G04CA53 - Tamsulosin and Solifenacin

Propably not porphyrinogenic

Rationale

Solifenacin: Solifenacin is extensively metabolized by Cyp3A4, but it has no capacity for Cyp-induction or significant Cyp-inhibition. Tamsulosin: Tamsulosin is not suspected to be an inducer or a mechanism-based inhibitor of CYP enzymes, and is not observed to alter the metabolism of other CYP metabolized drugs.

Chemical description

Solifenacin: Dihydroisoquinoline tertiary amine. Tamsulosin: Alpha1-adrenoceptor antagonist, sulphamoyl phenethylamine derivative

Therapeutic characteristics

Solifenacin: Solifenacin is an anticholinergic spasmolytic used in the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and increased urinary frequency. It is administered orally. Common adverse reactions of solifenacin that can be confused with an acute porphyric attack are constipation, nausea and abdominal pain. Side effects such as nausea may be potentially porphyrinogenic through reduction in caloric intake. Urinary infection is an uncommon side effect but may also potentially be porphyrinogenic. Tamsulosin: Tamsulosin is indicated for lower urinary tract symptoms associated with benign prostate hyperplasia. It is administered orally.

Hepatic exposure

Tamsulosin: The maximal plasma concentration of tamsulosin is about 16 ng/ml, which is equivalent to 40 nM (Franco-Salinas 2010).

Metabolism and pharmacokinetics

Solifenacin: Solifenacin is eliminated mainly via hepatic metabolism by Cyp3A4, and only 3-13 % is excreted as unchanged drug in urine. The absolute bioavailability is about 90%. Solifenacin has a high fraction of plasma protein-binding (93-96%). Solifenacin doses not influence the activities of Cyps 1A1, 1A2, 2C9, 2D6 and 3A4, but shows weak and clinically insignificant inhibitory potential for Cyp 2C19 and p-glycoprotein.(Doroshyenko 2009). In a well-controlled therapeutic trial solifenacin did not interact with the metabolism of ethinyl estradiol or levonorgestrel administered in oral contraception. (Taekema-Roelvink 2005). Tamsulosin: Tamsulosin is metabolized by CYP3A4 and CYP2D6 (Kamimura 1998). Tamsulosin has not been found to be an inhibitor of CYP1A2 (Miyazawa 2002), CYP2C9 (Rolan 2003), or CYP2D6 and CYP3A4 (Modi 2008). In the literature tamsulosin is not reported to be an inducer or inhibitor of any of the quantitatively major CYP enzymes and the absence of such characteristics is also in accordance with review-papers (FDA, Hisaka 2010, Isoherranen 2009 and Pelkonen 2008). No drug-drug interaction with tamsulosin as a perpetrator has been reported in the literature.

IPNet drug reports

Solifenacin: Uneventful use reported in 2 patients with acute porphyria. Tamsulosin: Uneventful use reported in 7 patients with acute porphyria.

Similar drugs

Explore alternative drugs in similar therapeutic classes G04C / G04CA or go back.

References

#	Citation details	PMID
*	Scientific articles
1.	Doroshyenko, O., Fur, U. Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin Pharmacokinet. 2009;48(5):281-302
2.	Franco-Salinas G1, de la Rosette JJ, et al. Pharmacokinetics and pharmacodynamics of tamsulosin in its modified-release and oral controlled absorption system formulations. Clin Pharmacokinet. 2010 Mar;49(3):177-88.
3.	Hisaka, A., Y. Ohno, et al. (2010). "Prediction of pharmacokinetic drug-drug interaction caused by changes in cytochrome P450 activity using in vivo information." Pharmacol Ther 125(2): 230-248.	19951720
4.	Isoherranen, N., H. Hachad, et al. (2009). "Qualitative analysis of the role of metabolites in inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database." Chem Res Toxicol 22(2): 294-298.	19216580
5.	Pelkonen, O., M. Turpeinen, et al. (2008). "Inhibition and induction of human cytochrome P450 enzymes: current status." Arch Toxicol 82(10): 667-715.
6.	Identification of cytochrome P450 isozymes involved in metabolism of the alpha1-adrenoceptor blocker tamsulosin in human liver microsomes. Kamimura H, Oishi S, et al. Xenobiotica. 1998 Oct;28(10):909-22.	9849639
7.	Effects of the concomitant administration of tamsulosin (0.8 mg/day) on the pharmacokinetic and safety profile of theophylline (5 mg/kg): a placebo-controlled evaluation. Miyazawa Y, Starkey LP, et al. J Int Med Res. 2002 Jan-Feb;30(1):34-43.
8.	Effect of dapoxetine on the pharmacokinetics and hemodynamic effects of tamsulosin in men on a stable dose of tamsulosin. Modi NB, Kell S, et al. J Clin Pharmacol. 2008 Dec;48(12):1438-50.	18832488
9.	A placebo-controlled pharmacodynamic and pharmacokinetic interaction study between tamsulosin and acenocoumarol. Rolan P, Terpstra IJ, et al. Br J Clin Pharmacol. 2003 Mar;55(3):314-6.	12630984
10.	E.J., Swart P.J., Pharmacokinetic interaction of solifenacin with an oral contraceptive containing ethinyl estradiol and levonorgestrel in healthy women: a double-blind, placebo-controlled study. Taekema-Roelvink M. Clin Ther. 2005;27(9):1403-10.	16291413
*	Drug reference publications
11.	Sweetman SC, editor. Martindale: The complete drug reference. Solifenacin succinate. Pharmaceutical Press 2009.
*	Government bodies
12.
*	Drug interaction databases
13.	U.S.FoodandDrugAdministration (FDA). (27.10.2014). "Drug Developement and Drug Interactions: Table of Substrates, Inhibitors and Inducers." Retrieved 09.03.2015, from
*	Summary of Product Characteristics
14.	Norwegian medicines agency. Summary of Product Characteristics (SPC). Vesicare.
15.	The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Vesicare.