Lurasidone drug-drug interaction studies: a comprehensive review

Area of Science:

• Pharmacology
• Drug Metabolism
• Clinical Pharmacology

Background:

• Lurasidone is an atypical antipsychotic.
• Understanding drug-drug interactions is crucial for safe and effective lurasidone use.

Purpose of the Study:

• To investigate potential drug-drug interactions with lurasidone.
• To assess the impact of co-administered drugs on lurasidone pharmacokinetics (PK).
• To evaluate the effect of lurasidone on the PK of other medications.

Main Methods:

• Seven Phase I studies examined PK of lurasidone with ketoconazole, diltiazem, rifampin, lithium, digoxin, midazolam, and oral contraceptives.
• Two Phase III studies assessed lurasidone interactions with lithium and valproate.
• Key PK parameters, including Cmax and AUC, were analyzed.

Main Results:

• Ketoconazole significantly increased lurasidone exposure (6.8-fold Cmax, 9.3-fold AUC).
• Diltiazem moderately increased lurasidone exposure (2.1-fold Cmax, 2.2-fold AUC).
• Rifampin decreased lurasidone exposure (one-seventh Cmax, one-fifth AUC).
• Lurasidone had minimal impact on digoxin, midazolam, and oral contraceptives.
• No significant interactions were observed between lurasidone and lithium or valproate.

Conclusions:

• Lurasidone PK is significantly affected by strong CYP3A4 inhibitors and inducers, necessitating contraindication.
• Moderate CYP3A4 inhibitors warrant dosage adjustments for lurasidone.
• Lurasidone coadministration does not require dose adjustments for lithium, valproate, digoxin, midazolam, or oral contraceptives.