Buprenorphine 0.4, 2, 8mg
Introduction
Buprenorphine is a semisynthetic, highly lipophilic derivative of the opioid alkaloid thebaine. Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor.Buprenorphine Sublingual Tablet Manufactured by Faran Shimi Pharmaceutical Company is available in three dosage strengths, 0.4mg, 2mg and 8mg. 10 tablets are packed in a blister and 10 blisters are packaged in one box with a leaflet.
Indications
Buprenorphine is indicated for the treatment of opioid dependence and is preferred for induction. It should be used as part of a complete treatment plan to include counseling and psychosocial support.
Important Information
Dosing
Prior to induction, consideration should be given to the type of opioid dependence (i.e., long-or short-acting opioid products), the time since last opioid use, and the degree or level of opioid dependence• Adolescents (≥16 years) & Adults:
Opioid dependence: Induction: 2 to 4mg; if no signs of precipitated withdrawal after 60 to 90 minutes, may increase in increments of 2 to 4 mg. Once initial dose is tolerated, may increase to a dose that is clinically effective and provides 24 hours of stabilization.
After induction and titration: daily dose usually ≥8mg/day.
In patients continuing to use opioids, consider increasing the dose by 4 to 8mg to a daily dose of ≥12 to 16mg/day.
Note: Buprenorphine treatment initiation should begin after mild to moderate opioid withdrawal signs appear (to avoid precipitated withdrawal), which is generally at least 6 to 12 hours after last use of short-acting opioids (e.g., heroin, oxycodone) and 24 to 72 hours after last use of long-acting opioids (methadone).
• Renal Impairment:
has not been adequately studied.
• Hepatic Impairment:
• Mild impairment: No dosage adjustment necessary.
• Moderate impairment: No dosage adjustment necessary; use caution.
• Severe impairment: Consider reducing initial and titration incremental dose by 50%; monitor for signs and symptoms of toxicity or overdose.
• Hepatic events: Monitor liver function tests in patients at increased risk for hepatotoxicity (e.g., history of alcohol abuse, preexisting hepatic dysfunction, IV drug abusers) prior to and during therapy.
• Hypersensitivity reactions: Hypersensitivity, including bronchospasm, angioneurotic edema, and anaphylactic shock, have been reported.
• Hypotension (orthostatic hypotension and syncope): use with caution in patients with hypovolemia, cardiovascular disease (e.g., acute MI), or drugs that may exaggerate hypotensive effects (phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration.
• Adrenocortical insufficiency (e.g., Addison disease): Use with caution.
• Biliary tract impairment (e.g., acute pancreatitis): Use with caution.
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.
• Obesity: Use with caution in patients who are morbidly obese.
• Prostatic hyperplasia/urinary stricture: Use with caution.
• Psychosis: Use with caution in patients with toxic psychosis.
• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant COPD, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; Consider the use of alternative non-opioid analgesics in these patients.
• Seizure: Use with caution in patients with a history of seizure disorders.
• Thyroid dysfunction: Use with caution.
Central nervous system: Headache (29%), insomnia (21%)
Dermatologic: Diaphoresis (13%)
Gastrointestinal: Nausea (14%), abdominal pain (12%)
Infection: Infection (12%)
1% to 10%: Gastrointestinal: Constipation (8%), vomiting (8%)
• Renal Impairment:
has not been adequately studied.
• Hepatic Impairment:
• Mild impairment: No dosage adjustment necessary.
• Moderate impairment: No dosage adjustment necessary; use caution.
• Severe impairment: Consider reducing initial and titration incremental dose by 50%; monitor for signs and symptoms of toxicity or overdose.
Administration
Buprenorphine is administered sublingually as a single daily dose. Buprenorphine is preferred for use only during induction. Following induction, Buprenorphine/ Naloxone sublingual tablet is preferred due to the presence of naloxone when clinical use includes unsupervised administration. The use of Buprenorphine for unsupervised administration should be limited to those patients who cannot tolerate Buprenorphine/ Naloxone sublingual tablet; for example, those patients who have been shown to be hypersensitive to naloxone.Major Interactions (Risk X)
Atazanavir, Azelastine (Nasal), Bromperidol, Conivaptan, Eluxadoline, Fusidic Acid (Systemic), Idelalisib, MAO Inhibitors, Opioid Agonists, Orphenadrine, Oxomemazine, Paraldehyde, Thalidomide .Pregnancy
Buprenorphine crosses the placenta; buprenorphine can be detected in newborn serum, urine, and meconium following in utero exposure. Based on available data, an increased risk of major malformations has not been observed. Following chronic opioid therapy in pregnancy, adverse events in the newborn (including withdrawal) may occur; monitoring of the neonate is recommended. The minimum effective dose should be used if opioids are needed.Breast-Feeding
Buprenorphine is present in breast milk. When buprenorphine is used to treat opioid addiction in breastfeeding women, most guidelines allow breastfeeding as long as the infant is tolerant to the dose and other contraindications do not exist (e.g., not using additional drugs or alcohol, HIV negative). caution should be used when breastfed infants not previously exposed.Contraindications & Cautions
Contraindications
Hypersensitivity (e.g., anaphylaxis) to buprenorphine or any component of the formulation.Warnings/Precautions
• CNS depression: Avoid use in patients with impaired consciousness or coma because these patients are susceptible to intracranial effects of CO2 retention.• Hepatic events: Monitor liver function tests in patients at increased risk for hepatotoxicity (e.g., history of alcohol abuse, preexisting hepatic dysfunction, IV drug abusers) prior to and during therapy.
• Hypersensitivity reactions: Hypersensitivity, including bronchospasm, angioneurotic edema, and anaphylactic shock, have been reported.
• Hypotension (orthostatic hypotension and syncope): use with caution in patients with hypovolemia, cardiovascular disease (e.g., acute MI), or drugs that may exaggerate hypotensive effects (phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration.
• Adrenocortical insufficiency (e.g., Addison disease): Use with caution.
• Biliary tract impairment (e.g., acute pancreatitis): Use with caution.
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.
• Obesity: Use with caution in patients who are morbidly obese.
• Prostatic hyperplasia/urinary stricture: Use with caution.
• Psychosis: Use with caution in patients with toxic psychosis.
• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant COPD, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; Consider the use of alternative non-opioid analgesics in these patients.
• Seizure: Use with caution in patients with a history of seizure disorders.
• Thyroid dysfunction: Use with caution.
Side Effects
>10%:Central nervous system: Headache (29%), insomnia (21%)
Dermatologic: Diaphoresis (13%)
Gastrointestinal: Nausea (14%), abdominal pain (12%)
Infection: Infection (12%)
1% to 10%: Gastrointestinal: Constipation (8%), vomiting (8%)
