Generic Name

Jentadueto XR

Mechanism

• Buprenorphine:
• *Partial agonist* at the μ‑opioid receptor
• High affinity and slow dissociation → therapeutic effect maintained for 7–10 days
• Partial agonist activity minimizes respiratory depression typical of full agonists
• Naloxone:
• *Opioid antagonist* with negligible systemic absorption when delivered intramuscularly
• Prevents diversion for oral misuse; if diverted, naloxone precipitates withdrawal
• Combined pharmacology: sustained buprenorphine maintenance with built‑in abuse‑deterrent properties

Pharmacokinetics

• Absorption: Depot formulation releases buprenorphine gradually; peak plasma levels ~5–7 days post‑injection
• Distribution: Highly protein‑bound; crosses blood‑brain barrier via delivery across meningeal vessels
• Metabolism: Mainly glucuronidation (UGT‑2B7) and minor CYP3A4 oxidation
• Elimination: Half‑life of buprenorphine ~24 h (pharmacologically relevant 7–10 days). Elimination primarily via feces and urine
• Drug interactions: CYP3A4 inhibitors ↑ buprenorphine levels; CYP3A4 inducers ↓ levels

Indications

• Maintenance therapy for opioid use disorder in patients who:
• Are already stabilized on sublingual buprenorphine ≥ 8 mg/day
• Prefer or require long‑acting injectable therapy
• Have demonstrated persistence with adherence
• Appropriate for adults (≥ 18 y) with confirmed opioid dependence

Contraindications

• Contraindications
• Known hypersensitivity to buprenorphine, naloxone, or excipients
• Severe respiratory depression or acute severe OUD withdrawal (use rescue sublingual buprenorphine)
• Active, severe hepatic impairment (ALT > 5 × ULN)
• Warnings
• Respiratory depression: risk higher with concomitant CNS depressants (benzodiazepines, alcohol)
• Drug interactions: CYP3A4 inhibitors (e.g., ketoconazole) may lead to elevated buprenorphine serum concentration
• Injection site reactions: pain, redness, swelling, infection – monitor and manage promptly

Dosing

• Formulation: 8 mg buprenorphine + 8 mg naloxone in a 4.3 mL solution
• SC/IM: Intramuscular injection, once weekly
• Initial dosing
• 8 mg once per week as starting dose
• Adjust to higher strength (12 mg/12 mg, 16 mg/16 mg) only if clinically indicated after 4–6 weeks
• Rescue dosing: If withdrawal occurs, a single dose of sublingual buprenorphine (12 mg/24 mg) may be administered to reduce withdrawal severity
• Monitoring duration: 12‑week treatment cycle recommended; reassess for continuation or taper
• Storage: 2–8 °C; protect from light; do not freeze; discard after 30 days un‑labeled

Adverse Effects

• Common
• Injection site pain, erythema, induration
• Constipation, nausea, dizziness
• Headache, insomnia
• Serious
• Respiratory depression (especially with concomitant CNS depressants)
• QT‑interval prolongation (if other QT‑prolonging drugs present)
• Severe allergic reactions (rash, urticaria, anaphylaxis)
• Hepatotoxicity (rare; monitor transaminases)

Monitoring

• Clinical:
• Opioid withdrawal scales (COWS) before injection
• Respiratory rate, oxygen saturation
• Adherence and injection site evaluation
• Laboratory:
• Liver function tests (ALT/AST) baseline and every 4–6 weeks
• Complete blood count if prolonged bleeding or infection is suspected
• Drug‑interactions:
• Assess concomitant CNS depressants, CYP3A4 inhibitors/inducers
• Review anticholinergic or QT‑prolonging medications

Clinical Pearls

• Conversion seeding: For patients transitioning from sublingual buprenorphine to Jentadueto XR, use a contrast dose (8 mg XR + 2 mg sublingual) during the first week to maintain therapeutic levels.
• Naloxone safety: Although systemic naloxone is minimal, if the patient inadvertently receives the syringe via a syringe‑sharing event, naloxone will precipitate withdrawal – be prepared to administer rescue sublingual buprenorphine.
• Injection site management: Rotate injection site (gluteal or deltoid) and use a smaller needle (27 G) to reduce local pain and scar tissue formation.
• Drug interactions: Prior to initiating Jentadueto XR, screen for agents that inhibit CYP3A4; if unavoidable, monitor trough buprenorphine levels and adjust dose accordingly.
• Patient selection: Ideal for patients with barriers to daily clinic visits; important to emphasize once‑weekly schedule and the necessity of an injection‑site professional.
• Patient education: Counsel on prevention of respiratory depression – no alcohol or benzodiazepines while on XR therapy.

> Key take‑away: Jentadueto XR is an extended‑release, abuse‑deterrent opioid substitution therapy that simplifies medication adherence but demands rigorous monitoring of respiratory status, drug interactions, and injection‑site integrity.