Tamsulosin (Flomax): Drug Monograph
- Treatment of the signs and symptoms of benign prostatic hyperplasia (BPH)
- Nephrolithiasis (off-label; not FDA approved indication):
- Note the SUSPEND Trial suggested no difference in outcomes when compared to nifedipine or placebo. Click Here
- Note: Not indicated for the treatment of hypertension
- Benign Prostatic Hyperplasia (BPH):
- 0.4 mg by mouth once daily 30 minutes after the same meal each day
- May increase to 0.8 mg once daily after 2-4 weeks if response is inadequate
- If therapy is discontinued or interrupted for several days at either the 0.4 mg or 0.8 mg dose restart with 0.4 mg once daily
- Known hypersensitivity to tamsulosin hydrochloride or any component of the capsules
- Possibility of symptoms related to postural hypotension - avoid situations where injury could result should syncope occur
- Should not be used in combination with strong inhibitors of CYP3A4. Use with caution in combination with moderate inhibitors of CYP3A4, with strong or moderate inhibitors of CYP2D6, in patients known to be CYP2D6 poor metabolizers, or in combination with other cytochrome P450 inhibitors.
- Should not be used in combination with other alpha adrenergic blocking agents
- Exercise caution with concomitant administration of warfarin
- Priapism - this condition can lead to permanent impotence if not properly treated
- Intraoperative Floppy Iris Syndrome - has been observed during cataract and glaucoma surgery in some patients. Advise patients considering cataract or glaucoma surgery to tell their ophthalmologist that they have taken tamsulosin capsules.
- Presence of prostrate cancer - advise patients to be screened prior to treatment and at regular intervals afterwards
- Abnormal ejaculation
- Back pain
- Chest pain
- Cough increased
- Libido decreased
- Tooth disorder
- Blurred vision
- May lead to hypotension
- Support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position.
- If this measure is inadequate, then administration of IV fluids should be considered. If necessary, vasopressors should then be used and renal function should be monitored and supported as needed.
- Dialysis is unlikely to be of benefit.
- Strong inhibitors of CYP3A4 (e.g., ketoconazole). Tamsulosin 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)
- Concomitant use of PDE5 inhibitors with tamsulosin can potentially cause symptomatic hypotension
- Pregnancy: Pregnancy Category B
- Labor and Delivery: None
- Nursing Mothers: Not indicated for use in women.
- Renal Impairment: Patients with renal impairment do not require an adjustment in dosing. Has not been studied in patients with end-stage renal disease.
- Hepatic Impairment: No dosage adjustment needed with moderate impairment. Has not been studied in patients with severe hepatic impairment.
- Pediatric Patients: Not indicated for use in pediatric populations.
- Geriatric Patients: No overall differences in efficacy or safety vs younger patients, but greater sensitivity of some older individuals cannot be ruled out
Scientific Name: (-)-(R)-5-[2-[[2-(o-Ethoxyphenoxy) ethyl]amino]propyl]-2- methoxybenzenesulfonamide, monohydrochloride
Empirical Formula: C20H28N2O5S.HCl
Molecular Weight: 444.98
- The symptoms associated with benign prostatic hyperplasia (BPH) are related to bladder outlet obstruction, which is comprised of two underlying components: static and dynamic. The static component is related to an increase in prostate size caused, in part, by a proliferation of smooth muscle cells in the prostatic stroma. However, the severity of BPH symptoms and the degree of urethral obstruction do not correlate well with the size of the prostate. The dynamic component is a function of an increase in smooth muscle tone in the prostate and bladder neck leading to constriction of the bladder outlet. Smooth muscle tone is mediated by the sympathetic nervous stimulation of alpha1 adrenoceptors, which are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck. Blockade of these adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH.
- Tamsulosin, an alpha1 adrenoceptor blocking agent, exhibits selectivity for alpha1 receptors in the human prostate. At least three discrete alpha1 adrenoceptor subtypes have been identified: alpha1A, alpha1B, and alpha1D; their distribution differs between human organs and tissue. Approximately 70% of the alpha1 receptors in the human prostate are of the alpha1A subtype.
- Tamsulosin capsules are not intended for use as an antihypertensive drug.
- Urologic pharmacodynamic effects have been evaluated in neurologically impaired pediatric patients and in adults with BPH.
- The pharmacokinetics of tamsulosin hydrochloride have been evaluated in adult healthy volunteers and patients with BPH after single and/or multiple administration with doses ranging from 0.1 mg to 1 mg.
- Absorption: Absorption of tamsulosin hydrochloride from tamsulosin capsules 0.4 mg is essentially complete (>90%) following oral administration under fasting conditions. Tamsulosin hydrochloride exhibits linear kinetics following single and multiple dosing, with achievement of steady-state concentrations by the fifth day of once- a-day dosing.
