Dutasteride And Tamsulosin Hydrochloride Capsules
FDA Drug Information • Also known as: Dutasteride And Tamsulosin Hydrochloride
- Brand Names
- Dutasteride And Tamsulosin Hydrochloride
- Drug Class
- 5-alpha Reductase Inhibitor [EPC]
- Route
- ORAL
- Dosage Form
- CAPSULE
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION 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 dutasteride and tamsulosin hydrochloride capsule contains the following: One dutasteride oblong, opaque, yellow gelatin capsule, containing 0.5 mg of dutasteride dissolved in a mixture of butylated hydroxytoluene and mono-and 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, titanium dioxide, lecithin, medium chain triglycerides, propylene glycol, iron oxide black, polyvinyl acetate phthalate, macrogol, and ammonium hydroxide. Tamsulosin hydrochloride white to off-white pellets, containing 0.4 mg tamsulosin hydrochloride and the inactive ingredients: methacrylic acid copolymer, sugar sphere, ethylcellulose, polyethylene glycol, triethyl citrate and talc. The above components are encapsulated in a hard-shell capsule made with the inactive ingredients of hypromellose, FD&C Blue #1, titanium dioxide, shellac, iron oxide black, propylene glycol, FD&C blue #2, FD&C red #40, D&C yellow #10. Blue opaque cap imprinted with “C280” and white opaque body imprinted with “0.5/0.4” in black ink containing white to off white spherical shaped pellets and one oblong, opaque yellow softgel capsule printed with “C300” 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...
What Is Dutasteride And Tamsulosin Hydrochloride Capsules Used For?
1 INDICATIONS AND USAGE Dutasteride and tamsulosin hydrochloride capsules are 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. ( 1.1 ) Limitations of Use: Dutasteride-containing products, including dutasteride and tamsulosin hydrochloride capsules, are not approved for the prevention of prostate cancer. ( 1.2 ) 1.1 Benign Prostatic Hyperplasia (BPH) Treatment Dutasteride and tamsulosin hydrochloride capsules are indicated for the treatment of symptomatic BPH in men with an enlarged prostate. 1.2 Limitations of Use Dutasteride-containing products, including dutasteride and tamsulosin hydrochloride capsules, are not approved for the prevention of prostate cancer.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION The recommended dosage of dutasteride and tamsulosin hydrochloride capsules 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 dutasteride and tamsulosin hydrochloride 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. ( 2 )
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The most common adverse reactions, reported in ≥1% of subjects treated with coadministered dutasteride and tamsulosin are ejaculation disorders, impotence, decreased libido, dizziness, and breast disorders. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience The clinical efficacy and safety of coadministered dutasteride and tamsulosin, which are individual components of dutasteride and tamsulosin hydrochloride capsules, have been evaluated in a multicenter, randomized, double-blind, parallel group trial (the Combination with Alpha-Blocker Therapy, or CombAT, trial). Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trial of another drug and may not reflect the rates observed in practice. The most common adverse reactions reported in subjects receiving coadministered dutasteride and tamsulosin were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), ejaculation disorders, and dizziness. Ejaculation disorders occurred significantly more in subjects receiving coadministration therapy (11%) compared with those receiving dutasteride (2%) or tamsulosin (4%) as monotherapy. Trial withdrawal due to adverse reactions occurred in 6% of subjects receiving coadministered