Gepirone Disease Interactions

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials; these trials did not show increased risk in patients older than 24 years and risk was reduced in patients 65 years and older. Adult and pediatric patients with major depressive disorder may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressants; this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders; such disorders are the strongest predictors of suicide. Patients of all ages treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of drug therapy, and at times of dose changes. Family members/caregivers should be advised to monitor for changes in behavior and to notify the health care provider. Changing the therapeutic regimen (including discontinuing the medication) should be considered in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

Exposure to gepirone is increased in patients with hepatic impairment. Use of gepirone in patients with severe hepatic impairment (Child-Pugh C) is contraindicated. A dose reduction is recommended in patients with moderate hepatic impairment (Child-Pugh B). No dosage adjustment is recommended patients with mild hepatic impairment (Child-Pugh A).

This drug prolongs the QT interval. Use of gepirone in patients with congenital long QT syndrome is contraindicated. Treatment is also contraindicated in patients with severe hepatic impairment or in patients receiving concomitant strong CYP450 3A4 inhibitors because plasma drug concentrations may be increased in these population. Gepirone should not be initiated in patients with baseline QTc greater than 450 msec, and the dosage of gepirone should not be escalated if the QTcF is greater than 450 msec. Electrolyte abnormalities should be corrected prior to starting treatment, and then monitored during dose titration and periodically during treatment in patients with electrolyte abnormalities, or who are receiving diuretics or glucocorticoids, or who have a history of hypokalemia or hypomagnesemia. An electrocardiogram (ECG) should be performed prior to initiating therapy, during dosage titration, and periodically during treatment. Monitor patients with ECGs more frequently if gepirone is used concomitantly with drugs known to prolong the QT interval, in patients who develop a QTc of 450 msec or greater during treatment, or in patients with a significant risk of developing torsade de pointes, including those with uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism. Reduce the dose of this drug when used concomitantly with moderate CYP3A4 inhibitors, as they may increase drug concentrations.

All antidepressants may occasionally cause mania or hypomania, particularly in patients with bipolar disorder. Therapy with antidepressants should be administered cautiously in patients with a history of mania/hypomania.

Patients with renal impairment may experience reduced metabolism and excretion of gepirone. The recommended dose of gepirone in patients with CrCl less than 50 mL/min is reduced as compared to patients with normal renal function. No dosage adjustment is recommended for patients with CrCl 50 mL/min or greater.