Dutasteride Capsules

Inhibition of DHT Conversion:

• Primary Mechanism: Dutasteride works by inhibiting the conversion of testosterone into 5-alpha-dihydrotestosterone (DHT), a potent androgen responsible for stimulating the development of prostate tissue. The enzyme 5-alpha-reductase facilitates this conversion, and it exists in two isoforms, type I and type II.
• Type II Isoenzyme: Primarily active in reproductive tissues like the prostate, seminal vesicles, and epididymites, the type II isoenzyme is responsible for about two-thirds of circulating DHT.
• Type I Isoenzyme: Mainly active in the skin and liver, this isoform also contributes to DHT production but to a lesser extent in reproductive tissues.

Effect on BPH:

• Benign Prostatic Hyperplasia (BPH): By reducing circulating DHT levels, dutasteride leads to a decrease in prostate hypertrophy, which helps alleviate urinary flow obstruction commonly associated with BPH.

Effect on Androgenetic Alopecia:

• Male Pattern Hair Loss: In androgenetic alopecia, the balding scalp shows miniaturized hair follicles and higher levels of DHT compared to non-balding areas. Dutasteride reduces both scalp and serum DHT concentrations, thereby interrupting the process that contributes to hair follicle miniaturization in genetically predisposed individuals.

Pharmacodynamic Effects:

• Decrease in Serum DHT: The reduction in DHT is dose-dependent and can be observed within 1 to 2 weeks of treatment initiation.
• Increase in Testosterone and TSH: While dutasteride decreases DHT, it simultaneously increases total testosterone and thyroid-stimulating hormone (TSH) levels.
• Decrease in PSA Levels: Dutasteride also lowers total serum prostate-specific antigen (PSA) levels, which can be relevant in monitoring prostate health.

No Androgen Receptor Binding:

• Dutasteride does not bind to androgen receptors, distinguishing its mechanism from that of other androgen-related treatments.

Impact on Other Hormones:

• Dutasteride does not significantly alter circulating levels of sex hormone-binding globulin, estradiol, luteinizing hormone, follicle-stimulating hormone, thyroxine (free T4), or dehydroepiandrosterone. It also does not affect the hypothalamic-pituitary-testicular axis, indicating a specific and targeted action on DHT production without widespread hormonal disruption.

Hypersensitivity:

• Contraindication: Dutasteride is contraindicated in patients with known hypersensitivity to the drug or any of its ingredients. Cross-sensitivity with other 5-alpha-reductase inhibitors is possible.

Renal Impairment:

• Precaution: The pharmacokinetics of dutasteride in patients with renal impairment have not been studied. However, since less than 0.1% of a steady-state dose is excreted in the urine, dosage adjustment is not expected to be necessary for patients with renal impairment.

Elderly Patients:

• Observation: No overall differences in safety or effectiveness have been observed between elderly patients (>65 years) and younger adults.

Females and Pregnancy:

• Contraindication: Dutasteride is contraindicated for use in females of childbearing potential, particularly during pregnancy. The drug inhibits the conversion of testosterone to DHT, potentially causing abnormalities in the external genitalia of male fetuses. Pregnant women or those trying to conceive should avoid handling dutasteride capsules, as absorption through the skin may result in fetal exposure. If skin contact occurs, the area should be washed with soap and water immediately. Dutasteride is also present in male semen, but the amount available for vaginal absorption is minimal, reducing the risk of fetal exposure.

Breastfeeding:

• Contraindication: Dutasteride is not indicated for women of childbearing potential and is contraindicated during breastfeeding. It is unknown whether dutasteride is excreted in human milk, so the effects on nursing infants cannot be determined.

Hepatic Disease:

• Precaution: Dutasteride should be used with caution in patients with hepatic disease. The drug is extensively metabolized by the liver, and there is limited data on adverse effects or drug accumulation in these patients. Caution is advised when administering dutasteride to patients taking potent CYP3A4 inhibitors, as their impact on dutasteride metabolism has not been studied.

Pediatric Use:

• Contraindication: Dutasteride is contraindicated for use in neonates, infants, children, and adolescents. The safety and effectiveness of the drug in these age groups have not been established.

Prostate-Specific Antigen (PSA) Levels:

• Precaution: Dutasteride reduces total serum PSA levels by approximately 40% after 3 months and 50% after 6, 12, and 24 months of treatment. A new baseline PSA should be established after 3-6 months for monitoring. In men treated with dutasteride for 6 months or more, the PSA value should be doubled for comparison with normal values in untreated men. Increased PSA levels during treatment may indicate potential prostate cancer and should be carefully evaluated.

