DESCRIPTION

Tamsulosin hydrochloride is an antagonist of alpha1A adrenoceptors in the prostate.

Tamsulosin hydrochloride is (-)-(R)-5-[2-[[2-(o-Ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide, monohydrochloride. Tamsulosin hydrochloride is a white crystalline powder that melts with decomposition at approximately 230°C. It is sparingly soluble in water and methanol, slightly soluble in glacial acetic acid and ethanol, and practically insoluble in ether.

The empirical formula of tamsulosin hydrochloride is C20H28N2O5S • HCl. The molecular weight of tamsulosin hydrochloride is 444.98. Its structural formula is:

Each FLOMAX capsule for oral administration contains tamsulosin hydrochloride 0.4 mg, and the following inactive ingredients: methacrylic acid copolymer, microcrystalline cellulose, triacetin, calcium stearate, talc, FD&C blue No. 2, titanium dioxide, ferric oxide, gelatin, and trace amounts black edible ink.

CLINICAL PHARMACOLOGY

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 human prostate are of the alpha1A subtype.

Flomax® (tamsulosin hydrochloride) capsules are not intended for use as an antihypertensive drug.

Pharmacokinetics

The pharmacokinetics of tamsulosin hydrochloride have been eva luated 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 FLOMAX 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 four to five hours under fasting conditions and by six to seven hours when FLOMAX capsules are administered with food. Taking FLOMAX 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 (Figure 1).

Figure 1 Mean Plasma Tamsulosin Hydrochloride Concentrations Following Single-Dose Administration of FLOMAX capsules 0.4 mg Under Fasted and Fed Conditions (n=8)

The effects of food on the pharmacokinetics of tamsulosin hydrochloride are consistent regardless of whether a Flomax® (tamsulosin hydrochloride) capsule is taken with a light breakfast or a high-fat breakfast (Table 1).

Table 1 Mean (± S.D.) Pharmacokinetic Parameters Following FLOMAX capsules 0.4 mg Once Daily or 0.8 mg Once Daily with a Light Breakfast, High-Fat Breakfast or Fasted

Pharmacokinetic
Parameter

0.4 mg QD to healthy
volunteers; n=23
(age range 18-32 years)

0.8 mg QD to healthy volunteers; n=22
(age range 55-75 years)

Light
Breakfast

Fasted

Light
Breakfast

High-Fat
Breakfast

Fasted

Cmin = observed minimum concentration

Cmax = observed maximum tamsulosin hydrochloride plasma concentration

Tmax = median time-to-maximum concentration

T1/2 = observed half-life