SUBLOCADE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SUBLOCADE (SUBLOCADE).
SUBLOCADE contains buprenorphine, a partial mu-opioid receptor agonist and weak kappa-opioid receptor antagonist. It binds to mu-opioid receptors, reducing cravings and withdrawal symptoms without producing full opioid effects, and blocks other opioids from binding due to high affinity.
| Metabolism | Primarily metabolized via CYP3A4-mediated N-dealkylation to norbuprenorphine, an active metabolite. Also undergoes glucuronidation via UGT1A1 and UGT2B7. |
| Excretion | Primarily fecal (biliary) elimination of unchanged buprenorphine and metabolites; approximately 30% excreted in urine, mostly as conjugated metabolites. |
| Half-life | Terminal elimination half-life is 43–50 days due to prolonged absorption from the depot; steady-state reached after 4–6 months of monthly dosing. |
| Protein binding | Approximately 96% bound, primarily to alpha and beta globulins, with minor binding to albumin. |
| Volume of Distribution | Volume of distribution is approximately 188 L (2.7 L/kg for a 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Subcutaneous injection: 100% bioavailability as it is a depot formulation; relative bioavailability compared to sublingual buprenorphine/naloxone is equivalent on a dose-adjusted basis. |
| Onset of Action | Subcutaneous injection: therapeutic plasma concentrations achieved within 24 hours; peak effects on opioid withdrawal symptoms within 3–7 days. |
| Duration of Action | Monthly subcutaneous injection provides sustained buprenorphine levels for approximately 28 days, with therapeutic plasma concentrations maintained above 2 ng/mL for at least 28 days. |
| Molecular Weight | 467.64 |
300 mg subcutaneously every 4 weeks for the first 2 doses, followed by 100 mg subcutaneously every 4 weeks; maintenance dose may be increased to 300 mg every 4 weeks if tolerating lower dose.
| Dosage form | SOLUTION, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min); use with caution in severe renal impairment (GFR <30 mL/min) due to limited data. |
| Liver impairment | No dose adjustment for mild hepatic impairment (Child-Pugh A); not recommended for moderate to severe hepatic impairment (Child-Pugh B or C) due to risk of buprenorphine accumulation. |
| Pediatric use | Not approved for use in pediatric patients (<18 years); safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; use with caution due to potential age-related decreases in renal and hepatic function, and increased sensitivity to adverse effects (e.g., CNS depression). |
| 1st trimester | Buprenorphine, the active component, crosses the placenta. Limited human data from buprenorphine use in pregnancy does not show increased risk of major malformations. However, chronic use during pregnancy can result in neonatal abstinence syndrome (NAS) and may cause neonatal respiratory depression near term. |
| 2nd trimester | Chronic use can lead to NAS. Consider benefit-risk. Tapering should be done cautiously under medical supervision to avoid precipitating withdrawal. |
| 3rd trimester | Chronic use can cause NAS and neonatal respiratory depression. Monitor neonate for signs of withdrawal and treat accordingly. |
Clinical note
Comprehensive clinical and safety monograph for SUBLOCADE (SUBLOCADE).
| Placental transfer | Buprenorphine crosses the placenta. In vitro studies show transfer; in vivo, cord blood concentrations are 10-50% of maternal serum concentrations. |
| Breastfeeding | Buprenorphine is excreted into human milk in low levels. With maternal doses of 2-24 mg/day, relative infant dose is estimated to be 0.2-1.2% of maternal weight-adjusted dose. No adverse reactions in breastfed infants have been reported. However, caution is advised; monitor infant for sedation, respiratory depression, or withdrawal if breastfeeding is discontinued abruptly. |
■ FDA Black Box Warning
Warning: Injection site necrosis; use only as part of an opioid treatment program. Risk of serious injury or death if administered intravenously. Requires administration by a healthcare provider. Keep out of reach of children.
| Serious Effects |
Hypersensitivity to buprenorphine or any component of the formulationSignificant respiratory depressionAcute or severe bronchial asthma in an unmonitored setting or lack of resuscitative equipmentKnown or suspected gastrointestinal obstruction including paralytic ileusModerate to severe hepatic impairment (Child-Pugh score ≥7)
| Precautions | Risk of respiratory depression, especially in patients with respiratory disease or when co-administered with CNS depressants, Risk of opioid withdrawal if administered too soon after last use of full opioid agonists, Injection site reactions including necrosis, abscess, and ulceration, Hepatotoxicity, especially in those with hepatic impairment or concurrent hepatotoxic drugs, Neonatal opioid withdrawal syndrome if used during pregnancy, Adrenal insufficiency, QT interval prolongation (dose-related, particularly at higher doses) |
| Food/Dietary |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Buprenorphine, the active component of SUBLOCADE, is classified as FDA Pregnancy Category C. In animal studies, buprenorphine caused maternal toxicity, embryolethality, and increased incidence of skeletal abnormalities at doses higher than human therapeutic doses. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy may cause neonatal opioid withdrawal syndrome (NOWS) after prolonged use. Risk is increased in the third trimester. |
| Fetal Monitoring | Monitor for maternal sedation, respiratory depression, and signs of opioid withdrawal. Assess fetal heart rate and uterine contractions if used near term. Monitor neonates for signs of NOWS (e.g., irritability, hypertonia, tremors, poor feeding) for at least 72 hours after delivery. Liver function tests (LFTs) should be monitored periodically due to risk of hepatic injury. |
| Fertility Effects | Animal studies have shown reduced fertility in female rats at doses similar to human therapeutic doses. In humans, buprenorphine may cause menstrual irregularities and sexual dysfunction. Effects on male fertility are not well studied. |
| No specific food interactions. Grapefruit and grapefruit juice may increase buprenorphine levels; consider avoiding excessive consumption. Alcohol should be avoided due to additive CNS depression. |
| Clinical Pearls | SUBLOCADE (buprenorphine extended-release) is a once-monthly subcutaneous injection for moderate-to-severe opioid use disorder. It must be administered only by a healthcare provider; do not attempt to self-inject or adjust dosing. Do not use in patients with moderate-to-severe hepatic impairment (Child-Pugh class B or C). Monitor for respiratory depression, especially at initiation. It contains a boxed warning for risk of serious harm or death if injected intravenously. Prior to initiation, patients should be on transmucosal buprenorphine for at least 7 days at a dose of 8-24 mg/day. The injection is for abdominal subcutaneous use only; rotate injection sites. Assess for signs of misuse or diversion. |
| Patient Advice | SUBLOCADE is a once-monthly injection given by a healthcare provider and is not for self-administration. · Avoid alcohol and other opioids unless prescribed by a doctor, as they may cause dangerous side effects. · Report any injection site reactions, such as pain, redness, or swelling that lasts more than a few days. · Do not drive or operate heavy machinery until you know how SUBLOCADE affects you, as it can cause drowsiness and dizziness. · Seek emergency medical attention if you experience difficulty breathing, swollen tongue or throat, or severe allergic reaction. · Keep the medication guide and injection record for your appointments. · Inform all healthcare providers that you are receiving SUBLOCADE before any surgery or new medication. |