buprenorphine subdermal implant (Rx)

  • Print
Brand and Other Names:Probuphine

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

subdermal implant

  • 80mg/implant buprenorphine HCl (equivalent to 74.2 mg of buprenorphine)

Opioid Addiction

Indicated for the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses of a transmucosal buprenorphine-containing product (ie, doses ≤8 mg/day of Subutex or Suboxone sublingual tablet equivalent or generic equivalent)

4 implants (80 mg/implant of buprenorphine HCl) are inserted in the upper arm for 6 months of treatment and removed by the end of the sixth month (see Administration)

Dosing Considerations

Only for patients who are opioid tolerant

Part of a complete treatment program to include counseling and psychosocial support

Not appropriate for new entrant to treatment and patients who have not achieved and sustained prolonged clinical stability while being maintained on buprenorphine ≤8 mg/day

May only be prescribed by physicians who have met qualifying requirements and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe or dispense this product for the treatment of opioid dependence

All healthcare providers who intend to prescribe and/or perform insertions/removals must successfully complete a live training program and demonstrate procedural competency

<16 years: Safety and efficacy not established

Next:

Interactions

Interaction Checker

and buprenorphine subdermal implant

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Headache (13%)

            Implant-site pain (13%)

            Implant-site pruritus (12%)

            1-10%

            Implant-site erythema (10%)

            Implant-site hematoma (7%)

            Implant-site hemorrhage (7%)

            Depression (6%)

            Constipation (6%)

            Nausea (6%)

            Vomiting (6%)

            Implant-site edema (5%)

            Toothache (5%)

            Pain (4%)

            Dizziness (4%)

            Cough (3%)

            Somnolence (3%)

            Fatigue (3%)

            Pyrexia (3%)

            Oropharyngeal pain (5%)

            Upper abdominal pain (3%)

            Laceration (3%)

            Migraine (2%)

            Excoriation (2%)

            Asthenia (2%)

            Chills (2%)

            Rash (2%)

            Scratch (1%)

            Chest pain (1%)

            Local swelling (1%)

            Flatulence (1%)

            Sedation (1%)

            Paraesthesia (1%)

            Dyspnea (1%)

            Skin lesion (1%)

            Previous
            Next:

            Warnings

            Black Box Warnings

            Risk associated with insertion and removal

            • Insertion and removal of the implants are associated with the risk of implant migration, protrusion, and expulsion resulting from the procedure
            • Rare but serious complications, including nerve damage and migration resulting in embolism and death, may result from improper insertion of drug implants inserted in the upper arm
            • Additional complications may include local migration, protrusion, and expulsion
            • Incomplete insertions or infections may lead to protrusion or expulsion
            • Because of these risks, buprenorphine subdermal implant is available only through a restricted program called the PROBUPHINE REMS Program
            • All healthcare providers must successfully complete a live training program on the insertion and removal procedures and become certified, prior to performing insertions or prescribing the implants
            • Patients must be monitored to ensure the implant is removed by a healthcare provider certified to perform insertions

            Contraindications

            Hypersensitivity

            Cautions

            Rare but serious complications, including nerve damage and migration resulting in embolism and death, may result from improper insertion of drug implants inserted in the upper arm; additional complications may include local migration, protrusion, and expulsion (see Black Box Warnings)

            Buprenorphine can be abused in a manner similar to other opioids; monitor patients

            Significant respiratory depression and death have occurred in association with buprenorphine, particularly when taken by the IV route in combination with benzodiazepines or other CNS depressants (including alcohol)

            Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy

            Adrenal insufficiency may occur; if diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off the opioid

            Unintentional pediatric exposure; in the event an implant protrudes or comes out, keep the implant away from children; buprenorphine can cause severe, possibly fatal, respiratory depression in children

            If treatment is temporarily interrupted or discontinued, monitor for withdrawal and treat appropriately

            Monitor liver function tests prior to initiation and during treatment

            Verify that patient is clinically stable on transmucosal buprenorphine and not dependent on full agonists before inserting

            Treat pain with a nonopioid analgesic whenever possible; if opioid therapy is required, monitor patients closely because higher doses may be required for analgesic effect

            May impair ability to drive and operate machinery

            May cause orthostatic hypotension in ambulatory patients

            May elevate CSF pressure; caution in patients with head injury or intracranial lesions

            Can produce miosis and changes in level of consciousness that may interfere with evaluating patient for head injury

            Increases intracholedochal pressure (as do other opioids); caution with biliary tract dysfunction

            May obscure diagnosis or clinical course of patients with acute abdominal conditions Infection may occur at insertion/removal site; excessive palpation shortly after insertion may increase risk of infection

            Administer with caution in debilitated patients and those with myxedema or hypothyroidism, adrenal cortical insufficiency, CNS depression or coma, toxic psychoses, prostatic hypertrophy or urethral stricture, acute alcoholism, delirium tremens, or kyphoscoliosis

            Caution with history of keloid formation, connective-tissue disease (eg, scleroderma), or recurrent MRSA infections

