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Tamsulosin (Systemic)


VA CLASSIFICATION
Primary: GU700

Commonly used brand name(s): Flomax.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Benign prostatic hyperplasia therapy agent—

Indications

Accepted

Benign prostatic hyperplasia (treatment)—Tamsulosin is indicated in the treatment of symptomatic benign prostatic hyperplasia (BPH) {01}. It has been shown to improve urinary flow and the symptoms of BPH {01}.

Unaccepted
Tamsulosin is not intended for use as an antihypertensive agent {01}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    444.98 {01}

Mechanism of action/Effect:

Tamsulosin is an alpha 1-adrenergic blocking agent exhibiting selectivity for alpha 1 receptors in the human prostate {01}. Relaxation of smooth muscle in the bladder neck and prostate produced by alpha 1-adrenergic blockade results in improvement in urine flow rate and a reduction in symptoms of BPH {01}.

Absorption:

Absorption is > 90% following oral administration of a 0.4-mg dose under fasting conditions {01}. Bioavailability is increased by 30% and peak concentration is increased by 40 to 70% when tamsulosin is taken in the fasting state compared to the nonfasting state {01}.

Distribution:

Animal studies have found that tamsulosin is widely distributed to most tissues, including aorta, brown fat, gallbladder, heart, kidney, liver, and prostate; it is minimally distributed into the brain, spinal cord, and testes {01}.

Protein binding:

Very high (94 to 99%) to plasma proteins, primarily to alpha-1 glycoprotein; binding is linear over a wide concentration range (20 to 600 nanograms per mL) {01}.

Biotransformation:

Tamsulosin is extensively metabolized by cytochrome P450 enzymes in the liver, with < 10% of the dose excreted in the urine unchanged. The metabolites undergo extensive conjugation to glucuronide or sulfate prior to renal excretion {01}.

Half-life:

Healthy individuals (fasting state)—9 to 13 hours {01}.

Target population—14 to 15 hours {01}.


Elimination:

5 to 7 hours in plasma following intravenous or oral administration of an immediate-release formulation of tamsulosin {01}.


Time to peak concentration:

4 to 5 hours under fasting conditions and 6 to 7 hours when administered with food {01}.

Peak serum concentration:

Peak plasma concentrations achieved with a 0.4-mg once-daily dose are 10.1 ± 4.8 nanograms per mL after a light breakfast and 17.1 ± 17.1 nanograms per mL in the fasting state; peak plasma concentrations after administration of a 0.8-mg dose are 29.8 ± 10.3 nanograms per mL after a light breakfast, 29.1 ± 11 nanograms per mL after a high-fat breakfast, and 41.6 ± 15.6 nanograms per mL in the fasting state {01}.

Elimination:
    After administration of a radiolabeled dose of tamsulosin, 76% of the dose is recovered in the urine and 21% is recovered in the feces over 168 hours {01}.


In dialysis—
        Tamsulosin is unlikely to be removed because of its high protein binding (94 to 99%) {01}.



Precautions to Consider

Carcinogenicity

Male rats given doses of up to 43 mg per kg of body weight (mg/kg) a day and female rats given doses of 52 mg/kg a day had no increase in tumor incidence, with the exception of a modest increase in the frequency of mammary gland fibroadenomas in female rats receiving doses ³ 5.4 mg/kg {01}. There were no significant tumor findings in male mice receiving doses of up to 127 mg/kg a day {01}. However, female mice treated for 2 years had statistically significant increases in the incidence of mammary gland fibroadenomas and adenocarcinomas with the highest doses given (45 and 158 mg/kg a day) {01}. The highest dose concentrations of tamsulosin evaluated in the rat and mice carcinogenicity studies produced systemic exposures (area under the plasma concentration–time curve [AUC]) in rats and mice eight times the exposures in men receiving 0.8 mg of tamsulosin a day {01}. The increased incidences of mammary gland neoplasms in female rats and mice were considered secondary to tamsulosin-induced hyperprolactinemia {01}. It is not known if tamsulosin elevates prolactin secretion in humans {01}.

Mutagenicity

Tamsulosin was found nonmutagenic in vitro in the Ames reverse mutation test, the mouse lymphoma thymidine kinase assay, the unscheduled DNA repair synthesis assay, and the chromosomal aberration assays in Chinese hamster ovary cells or human lymphocytes {01}. There were no mutagenic effects in the in vivo sister chromatid exchange and mouse micronucleus assay {01}.

