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  • Zubsolv
    (buprenorphine/naloxone)

    THERAPEUTIC CLASS

    Partial opioid agonist/opioid antagonist

    DEA CLASS

    CIII

    ADULT DOSAGE & INDICATIONS

    Opioid Dependence

    Used as part of a complete treatment plan to include counseling and psychosocial support

    Administer as single daily dose for maint treatment or in divided doses for induction treatment

    One Zubsolv 5.7mg/1.4mg SL tab provides equivalent buprenorphine exposure to one Suboxone 8mg/2mg SL tab

    Prior to Induction:
    Consider type of opioid dependence (eg, long- or short-acting opioid products), the time since last opioid use, and degree or level of opioid dependence. The 1st dose of therapy should be started only when objective and clear signs of moderate withdrawal are evident

    Induction:
    Day 1:
    Up to 5.7mg/1.4mg is recommended, given as:
    Initial: 1.4mg/0.36mg
    Remainder of Day 1: Dose of up to 4.2mg/1.08mg should be divided into doses of 1-2 tabs of 1.4mg/0.36mg at 1.5- to 2-hr intervals; some patients (eg, those w/ recent exposure to buprenorphine) may tolerate up to 3 x 1.4mg/0.36mg tabs as a single, second dose

    Day 2:
    Recommended:
    Single daily dose of up to 11.4mg/2.9mg

    Patients Dependent on Methadone or Long-Acting Opioid Products:
    Buprenorphine monotherapy is recommended in patients taking long-acting opioids when used according to approved administration instructions. Following induction, may transition patient to Zubsolv SL tab qd

    Patients Dependent on Heroin or Other Short-Acting Opioid Products:
    May be induced w/ Zubsolv SL tab or w/ SL buprenorphine monotherapy. At treatment initiation, Zubsolv dose should be administered when moderate objective signs of opioid withdrawal appear, not <6 hrs after the patient last used opioids

    Maint:
    Target Dose: 11.4mg/2.9mg as single daily dose
    Titrate: Adjust dose progressively in increments/decrements of 1.4mg/0.36mg or 2.9mg/0.71mg to maintain treatment and suppress opioid withdrawal signs and symptoms
    Range: 2.9mg/0.71mg to 17.2mg/4.2mg per day, based on individual needs

    Conversions

    Switching Between Zubsolv and Other Buprenorphine/Naloxone Combination Products:
    Dose adjustments may be necessary
    Monitor for signs of over-medication or under-dosing (eg, withdrawal)

    Corresponding Dosage Strengths When Switching Between Suboxone SL Tabs (Including Generic Equivalents) and Zubsolv:
    One 2mg/0.5mg Buprenorphine/Naloxone SL Tab:
    One 1.4mg/0.36mg Zubsolv SL tab
    4mg/1mg Buprenorphine/Naloxone (Two 2mg/0.5mg SL Tabs):
    One 2.9mg/0.71mg Zubsolv SL tab
    One 8mg/2mg Buprenorphine/Naloxone SL Tab:
    One 5.7mg/1.4mg Zubsolv SL tab
    12mg/3mg Buprenorphine/Naloxone (One 8mg/2mg SL Tab and Two 2mg/0.5mg SL Tabs):
    One 8.6mg/2.1mg Zubsolv SL tab
    16mg/4mg Buprenorphine/Naloxone (Two 8mg/2mg SL Tabs):
    One 11.4mg/2.9mg Zubsolv SL tab

    DOSING CONSIDERATIONS

    Hepatic Impairment
    Moderate: Use may not be appropriate
    Severe:
    Avoid use

    Elderly
    Start at low end of dosing range

    Discontinuation
    Should be made as part of a comprehensive treatment plan

    ADMINISTRATION

    SL route

    Do not cut, crush, break, chew, or swallow; SL tab should be placed under tongue until dissolved.
    For dosages requiring more than one SL tab, place all tabs in different places under tongue at same time.
    Advise patients not to eat or drink anything until tab is completely dissolved.
    Follow the same manner of dosing w/ continued use to ensure consistency in bioavailability.
    If sequential mode of administration is preferred, follow the same manner of dosing w/ continued use to ensure consistency in bioavailability.