- Effect of Food: The time to maximum concentration (Tmax) is reached by 4 to 5 hours under fasting conditions and by 6 to 7 hours when the capsules are administered with food. Taking the capsules under fasted conditions results in a 30% increase in bioavailability (AUC) and 40% to 70% increase in peak concentrations (Cmax) compared to fed conditions. The effects of food on the pharmacokinetics of tamsulosin are consistent regardless of whether a capsule is taken with a light breakfast or a high-fat breakfast.
- Distribution: The mean steady-state apparent volume of distribution of tamsulosin hydrochloride after intravenous administration to 10 healthy male adults was 16 L, which is suggestive of distribution into extracellular fluids in the body. Tamsulosin hydrochloride is extensively bound to human plasma proteins (94% to 99%), primarily alpha1 acid glycoprotein (AAG), with linear binding over a wide concentration range (20 to 600 ng/mL). The results of two-way in vitro studies indicate that the binding of tamsulosin hydrochloride to human plasma proteins is not affected by amitriptyline, diclofenac, glyburide, simvastatin plus simvastatin-hydroxy acid metabolite, warfarin, diazepam, propranolol, trichlormethiazide, or chlormadinone. Likewise, tamsulosin hydrochloride had no effect on the extent of binding of these drugs.
- Metabolism: There is no enantiomeric bioconversion from tamsulosin hydrochloride [R(-) isomer] to the S(+) isomer in humans. Tamsulosin hydrochloride is extensively metabolized by cytochrome P450 enzymes in the liver and less than 10% of the dose is excreted in urine unchanged. However, the pharmacokinetic profile of the metabolites in humans has not been established. Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6 as well as via some minor participation of other CYP isoenzymes. Inhibition of hepatic drug- metabolizing enzymes may lead to increased exposure to tamsulosin. The metabolites of tamsulosin hydrochloride undergo extensive conjugation to glucuronide or sulfate prior to renal excretion. Incubations with human liver microsomes showed no evidence of clinically significant metabolic interactions between tamsulosin hydrochloride and amitriptyline, albuterol (beta agonist), glyburide (glibenclamide) and finasteride (5alpha-reductase inhibitor for treatment of BPH). However, results of the in vitro testing of the tamsulosin hydrochloride interaction with diclofenac and warfarin were equivocal.
- Elimination: On administration of the radiolabeled dose of tamsulosin hydrochloride to 4 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. Following intravenous or oral administration of an immediate-release formulation, the elimination half-life of tamsulosin hydrochloride in plasma ranged from 5 to 7 hours. Because of absorption rate-controlled pharmacokinetics with FLOMAX capsules, the apparent half-life of tamsulosin hydrochloride is approximately 9 to 13 hours in healthy volunteers and 14 to 15 hours in the target population. Tamsulosin hydrochloride undergoes restrictive clearance in humans, with a relatively low systemic clearance (2.88 L/h).
- Special Populations
- Pediatric Use: Tamsulosin capsules are not indicated for use in pediatric populations.
- Geriatric Use: Cross-study comparison of tamsulosin capsules overall exposure (AUC) and half-life indicates that the pharmacokinetic disposition of tamsulosin hydrochloride may be slightly prolonged in geriatric males compared to young, healthy male volunteers. Intrinsic clearance is independent of tamsulosin hydrochloride binding to AAG, but diminishes with age, resulting in a 40% overall higher exposure (AUC) in subjects of age 55 to 75 years compared to subjects of age 20 to 32 years.
- Renal Impairment: The pharmacokinetics of tamsulosin hydrochloride have been compared in 6 subjects with mild-moderate (30≤ ClCr<70 mL/min/1.73m2) or moderate-severe (10≤ClCr<30 mL/min/1.73m2) renal impairment and 6 normal subjects (ClCr>90 mL/min/1.73m2). While a change in the overall plasma concentration of tamsulosin hydrochloride was observed as the result of altered binding to AAG, the unbound (active) concentration of tamsulosin, as well as the intrinsic clearance, remained relatively constant. Therefore, patients with renal impairment do not require an adjustment in dosing. However, patients with end-stage renal disease (ClCr<10 mL/min/1.73m2) have not been studied.
- Hepatic Impairment: The pharmacokinetics of tamsulosin hydrochloride have been compared in 8 subjects with moderate hepatic impairment (Child-Pugh's classification: Grades A and B) and 8 normal subjects. While a change in the overall plasma concentration of tamsulosin hydrochloride was observed as the result of altered binding to AAG, the unbound (active) concentration of tamsulosin hydrochloride does not change significantly, with only a modest (32%) change in intrinsic clearance of unbound tamsulosin hydrochloride. Therefore, patients with moderate hepatic impairment do not require an adjustment in dosage. Tamsulosin has not been studied in patients with severe hepatic impairment.