dutasteride and tamsulosin and in 4% of subjects receiving dutasteride or tamsulosin as monotherapy. The most common adverse reaction in all treatment arms leading to trial withdrawal was erectile dysfunction (1% to 1.5%). In the CombAT trial, over 4,800 male subjects with BPH were randomly assigned to receive 0.5 mg dutasteride, 0.4 mg tamsulosin hydrochloride, or coadministration therapy (0.5 mg dutasteride and 0.4 mg tamsulosin hydrochloride) administered once daily in a 4-year double-blind trial. Overall, 1,623 subjects received monotherapy with dutasteride; 1,611 subjects received monotherapy with tamsulosin; and 1,610 subjects received coadministration therapy. The population was aged 49 to 88 years (mean age: 66 years) and 88% were white. Table 1 summarizes adverse reactions reported in at least 1% of subjects receiving coadministration therapy and at a higher incidence than subjects receiving either dutasteride or tamsulosin as monotherapy. Table 1. Adverse Reactions Reported over a 48-Month Period in ≥1% of Subjects and More Frequently in the Coadministration Therapy Group than the Dutasteride or Tamsulosin Monotherapy Group (CombAT) by Time of Onset Adverse Reaction Adverse Reaction Time of Onset Year 1 Year 2 Year 3 Year 4 Months 0-6 Months 7-12 Coadministration a (n = 1,610) (n = 1,527) (n = 1,428) (n = 1,283) (n = 1,200) Dutasteride (n = 1,623) (n = 1,548) (n = 1,464) (n = 1,325) (n = 1,200) Tamsulosin (n = 1,611) (n = 1,545) (n = 1,468) (n = 1,281) (n = 1,112) Ejaculation disorders b,c Coadministration 7.8% 1.6% 1.0% 0.5% <0.1% Dutasteride 1.0% 0.5% 0.5% 0.2% 0.3% Tamsulosin 2.2% 0.5% 0.5% 0.2% 0.3% Impotence c,d Coadministration 5.4% 1.1% 1.8% 0.9% 0.4% Dutasteride 4.0% 1.1% 1.6% 0.6% 0.3% Tamsulosin 2.6% 0.8% 1.0% 0.6% 1.1% Decreased libido c,e Coadministration 4.5% 0.9% 0.8% 0.2% 0.0% Dutasteride 3.1% 0.7% 1.0% 0.2% 0.0% Tamsulosin 2.0% 0.6% 0.7% 0.2% <0.1% Breast disorders ,f Coadministration 1.1% 1.1% 0.8% 0.9% 0.6% Dutasteride 0.9% 0.9% 1.2% 0.5% 0.7% Tamsulosin 0.4% 0.4% 0.4% 0.2% 0.0% Dizziness Coadministration 1.1% 0.4% 0.1% <0.1% 0.2% Dutasteride 0.5% 0.3% 0.1% <0.1% <0.1% Tamsulosin 0.9% 0.5% 0.4% <0.1% 0.0% a Coadministration = dutasteride 0.5 mg once daily plus tamsulosin 0.4 mg once daily. b Includes anorgasmia, retrograde ejaculation, semen volume decreased, orgasmic sensation decreased, orgasm abnormal, ejaculation delayed, ejaculation disorder, ejaculation failure, and premature ejaculation. c These sexual adverse reactions are...
Drug Interactions
7 DRUG INTERACTIONS There have been no drug interaction trials using dutasteride and tamsulosin hydrochloride capsules. The following sections reflect information available for the individual components. 7.1 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 dutasteride and tamsulosin hydrochloride capsules, to patients taking potent, chronic CYP3A4 enzyme inhibitors (e.g., ritonavir) [see Clinical Pharmacology ( 12.3 ) ] . 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 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 area under the concentration-time curve (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 with 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 [see Warnings and Precautions ( 5.2 ), Clinical Pharmacology ( 12.3 ) ] . Cimetidine : Treatment with cimetidine resulted in a moderate increase in tamsulosin hydrochloride AUC (44%) [see Warnings and Precautions ( 5.2 ), Clinical Pharmacology ( 12.3 ) ] . 7.2 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 [see Clinical Pharmacology ( 12.3 ) ] . 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 dutasteride and tamsulosin hydrochloride capsules [see Warnings and Precautions ( 5.2 ), Clinical Pharmacology ( 12.3 ) ] . 7.3 Nifedipine, Atenolol, Enalapril Tamsulosin Dosage adjustments are not necessary when...
