Interactions
Tamsulosin hydrochloride capsules 0.4 mg should not be used with strong inhibitors of CYP3A4 (e.g., ketoconazole). Tamsulosin hydrochloride capsules should be used with caution in combination with moderate inhibitors of CYP3A4 (e.g., erythromycin), in combination with strong (e.g., paroxetine) or moderate (e.g., terbinafine) inhibitors of CYP2D6, or in patients known to be CYP2D6 poor metabolizers, particularly at a dose higher than 0.4 mg (e.g., 0.8 mg).
( 5.2 , 7.1 , 12.3 ) Concomitant use of PDE5 inhibitors with tamsulosin can potentially cause symptomatic hypotension ( 5.2 , 7.3 , 12.3 )
7.1Cytochrome P450 Inhibition Strong and Moderate Inhibitors of CYP3A4 or CYP2D6
Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6. Concomitant treatment with ketoconazole (a strong inhibitor of CYP3A4) resulted in an increase in the C max and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively [ see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 ) ]. The effects of concomitant administration of a moderate CYP3A4 inhibitor (e.g., erythromycin) on the pharmacokinetics of tamsulosin hydrochloride have not been evaluated [ see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 ) ].
Concomitant treatment with paroxetine (a strong inhibitor of CYP2D6) resulted in an increase in the C max and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively [ see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 ) ]. A similar increase in exposure is expected in CYP2D6 poor metabolizers (PM) as compared to extensive metabolizers (EM). Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in tamsulosin exposure exists when tamsulosin hydrochloride 0.4 mg is coadministered with strong CYP3A4 inhibitors in CYP2D6 PMs, tamsulosin hydrochloride 0.4 mg capsules should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [ see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 ) ].
The effects of concomitant administration of a moderate CYP2D6 inhibitor (e.g., terbinafine) on the pharmacokinetics of tamsulosin hydrochloride have not been evaluated [ see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 ) ]. The effects of coadministration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin hydrochloride capsules have not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin hydrochloride 0.4 mg is coadministered with a combination of both CYP3A4 and CYP2D6 inhibitors [ see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 ) ].
Cimetidine Treatment with cimetidine resulted in a significant decrease (26%) in the clearance of tamsulosin hydrochloride, which resulted in a moderate increase in tamsulosin hydrochloride AUC (44%) [ see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 ) ].
7.2Other Alpha Adrenergic Blocking Agents
The pharmacokinetic and pharmacodynamic interactions between tamsulosin hydrochloride capsules and other alpha adrenergic blocking agents have not been determined; however, interactions between tamsulosin hydrochloride capsules and other alpha adrenergic blocking agents may be expected [ see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 ) ].
7.3PDE5 Inhibitors
Caution is advised when alpha adrenergic blocking agents including tamsulosin hydrochloride are coadministered with PDE5 inhibitors. Alpha-adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension [ see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 ) ].
7.4Warfarin
A definitive drug-drug interaction study between tamsulosin hydrochloride and warfarin was not conducted. Results from limited in vitro and in vivo studies are inconclusive. Caution should be exercised with concomitant administration of warfarin and tamsulosin hydrochloride capsules [ see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 ) ].
7.5Nifedipine, Atenolol, Enalapril
Dosage adjustments are not necessary when tamsulosin hydrochloride capsules are administered concomitantly with nifedipine, atenolol, or enalapril [ see Clinical Pharmacology ( 12.3 ) ].
7.6Digoxin and Theophylline
Dosage adjustments are not necessary when a tamsulosin hydrochloride capsule is administered concomitantly with digoxin or theophylline [ see Clinical Pharmacology ( 12.3 ) ].
7.7Furosemide
Tamsulosin hydrochloride capsules had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in tamsulosin hydrochloride C max and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the tamsulosin hydrochloride capsules dosage [ see Clinical Pharmacology ( 12.3 ) ].