- Drug Interactions
- Cytochrome P450 Inhibition
- Strong and Moderate Inhibitors of CYP3A4 or CYP2D6:The effects of ketoconazole (a strong inhibitor of CYP3A4) at 400 mg once daily for 5 days on the pharmacokinetics of a single capsule 0.4 mg dose was investigated in 24 healthy volunteers (age range 23 to 47 years). Concomitant treatment with ketoconazole resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively. The effects of concomitant administration of a moderate CYP3A4 inhibitor (e.g., erythromycin) on the pharmacokinetics of tamsulosin have not been evaluated.
- The effects of paroxetine (a strong inhibitor of CYP2D6) at 20 mg once daily for 9 days on the pharmacokinetics of a single capsule 0.4 mg dose was investigated in 24 healthy volunteers (age range 23 to 47 years). Concomitant treatment with paroxetine resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. A similar increase in exposure is expected in CYP2D6 poor metabolizers (PM) as compared to extensive metabolizers (EM). A fraction of the population (about 7% of Caucasians and 2% of African Americans) are CYP2D6 PMs. Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in tamsulosin exposure exists when tamsulosin 0.4 mg is co-administered with strong CYP3A4 inhibitors in CYP2D6 PMs, tamsulosin 0.4 mg capsules should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole).
- The effects of concomitant administration of a moderate CYP2D6 inhibitor (e.g., terbinafine) on the pharmacokinetics of tamsulosin have not been evaluated.
- The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin capsules have not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin 0.4 mg is co-administered with a combination of both CYP3A4 and CYP2D6 inhibitors.
- Cimetidine: The effects of cimetidine at the highest recommended dose (400 mg every 6 hours for 6 days) on the pharmacokinetics of a single capsule 0.4 mg dose was investigated in 10 healthy volunteers (age range 21 to 38 years). 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%).
- Other Alpha Adrenergic Blocking Agents: The pharmacokinetic and pharmacodynamic interactions between tamsulosin capsules and other alpha adrenergic blocking agents have not been determined; however, interactions between the capsules and other alpha-adrenergic blocking agents may be expected.
- PDE5 Inhibitors: Caution is advised when alpha-adrenergic blocking agents, including tamsulosin, are co-administered 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.
- Warfarin: 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. Therefore, caution should be exercised with concomitant administration of warfarin and tamsulosin.
- Nifedipine, Atenolol, Enalapril: In three studies in hypertensive subjects (age range 47 to 79 years) whose blood pressure was controlled with stable doses of nifedipine, atenolol, or enalapril for at least 3 months, tamsulosin capsules 0.4 mg for 7 days followed by tamsulosin capsules 0.8 mg for another 7 days (n=8 per study) resulted in no clinically significant effects on blood pressure and pulse rate compared to placebo (n=4 per study). Therefore, dosage adjustments are not necessary when tamsulosin capsules are administered concomitantly with nifedipine, atenolol, or enalapril.
- Digoxin and Theophylline: In two studies in healthy volunteers (n=10 per study; age range 19 to 39 years) receiving tamsulosin capsules 0.4 mg/day for 2 days, followed by tamsulosin capsules 0.8 mg/day for 5 to 8 days, single intravenous doses of digoxin 0.5 mg or theophylline 5 mg/kg resulted in no change in the pharmacokinetics of digoxin or theophylline. Therefore, dosage adjustments are not necessary when tamsulosin is administered concomitantly with digoxin or theophylline.
- Furosemide: The pharmacokinetic and pharmacodynamic interaction between tamsulosin capsules 0.8 mg/day (steady-state) and furosemide 20 mg intravenously (single dose) was evaluated in 10 healthy volunteers (age range 21 to 40 years). The capsules had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in tamsulosin hydrochloride Cmax and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the capsules dosage.
- Advise the patient about the possible occurrence of symptoms related to postural hypotension, such as dizziness, when taking tamsulosin capsules, and they should be cautioned about driving, operating machinery, or performing hazardous tasks.
- Advise the patient that tamsulosin should not be used in combination with strong inhibitors of CYP3A4.
- Advise the patient about the possibility of priapism as a result of treatment with tamsulosin and other similar medications. Patients should be informed that this reaction is extremely rare, but if not brought to immediate medical attention, can lead to permanent erectile dysfunction (impotence).
- Prostrate cancer and BPH frequently co-exist; therefore, screen patients for the presence of prostrate cancer prior to treatment with tamsulosin and at regular intervals afterwards.
- Advise the patient when considering cataract or glaucoma surgery to tell their ophthalmologist that they have taken tamsulosin.
- Advise the patient that tamsulosin should not be crushed, chewed or opened.
General Notes: Do not crush, chew, or open capsules
Mechanism of Action
MESH Terms & Keywords