JALYN (dutasteride and tamsulosin hydrochloride) capsules contain dutasteride (a selective inhibitor of both the type 1 and type 2 isoforms of steroid 5 alpha-reductase, an intracellular enzyme that converts testosterone to DHT and tamsulosin (an antagonist of alpha 1A -adrenoceptors in the prostate). Each JALYN capsule contains the following: One dutasteride oblong, opaque, dull-yellow soft gelatin capsule, containing 0.5 mg of dutasteride dissolved in a mixture of butylated hydroxytoluene and mono-di-glycerides of caprylic/capric acid. The inactive ingredients in the soft-gelatin capsule shell are ferric oxide (yellow), gelatin (from certified BSE-free bovine sources), glycerin, and titanium dioxide. Tamsulosin hydrochloride white to off-white pellets, containing 0.4 mg tamsulosin hydrochloride and the inactive ingredients: methacrylic acid copolymer dispersion, microcrystalline cellulose, talc, and triethyl citrate. The above components are encapsulated in a hard-shell capsule made with the inactive ingredients of carrageenan, FD&C yellow 6, hypromellose, iron oxide red, potassium chloride, titanıum dioxide, and imprinted with "GS 7CZ" in black ink. Dutasteride: Dutasteride is a synthetic 4-azasteroid compound chemically designated as (5α,17β)-N-{2,5 bis(trifluoromethyl)phenyl}-3-oxo-4-azaandrost-1-ene-17-carboxamide. The empirical formula of dutasteride is C 27 H 30 F 6 N 2 O 2 , representing a molecular weight of 528.5 with the following structural formula: Dutasteride is a white to pale yellow powder with a melting point of 242° to 250°C. It is soluble in ethanol (44 mg/mL), methanol (64 mg/mL), and polyethylene glycol 400 (3 mg/mL), but it is insoluble in water. Chemical Structure Tamsulosin: Tamsulosin hydrochloride is a synthetic compound chemically designated as (-)-( R )-5-[2-[[2-( o -Ethoxyphenoxy)ethyl]amino]propyl]-2-methoxybenzenesulfonamide, monohydrochloride. The empirical formula of tamsulosin hydrochloride is C 20 H 28 N 2 O 5 S∙HCl. The molecular weight of tamsulosin hydrochloride is 444.97. Its structural formula is: Tamsulosin hydrochloride is a white or almost white crystalline powder that melts with decomposition at approximately 234°C. It is sparingly soluble in water and slightly soluble in methanol, ethanol, acetone, and ethyl acetate. Chemical Structure

JALYN is a combination of dutasteride, a 5-alpha-reductase inhibitor, and tamsulosin, an alpha-adrenergic antagonist, indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate. Limitations of Use: Dutasteride-containing products, including JALYN, are not approved for the prevention of prostate cancer

Benign Prostatic Hyperplasia (BPH) Treatment JALYN (dutasteride and tamsulosin hydrochloride) capsules are indicated for the treatment of symptomatic BPH in men with an enlarged prostate

Limitations of Use Dutasteride-containing products, including JALYN, are not approved for the prevention of prostate cancer.

JALYN capsules, containing 0.5 mg dutasteride and 0.4 mg tamsulosin hydrochloride, are oblong, hard-shell capsules with a brown body and an orange cap imprinted with "GS 7CZ" in black ink

mg dutasteride and 0.4 mg tamsulosin hydrochloride.

The recommended dosage of JALYN is 1 capsule (0.5 mg dutasteride and 0.4 mg tamsulosin hydrochloride) taken once daily approximately 30 minutes after the same meal each day. The capsules should be swallowed whole and not chewed or opened. Contact with the contents of the JALYN capsule may result in irritation of the oropharyngeal mucosa. Take one capsule daily approximately 30 minutes after the same meal each day.( 2 ) Swallow capsule whole.

Orthostatic hypotension and/or syncope can occur. Advise patients of symptoms related to postural hypotension and to avoid situations where injury could result if syncope occurs. Do not use JALYN with other alpha-adrenergic antagonists, as this may increase the risk of hypotension. JALYN reduces serum prostate-specific antigen (PSA) concentration by approximately 50%. However, any confirmed increase in PSA while on JALYN may signal the presence of prostate cancer and should be evaluated, even if those values are still within the normal range for untreated men. Do not use JALYN with strong inhibitors of cytochrome P450 (CYP) 3A4 (e.g., ketoconazole). Use caution in combination with moderate CYP3A4 inhibitors (e.g., erythromycin) or strong (e.g., paroxetine) or moderate CYP2D6 inhibitors, a combination of both CYP3A4 and CYP2D6 inhibitors, or known poor metabolizers of CYP2D6. Concomitant use with known inhibitors can cause a marked increase in drug exposure. ( 5.2 , 7.1 , 12.3 ) Exercise caution with concomitant use of phosphodiesterase-5 (PDE-5) inhibitors, as this may increase the risk of hypotension. Drugs that contain dutasteride, including JALYN, may increase the risk of high-grade prostate cancer. Prior to initiating treatment with JALYN, consideration should be given to other urological conditions that may cause similar symptoms. Females who are pregnant or may be pregnant should not handle JALYN capsules due to potential risk to a male fetus. Advise patients about the possibility and seriousness of priapism. Patients should not donate blood until 6 months after their last dose of JALYN. Intraoperative Floppy Iris Syndrome has been observed during cataract and glaucoma surgery after alpha-adrenergic antagonist exposure. Advise patients considering cataract or glaucoma surgery to tell their ophthalmologist that they take or have taken JALYN capsules. Exercise caution with concomitant use of warfarin. ( 5.2 , 7.2 , 12.3 ) 5.1 Orthostatic Hypotension As with other alpha-adrenergic antagonists, orthostatic hypotension (postural hypotension, dizziness, and vertigo) may occur in patients treated with tamsulosin-containing products, including JALYN, and can result in syncope. Patients starting treatment with JALYN should be cautioned to avoid situations where syncope could result in an injury

