h renal impairment do not require an adjustment in tamsulosin dosing. However, patients with end-stage renal disease (CLcr<10mL/min/1.73m2) have not been studied.
Hepatic Impairment: The effect of hepatic impairment on dutasteride and tamsulosin pharmacokinetics has not been studied using JALYN. The following text reflects information available for the individual components.
Dutasteride: The effect of hepatic impairment on dutasteride pharmacokinetics has not been studied. Because dutasteride is extensively metabolized, exposure could be higher in hepatically impaired patients.
Tamsulosin: The pharmacokinetics of tamsulosin have been compared in 8subjects with moderate hepatic impairment (Child-Pugh classification: GradesA and B) and 8normal subjects. While a change in the overall plasma concentration of tamsulosin was observed as the result of altered binding to AAG, the unbound (active) concentration of tamsulosin does not change significantly with only a modest (32%) change in intrinsic clearance of unbound tamsulosin. Therefore, patients with moderate hepatic impairment do not require an adjustment in tamsulosin dosage. Tamsulosin has not been studied in patients with severe hepatic impairment.
Drug Interactions: There have been no drug interaction studies using JALYN. The following text reflects information available for the individual components.
Cytochrome P450 Inhibitors:Dutasteride: No clinical drug interaction studies have been performed to eva luate the impact of CYP3A enzyme inhibitors on dutasteride pharmacokinetics. However, based on in vitro data, blood concentrations of dutasteride may increase in the presence of inhibitors of CYP3A4/5 such as ritonavir, ketoconazole, verapamil, diltiazem, cimetidine, troleandomycin, and ciprofloxacin.
Dutasteride does not inhibit the in vitro metabolism of model substrates for the major human cytochrome P450 isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) at a concentration of 1,000ng/mL, 25times greater than steady-state serum concentrations in humans.
Tamsulosin:Strong and Moderate Inhibitors of CYP3A4 or CYP2D6: The effects of ketoconazole (a strong inhibitor of CYP3A4) at 400mg once daily for 5days on the pharmacokinetics of a single tamsulosin hydrochloride capsule 0.4mg dose was investigated in 24 healthy volunteers (age range: 23 to 47years). Concomitant treatment with ketoconazole resulted in increases in the Cmax and AUC of tamsulosin by factors of 2.2 and 2.8, respectively. The effects of concomitant administration of a moderate CYP3A4 inhibitor (e.g., erythromycin) on the pharmacokinetics of tamsulosin have not been eva luated.
The effects of paroxetine (a strong inhibitor of CYP2D6) at 20mg once daily for 9days on the pharmacokinetics of a single tamsulosin capsule 0.4mg dose was investigated in 24healthy volunteers (age range: 23 to 47years). Concomitant treatment with paroxetine resulted in increases in the Cmax and AUC of tamsulosin by factors of 1.3 and 1.6, respectively. A similar increase in exposure is expected in poor metabolizers (PM) of CYP2D6 as compared to extensive metabolizers (EM). A fraction of the population (about 7% of Caucasians and 2% of African-Americans) are CYP2D6 PMs. Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in tamsulosin exposure exists when tamsulosin 0.4mg is coadministered with strong CYP3A4 inhibitors in CYP2D6 PMs, tamsulosin 0.4mg capsules should n |
