)].
7.6 Calcium Channel Antagonists
Dutasteride: Coadministration of verapamil or diltiazem decreases dutasteride clearance and leads to increased exposure to dutasteride. The change in dutasteride exposure is not considered to be clinically significant. No dosage adjustment of dutasteride is recommended [see Clinical Pharmacology (12.3)].
7.7 Cholestyramine
Dutasteride: Administration of a single 5-mg dose of dutasteride followed 1hour later by a 12-g dose of cholestyramine does not affect the relative bioavailability of dutasteride [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category X. There are no adequate and well-controlled studies in pregnant women with JALYN or its individual components.
Dutasteride: Dutasteride is contraindicated for use in women of childbearing potential and during pregnancy. Dutasteride is a 5 alpha-reductase inhibitor that prevents conversion of testosterone to dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. In animal reproduction and developmental toxicity studies, dutasteride inhibited normal development of external genitalia in male fetuses. Therefore, dutasteride may cause fetal harm when administered to a pregnant woman. If dutasteride is used during pregnancy or if the patient becomes pregnant while taking dutasteride, the patient should be apprised of the potential hazard to the fetus.
Abnormalities in the genitalia of male fetuses is an expected physiological consequence of inhibition of the conversion of testosterone to DHT by 5 alpha-reductase inhibitors. These results are similar to observations in male infants with genetic 5 alpha-reductase deficiency. Dutasteride is absorbed through the skin. To avoid potential fetal exposure, women who are pregnant or could become pregnant should not handle dutasteride-containing capsules, including JALYN Capsules. If contact is made with leaking capsules, the contact area should be washed immediately with soap and water [see Warnings and Precautions (5.6)]. Dutasteride is secreted into semen. The highest measured semen concentration of dutasteride in treated men was 14ng/mL. Assuming exposure of a 50-kg woman to 5mL of semen and 100% absorption, the woman’s dutasteride concentration would be about 0.0175ng/mL. This concentration is more than 100times less than concentrations producing abnormalities of male genitalia in animal studies. Dutasteride is highly protein bound in human semen (greater than 96%), which may reduce the amount of dutasteride available for vaginal absorption.
In an embryo-fetal development study in female rats, oral administration of dutasteride at doses 10times less than the maximum recommended human dose (MRHD) of 0.5mg daily resulted in abnormalities of male genitalia in the fetus (decreased anogenital distance at 0.05mg/kg/day), nipple development, hypospadias, and distended preputial glands in male offspring (at all doses of 0.05, 2.5, 12.5, and 30mg/kg/day). An increase in stillborn pups was observed at 111times the MRHD, and reduced fetal body weight was observed at doses of about 15times the MRHD (animal dose of 2.5mg/kg/day). Increased incidences of skeletal variations considered to be delays in ossification associated with reduced body weight were observed at doses at about 56times the MRHD (animal dose of 12.5mg/kg/day).
In a rabbit embryo-fetal study, doses 28- to 93-fold the MRHD (animal doses |
