How Much Does Dutasteride Cost in Mexico vs the USA?

Dutasteride is a 5 alpha-reductase inhibitor indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to: (1.1) improve symptoms, reduce the risk of acute urinary retention, and reduce the risk of the need for BPH-related surgery. Dutasteride in combination with the alpha-adrenergic antagonist, tamsulosin, is indicated for the treatment of symptomatic BPH in men with an enlarged prostate. (1.2) Limitations of Use: Dutasteride is not approved for the prevention of prostate cancer. (1.3) 1.1 Monotherapy Dutasteride capsules are indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to: improve symptoms, reduce the risk of acute urinary retention (AUR), and reduce the risk of the need for BPH-related surgery. 1.2 Combination with Alpha-adrenergic Antagonist Dutasteride in combination with the alpha-adrenergic antagonist, tamsulosin, is indicated for the treatment of symptomatic BPH in men with an enlarged prostate. 1.3 Limitations of Use Dutasteride is not approved for the prevention of prostate cancer.

The capsules should be swallowed whole and not chewed or opened, as contact with the capsule contents may result in irritation of the oropharyngeal mucosa. Dutasteride may be administered with or without food. Monotherapy: 0.5 mg once daily. (2.1) Combination with tamsulosin: 0.5 mg once daily and tamsulosin 0.4 mg once daily. (2.2) Dosing considerations: Swallow whole. May take with or without food. (2) 2.1 Monotherapy The recommended dose of dutasteride is 1 capsule (0.5 mg) taken once daily. 2.2 Combination with Alpha-adrenergic Antagonist The recommended dose of dutasteride is 1 capsule (0.5 mg) taken once daily and tamsulosin 0.4 mg taken once daily.

Dutasteride is contraindicated for use in: Pregnancy. Dutasteride use is contraindicated in women who are pregnant. In animal reproduction and developmental toxicity studies, dutasteride inhibited development of male fetus external genitalia. Therefore, dutasteride may cause fetal harm when administered to a pregnant woman [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)] . Patients with previously demonstrated clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride or other 5 alpha-reductase inhibitors [see Adverse Reactions (6.2)] . Pregnancy. Dutasteride use is contraindicated in women who are pregnant. (4, 5.4, 8.1) Patients with previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride or other 5 alpha-reductase inhibitors. (4)

Dutasteride reduces serum prostate-specific antigen (PSA) concentration by approximately 50%. However, any confirmed increase in PSA while on dutasteride may signal the presence of prostate cancer and should be evaluated, even if those values are still within the normal range for untreated men. (5.1) Dutasteride may increase the risk of high-grade prostate cancer. (5.2, 6.1) Prior to initiating treatment with dutasteride, consideration should be given to other urological conditions that may cause similar symptoms. (5.3) Women who are pregnant or may be pregnant should not handle dutasteride capsules due to potential risk to a male fetus. (5.4, 8.1) Patients should not donate blood until 6 months after their last dose of dutasteride. (5.5) 5.1 Effects on Prostate-Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection 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 subjects with symptomatic BPH, although it may vary in individuals. Dutasteride may also cause decreases in serum PSA in the presence of prostate cancer. To interpret serial PSAs in men taking dutasteride, a new PSA baseline 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 dutasteride 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 dutasteride may also affect PSA test results. To interpret an isolated PSA value in a man treated with dutasteride 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 dutasteride, no adjustment to its value appears necessary. Coadministration of dutasteride and tamsulosin resulted in similar changes to serum PSA as dutasteride monotherapy. 5.2 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 8-10 prostate cancer compared with men taking placebo (dutasteride 1.0% versus placebo 0.5%) [see Indications and Usage (1.3), Adverse Reactions (6.1)] . In a 7-year placebo-controlled clinical trial with another 5 alpha-reductase inhibitor (finasteride 5 mg, PROSCAR), similar results for Gleason score 8-10 prostate cancer were observed (finasteride 1.8% versus placebo 1.1%). 5 alpha-reductase inhibitors may increase the risk of development of high-grade prostate cancer. Whether the effect of 5 alpha-reductase inhibitors to reduce prostate volume or trial-related factors impacted the results of these trials has not been established. 5.3 Evaluation for Other Urological Diseases Prior to initiating treatment with dutasteride, consideration should be given to other urological conditions that may cause similar symptoms. In addition, BPH and prostate cancer may coexist. 5.4 Transdermal Exposure of Dutasteride in Pregnant Women—Risk to Male Fetus Dutasteride capsules should not be handled by women 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 pregnant woman comes in contact with leaking dutasteride capsules, the contact area should be washed immediately with soap and water [see Use in Specific Populations (8.1)] . Dutasteride can be absorbed through the skin based on animal studies [see Nonclinical Toxicology (13.2)] . 5.5 Blood Donation Men being treated with dutasteride 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. 5.6 Effect on Semen Characteristics 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 with 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 [see Use in Specific Populations (8.3)] .

