CV: hypertension, hypotension, palpitations, QT interval prolongation.
Derm: sweating, clammy feeling, erythema, pruritus, rash.
EENT: blurred vision, diplopia, miosis (high doses).
Endo: adrenal insufficiency.
GI: nausea, constipation, dry mouth, HEPATOTOXICITY, ileus, vomiting.
GU: urinary retention.
Neuro: confusion, dysphoria, hallucinations, sedation, dizziness, euphoria, floating feeling, headache, unusual dreams.
Resp: RESPIRATORY DEPRESSION (INCLUDING CENTRAL SLEEP APNEA AND SLEEP-RELATED HYPOXEMIA).
Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS, ANGIOEDEMA, AND BRONCHOSPASM), injection site reactions, physical dependence, psychological dependence, tolerance.
Analgesia
- IM, IV (Adults): 0.3 mg every 4–6 hr as needed. May repeat initial dose after 30 min (up to 0.3 mg every 4 hr or 0.6 mg every 6 hr); 0.6-mg doses should be given only IM.
- IM, IV (Children 2–12 yr): 2–6 mcg (0.002–0.006 mg)/kg every 4–6 hr.
- Transdermal (Adults): Opioid-nave: Transdermal system delivering 5–20 mcg/hr applied every 7 days. Initiate with 5 mcg/hr system; each dose titration may occur after 72 hr; do not exceed dose of 20 mcg/hr (due to ↑ risk of QT interval prolongation); Previously taking <30 mg/day of morphine or equivalent: Initiate with 5 mcg/hr system; each dose titration may occur after 72 hr; do not exceed dose of 20 mcg/hr (due to ↑ risk of QT interval prolongation); apply patch every 7 days; Previously taking 30–80 mg/day of morphine or equivalent: Initiate with 10 mcg/hr system; each dose titration may occur after 72 hr; do not exceed dose of 20 mcg/hr (due to ↑ risk of QT interval prolongation); apply patch every 7 days; Previously taking >80 mg/day of morphine or equivalent: Consider use of alternate analgesic.
- Buccal (Adults): Opioid-nave: Initiate therapy with 75 mcg once daily or every 12 hr for
4 days, then ↑ dose to 150 mcg every 12 hr; may then titrate dose in increments of 150 mcg every 12 hr no more frequently than every 4 days; do not exceed dose of 450 mcg every 12 hr (based on clinical studies); Previously taking <30 mg/day of morphine or equivalent: Initiate therapy with 75 mcg once daily or every 12 hr for 4 days, then ↑ dose to 150 mcg every 12 hr; may then titrate dose in increments of 150 mcg every 12 hr no more frequently than every 4 days; do not exceed dose of 900 mcg every 12 hr (due to ↑ risk of QT interval prolongation); Previously taking 30–89 mg/day of morphine or equivalent: Initiate therapy with 150 mcg every 12 hr for 4 days; may then titrate dose in increments of 150 mcg every 12 hr no more frequently than every 4 days; do not exceed dose of 900 mcg every 12 hr (due to ↑ risk of QT interval prolongation); Previously taking 90–160 mg/day of morphine or equivalent: Initiate therapy with 300 mcg every 12 hr for 4 days; may then titrate dose in increments of 150 mcg every 12 hr no more frequently than every 4 days; do not exceed dose of 900 mcg every 12 hr (due to ↑ risk of QT interval prolongation); Previously taking >160 mg/day of morphine or equivalent: Consider use of alternate analgesic; Patients with oral mucositis:↓ initial dose by 50% then titrate dose in increments of 75 mcg every 12 hr no more frequently than every 4 days.
Hepatic Impairment
- Transdermal (Adults): Mild to moderate hepatic impairment: Initiate with 5 mcg/hr system.
Hepatic Impairment
- Buccal (Adults): Severe hepatic impairment:↓ initial dose by 50% then titrate dose in increments of 75 mcg every 12 hr no more frequently than every 4 days.
