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OLANZAPINE/ SAMIDORPHAN TAB

Clinical Criteria Summary

Indications

  • Schizophrenia in adults
  • Bipolar I disorder in adults (acute treatment of manic or mixed episodes as monotherapy and adjunct to lithium or valproate; maintenance monotherapy treatment)

Patient Selection & Clinical Guidance

  • Indicated for patients where olanzapine is indicated based on individual patient characteristics who are at high risk for weight gain
  • Not recommended for switching from another antipsychotic to prevent further weight gain or promote weight loss
  • Requires assessment and screening for opioid use prior to initiation
  • Recommended that patients have a patient identifier/medical alert identifier with them

Dosing & Administration Limits

  • Available tablet strengths: 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, and 20 mg/10 mg
  • Maximum dose of olanzapine available in the combination tablet is 20 mg; no guidance provided for patients requiring more than 20 mg of olanzapine

Contraindications

  • Patients currently using opioids
  • Patients undergoing acute opioid withdrawal
  • Refer to lithium or valproate prescribing information for contraindications if used concomitantly

Warnings & Precautions

  • Increased mortality and cerebrovascular adverse reactions in elderly patients with dementia-related psychosis
  • Precipitation of opioid withdrawal in opioid-dependent patients
  • Vulnerability to life-threatening opioid overdose due to potential increased sensitivity to opioids and attempts to overcome samidorphan’s receptor blockade
  • Neuroleptic malignant syndrome, DRESS, metabolic changes, tardive dyskinesia, orthostatic hypotension and syncope, falls, leukopenia/neutropenia/agranulocytosis, seizures, potential for cognitive and motor impairment, anticholinergic effects, hyperprolactinemia
  • Most common adverse effects (>5% of patients): weight gain, somnolence, dry mouth, headache, increased appetite

Special Populations & Interactions

  • Renal Impairment: Not recommended for use in end-stage renal disease (eGFR <15 ml/min/1.73 m2)
  • Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third-trimester exposure; pregnancy exposure registry available
  • Opioid-Free Interval Requirement: 7 days for short-acting opioids and 14 days for long-acting opioids required before initiation
  • Drug Interactions: Avoid use with strong CYP3A4 inducers; avoid use with levodopa and dopamine agonists
  • Pharmacokinetic properties of samidorphan are not affected by smoking status or sex

Source Documents