Lurasidone and Selegiline Co-Administration
Lurasidone can be co-administered with selegiline without dose adjustment, as selegiline is not a strong CYP3A4 inhibitor or inducer, which are the only contraindicated drug interactions for lurasidone. 1
Drug Interaction Profile
Lurasidone is primarily metabolized through the CYP3A4 enzyme system 1. The FDA labeling explicitly identifies only two categories of contraindicated medications:
- Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil)
- Strong CYP3A4 inducers (rifampin, avasimibe, St. John's wort, phenytoin, carbamazepine) 1
Selegiline is a monoamine oxidase inhibitor (MAO-B selective at low doses) and does not significantly affect CYP3A4 metabolism. It is not listed among the contraindicated or cautionary medications in the lurasidone FDA labeling.
Dosing Recommendations
When prescribing lurasidone with selegiline:
- Standard dosing applies: Start at 40 mg/day for schizophrenia, 20 mg/day for bipolar depression
- Maximum dose: 80 mg/day (160 mg/day for schizophrenia in some cases, though 80 mg is the recommended maximum) 1
- Critical requirement: Must be taken with food (at least 350 calories) to ensure adequate absorption—food increases AUC 2-fold and Cmax 3-fold 1
Monitoring Parameters
Standard monitoring for lurasidone applies, with no additional requirements specific to selegiline co-administration:
- Extrapyramidal symptoms (akathisia, parkinsonism)—dose-dependent, with higher rates at doses >80 mg/day 2
- Somnolence—dose-dependent (NNH of 20 at 20 mg/day vs. NNH of 6 at 120 mg/day) 2
- Metabolic parameters: Lurasidone has a favorable metabolic profile with minimal weight gain and no clinically meaningful alterations in glucose or lipids 3, 2
Clinical Caveats
The only dose adjustments required for lurasidone are with:
- Moderate CYP3A4 inhibitors (reduce lurasidone dose by half) 1
- Moderate CYP3A4 inducers (may need to increase dose after 7+ days) 1
- Renal impairment (start 20 mg/day, max 80 mg/day for CrCl <50 mL/min) 1
- Hepatic impairment (start 20 mg/day, max 80 mg/day for moderate, 40 mg/day for severe) 1
Avoid grapefruit juice, which inhibits CYP3A4 and can increase lurasidone levels 1.