Use with caution in patients taking potent, chronic cytochrome P450 (CYP)3A4 enzyme inhibitors (e.g., ritonavir). (7) 7.1 Cytochrome P450 3A Inhibitors Dutasteride is extensively metabolized in humans by the cytochrome P450 (CYP)3A4 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 dutasteride to patients taking potent, chronic CYP3A4 enzyme inhibitors (e.g., ritonavir) [see Clinical Pharmacology (12.3)] . 7.2 Alpha-adrenergic Antagonists The administration of dutasteride in combination with tamsulosin or terazosin has no effect on the steady-state pharmacokinetics of either alpha-adrenergic antagonist. The effect of administration of tamsulosin or terazosin on dutasteride pharmacokinetic parameters has not been evaluated. 7.3 Calcium Channel Antagonists 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 dose adjustment is recommended [see Clinical Pharmacology (12.3)]. 7.4 Cholestyramine Administration of a single 5-mg dose of dutasteride followed 1 hour later by 12 g of cholestyramine does not affect the relative bioavailability of dutasteride [see Clinical Pharmacology (12.3)] . 7.5 Digoxin Dutasteride does not alter the steady-state pharmacokinetics of digoxin when administered concomitantly at a dose of 0.5 mg/day for 3 weeks [see Clinical Pharmacology (12.3)] . 7.6 Warfarin 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)] .

