Buprenorphine/Naloxone
Sublingual tablet
Introduction
Buprenorphine/Naloxone Sublingual tablet contains buprenorphine, a partial‐opioid agonist, and naloxone, an opioid antagonist.Buprenorphine/Naloxone sublingual tablet_Manufactured by Faran Shimi Pharmaceutical Company_ is available in two dosage strengths, 2/0.5mg and 8/2mg. 10 tablets are packed in a blister and 10 blisters are packaged in one box with a leaflet.
Indications
Buprenorphine/Naloxone is indicated for the treatment of opioid dependence. It should be used as part of a complete treatment plan to include counseling and psychosocial support.Important Information
Dosing
• Adults:Notes:
long-acting opioids or methadone: Buprenorphine/naloxone is not recommended for use during the induction period; initial treatment should begin using buprenorphine (the other product, manufactured by Faran Shimi Pharmaceutical Company) monotherapy under supervision. Patients should be switched to the combination product for maintenance and unsupervised therapy.
Short-acting opioids or heroin: Initiate treatment with sublingual buprenorphine/naloxone or sublingual buprenorphine monotherapy during the induction period; initiate treatment only when signs of moderate opioid withdrawal appear and not less than 6 hours after last opioid use. Titrate to adequate maintenance dose as rapidly as possible based on control of acute withdrawal symptoms.
Initial: Buprenorphine 2mg/naloxone 0.5mg; may titrate dose, based on control of acute withdrawal symptoms, in buprenorphine 2mg/naloxone 0.5mg increments approximately every 2 hours up to a total dose of buprenorphine 8mg/naloxone 2mg.
Day 2:
Up to buprenorphine 16mg/naloxone 4mg as a single dose.
• Renal Impairment:
has not been adequately studied.
• Hepatic Impairment:
Mild impairment: No dosage adjustment necessary.
Moderate impairment: Use with caution during maintenance treatment (due to reduced clearance of naloxone and potential for reduced buprenorphine efficacy, use may not be appropriate). Use is not recommended during induction therapy.
Severe impairment: Use is not recommended.
Induction (Heroin or other short-acting opioid dependency):
Day 1:Initial: Buprenorphine 2mg/naloxone 0.5mg; may titrate dose, based on control of acute withdrawal symptoms, in buprenorphine 2mg/naloxone 0.5mg increments approximately every 2 hours up to a total dose of buprenorphine 8mg/naloxone 2mg.
Day 2:
Up to buprenorphine 16mg/naloxone 4mg as a single dose.
Maintenance:
Target dose: Buprenorphine 16mg/naloxone 4mg once daily; dosage should be adjusted in increments/decrements of buprenorphine 2mg/naloxone 0.5mg to a level that maintains treatment and suppresses opioid withdrawal symptoms; usual range: Buprenorphine 4 to 24mg/naloxone 1 to 6mg once daily.• Renal Impairment:
has not been adequately studied.
• Hepatic Impairment:
Mild impairment: No dosage adjustment necessary.
Moderate impairment: Use with caution during maintenance treatment (due to reduced clearance of naloxone and potential for reduced buprenorphine efficacy, use may not be appropriate). Use is not recommended during induction therapy.
Severe impairment: Use is not recommended.
Administration
Buprenorphine/ Naloxone is administered sublingually. In patients requiring more than one sublingual tablet, place all tablets in different places under the tongue at the same time. To ensure consistent bioavailability, subsequent doses should always be taken the same way.Major Interactions (Risk X)
Atazanavir, Azelastine (Nasal), Bromperidol, Conivaptan, Eluxadoline, Fusidic Acid (Systemic), Idelalisib, Methylnaltrexone, MAOIs, Naldemedine, Naloxegol, Opioid Agonists, Orphenadrine, Oxomemazine, Paraldehyde, Thalidomide .Pregnancy
Neonatal opioid withdrawal syndrome may occur after chronic maternal exposure to opioids. In the treatment of addiction involving opioid use in pregnant women, the buprenorphine/naloxone combination product is not recommended for use; however, the buprenorphine monoproduct (the other product, manufactured by Faran Shimi Pharmaceutical Company) recommended option for use.Breast-Feeding
Buprenorphine is present in breast milk. It is not known if naloxone is present in breast milk; the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.Contraindications & Cautions
Contraindications
Hypersensitivity (e.g., anaphylaxis) to buprenorphine, naloxone, or any component of the formulation.Warnings/Precautions
• CNS depression: may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (e.g., operating machinery or driving).• 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: 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.
• Respiratory depression: Monitor closely for respiratory depression, especially during initiation or dose escalation. the concomitant use of buprenorphine and benzodiazepines (or other CNS depressants, including alcohol) may result in coma or death. Use with caution in patients with respiratory disease (e.g., COPD, hypoxia, hypercapnia, or preexisting respiratory depression).
• 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.
• Seizure: Use with caution in patients with a history of seizure disorders.
• Thyroid dysfunction: Use with caution.
Side Effects
>10%:Central nervous system: Headache (7-37%), pain (22%)
Dermatologic: Diaphoresis (1-14%)
Gastrointestinal: Nausea (5-15%), abdominal pain (11%)
1% to 10%:
Cardiovascular: Vasodilation (9%), palpitations
Central nervous system: Disturbance in attention, insomnia, withdrawal syndrome Gastrointestinal: Vomiting (5-8%), oral hypoesthesia, oral mucosa erythema
Ophthalmic: Blurred vision
