Durotam Drug Interactions

There have been no drug interaction studies for Dutasteride + Tamsulosin HCl (Durotam). The following statements reflect the information available on the individual components.
Dutasteride: For information on the decrease of serum PSA levels during treatment with Dutasteride and guidance concerning prostate cancer detection.
Effects of other drugs on the pharmacokinetics of Dutasteride: Dutasteride is mainly eliminated via metabolism. In vitro studies indicate that this metabolism is catalyzed by CYP3A4 and CYP3A5. No formal interaction studies have been performed with potent CYP3A4 inhibitors. However, in a population pharmacokinetic study, Dutasteride serum concentrations were on average 1.6 to 1.8 times greater, respectively, in a small number of patients treated concurrently with verapamil or diltiazem (moderate inhibitors of CYP3A4 and inhibitors of P-glycoprotein) than in other patients.
Long-term combination of Dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 (e.g., ritonavir, indinavir, nefazodone, itraconazole, ketoconazole administered orally) may increase serum concentrations of Dutasteride. Further inhibition of 5-alpha reductase at increased Dutasteride exposure, is not likely. However, a reduction of the Dutasteride dosing frequency can be considered if side effects are noted. It should be noted that in the case of enzyme inhibition, the long half-life may be further prolonged and it can take more than 6 months of concurrent therapy before a new steady state is reached.
Administration of 12 g cholestyramine one hour after a 5 mg single dose of Dutasteride did not affect the pharmacokinetics of Dutasteride.
Effects of Dutasteride on the pharmacokinetics of other drugs: In a small study (n=24) of two weeks duration in healthy men, Dutasteride (0.5 mg daily) had no effect on the pharmacokinetics of Tamsulosin or terazosin. There was also no indication of a pharmacodynamic interaction in this study.
Dutasteride has no effect on the pharmacokinetics of warfarin or digoxin. This indicates that Dutasteride does not inhibit/induce CYP2C9 or the transporter P-glycoprotein. In vitro interaction studies indicate that Dutasteride does not inhibit the enzymes CYP1A2,CYP2D6, CYP2C9, CYP2C19, or CYP3A4.
Tamsulosin: Concomitant administration of Tamsulosin hydrochloride with drugs that can reduce blood pressure, including anesthetic agents, PDE5 inhibitors, and other alpha₁-adrenoceptor antagonists could lead to enhanced hypotensive effects.
Dutasteride-Tamsulosin should not be used in combination with other alpha₁-adrenoceptor antagonists.
Concomitant administration of Tamsulosin hydrochloride and ketoconazole (a strong CYP3A4 inhibitor) resulted in an increase of the C_max and AUC of Tamsulosin hydrochloride by a factor of 2.2 and 2.8 respectively. Concomitant administration of Tamsulosin hydrochloride and paroxetine (a strong CYP2D6 inhibitor) resulted in an increase of the C_max and AUC of Tamsulosin hydrochloride by a factor of 1.3 and 1.6 respectively.
Concomitant administration of Tamsulosin hydrochloride (0.4 mg) and cimetidine (400 mg every six hours for six days) resulted in a decrease in the clearance (26%) and an increase in the AUC (44%) of Tamsulosin hydrochloride. Caution should be used when Dutasteride-Tamsulosin is used in combination with cimetidine.
A definitive drug-drug interaction study between Tamsulosin hydrochloride and warfarin has not been conducted. Results from limited in vitro and in vivo studies are inconclusive. Diclofenac and warfarin, however, may increase the elimination rate of Tamsulosin.