G04CA52 - Tamsulosin and Dutasteride |
Propably not porphyrinogenic |
PNP |
Rationale
This combination product contains two substances: tamsulosin (ATC-code: G04CA02) and dutasteride (ATC-code: G04CB02). Both of them are safety classified as probably not porphyrinogenic. The classification of the combination is therefore safety classified as probably not porphyrinogenic. For more details please refer to the monographs of the two substances.
Chemical description
Tamsulosin is a sulphamoyl phenethylamine derivative
Dutasteride is an oxosteroide derivative
Therapeutic characteristics
Tamsulosin is an alpha-1-adrenoceptor antagonist and dutasteride is a testosterone 5-alpha-reductase inhibitor, and the combination is used in the treatment of moderate to severe symptoms of benign prostatic hyperplasia (BPH).
It is administered orally.
Metabolism and pharmakokinetics
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 (Hisaka 2010, Isoherranen 2009 and Pelkonen 2008). No drug-drug interaction with tamsulosin as a perpetrator has been reported in the literature (Lexi-Interact).
Dutasteride is metabolized by CYP3A4/5 (SPC). Dutasteride and its metabolites are mainly excreted in the feaces (SPC). Dutasteride does not have an effect on warfarin or digoxin and is thus not an inhibitor or inducer of CYP2C9 (SPC). In vitro interaction studies report that it is not an inhibitor of CYP1A2, 2A6, 2E1, 2C8, 2D6, 2C9, 2C19, 2B6 or 3A4 (SPC). No drug-drug interactions with dutasteride as perpetrator have been reported in the literature (Lexi-Interact, Keam 2008).
IPNet drug reports
For tamsulosin (ATC-code: G04CA02) there are 7 reports of uneventful use in patients with acute porphyria.
References
- Scientific articles
- 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. #1567
- 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. #1568
- Pelkonen, O., M. Turpeinen, et al. (2008). "Inhibition and induction of human cytochrome P450 enzymes: current status." Arch Toxicol 82(10): 667-715. #1572
- Kamimura H, Oishi S, et al. Identification of cytochrome P450 isozymes involved in metabolism of the alpha1-adrenoceptor blocker tamsulosin in human liver microsomes. Xenobiotica. 1998 Oct;28(10):909-22. PMID 9849639. #4483
- Keam SJ, Scott LJ. Dutasteride: a review of its use in the management of prostate disorders. Drugs. 2008;68(4):463-85. PMID 18318566. #1576
- Miyazawa Y, Starkey LP, et al. 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. J Int Med Res. 2002 Jan-Feb;30(1):34-43. #1570
- Modi NB, Kell S, et al. Effect of dapoxetine on the pharmacokinetics and hemodynamic effects of tamsulosin in men on a stable dose of tamsulosin. J Clin Pharmacol. 2008 Dec;48(12):1438-50. PMID 18832488. #4484
- Rolan P, Terpstra IJ, et al. A placebo-controlled pharmacodynamic and pharmacokinetic interaction study between tamsulosin and acenocoumarol. Br J Clin Pharmacol. 2003 Mar;55(3):314-6. PMID 12630984. #4485
- Government bodies
- #1302
- Drug interaction databases
- Lexi-Interact in UpToDate. Tamsulosin and dutasteride: Drug interaction program. #3175
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). (Combodart). #3176
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