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  • Zubsolv
    (Naloxone, Buprenorphine) - Orexo

    THERAPEUTIC CLASS

    Partial opioid agonist/opioid antagonist

    DEA CLASS

    CIII

    INDICATIONS

    Maintenance treatment of opioid dependence and should be used as part of a complete treatment plan to include counseling and psychosocial support.

    ADULT DOSAGE

    Adults: Administer SL as single daily dose in patients initially inducted using buprenorphine SL tab. Zubsolv compared to Suboxone tab requires a different tab strength. One Zubsolv 5.7mg-1.4mg SL tab provides equivalent buprenorphine exposure to one Suboxone 8mg-2mg SL tab. Refer to PI for the corresponding doses from induction to maintenance treatment. Maint: Target Dose: 11.4mg-2.8mg/day as single dose. Titrate: Adjust dose progressively in increments/decrements of 1.4mg-0.36mg or 2.8mg-0.72mg to maintain treatment and suppress opioid withdrawal signs and symptoms. Range: 2.8mg-0.72mg to 17.1mg-4.2mg/day depending on the patient. Discontinuing Therapy: Should be made as part of a comprehensive treatment plan. Switching Between Other Buprenorphine/Naloxone Combination Products: Dose adjustments may be necessary. Monitor for over-medication as well as withdrawal or other signs of under-dosing. Refer to PI for corresponding dosing strengths when switching between Suboxone and Zubsolv dosage strengths. Hepatic Impairment: Adjust dose and observe for precipitated opioid withdrawal. Elderly: Start at low end of dosing range.

    HOW SUPPLIED

    Tab, SL: (Buprenorphine-Naloxone) 1.4mg-0.36mg, 5.7mg-1.4mg

    WARNINGS/PRECAUTIONS

    Not appropriate as an analgesic. Hypersensitivity reactions, bronchospasm, angioneurotic edema, and anaphylactic shock reported. May precipitate opioid withdrawal signs and symptoms if administered before the agonist effects of the opioid have subsided. May impair mental/physical abilities. May produce orthostatic hypotension in ambulatory patients. Caution with debilitated patients, myxedema or hypothyroidism, adrenal cortical insufficiency (eg, Addison's disease), CNS depression or coma, toxic psychoses, prostatic hypertrophy, urethral stricture, acute alcoholism, delirium tremens, kyphoscoliosis, hepatic impairment, and in elderly. Buprenorphine: Potential for abuse. Significant respiratory depression reported; caution with compromised respiratory function. To manage overdose, higher than normal doses and repeated administration of naloxone may be necessary. Accidental pediatric exposure can cause fatal respiratory depression. Chronic use produces physical dependence. Cytolytic hepatitis and hepatitis with jaundice reported; obtain LFTs prior to initiation and periodically thereafter. If a hepatic event is suspected, biological and etiological evaluation is recommended; careful discontinuation may be needed depending on the case. Caution with preexisting liver enzyme abnormalities, hepatitis B or C infection, use with other potentially hepatotoxic drugs, and ongoing injecting drug use. Neonatal abstinence syndrome reported when used during pregnancy. May elevate CSF pressure; caution with head injury, intracranial lesions, and other circumstances when cerebrospinal pressure may be increased. May produce miosis and changes in consciousness level that may interfere with patient evaluation. May increase intracholedochal pressure; caution with biliary tract dysfunction. May obscure diagnosis or clinical course of patients with acute abdominal conditions.

    ADVERSE REACTIONS

    Headache, withdrawal syndrome, pain, N/V, insomnia, sweating, constipation, abdominal pain, vasodilation, chills, asthenia, infection, rhinitis, back pain, diarrhea.