            Drug interaction overview

            • Coadministration of opioids with serotonergic drugs may cause serotonin syndrome, a potentially life-threatening condition
            • Buprenorphine is metabolized by CYP3A4; caution if CYP3A4 inhibitors or inducers are initiated or discontinued; monitor to ensure plasma buprenorphine levels are adequate and not excessive
            • Postmarketing report of coma and death associated with concomitant use of buprenorphine and benzodiazepine; coadministration with other CNS depressants should only occur with cautious medical supervision
            Previous
            Next:

            Pregnancy

            Pregnancy

            May cause fetal harm

            Neonatal opioid withdrawal syndrome has been reported in the infants of women treated with buprenorphine sublingual tablets during pregnancy

            Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes (eg, low birth weight, preterm birth, and fetal death); untreated opioid addiction often results in continued or relapsing illicit opioid use

            Lactation

            Based on two studies in 13 lactating women, buprenorphine and the metabolite norbuprenorphine are present at low levels in human milk and infant urine

            Available data have not shown adverse reactions in breastfed infants

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Semisynthetic narcotic mixed agonist-antagonist analgesic; exerts partial agonistic effects at the mu opioid receptor in the CNS and antagonistic effects at the kappa opioid receptor

            Absorption

            Implants deliver circulating drug blood levels comparable to the average plasma concentrations observed following daily doses of ≤8 mg Subutex or Suboxone tablet equivalent

            Initial peak plasma concentration observed ~12 hr after insertion, and then concentrations decrease slowly

            Steady-state plasma levels observed by ~4 wk

            Distribution

            Protein bound: 96%, primarily to alpha and beta globulin

            Metabolism

            Buprenorphine undergoes both N-dealkylation to norbuprenorphine and glucuronidation

            N-dealkylation pathway is mediated primarily by the CYP3A4

            Norbuprenorphine, the major metabolite, can further undergo glucuronidation

            Norbuprenorphine has been found to bind opioid receptors in vitro; however, it has not been studied clinically for opioidlike activity

            Elimination

            Excretion: 30% urine; 69% (feces) collected up to 11 days after dosing

            Previous
            Next:

            Administration

            Subdermal implantation

            Each dose consists of 4 implants inserted subdermally in the inner side of the upper arm

            Examine the insertion site 1 week following insertion for signs of infection or other problems

            The implants are intended to be in place for 6 months of treatment; remove implants by the end of the sixth month

            New implants may be inserted subdermally in an area of the inner side of either upper arm that has not been previously used at the time of removal, if continued treatment is desired

            If new implants are not inserted on the same day as the removal of implants, maintain patients on their previous dosage of transmucosal buprenorphine (ie, the dose from which they were transferred to buprenorphine subdermal treatment) prior to additional buprenorphine subdermal treatment

            After one insertion in each arm, most patients should be transitioned back to a transmucosal buprenorphine-containing product for continued treatment

            There is no experience with inserting additional implants into other sites in the arm to recommend an approach to a second insertion into a previously used arm

            Neither reinsertion into previously used administration sites, nor into sites other than the upper arm, has been studied

            Clinical supervision

            • Examine insertion site 1 week following insertion for signs of infection and any problems with wound healing, including evidence of implant extrusion from the skin
            • Recommended visit schedule for most patients is a frequency of no less than once-monthly for continued counseling and psychosocial support
            • Although some patients may require occasional supplemental dosing with buprenorphine, patients should not be provided with prescriptions for transmucosal buprenorphine-containing products for as-needed use; instead, patients who feel the need for supplemental dosing should be seen and evaluated promptly
            • Ongoing use of supplemental dosing with transmucosal buprenorphine indicates that the amount of buprenorphine delivered by buprenorphine subdermal implant is not adequate for stable maintenance; consider use of alternate buprenorphine products for maintenance of treatment

            Patient Selection

            Implants are only for use in patients who meet ALL of the following criteria:

            • Achieved and sustained prolonged clinical stability on transmucosal buprenorphine
            • Are currently on a maintenance dose of &le:8 mg/day of a Subutex or Suboxone sublingual tablet or its transmucosal buprenorphine product equivalent (the dose of transmucosal buprenorphine providing blood levels comparable or lower than the level provided by buprenorphine subdermal implant)
            • Note: Patients should not be tapered to a lower dose for the sole purpose of transitioning to buprenorphine subdermal implant
            • Stable transmucosal buprenorphine dose for ≥3 months without any need for supplemental dosing or adjustments

            Examples of acceptable doses of transmucosal buprenorphine

            • Subutex SL tablet ≤8 mg
            • Suboxone (buprenorphine/naloxone) SL tablet ≤8 mg/2 mg
            • Bunavail (buprenorphine/naloxone) buccal film ≤4.2 mg/0.7 mg
            • Zubsolv (buprenorphine/naloxone) SL tablet ≤5.7 mg/1.4 mg
            • Or generic equivalents of the above examples

            Factors to consider in determining clinical stability/suitability

            • Period free from illicit opioid drug use
            • Stability of living environment
            • Participation in a structured activity/job
            • Consistency in participation in recommended behavioral therapy/peer support program
            • Consistency in compliance with clinic visit requirements
            • Minimal-to-no desire or need to use illicit opioids
            • Period without episodes of hospitalizations (addiction or mental health issues), emergency department visits, or crisis interventions
            • Social support system

            Storage

            Store at controlled room temperature (20-25°C [68-77°F]); excursions permitted at 15-30°C (59-86°F)

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous