Dutasteride 0.5 mg, Tamsulosin 0.4 mg Tablets

JALYN is a combination of 2 drugs with different mechanisms of action to improve symptoms in patients with BPH: dutasteride, a 5-alpha-reductase inhibitor, and tamsulosin, an antagonist of alpha1A-adrenoreceptors.

Dutasteride — Dutasteride inhibits the conversion of testosterone to DHT. DHT is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. Testosterone is converted to DHT by the enzyme 5 alpha-reductase, which exists as 2 isoforms, type 1 and type 2. The type 2 isoenzyme is primarily active in the reproductive tissues, while the type 1 isoenzyme is also responsible for testosterone conversion in the skin and liver.

Dutasteride is a competitive and specific inhibitor of both type 1 and type 2 5-alpha-reductase isoenzymes, with which it forms a stable enzyme complex. Dissociation from this complex has been evaluated under in vitro and in vivo conditions and is extremely slow. Dutasteride does not bind to the human androgen receptor.

Tamsulosin — 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 3 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. Tamsulosin is not intended for use as an antihypertensive.

The pharmacokinetics of dutasteride and tamsulosin from JALYN are comparable to the pharmacokinetics of dutasteride and tamsulosin when administered separately.

Absorption — The pharmacokinetic parameters of dutasteride and tamsulosin observed after administration of JALYN in a single-dose, randomized, 3-period, partial cross-over trial are summarized in Table 2 below.

Effect of Food — Food does not affect the pharmacokinetics of dutasteride following administration of JALYN. However, a mean 30% decrease in tamsulosin Cmax was observed when JALYN was administered with food, similar to that seen when tamsulosin monotherapy was administered under fed versus fasting conditions.

Drug Interaction Studies — There have been no drug interaction studies using JALYN. The following text reflects information available for the individual components.