    DRUG INTERACTIONS

    May cause respiratory depression, coma, and death with benzodiazepines or other CNS depressants (eg, alcohol); caution when used concurrently. May cause increased CNS depression with opioid analgesics, general anesthetics, benzodiazepines, phenothiazines, other tranquilizers, sedative/hypnotics, or other CNS depressants (eg, alcohol); consider dose reduction of one or both agents. Concomitant use with CYP3A4 inhibitors (eg, azole antifungals such as ketoconazole, macrolides such as erythromycin, and HIV protease inhibitors) should be monitored and may require dose reduction of one or both agents. Monitor for signs and symptoms of opioid withdrawal with CYP3A4 inducers (eg, efavirenz, phenobarbital, carbamazepine, phenytoin, rifampicin). Monitor dose if non-nucleoside reverse transcriptase inhibitors are added to treatment regimen. Atazanavir and atazanavir/ritonavir may increase levels; monitor and consider dose reduction of buprenorphine.

    PREGNANCY

    Category C, caution in nursing.

    MECHANISM OF ACTION

    Buprenorphine: Partial agonist at the µ-opioid receptor and antagonist at the kappa-opioid receptor. Naloxone: Potent antagonist at the µ-opioid receptor.

    PHARMACOKINETICS

    Distribution: Plasma protein binding (96%, buprenorphine; 45%, naloxone); found in breast milk (buprenorphine). Metabolism: Buprenorphine: N-dealkylation (by CYP3A4) and glucuronidation; norbuprenorphine (major metabolite). Naloxone: Glucuronidation, N-dealkylation, and reduction; naloxone-3-glucoronide (metabolite). Elimination: Buprenorphine: Urine (30%), feces (69%); T1/2=24-42 hrs. Naloxone: T1/2=2-12 hrs.

    ASSESSMENT

    Assess for history of hypersensitivity reactions, debilitation, myxedema, hypothyroidism, acute alcoholism, adrenal cortical insufficiency (eg, Addison's disease), CNS depression or coma, toxic psychoses, prostatic hypertrophy, urethral stricture, delirium tremens, kyphoscoliosis, biliary tract dysfunction, hepatic impairment, compromised respiratory function, hepatitis B or C infection, head injury, intracranial lesions and other circumstances in which cerebrospinal pressure may be increased, acute abdominal conditions, pregnancy/nursing status, and possible drug interactions. Perform LFTs prior to therapy.

    MONITORING

    Monitor for hypersensitivity reactions, signs/symptoms of opioid withdrawal, impaired mental/physical ability, orthostatic hypotension, respiratory depression, drug abuse/dependence, cytolytic hepatitis, hepatitis with jaundice, elevation of CSF, miosis, changes in consciousness levels, and other adverse reactions. Monitor LFTs periodically. Monitor for over-medication as well as withdrawal or other signs of under-dosing when switching between other buprenorphine/naloxone products. Monitor breastfed infant for increased drowsiness and breathing difficulties.

    PATIENT COUNSELING

    Warn patient on danger of self-administration of benzodiazepines and other CNS depressants, including alcohol, while on therapy. Advise that the drug contains an opioid that can be a target for abuse; instruct to keep tabs in safe place protected from theft and children. Instruct to seek medical attention immediately if a child is exposed to the drug. Caution that the drug may impair mental/physical abilities and cause orthostatic hypotension. Advise to take tab qd and not to change dose without consulting physician. Advise that if a dose is missed, take dose as soon as remembered; if it is almost time for the next dose, instruct to skip the missed dose and take next dose at the regular time. Inform that treatment can cause dependence and withdrawal syndrome may occur upon discontinuation. Advise patients seeking to d/c treatment with buprenorphine for opioid dependence to work closely with physician on a tapering schedule, and apprise of the potential to relapse to illicit drug use associated with discontinuation of treatment. Advise to report to physician all medications prescribed or currently being used. Advise women regarding possible effects during pregnancy. Advise women who are breastfeeding to monitor the infant for drowsiness and difficulty breathing. Advise to instruct family members that, in event of emergency, the treating physician or staff should be informed that patient is physically dependent on an opioid. Advise to dispose of unused drugs as soon as they are no longer needed by flushing the tabs down the toilet.

    ADMINISTRATION/STORAGE

    Administration: SL route. Refer to PI for further information on method of administration, clinical supervision, and unstable patients. Storage: 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F).