The most common adverse reactions, reported in ≥1% of subjects treated with dutasteride and more commonly than in subjects treated with placebo, are impotence, decreased libido, ejaculation disorders, and breast disorders. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Camber Pharmaceuticals, Inc., at 1-866-495-8330 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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. From clinical trials with dutasteride as monotherapy or in combination with tamsulosin: The most common adverse reactions reported in subjects receiving dutasteride were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), and ejaculation disorders. The most common adverse reactions reported in subjects receiving combination therapy (dutasteride plus tamsulosin) were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), ejaculation disorders, and dizziness. Ejaculation disorders occurred significantly more in subjects receiving combination therapy (11%) compared with those receiving dutasteride (2%) or tamsulosin (4%) as monotherapy. Trial withdrawal due to adverse reactions occurred in 4% of subjects receiving dutasteride and 3% of subjects receiving placebo in placebo-controlled trials with dutasteride. The most common adverse reaction leading to trial withdrawal was impotence (1%). In the clinical trial evaluating the combination therapy, trial withdrawal due to adverse reactions occurred in 6% of subjects receiving combination therapy (dutasteride plus tamsulosin) and 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%). Monotherapy Over 4,300 male subjects with BPH were randomly assigned to receive placebo or 0.5-mg daily doses of dutasteride in 3 identical 2-year, placebo-controlled, double-blind, Phase 3 treatment trials, each followed by a 2-year open-label extension. During the double-blind treatment period, 2,167 male subjects were exposed to dutasteride, including 1,772 exposed for 1 year and 1,510 exposed for 2 years. When including the open-label extensions, 1,009 male subjects were exposed to dutasteride for 3 years and 812 were exposed for 4 years. The population was aged 47 to 94 years (mean age: 66 years) and greater than 90% were white. Table 1 summarizes clinical adverse reactions reported in at least 1% of subjects receiving dutasteride and at a higher incidence than subjects receiving placebo. Long-term Treatment (Up to 4 Years) High-grade Prostate Cancer: The REDUCE trial was a randomized, double-blind, placebo-controlled trial that enrolled 8,231 men aged 50 to 75 years with a serum PSA of 2.5 ng/mL to 10 ng/mL and a negative prostate biopsy within the previous 6 months. Subjects were randomized to receive placebo (n = 4,126) or 0.5-mg daily doses of dutasteride (n = 4,105) for up to 4 years. The mean age was 63 years and 91% were white. Subjects underwent protocol-mandated scheduled prostate biopsies at 2 and 4 years of treatment or had “for-cause biopsies” at non-scheduled times if clinically indicated. There was a higher incidence of Gleason score 8-10 prostate cancer in men receiving dutasteride (1.0%) compared with men on placebo (0.5%) [see Indications and Usage (1.3), Warnings and Precautions (5.2)]. In a 7-year placebo-controlled clinical trial with another 5 alpha-reductase inhibitor (finasteride 5 mg, PROSCAR), similar results for Gleason score 8-10 prostate cancer were observed (finasteride 1.8% versus placebo 1.1%). No clinical benefit has been demonstrated in patients with prostate cancer treated with dutasteride. Reproductive and Breast Disorders In the 3 pivotal placebo-controlled BPH trials with dutasteride, each 4 years in duration, there was no evidence of increased sexual adverse reactions (impotence, decreased libido, and ejaculation disorder) or breast disorders with increased duration of treatment. Among these 3 trials, there was 1 case of breast cancer in the dutasteride group and 1 case in the placebo group. No cases of breast cancer were reported in any treatment group in the 4-year CombAT trial or the 4-year REDUCE trial. The relationship between long-term use of dutasteride and male breast neoplasia is currently unknown. Combination with Alpha-blocker Therapy (CombAT) Over 4,800 male subjects with BPH were randomly assigned to receive 0.5-mg dutasteride, 0.4-mg tamsulosin, or combination therapy (0.5-mg dutasteride plus 0.4-mg tamsulosin) 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 combination therapy. The population was aged 49 to 88 years (mean age: 66 years) and 88% were white. Table 2 summarizes adverse reactions reported in at least 1% of subjects in the combination group and at a higher incidence than subjects receiving monotherapy with dutasteride or tamsulosin. Cardiac Failure: In CombAT, after 4 years of treatment, the incidence of the composite term cardiac failure in the combination therapy group (12/1,610; 0.7%) was higher than in either monotherapy group: dutasteride, 2/1,623 (0.1%) and tamsulosin, 9/1,611 (0.6%). Composite cardiac failure was also examined in a separate 4-year placebo-controlled trial evaluating dutasteride in men at risk for development of prostate cancer. The incidence of cardiac failure in subjects taking dutasteride was 0.6% (26/4,105) compared with 0.4% (15/4,126) in subjects on placebo. A majority of subjects with cardiac failure in both trials had comorbidities associated with an increased risk of cardiac failure. Therefore, the clinical significance of the numerical imbalances in cardiac failure is unknown. No causal relationship between dutasteride alone or in combination with tamsulosin and cardiac failure has been established. No imbalance was observed in the incidence of overall cardiovascular adverse events in either trial. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of dutasteride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to dutasteride. Immune System Disorders Hypersensitivity reactions, including rash, pruritus, urticaria, localized edema, serious skin reactions, and angioedema. Neoplasms Male breast cancer. Psychiatric Disorders Depressed mood. Reproductive System and Breast Disorders Testicular pain and testicular swelling.