indication

Used in the treatment of signs and symptoms of benign prostatic hyperplasia (reduction in urinary obstruction and relief of associated manifestations such as hesitancy, terminal dribbling of urine, interrupted or weak stream...etc.)

pharmacology

Tamsulosin, a sulfamoylphenethylamine-derivative alpha-adrenoceptor blocker with enhanced specificity for the alpha-adrenoceptors of the prostate, is commonly used to treat benign prostatic hyperplasia (BPH). The drug is commercially available in a racemic mixture of 2 isomers, and is pharmacologically related to doxazocin, prazosin, and terazosin. However, unlike these drugs, tamsulosin has a higher affinity for the alpha-1A- adrenergic receptors, which are located in vascular smooth muscle. Studies show that tamsulosin has about 12 times greater affinity for alpha-1 adrenergic receptors in the prostate than those in the aorta, which may result in a reduced incidence of adverse cardiovascular effects.

mechanism of action

Tamsulosin is a selective antagonist at alpha-1A and alpha-1B-adrenoceptors in the prostate, prostatic capsule, prostatic urethra, and bladder neck. At least three discrete alpha1-adrenoceptor subtypes have been identified: alpha-1A, alpha-1B and alpha-1D; their distribution differs between human organs and tissue. Approximately 70% of the alpha1-receptors in human prostate are of the alpha-1A subtype. Blockage of these receptors causes relaxation of smooth muscles in the bladder neck and prostate, and thus decreases urinary outflow resistance in men.

toxicity

LD₅₀ = 650 mg/kg (in rats)

biotransformation

Tamsulosin HCI is extensively metabolized by cytochrome P450 enzymes in the liver, however, the pharmacokinetic profile of the metabolites in humans has not been established.

absorption

Absorption of tamsulosin HCI from capsules 0.4 mg is essentially complete (>90%) following oral administration under fasting conditions.

half life

5-7 hours

route of elimination

Tamsulosin hydrochloride is extensively metabolized by cytochrome P450 enzymes in the liver and less than 10% of the dose is excreted in urine unchanged. The metabolites of tamsulosin hydrochloride undergo extensive conjugation to glucuronide or sulfate prior to renal excretion. On administration of the radiolabeled dose of tamsulosin hydrochloride to four healthy volunteers, 97% of the administered radioactivity was recovered, with urine (76%) representing the primary route of excretion compared to feces (21%) over 168 hours.

drug interactions

Alfuzosin: Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Alfuzosin, may result in additive antihypertensive effects. Combination therapy is not recommended.

Amiodarone: Amiodarone, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Amiodarone is initiated, discontinued, or dose changed.

Amprenavir: Amprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Amprenavir is initiated, discontinued, or dose changed.

Aprepitant: Aprepitant, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Aprepitant is initiated, discontinued, or dose changed.

Atazanavir: Atazanvir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Atazanavir is initiated, discontinued, or dose changed.

Caffeine: Caffeine, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Caffeine is initiated, discontinued, or dose changed.

Chloroquine: Chloroquine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Chloroquine is initiated, discontinued, or dose changed.

Chlorpromazine: Chlorpromazine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Chlorpromazine is initiated, discontinued, or dose changed.

Cimetidine: Cimetidine, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Cimetidine is initiated, discontinued, or dose changed.

Cinacalcet: Cinacalcet, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Cinacalcet is initiated, discontinued, or dose changed.

Clarithromycin: Clarithromycin, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clarithromycin is initiated, discontinued, or dose changed.

Clomipramine: Clomipramine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clomipramine is initiated, discontinued, or dose changed.

Clotrimazole: Clotrimazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clotrimazole is initiated, discontinued, or dose changed.

Clozapine: Clozapine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clozapine is initiated, discontinued, or dose changed.

Cocaine: Cocaine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Cocaine is initiated, discontinued, or dose changed.

Conivaptan: Conivaptan, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Conivaptan is initiated, discontinued, or dose changed.

Cyclosporine: Cyclosporine, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Cyclosporine is initiated, discontinued, or dose changed.

Dapiprazole: Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Dapiprazole, may result in additive antihypertensive effects. Combination therapy is not recommended.

Darifenacin: Darifenacin, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Darifenacin is initiated, discontinued, or dose changed.

Darunavir: Darunavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Darunavir is initiated, discontinued, or dose changed.

Delavirdine: Delavirdine, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Delavirdine is initiated, discontinued, or dose changed.

Desipramine: Desipramine, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Desipramine is initiated, discontinued, or dose changed.

Diltiazem: Diltiazem, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Diltiazem is initiated, discontinued, or dose changed.

Diphenhydramine: Diphenhydramine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Diphenhydramine is initiated, discontinued, or dose changed.

Doxazosin: Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Doxazosin, may result in additive antihypertensive effects. Combination therapy is not recommended.

Doxycycline: Doxycycline, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Doxycycline is initiated, discontinued, or dose changed.

Duloxetine: Duloxetine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Duloxetine is initiated, discontinued, or dose changed.