Pregnancy/Reproduction
Fertility—
Studies in rats receiving tamsulosin in single or multiple daily doses of 300 mg/kg a day (AUC exposure in rats approximately 50 times the maximum human exposure using the maximum therapeutic dose) found a significant reduction in fertility in males {01}. This reduction is thought to be due to an effect of the compound on the vaginal plug formation in female rats, possibly due to changes of semen content or impairment of ejaculation {01}. These effects were reversible, showing improvement by 3 days after a single dose and by 4 weeks after multiple dosing; the effects were completely reversed 9 weeks after discontinuation of multiple dosing {01}. Multiple doses of 10 and 100 mg/kg a day (1/5 and 16 times the anticipated human AUC exposure, respectively) produced no significant effects on fertility in male rats {01}. Studies in female rats found a significant reduction in fertility after single or multiple dosing using 300 mg/kg a day of the R-isomer or a racemic mixture of tamsulosin, respectively {01}. In female rats, the reductions in fertility after single doses of tamsulosin were considered to be associated with impairments in fertilization {01}. Multiple dosing with 10 or 100 mg/kg a day of the racemic mixture of tamsulosin did not significantly alter fertility in female rats {01}.

Pregnancy—
Tamsulosin is not indicated for use in women {01}.

Administration of tamsulosin to pregnant female rats at doses of up to 300 mg/kg a day (approximately 50 times the human therapeutic AUC exposure) and to pregnant rabbits at doses of up to 50 mg/kg a day produced no evidence of fetal harm {01}.

FDA Pregnancy Category B {01}.

Breast-feeding

Tamsulosin is not indicated for use in women {01}.

Pediatrics

Tamsulosin is not indicated for use in children {01}.


Geriatrics


The pharmacokinetic disposition of tamsulosin may be slightly prolonged, resulting in a 40% higher exposure (AUC) in older males compared to that of young, healthy males {01}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication {01}.
Tamsulosin is extensively metabolized by cytochrome P450 enzymes in the liver {01}. Potential interactions with other cytochrome P450–metabolized compounds have not been determined {01}.

» Alpha 1-adrenergic blocking agents, other, such as doxazosin, phentolamine, prazosin, and terazosin    (concurrent administration may produce an additive effect {01})


Cimetidine    (concurrent administration resulted in a 26% decrease in the clearance of tamsulosin and a 44% increase in tamsulosin AUC; tamsulosin should be used with caution in combination with cimetidine, particularly at daily doses higher than 0.4 mg {01})


» Warfarin    (caution should be exercised with concurrent administration because of inconclusive results from in vitro and in vivo studies {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problem exists
Sensitivity to tamsulosin or any component{01}


Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
(5 to 21%, except as indicated)
    
Abnormal ejaculation {01}
    
asthenia (unusual weakness){01}
    
back pain {01}
    
diarrhea —incidence 4.3% with 0.8-mg dose{01}
    
dizziness {01}
    
headache {01}
    
rhinitis (stuffy or runny nose)

Note: Incidence of abnormal ejaculation is 8.4% with the 0.4-mg dose and 18% with the 0.8-mg dose {01}.


Incidence less frequent
(< 5%)
    
Chest pain {01}
    
decreased libido {01}
    
drowsiness {01}
    
insomnia (difficulty in sleeping){01}
    
nausea
    
orthostatic hypotension (dizziness, fainting, or lightheadedness, especially when getting up from a lying or sitting position){01}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Treatment of overdose
Specific treatment—Intravenous fluids and vasopressors should be administered if needed {01}.

Monitoring—Renal function should be monitored {01}.

Supportive care—Cardiovascular system must be maintained; to restore blood pressure and normalize the heart rate, patient should be kept in the supine position {01}. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Tamsulosin (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to tamsulosin or any component
Other medications, especially alpha 1-adrenergic blocking agents or warfarin

Proper use of this medication
Taking at the same time each day to help increase compliance

Not crushing, chewing, or opening capsules, unless otherwise directed by a physician

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress

» Caution when getting up suddenly from a lying or sitting position

» Possible dizziness; caution when driving or doing things requiring alertness


Side/adverse effects
Signs of potential side effects, especially abnormal ejaculation, decreased libido, or orthostatic hypotension


General Dosing Information

Diet/Nutrition
Tamsulosin should be taken once a day one-half hour after the same meal each day {01}.


Oral Dosage Forms

TAMSULOSIN HYDROCHLORIDE CAPSULES

Usual adult dose
Benign prostatic hyperplasia
Oral, 0.4 mg once a day, approximately one-half hour after the same meal each day {01}. If there is no response after two to four weeks, the dose may be increased to 0.8 mg once a day {01}.

Note: If tamsulosin administration is discontinued or interrupted for several days at either dose, therapy should be restarted with the 0.4-mg dose {01}.



Usual geriatric dose
See Usual adult dose .

Strength(s) usually available
U.S.—


0.4 mg (Rx) [Flomax]

Packaging and storage:
Store at 20 to 25 ºC (68 to 77 ºF) {01}.

Auxiliary labeling:
   • Do not crush, chew, or open capsules.



Revised: 03/02/1998



References
  1. Flomax package insert (Boehringer Ingelheim—US), Rev 5/97, Rec 6/97.
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