Usage
- Buprenorphine + Naloxone is prescribed for the maintenance treatment of opioid dependence (addiction to opioid drugs such as heroin or morphine) as part of a comprehensive treatment plan that includes counseling and psychosocial support.
- Pharmacological Classification: Opioid partial agonist (buprenorphine) and opioid antagonist (naloxone).
- Mechanism of Action: Buprenorphine acts as a partial agonist at the mu-opioid receptor, reducing cravings and withdrawal symptoms. Naloxone, an opioid antagonist, is added to deter intravenous misuse; it has poor sublingual/buccal bioavailability and minimal effect when the combination product is taken as directed.
Alternate Names
- International/Regional Variations: Suboxone (sublingual film), Bunavail (buccal film), Zubsolv (sublingual tablet).
How It Works
- Pharmacodynamics: Buprenorphine produces a ceiling effect on respiratory depression, making overdose less likely than with full opioid agonists. Naloxone is only active when injected, deterring misuse.
- Pharmacokinetics: Both drugs are well-absorbed sublingually/buccally. Buprenorphine is primarily metabolized by the liver (CYP3A4 enzyme), while naloxone is metabolized by the liver and undergoes glucuronidation. Both drugs and their metabolites are primarily eliminated in urine, with some fecal excretion.
- Mode of Action: Buprenorphine binds to mu-opioid receptors, producing partial agonist effects. Naloxone binds to opioid receptors but acts as an antagonist, blocking the effects of other opioids.
- Receptor Binding: Mu-opioid receptor.
- Elimination Pathways: Hepatic metabolism (CYP3A4 for buprenorphine), renal and fecal excretion.
Dosage
Standard Dosage
Adults:
- Induction: For patients dependent on short-acting opioids, administer up to 8 mg/2 mg of buprenorphine/naloxone on Day 1, divided into two or more doses as needed to manage withdrawal. On Day 2, administer up to 16 mg/4 mg as a single dose. For patients dependent on long-acting opioids (e.g., methadone), buprenorphine monotherapy is recommended for induction.
- Maintenance: The target dosage is 16 mg/4 mg of buprenorphine/naloxone as a single daily dose. Dosages up to 24mg/6mg per day can be used.
Children:
- Use and dose must be determined by a physician.
- Safety and efficacy haven’t been established in children under 15 years of age (Suboxone film) or 16 (Zubsolv tablets).
Special Cases:
- Elderly Patients: Start with lower doses due to potential for decreased hepatic, renal, or cardiac function.
- Patients with Renal Impairment: Caution is advised in severe renal impairment (creatinine clearance < 30 mL/min). Dose adjustment may be necessary.
- Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment. Dosage adjustments are needed for mild to moderate dysfunction.
- Patients with Comorbid Conditions: Careful consideration should be given to patients with respiratory disorders, head injuries, adrenal insufficiency, prostatic hypertrophy, or those taking CNS depressants or QT interval prolonging drugs.
Clinical Use Cases
Buprenorphine + Naloxone is specifically indicated for the treatment of opioid use disorder. Its use in other clinical settings, like those described below, would typically be considered off-label and not recommended. There are other medications specifically indicated for use in such settings.
Dosage Adjustments
- Dose modification may be needed based on individual patient response and tolerability, hepatic and renal function, and concurrent medications.
Side Effects
Common Side Effects
- Headache, nausea, vomiting, constipation, insomnia, sweating, dizziness, drowsiness, withdrawal symptoms, mouth pain/numbness/redness.
Rare but Serious Side Effects
- Respiratory depression, liver damage (hepatotoxicity), adrenal insufficiency, allergic reactions (anaphylaxis), QT prolongation, serotonin syndrome (with serotonergic drugs).
Long-Term Effects
- Adrenal insufficiency, dependence.
Adverse Drug Reactions (ADR)
- Respiratory depression, anaphylaxis, QT prolongation, serotonin syndrome.
Contraindications
- Hypersensitivity to buprenorphine or naloxone.
- Severe respiratory insufficiency.
- Severe hepatic impairment.
- Acute alcoholism or delirium tremens.
Drug Interactions
- CNS Depressants (e.g., benzodiazepines, alcohol): Increased risk of respiratory depression and sedation.