Efavirenz: Efavirenz, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Efavirenz is initiated, discontinued, or dose changed.

Erythromycin: Erythromycin, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Erythromycin is initiated, discontinued, or dose changed.

Fluconazole: Fluconzole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Fluconazole is initiated, discontinued, or dose changed.

Fluoxetine: Fluoxetine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Fluoxetine is initiated, discontinued, or dose changed.

Fosamprenavir: Fosamprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Fosamprenavir is initiated, discontinued, or dose changed.

Haloperidol: Haloperidol, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Haloperidol is initiated, discontinued, or dose changed.

Imatinib: Imatinib, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Imatinib is initiated, discontinued, or dose changed.

Imipramine: Imipramine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Imipramine is initiated, discontinued, or dose changed.

Indinavir: Indinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Indinavir is initiated, discontinued, or dose changed.

Isoniazid: Isoniazid, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Isoniazid is initiated, discontinued, or dose changed.

Itraconazole: Itraconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Itraconazole is initiated, discontinued, or dose changed.

Ketoconazole: Ketoconazole, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Ketoconzole is initiated, discontinued, or dose changed.

Lapatinib: Lapatinib, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Lapatinib is initiated, discontinued, or dose changed.

Lidocaine: Lidocaine, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Lidocaine is initiated, discontinued, or dose changed.

Lopinavir: Lopinavir, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Lopinavir is initiated, discontinued, or dose changed.

Methadone: Methadone, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Methadone is initiated, discontinued, or dose changed.

Methimazole: Methimazole, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Methimazole is initiated, discontinued, or dose changed.

Metronidazole: Metronidazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Metronidazole is initiated, discontinued, or dose changed.

Miconazole: Miconazole, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Miconazole is initiated, discontinued, or dose changed.

Nefazodone: Nefazodone, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Nefazodone is initiated, discontinued, or dose changed.

Nelfinavir: Nelfinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Nelfinavir is initiated, discontinued, or dose changed.

Nicardipine: Nicardipine, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Nicardipine is initiated, discontinued, or dose changed.

Nilotinib: Nilotinib, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Nilotinib is initiated, discontinued, or dose changed.

Norfloxacin: Norfloxacin, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Norfloxacin is initiated, discontinued, or dose changed.

Paroxetine: Paroxetine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Paroxetine is initiated, discontinued, or dose changed.

Pergolide: Pergolide, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Pergolide is initiated, discontinued, or dose changed.

Phenoxybenzamine: Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Phenoxybenzamine, may result in additive antihypertensive effects. Combination therapy is not recommended.

Phentolamine: Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Phentolamine, may result in additive antihypertensive effects. Combination therapy is not recommended.

Pioglitazone: Pioglitazone, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Pioglitazone is initiated, discontinued, or dose changed.

Posaconazole: Posaconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Posaconazole is initiated, discontinued, or dose changed.

Prazosin: Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Prazosin, may result in additive antihypertensive effects. Combination therapy is not recommended.

Pyrimethamine: Pyrimethamine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Pyrimethamine is initiated, discontinued, or dose changed.

Quinidine: Quinidine, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Quinidine is initiated, discontinued, or dose changed.

Quinine: Quinine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Quinine is initiated, discontinued, or dose changed.

Ranolazine: Ranolazine, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Ranolazine is initiated, discontinued, or dose changed.

Ritonavir: Ritonavir, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Ritonavir is initiated, discontinued, or dose changed.

Saquinavir: Saquinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Saquinavir is initiated, discontinued, or dose changed.

Sertraline: Sertraline, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Sertraline is initiated, discontinued, or dose changed.

Sitaxentan: Sitaxsentan, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Sitaxsentan is initiated, discontinued, or dose changed.

Tadalafil: Tadalafil may enhance the hypotensive effect of Tamsulosin. Monitor for hypotension during concomitant therapy.

Telithromycin: Telithromycin, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic/adverse effects of Tamsulosin if Telithromycin is initiated, discontinued, or dose changed.

Terazosin: Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Terazosin, may result in additive antihypertensive effects. Combination therapy is not recommended.

Terbinafine: Terbinafine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic/adverse effects of Tamsulosin if Terbinafine is initiated, discontinued, or dose changed.

Tetracycline: Tetracycline, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Tetracycline is initiated, discontinued, or dose changed.

Thioridazine: Thioridazine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Thioridazine is initiated, discontinued, or dose changed.

Ticlopidine: Ticlopidine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Ticlopidine is initiated, discontinued, or dose changed.

Tranylcypromine: Tranylcypromine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Tranylcypromine is initiated, discontinued, or dose changed.

Trazodone: Trazodone, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Trazodone is initiated, discontinued, or dose changed.

Vardenafil: Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Tamsulosin, may occur. Monitor for hypotension during concomitant therapy.

Verapamil: Verapamil, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Verapamil is initiated, discontinued, or dose changed.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of tamsulosin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of tamsulosin if voriconazole is initiated, discontinued or dose changed.