Drug-Drug Interactions Strong Inhibitors of Cytochrome P450 (CYP) 3A4 Tamsulosin-containing products, including JALYN, should not be coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole) as this can significantly increase tamsulosin exposure . Moderate Inhibitors of CYP3A4, Inhibitors of CYP2D6, or a Combination of Both CYP3A4 and CYP2D6 Inhibitors Tamsulosin-containing products, including JALYN, should be used with caution when coadministered with moderate inhibitors of CYP3A4 (e.g., erythromycin), strong (e.g., paroxetine) or moderate (e.g., terbinafine) inhibitors of CYP2D6, a combination of both CYP3A4 and CYP2D6 inhibitors, or in patients known to be poor metabolizers of CYP2D6, as there is a potential for significant increase in tamsulosin exposure . Cimetidine Caution is advised when tamsulosin-containing products, including JALYN, are coadministered with cimetidine . Other Alpha-adrenergic Antagonists Tamsulosin-containing products, including JALYN, should not be coadministered with other alpha-adrenergic antagonists because of the increased risk of symptomatic hypotension. Phosphodiesterase-5 (PDE-5) Inhibitors Caution is advised when alpha-adrenergic–antagonist-containing products, including JALYN, are coadministered with PDE-5 inhibitors. Alpha-adrenergic antagonists and PDE-5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these 2 drug classes can potentially cause symptomatic hypotension. Warfarin Caution should be exercised with concomitant administration of warfarin and tamsulosin-containing products, including JALYN

Effects on Prostate-Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection Coadministration of dutasteride with tamsulosin resulted in similar changes to serum PSA as with dutasteride monotherapy. In clinical trials, dutasteride reduced serum PSA concentration by approximately 50% within 3 to 6 months of treatment. This decrease was predictable over the entire range of PSA values in patients with symptomatic BPH, although it may vary in individuals. Dutasteride-containing treatment, including JALYN, may also cause decreases in serum PSA in the presence of prostate cancer. To interpret serial PSAs in men treated with a dutasteride-containing product, including JALYN, a new baseline PSA should be established at least 3 months after starting treatment and PSA monitored periodically thereafter. Any confirmed increase from the lowest PSA value while on a dutasteride-containing treatment, including JALYN, may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5-alpha-reductase inhibitor. Noncompliance with JALYN may also affect PSA test results. To interpret an isolated PSA value in a man treated with JALYN, for 3 months or more, the PSA value should be doubled for comparison with normal values in untreated men. The free-to-total PSA ratio (percent free PSA) remains constant, even under the influence of dutasteride. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men receiving JALYN, no adjustment to its value appears necessary

Increased Risk of High-Grade Prostate Cancer In men aged 50 to 75 years with a prior negative biopsy for prostate cancer and a baseline PSA between 2.5 ng/mL and 10.0 ng/mL taking dutasteride in the 4-year Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, there was an increased incidence of Gleason score 8 to 10 prostate cancer compared with men taking placebo (dutasteride 1.0% versus placebo 0.5%) [see Indications and Usage 5.5 Evaluation for Other Urological Diseases Prior to initiating treatment with JALYN, consideration should be given to other urological conditions that may cause similar symptoms. In addition, BPH and prostate cancer may coexist

Transdermal Exposure of JALYN in Pregnant Females—Risk to Male Fetus JALYN capsules should not be handled by females who are pregnant or may be pregnant. Dutasteride can be absorbed through the skin and could result in unintended fetal exposure and potential risk to a male fetus. If a female who is or may be pregnant comes in contact with a leaking capsule, the contact area should be washed immediately with soap and water . Dutasteride can be absorbed through the skin based on animal studies

Priapism Priapism (persistent painful penile erection unrelated to sexual activity) has been associated (probably less than 1 in 50,000) with the use of alpha-adrenergic antagonists, including tamsulosin, which is a component of JALYN. Because this condition can lead to permanent impotence if not properly treated, patients should be advised about the seriousness of the condition

Blood Donation Men being treated with a dutasteride-containing product, including JALYN, should not donate blood until at least 6 months have passed following their last dose. The purpose of this deferred period is to prevent administration of dutasteride to a pregnant female transfusion recipient

