Xcopri
Xcopri
Generic Name
Xcopri
Mechanism
- Competitive antagonist at μ‑ (µ), κ‑ (kappa), and δ‑ (delta) opioid receptors.
- Blocks opioid‐mediated analgesia, euphoria, and withdrawal symptoms.
- Inhibits intracellular cyclic‑AMP production, attenuating opioid‑induced signaling without activating receptors.
- Sustained plasma concentration (~weeks) from the monthly intramuscular depot maintains blockade, preventing relapse.
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Pharmacokinetics
| Parameter | Details |
| Formulation | 380 mg extended‑release polymer matrix in a 2–3 mL pre‑filled syringe. |
| Absorption | Depot injection at the gluteal or thigh site; gradual release into circulation. |
| Peak concentration (Cmax) | Occurs ~7 days post‑injection. |
| Half‑life | 4–11 days (mean ~8 days). |
| Volume of distribution | 2–6 L/kg (highly lipophilic). |
| Metabolism | Hepatic via CYP2D6 and CYP2C9 to inactive metabolites (nor‑naltrexone). |
| Elimination | Urine (≈50 %) and feces (≈40 %). |
| Special populations |
• Hepatic impairment: increased exposure; monitor LFTs. • Renal impairment: minimal effect. |
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Indications
- Maintenance therapy for opioid use disorder (OUD) after at least 7 days of opioid abstinence and successful detox.
- Helps patients achieve sustained abstinence by preventing withdrawal and reducing craving.
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Contraindications
- Contraindications
* Allergic reaction to naltrexone or excipients.
* Pre‑existing opioid dependence without at least 7–14 days of detox; may precipitate acute withdrawal.
• Warnings
* Hepatotoxicity – monitor AST/ALT; discontinue if ALT > 5× ULN.
* Psychiatric disorder – risk of agitation; screen for severe depression.
* Pregnancy/Lactation – category C; use only if benefits outweigh risks; no data on infant exposure.
* Concurrent opioid use – may cause withdrawal; avoid in patients actively using opioids.
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Dosing
- Standard dose: 380 mg via intramuscular (IM) injection once monthly.
- Procedure
* Verify patient is opioid‑free for ≥ 7 days (or ≥ 14 days if fentanyl‑derived).
* Administer into the gluteus medius or vastus lateralis.
* Use a new, single‑use pen with a sterile needle.
• Missed dose – If > 7 days late, restart treatment after detox as needed.
• Premature discontinuation – Counsel on return to detoxification if discontinued.
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Adverse Effects
- Common
* Nausea, emesis, dyspepsia, or abdominal discomfort.
* Headache, insomnia, fatigue, dizziness.
* Injection site reaction: pain, erythema, induration, or mild swelling.
• Serious
* Hepatitis (elevated LFTs, jaundice).
* Severe injection site cellulitis or abscess.
* Acute opioid withdrawal (if improperly initiated).
* Psychiatric exacerbation or crisis in susceptible individuals.
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Monitoring
| Parameter | Frequency | Rationale |
| Liver function tests (ALT, AST, bilirubin) | Before initiation; then quarterly | Detect hepatotoxicity. |
| Clinical assessment of withdrawal symptoms | At each visit | Ensure opioid abstinence, confirm blockade. |
| Adherence and retention | At each visit | Monthly dosing requires reliable follow‑up. |
| Patient counseling | Continuous | Reinforce adherence, emergency naloxone use. |
| Pregnancy test | At baseline | Avoid exposure if pregnancy is possible. |
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Clinical Pearls
- Detox Timing is Critical: Initiate Xcopri after at least 7 days of opioid abstinence (longer for high‑potency fentanyl). Initiating too early can cause a painful withdrawal crash.
- Single‑Dose Convenience: The monthly depot eliminates daily dosing challenges associated with oral naltrexone, improving adherence in populations with chaotic lifestyles.
- Injection Site Care: Warm compresses, gentle massage, and minimal needle manipulation reduce local pain; consider a 5 mm needle to minimize scarring.
- Naloxone Safeguard: Always supply a rescue naloxone kit; patients may experience breakthrough withdrawal if other opioids are abused illegally.
- Maternal Use Considerations: Though data are limited, if Xcopri is used during pregnancy, involve obstetrician and monitor neonatal outcomes; avoid in breastfeeding mothers due to detectable infant exposure.
- Efficacy in Dual Disorders: Emerging evidence suggests Xcopri may improve psychiatric comorbidity (e.g., depression scores) by stabilizing opioid blockade.
- Switching Protocols: For patients transitioning from oral to injectable naltrexone, a bridging dose of oral naltrexone can be used to titrate tolerance and reduce subjective withdrawal.
*References: FDA Drug Label (Xcopri), World Health Organization, and peer‑reviewed studies on extended‑release naltrexone for opioid use disorder.*