Contraindications
4 CONTRAINDICATIONS Dutasteride and tamsulosin hydrochloride capsules are contraindicated for use in: Pregnancy. Dutasteride use is contraindicated in females who are pregnant. In animal reproduction and developmental toxicity studies, dutasteride inhibited development of male fetus external genitalia. Therefore, dutasteride and tamsulosin hydrochloride capsules may cause fetal harm when administered to a pregnant female. [see Warnings and Precautions ( 5.6 ), Use in Specific Populations ( 8.1 ) ] . Patients with previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema, urticaria, pruritus, respiratory symptoms) to dutasteride, other 5-alpha-reductase inhibitors, tamsulosin, or any other component of dutasteride and tamsulosin hydrochloride capsules [see Adverse Reactions ( 6.2 ) ] . Pregnancy. Dutasteride use is contraindicated in females who are pregnant. ( 4 , 5.6 , 8.1 ) Patients with previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema, urticaria, pruritus, respiratory symptoms) to dutasteride, other 5-alpha-reductase inhibitors, tamsulosin, or any component of dutasteride and tamsulosin hydrochloride capsules. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Dutasteride and tamsulosin hydrochloride capsules are contraindicated for use in pregnancy because it may cause harm to the male fetus [see Contraindications (4) ] . Dutasteride and tamsulosin hydrochloride capsules are not indicated for use in females. Dutasteride, a component of dutasteride and tamsulosin hydrochloride capsules, is a 5-alpha-reductase inhibitor that prevents conversion of testosterone to dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. Abnormalities in the genitalia of male fetuses are an expected physiological consequence of inhibition of this conversion. These results are similar to observations in male infants with genetic 5-alpha-reductase deficiency. In animal reproduction studies, dutasteride inhibited normal development of external genitalia in male offspring when given to rats or rabbits during organogenesis at less than the maximum recommended human dose (MRHD) of 0.5 mg daily, in the absence of maternal toxicity. At 15 times the MRHD, prolonged pregnancy, decreased reproductive organ weights, and delayed puberty in male offspring were observed in rats, with no-effect levels less than the MRHD of 0.5 mg daily. Increased placental weights in rabbits were also observed, with no-effect levels less than the MRHD of 0.5 mg daily (see Data) . Although dutasteride is secreted into human semen, the drug concentration in the human female partner is approximately 100 times less than concentrations producing abnormalities of male genitalia in animal studies (see Data) . In monkeys dosed during organogenesis at blood concentrations comparable to or above levels to which a human female partner is estimated to be exposed, male offspring external genitalia was not adversely affected. No feminization occurred in male offspring of untreated female rats mated to treated male rats even though detectable blood levels of dutasteride were observed in the female rats [see Nonclinical Toxicology...
Overdosage
10 OVERDOSAGE No data are available with regard to overdosage with dutasteride and tamsulosin hydrochloride capsules. The following text reflects information available for the individual components. Dutasteride In volunteer trials, single doses of dutasteride up to 40 mg (80 times the therapeutic dose) for 7 days have been administered without significant safety concerns. In a clinical trial, daily doses of 5 mg (10 times the therapeutic dose) were administered to 60 subjects for 6 months with no additional adverse effects to those seen at therapeutic doses of 0.5 mg. There is no specific antidote for dutasteride. Therefore, in cases of suspected overdosage symptomatic and supportive treatment should be given as appropriate, taking the long half-life of dutasteride into consideration. Tamsulosin Should overdosage of tamsulosin lead to hypotension [see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6.1 ) ] , 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 intravenous fluids should be considered. If necessary, vasopressors should then be used and renal function should be monitored and supported as needed. Laboratory data indicate that tamsulosin is 94% to 99% protein bound; therefore, dialysis is unlikely to be of benefit.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Dutasteride and tamsulosin hydrochloride capsules, containing 0.5 mg dutasteride and 0.4 mg tamsulosin hydrochloride, are blue, opaque cap imprinted with “C280” and white, opaque body imprinted with “0.5/0.4” in black ink containing white to off-white spherical shaped pellets and one oblong, opaque yellow softgel capsule printed with “C300” in black ink. They are available in bottles with child-resistant closures as follows: Bottle of 30 (NDC 42291-031-30). Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Capsules may become deformed and/or discolored if kept at high temperatures. Dutasteride is absorbed through the skin. Dutasteride and tamsulosin hydrochloride capsules should not be handled by females who are pregnant or who could become pregnant because of the potential for absorption of dutasteride and the subsequent potential risk to a developing male fetus [see Warnings and Precautions ( 5.6 ) ] .
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.