Intraoperative Floppy Iris Syndrome Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract and glaucoma surgery in some patients on or previously treated with alpha-adrenergic antagonists, including tamsulosin, which is a component of JALYN. Most reports were in patients taking the alpha-adrenergic antagonist when IFIS occurred, but in some cases, the alpha-adrenergic antagonist had been stopped prior to surgery. In most of these cases, the alpha-adrenergic antagonist had been stopped recently prior to surgery (2 to 14 days), but in a few cases, IFIS was reported after the patients had been off the alpha-adrenergic antagonist for a longer period (5 weeks to 9 months). IFIS is a variant of small pupil syndrome and is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. The patient's ophthalmologist should be prepared for possible modifications to their surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances. IFIS may increase the risk of eye complications during and after the operation. The benefit of stopping alpha-adrenergic antagonist therapy prior to cataract or glaucoma surgery has not been established. The initiation of therapy with tamsulosin in patients for whom cataract or glaucoma surgery is scheduled is not recommended

Sulfa Allergy In patients with sulfa allergy, allergic reaction to tamsulosin has been rarely reported. If a patient reports a serious or life-threatening sulfa allergy, caution is warranted when administering tamsulosin-containing products, including JALYN

Effect on Semen Characteristics Dutasteride The effects of dutasteride 0.5 mg/day on semen characteristics were evaluated in healthy men throughout 52 weeks of treatment and 24 weeks of post-treatment follow-up. At 52 weeks, compared wıth placebo, dutasteride treatment resulted in mean reduction in total sperm count, semen volume, and sperm motility; the effects on total sperm count were not reversible after 24 weeks of follow-up. Sperm concentration and sperm morphology were unaffected and mean values for all semen parameters remained within the normal range at all timepoints. The clinical significance of the effect of dutasteride on semen characteristics for an individual patient's fertility is not known . Tamsulosin The effects of tamsulosin hydrochloride on sperm counts or sperm function have not been evaluated.

There have been no drug interaction trials using JALYN. The following sections reflect information available for the individual components

Cytochrome P450 Inhibition Dutasteride Dutasteride is extensively metabolized in humans by the CYP3A4 and CYP3A5 isoenzymes. The effect of potent CYP3A4 inhibitors on dutasteride has not been studied. Because of the potential for drug-drug interactions, use caution when prescribing a dutasteride-containing product, including JALYN, to patients taking potent, chronic CYP3A4 enzyme inhibitors (e.g., ritonavir) Tamsulosin Strong and Moderate Inhibitors of CYP3A4 or CYP2D6: Tamsulosin is extensively metabolized, mainly by CYP3A4 or CYP2D6. Concomitant treatment with ketoconazole (a strong inhibitor of CYP3A4) resulted in increases in the C max and area under the concentration-time curve (AUC) of tamsulosin by factors of 2.2 and 2.8, respectively. Concomitant treatment with paroxetine (a strong inhibitor of CYP2D6) resulted in increases in the C max and AUC of tamsulosin by factors of 1.3 and 1.6, respectively. A similar increase in exposure is expected in poor metabolizers (PM) of CYP2D6 as compared to extensive metabolizers (EM). Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in tamsulosin exposure exists when tamsulosin 0.4 mg is coadministered with strong CYP3A4 inhibitors in CYP2D6 PMs, tamsulosin 0.4 mg capsules should not be used in combination wıth strong inhibitors of CYP3A4 (e.g., ketoconazole). The effects of coadministration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin have not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin 0.4 mg is coadministered with a combination of both CYP3A4 and CYP2D6 inhibitors . Cimetidine: Treatment with cimetidine resulted in a moderate increase in tamsulosin hydrochloride AUC (44%)

Warfarin Dutasteride Concomitant administration of dutasteride 0.5 mg/day for 3 weeks with warfarin does not alter the steady-state pharmacokinetics of the S- or R-warfarin isomers or alter the effect of warfarin on prothrombin time . Tamsulosin A definitive drug-drug interaction trial between tamsulosin hydrochloride and warfarin was not conducted. Results from limited in vitro and in vivo studies are inconclusive. Caution should be exercised with concomitant administration of warfarin and tamsulosin-containing products, including JALYN

Nifedipine, Atenolol, Enalapril Tamsulosin Dosage adjustments are not necessary when tamsulosin is administered concomitantly with nifedipine, atenolol, or enalapril

Digoxin and Theophylline Dutasteride Dutasteride does not alter the steady-state pharmacokinetics of digoxin when administered concomitantly at a dose of 0.5 mg/day for 3 weeks . Tamsulosin Dosage adjustments are not necessary when tamsulosin is administered concomitantly with digoxin or theophylline

Furosemide Tamsulosin Tamsulosin had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in tamsulosin hydrochloride C max and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the dose of tamsulosin

Calcium Channel Antagonists Dutasteride Coadministration of verapamil or diltiazem decreases dutasteride clearance and leads to increased exposure to dutasteride. The change in dutasteride exposure is not considered to be clinically significant. No dosage adjustment of dutasteride is recommended

Cholestyramine Dutasteride Administration of a single 5-mg dose of dutasteride followed 1 hour later by a 12-g dose of cholestyramine does not affect the relative bioavailability of dutasteride .