Generic Name

Probuphine

Mechanism

Probuphine delivers buprenorphine, a potent μ‑opioid receptor (μOR) partial agonist with high affinity and modest intrinsic activity. Its action balances analgesia, euphoria, and respiratory depression while providing opioid substitution therapy. Key features:
• μOR Partial Agonism – produces analgesia and reduces withdrawal symptoms with ceiling effects on respiratory depression.
• κ‑Receptor Antagonism – mitigates dysphoric and anti‑reward effects associated with full μ agonists.
• Low Abuse Potential – slow, steady release limits peak concentrations, discouraging misuse.
• Neurotransmitter Modulation – normalizes dopaminergic pathways, decreasing craving and relapse risk.

Pharmacokinetics

• Absorption – Gradual release from polyethylene‑tetracene matrix; peak steady‑state plasma concentration (Css) at ~4–6 weeks.
• Distribution – Large CNS penetration; extensive plasma protein binding (~82 %).
• Metabolism – Primarily glucuronidation via UGT3A1; minor CYP3A4 oxidation.
• Elimination – First‑order elimination with a terminal half‑life of ~30–36 hours; 85 % excreted via feces, 3 % via urine.
• Dose‑Response – Linear up to 200 mg implant; no significant accumulation beyond 12 months.

Indications

• Stable opioid‑dependent adults who have transitioned from oral buprenorphine or methadone and meet criteria for maintenance therapy.
• Patients seeking improved adherence and reduced daily dosing burden.
• Indicated for continuous opioid substitution for 6–12 months, with re‑implantation upon cessation of therapeutic effect.

Contraindications

• Absolute contraindication: Pregnancy, lactation, or unknown pregnancy status.
• Relative contraindication: Severe CNS depression, uncontrolled respiratory disease, or significant hepatic impairment (Child‑Pugh > B).
• Drug interactions: Concurrent use of potent CYP3A4 inhibitors/inducers may alter buprenorphine levels; avoid opioid analgesics requiring dose reduction post‑implant.
• Alert – Monitor for signs of respiratory depression, especially within first 48 h post‑implant.

Dosing

• Initial implant: 288 mg of buprenorphine (single‑dose implant).
• Procedure:

1. Prepare the implant under sterile conditions.

2. Insert subcutaneously in the inner forearm (or alternate site, per manufacturer guidance) using a pre‑specified needle.

3. Leave the implant buried; no need for external access.
• After implantation: Taper outpatient oral buprenorphine or methadone as directed by a qualified prescriber.
• Re‑implantation: After 6–12 months, when plasma levels fall below therapeutic threshold, perform a second implant following the same protocol.

Adverse Effects

• Note: High‑dose buprenorphine during early post‑implant is uncommon due to slow release, but may still cause constipation or sedation.

Monitoring

• Baseline – Liver function tests, respiratory assessment if comorbid conditions, pregnancy test if appropriate.
• Follow‑ups: Every 6–8 weeks for the first 3 months, then every 3 months:
• Plasma buprenorphine levels (optional; not required for routine care).
• Withdrawal screens (SOWS/SHAS), craving assessment.
• Physical exam for local site complications.
• Adherence checks – Document patient compliance, implant site integrity, and any overdose episodes.

Clinical Pearls

• Patient Education: Emphasize that the implant is non‑removable and never to be left alone; educate on no‑touch policies to avoid accidental removal.
• Insertion Technique: Use a 21‑gauge needle, insert at a 45‑degree angle; verify correct subcutaneous placement with firm, generous tissue tension to prevent migration.
• Duration Accuracy: Although the implant releases buprenorphine for up to 12 months, most patients maintain therapeutic levels for ~6–8 months; anticipate early re‑implant if 6‑month threshold is exceeded.
• Co‑prescribing Caution: Discontinue oral opioids as soon as plasma buprenorphine exceeds 0.75 ng/mL to avoid respiratory depression; apply gradual weaning if necessary.
• Off‑Label Use: As of 2024, Probuphine has not cleared off‑label indications (e.g., chronic pain); restrict use to opioid‑dependence maintenance per guidelines.
• Storage: Keep the implant at room temperature (20–25 °C) away from moisture; avoid freezing or prolonged exposure to heat.
• Insulin‑Regulated Patients: No proven impact, but maintain routine glucose monitoring; monitor for potential sedation interfering with medication adherence.

Probuphine remains a cornerstone in opioid‑dependence therapy for patients requiring long‑term maintenance and high adherence, offering a cost‑effective and patient‑friendly alternative to daily oral or sublingual buprenorphine.