- CYP3A4 Inhibitors (e.g., macrolide antibiotics, antifungals): Increased buprenorphine levels.
- CYP3A4 Inducers (e.g., rifampin, phenytoin): Decreased buprenorphine levels.
- Serotonergic drugs (e.g., some antidepressants, migraine medication): Increased risk of serotonin syndrome
- MAO inhibitors (e.g., phenelzine): Contraindicated, increased risk of hypertensive crisis and serotonin syndrome.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Suboxone film). Weigh risks and benefits.
- Fetal Risks: Neonatal opioid withdrawal syndrome (NOWS).
- Breastfeeding: Buprenorphine and naloxone are present in breast milk at low levels. Monitor infants for side effects (e.g., excessive sleepiness, breathing problems).
Drug Profile Summary
- Mechanism of Action: Buprenorphine is a partial opioid agonist, naloxone is an opioid antagonist to deter misuse.
- Side Effects: Headache, nausea, constipation, respiratory depression (rare), liver damage (rare).
- Contraindications: Severe respiratory or hepatic insufficiency, acute alcoholism.
- Drug Interactions: CNS depressants, CYP3A4 inhibitors/inducers, serotonergic drugs.
- Pregnancy & Breastfeeding: Category C, excreted in breastmilk, monitor infant.
- Dosage: Induction: up to 8/2 mg Day 1, up to 16/4 mg Day 2. Maintenance: 16/4 mg daily.
- Monitoring Parameters: Respiratory rate, liver function tests, signs of withdrawal or overdose.
Popular Combinations
Buprenorphine + Naloxone is typically used as a single medication. Combining it with other opioid agonists or antagonists is generally avoided or done very cautiously under close supervision. Non-opioid medications for symptom management, such as for anxiety, sleep disturbances or pain, may be combined with Buprenorphine + Naloxone as clinically indicated.
Precautions
- General Precautions: Screen patients for allergies, respiratory or hepatic disease, and substance use. Monitor for signs of opioid withdrawal, respiratory depression, and misuse.
- Specific Populations: See “Dosage” section.
- Lifestyle Considerations: Avoid alcohol and other CNS depressants. Caution when driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Buprenorphine + Naloxone?
A: Induction: Up to 8/2mg on Day 1 (divided doses) and up to 16/4 mg on Day 2 (single dose), adjusting based on symptoms. Maintenance: Target dose is 16/4 mg daily, adjustable up to 24/6 mg daily.
Q2: How should Buprenorphine + Naloxone be administered?
A: Place the film or tablet under the tongue or inside the cheek (buccal film) and let it dissolve completely. Do not chew, cut, or swallow.
Q3: What are the common side effects?
A: Headache, nausea, constipation, insomnia, sweating, dizziness, and withdrawal symptoms are common.
Q4: What are the serious side effects to watch for?
A: Respiratory depression, liver damage, and allergic reactions are rare but serious.
Q5: Can Buprenorphine + Naloxone be used during pregnancy?
A: It is Pregnancy Safety Category C. Weigh the risks and benefits. Neonatal opioid withdrawal syndrome (NOWS) can occur.
Q6: Is it safe to breastfeed while taking Buprenorphine + Naloxone?
A: Both drugs are present in breast milk at low levels. Monitor the infant for excessive sleepiness, weight loss, and breathing difficulties.
Q7: What are the contraindications for Buprenorphine + Naloxone?
A: Severe respiratory problems, severe liver impairment, acute alcoholism, and hypersensitivity to buprenorphine or naloxone are contraindications.
Q8: What if a patient misses a dose?
A: Patients who miss a dose should take it as soon as remembered. Patients should contact their healthcare provider if multiple doses are missed or if they are unsure how to proceed. Relapse prevention and appropriate clinical management are essential for patient safety.
Q9: What if a patient experiences precipitated withdrawal?
A: Precipitated withdrawal can occur if Buprenorphine + Naloxone is administered while other opioids are still active in the patient’s system. Treat precipitated withdrawal with supportive care, non-opioid analgesics, and comfort measures. Re-evaluate the induction strategy.
Q10: What are the key drug interactions?
A: CNS depressants (e.g., alcohol, benzodiazepines), CYP3A4 inhibitors and inducers, certain antidepressants.