Treatment of Opioid Use Disorder
- SL (Adults): Induction: 8 mg once daily on Day 1, then 16 mg once daily on Day 2–4; Maintenance: Patients should preferably be transitioned to buprenorphine/naloxone; if patient cannot tolerate naloxone, then can use buprenorphine (usual dosage range = 4–24 mg/day); recommended target dose = 16 mg/day; dose can be ↑ or ↓ by 2–4 mg, as needed to prevent signs/symptoms of opioid withdrawal.
- SC (Adults): Sublocade: 300 mg once monthly for 2 mo, then 100 mg once monthly; may ↑ maintenance dose to 300 mg once monthly if patient reports illicit opioid use or has positive urine drug screen for illicit opioid use.
- SC (Adults): Patients not currently receiving buprenorphine treatment (Brixadi [weekly formulation] only): To avoid precipitating an opioid withdrawal syndrome, a single 4-mg test dose of transmucosal buprenorphine-containing product should be administered prior to administration of Brixadi weekly injection. If the test dose is tolerated without precipitating withdrawal, administer 16 mg (weekly formulation) initially, followed by an additional 8 mg (weekly formulation) within 3 days of the initial dose for a total recommended weekly dose of 24 mg. If needed, during the 1st wk of treatment, may administer an additional 8 mg (weekly formulation) after 24 hr after the previous dose, for a total weekly dose of 32 mg. Administer subsequent injections (weekly formulation) once weekly based on the total weekly dose that was established during Wk 1 (16–32 mg). Dose adjustments can be made at weekly intervals (max dose = 32 mg once weekly). Patients currently receiving buprenorphine treatment (Brixadi [weekly formulation]): If daily dose of SL buprenorphine
6 mg, administer 8 mg once weekly (weekly formulation). If daily dose of SL buprenorphine 8–10 mg, administer 16 mg once weekly (weekly formulation). If daily dose of SL buprenorphine 12–16 mg, administer 24 mg once weekly (weekly formulation). If daily dose of SL buprenorphine 18–24 mg, administer 32 mg once weekly (weekly formulation). Patients currently receiving buprenorphine treatment (Brixadi [monthly formulation]): If daily dose of SL buprenorphine 8–10 mg, administer 64 mg once monthly (monthly formulation). If daily dose of SL buprenorphine 12–16 mg, administer 96 mg once monthly (monthly formulation). If daily dose of SL buprenorphine 18–24 mg, administer 128 mg once monthly (monthly formulation). Transitioning between Brixadi (monthly formulation) and Brixadi (monthly formulation): If dose of weekly formulation 16 mg once weekly, convert to 64 mg once monthly (monthly formulation). If dose of weekly formulation 24 mg once weekly, convert to 96 mg once monthly (monthly formulation). If dose of weekly formulation 32 mg once weekly, convert to 128 mg once monthly (monthly formulation).
Hepatic Impairment
- SL (Adults): Severe hepatic impairment:↓ initial dose and adjustment dose by 50%.
Belbuca, Brixadi, Buprenex, Butrans, Sublocade, Subutex
Therapeutic Classification: opioid analgesics
Pharmacologic Classification: opioid agonists antagonists
Absorption: Well absorbed after IM and SL use; 46–65% absorbed with buccal use; 15% of transdermal dose absorbed through skin; IV administration results in complete bioavailability.
Distribution: Crosses the placenta; enters breast milk. CNS concentration is 15–25% of plasma.
Protein Binding: 96%.
Metabolism/Excretion: Mostly metabolized by the liver mostly via the CYP3A4 isoenzyme; one metabolite is active; 70% excreted in feces; 27% excreted in urine.
Half-life: 2–3 hr (IV); 27 hr (buccal); 26 hr (transdermal); 37 hr (SL); 24–48 hr (subdermal); 43–60 days (SUBQ).