    HOW SUPPLIED

    Tab, SL: (Buprenorphine/Naloxone) 1.4mg/0.36mg, 2.9mg/0.71mg, 5.7mg/1.4mg, 8.6mg/2.1mg, 11.4mg/2.9mg

    CONTRAINDICATIONS

    Hypersensitivity to buprenorphine or naloxone.

    WARNINGS/PRECAUTIONS

    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. Not appropriate as an analgesic. Avoid w/ severe hepatic impairment; may be used w/ caution for maintenance treatment in patients w/ moderate hepatic impairment who have initiated treatment on a buprenorphine product w/o naloxone. May impair mental/physical abilities. May produce orthostatic hypotension in ambulatory patients. Caution w/ 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, and in elderly. Buprenorphine: Potential for abuse. Significant respiratory depression reported; caution w/ 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 w/ jaundice reported. If a hepatic event is suspected, biological and etiological evaluation is recommended; careful discontinuation may be needed depending on the case. Neonatal abstinence syndrome reported when used during pregnancy. May elevate CSF pressure; caution w/ head injury, intracranial lesions, and other circumstances when CSF pressure may be increased. May produce miosis and changes in consciousness level that may interfere w/ patient evaluation. May increase intracholedochal pressure; caution w/ biliary tract dysfunction. May obscure diagnosis or clinical course of patients w/ acute abdominal conditions.

    ADVERSE REACTIONS

    Headache, withdrawal syndrome, pain, N/V, sweating, constipation, abdominal pain, vasodilation.

    DRUG INTERACTIONS

    May cause respiratory depression, coma, and death w/ benzodiazepines or other CNS depressants (eg, alcohol); caution when used concurrently. May cause increased CNS depression w/ opioid analgesics, general anesthetics, benzodiazepines, phenothiazines, other tranquilizers, sedative/hypnotics, or other CNS depressants (eg, alcohol); consider dose reduction of one or both agents if used concomitantly. Concomitant use w/ CYP3A4 inhibitors (eg, ketoconazole, erythromycin, HIV protease inhibitors) should be monitored and may require dose reduction of one or both agents. Monitor for signs/symptoms of opioid withdrawal w/ CYP3A4 inducers (eg, efavirenz, phenobarbital, carbamazepine). Monitor buprenorphine dose in patients on chronic buprenorphine treatment 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 AND LACTATION

    Pregnancy: Category C.
    Lactation: 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 and norbuprenorphine). Metabolism: Buprenorphine: N-dealkylation (by CYP3A4) and glucuronidation; norbuprenorphine (major metabolite). Naloxone: Glucuronidation, N-dealkylation, and reduction; naloxone-3-glucuronide (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 CSF pressure may be increased, acute abdominal conditions, pregnancy/nursing status, and possible drug interactions. Obtain baseline LFTs.

    MONITORING

    Monitor for hypersensitivity reactions, signs/symptoms of opioid withdrawal, impaired mental/physical ability, orthostatic hypotension, respiratory depression, drug abuse/dependence, cytolytic hepatitis, hepatitis w/ jaundice, elevation of CSF pressure, 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.

    PATIENT COUNSELING

    Warn about 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 drug may impair mental/physical abilities and cause orthostatic hypotension. Advise to take tab qd after induction and not to change dose w/o consulting physician. Counsel about instructions for missed dose. Inform that treatment can cause dependence and withdrawal syndrome may occur upon discontinuation. Advise patients seeking to d/c treatment w/ buprenorphine for opioid dependence to work closely w/ physician on a tapering schedule, and apprise of the potential to relapse to illicit drug use associated w/ 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.

    STORAGE

    20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F).