Tamsoli Drug Interactions

Concomitant medication with any medicinal products with anticholinergic properties may result in more pronounced therapeutic effects and undesirable effects. An interval of approximately one week should be allowed after stopping treatment with Tamsoli, before commencing any anticholinergic therapy. The therapeutic effect of solifenacin may be reduced by concomitant administration of cholinergic receptor agonists.
Interactions with CYP3A4 and CYP2D6 inhibitors: Concomitant administration of solifenacin with ketoconazole (a strong inhibitor of CYP3A4) (200 mg/day) resulted in a 1.4- and 2.0-fold increase in C_max and area under the curve (AUC) of solifenacin, while ketoconazole at a dose of 400 mg/day resulted in a 1.5- and 2.8-fold increase in C_max and AUC of solifenacin.
Concomitant administration of tamsulosin with ketoconazole at a dose of 400 mg/day resulted in a 2.2- and 2.8-fold increase in C_max and AUC of tamsulosin, respectively.
Since concomitant administration with strong inhibitors of CYP3A4, such as ketoconazole, ritonavir, nelfinavir and itraconazole may lead to increased exposure to both solifenacin and tamsulosin, Tamsoli should be used with caution in combination with strong CYP3A4 inhibitors.
Tamsoli should not be given together with strong CYP3A4 inhibitors in patients who are also CYP2D6 poor metaboliser phenotype or who are already using strong CYP2D6 inhibitors.
Concomitant administration of Tamsoli with verapamil (a moderate CYP3A4 inhibitor) resulted in an approximately 2.2-fold increase in C_max and AUC of tamsulosin and an approximately 1.6-fold increase in the C_max and AUC of solifenacin. Tamsoli should be used with caution in combination with moderate inhibitors of CYP3A4.
Concomitant administration of tamsulosin with the weak CYP3A4 inhibitor cimetidine (400 mg every 6 hours) resulted in a 1.44-fold increase in the AUC of tamsulosin, while C_max was not significantly changed. Tamsoli can be used with weak CYP3A4 inhibitors.
Concomitant administration of tamsulosin with the strong CYP2D6 inhibitor paroxetine (20 mg/day) resulted in an increase in C_max and AUC of tamsulosin by 1.3- and 1.6-fold, respectively. Tamsoli can be used with CYP2D6 inhibitors.
The effect of enzyme induction on the pharmacokinetics of solifenacin and tamsulosin has not been studied. Since solifenacin and tamsulosin are metabolised by CYP3A4, pharmacokinetic interactions are possible with CYP3A4 inducers (e.g., rifampicin) which may decrease the plasma concentration of solifenacin and tamsulosin.
Other Interactions: The following statements reflect the information available on the individual active substances.
Solifenacin: Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastrointestinal tract, such as metoclopramide and cisapride.
In vitro studies with solifenacin have demonstrated that at therapeutic concentrations, solifenacin does not inhibit CYP1A1/2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4. Therefore, no interactions are expected between solifenacin and drugs metabolised by these CYP enzymes.
Intake of solifenacin did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.
Intake of solifenacin showed no effect on the pharmacokinetics of digoxin.
Tamsulosin: Co-administration with other alpha1-adrenoceptor antagonists could lead to hypotensive effects.
In vitro, the free fraction of tamsulosin in human plasma was not changed by diazepam, propranolol, trichlormethiazide, chlormadinone, amitriptyline, diclofenac, glibenclamide, simvastatin or warfarin. Tamsulosin does not change the free fraction of diazepam, propranolol, trichlormethiazide or chlormadinone. Diclofenac and warfarin, however, may increase the elimination rate of tamsulosin.
Co-administration with furosemide causes a fall in plasma levels of tamsulosin, but as levels remain within the normal range, concurrent use is acceptable.
In vitro studies with tamsulosin have demonstrated that at therapeutic concentrations, tamsulosin does not inhibit CYP1A2, 2C9, 2C19, 2D6, 2E1 or 3A4. Therefore, no interactions are expected between tamsulosin and drugs metabolised by these CYP enzymes.
No interactions have been seen when tamsulosin was given concomitantly with atenolol, enalapril, or theophylline.