lurasidone-hydrochloride and Obesity

The antipsychotic agent lurasidone (Latuda®) is metabolized by Cytochrome P450-3A (CYP3A) enzymes. Coadministration with strong CYP3A inhibitors (such as ketoconazole, posaconazole, and ritonavir) is contraindicated due to the risk of sedation and movement disorders from high levels of lurasidone. This study evaluated the time-course of recovery from the posaconazole drug interaction, and the effect of obesity on the recovery process.. Healthy normal-weight volunteers (n = 11, mean body mass index, BMI, = 23.1 kg/m) and otherwise healthy obese subjects (n = 13, mean BMI = 49.3 kg/m) received single doses of lurasidone in the baseline control condition, again during coadministration of posaconazole, and at 4 additional time points during the 2 weeks after posaconazole discontinuation.. With posaconazole coadministration, lurasidone area under the concentration curve (AUC) increased by an arithmetic mean factor of 6.2 in normals, and by 4.9 in obese subjects. Post-treatment washout of posaconazole was slow in normals (mean half-life 31 hours), and further prolonged in obese subjects (53 hours). Recovery of lurasidone AUC toward baseline was correspondingly slow, and was incomplete. AUC remained significantly elevated above baseline both in normals (factor of 2.1) and obese subjects (factor of 3.4) even at 2 weeks after stopping posaconazole.. Product labeling does not address the necessary delay after discontinuation of a strong CYP3A inhibitor before lurasidone can be safely administered. We recommend requiring normal-weight and obese patients to limit the dosage of lurasidone, or undergo a washout period, for two and three weeks, respectively, after discontinuation of posaconazole.

Topics: Adult; Antifungal Agents; Antipsychotic Agents; Body Mass Index; Cytochrome P-450 CYP3A Inhibitors; Drug Administration Schedule; Drug Interactions; Female; Humans; Lurasidone Hydrochloride; Male; Obesity; Triazoles

A significant segment of the United States adult population is obese. Bariatric surgery is one approach to weight loss when nonsurgical efforts have failed. In individuals with a body mass index ≥50, gastric reduction with duodenal switch is more effective than gastric bypass. More than half of bariatric surgery candidates report a history of mental illness and more than one third were taking at least one psychotropic medication at the time of surgery. Thus, the impact of surgery on absorption of psychiatric medications should be considered. Lurasidone, a second-generation antipsychotic used to treat schizophrenia and bipolar disorder, is recommended to be taken with food of at least 350 calories. We describe the case of a patient with incomplete response to lurasidone therapy in the year following a duodenal switch procedure. This case raises concern about the effect that the duodenal switch procedure may have on lurasidone absorption.

Topics: Antipsychotic Agents; Bariatric Surgery; Bipolar Disorder; Humans; Intestinal Absorption; Lurasidone Hydrochloride; Obesity