monitoring (if high doses used or cardiac risk factors present)
• Signs of adrenal insufficiency
• Withdrawal symptoms upon discontinuation

Patient Education

• This medication can cause drowsiness and dizziness; avoid driving or operating machinery until effects are known
• Do not consume alcohol or other sedating medications while taking Buprenex
• Report any difficulty breathing, extreme drowsiness, or slow heart rate immediately
• Maintain adequate fluid intake and dietary fiber to prevent constipation
• Do not stop medication abruptly without medical supervision
• Store securely away from children and pets
• Dispose of unused medication properly
• Inform all healthcare providers about Buprenex use before any procedures
• Use exactly as prescribed; do not increase dose without medical advice
• Be aware of potential for dependency with long-term use

References

1. FDA Prescribing Information: Buprenex (buprenorphine hydrochloride) Injection 2. Strain EC. "Buprenorphine for chronic pain: a review of the clinical evidence." Journal of Pain Research. 2018;11:1369-1377 3. Johnson RE, et al. "Buprenorphine: considerations for pain management." Journal of Pain and Symptom Management. 2005;29(3):297-326 4. Dahan A, et al. "Incidence, reversal, and prevention of opioid-induced respiratory depression." Anesthesiology. 2010;112(1):226-238 5. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. SAMHSA Treatment Improvement Protocol 40 6. Pergolizzi JV, et al. "Buprenorphine for chronic pain: a review of the literature." Expert Opinion on Pharmacotherapy. 2021;22(11):1439-1454 7. Webster LR, et al. "Understanding buprenorphine for the treatment of chronic pain: a review of the literature." Pain Medicine. 2020;21(10):2153-2167