Prostate Cancer Risk:

• Precaution: Dutasteride may increase the risk of high-grade prostate cancer. Although it reduces the risk of being diagnosed with lower-grade prostate cancer, there was an increased incidence of Gleason score (GS) 8-10 prostate cancers in clinical trials. Therefore, the benefits of treatment must be weighed against the potential risk, and patients should be regularly assessed for other urological diseases.

Urinary Tract Symptoms:

• Precaution: Patients with large residual urinary volumes and/or severely diminished urinary flow may not be suitable for dutasteride therapy and should be monitored closely for urinary tract obstruction.

Blood Donation:

• Precaution: Males treated with dutasteride should not donate blood until at least 6 months after their last dose to prevent the risk of administering dutasteride to a pregnant female through transfusion. Dutasteride can be detected in serum for 4-6 months after therapy ends.

Spermatogenesis and Fertility:

• Precaution: Dutasteride may cause inhibition of spermatogenesis, oligospermia, decreased sperm motility, and decreased semen volume. The clinical significance of these effects on male fertility is not fully known, but they should be considered when assessing fertility in men undergoing treatment with dutasteride. Studies have shown reductions in total sperm count and semen volume, with partial recovery after discontinuation. However, some individuals may experience significant reductions in sperm count.

Hypersensitivity:

• Contraindication: Dutasteride is contraindicated in patients with known hypersensitivity to the drug or any of its ingredients. Cross-sensitivity with other 5-alpha-reductase inhibitors is possible.

Renal Impairment:

• Precaution: The pharmacokinetics of dutasteride in patients with renal impairment have not been studied. However, since less than 0.1% of a steady-state dose is excreted in the urine, dosage adjustment is not expected to be necessary for patients with renal impairment.

Elderly Patients:

• Observation: No overall differences in safety or effectiveness have been observed between elderly patients (>65 years) and younger adults.

Females and Pregnancy:

• Contraindication: Dutasteride is contraindicated for use in females of childbearing potential, particularly during pregnancy. The drug inhibits the conversion of testosterone to DHT, potentially causing abnormalities in the external genitalia of male fetuses. Pregnant women or those trying to conceive should avoid handling dutasteride capsules, as absorption through the skin may result in fetal exposure. If skin contact occurs, the area should be washed with soap and water immediately. Dutasteride is also present in male semen, but the amount available for vaginal absorption is minimal, reducing the risk of fetal exposure.

Breastfeeding:

• Contraindication: Dutasteride is not indicated for women of childbearing potential and is contraindicated during breastfeeding. It is unknown whether dutasteride is excreted in human milk, so the effects on nursing infants cannot be determined.

Hepatic Disease:

• Precaution: Dutasteride should be used with caution in patients with hepatic disease. The drug is extensively metabolized by the liver, and there is limited data on adverse effects or drug accumulation in these patients. Caution is advised when administering dutasteride to patients taking potent CYP3A4 inhibitors, as their impact on dutasteride metabolism has not been studied.

Pediatric Use:

• Contraindication: Dutasteride is contraindicated for use in neonates, infants, children, and adolescents. The safety and effectiveness of the drug in these age groups have not been established.

Prostate-Specific Antigen (PSA) Levels:

• Precaution: Dutasteride reduces total serum PSA levels by approximately 40% after 3 months and 50% after 6, 12, and 24 months of treatment. A new baseline PSA should be established after 3-6 months for monitoring. In men treated with dutasteride for 6 months or more, the PSA value should be doubled for comparison with normal values in untreated men. Increased PSA levels during treatment may indicate potential prostate cancer and should be carefully evaluated.

Prostate Cancer Risk:

• Precaution: Dutasteride may increase the risk of high-grade prostate cancer. Although it reduces the risk of being diagnosed with lower-grade prostate cancer, there was an increased incidence of Gleason score (GS) 8-10 prostate cancers in clinical trials. Therefore, the benefits of treatment must be weighed against the potential risk, and patients should be regularly assessed for other urological diseases.

Urinary Tract Symptoms:

• Precaution: Patients with large residual urinary volumes and/or severely diminished urinary flow may not be suitable for dutasteride therapy and should be monitored closely for urinary tract obstruction.

Blood Donation:

• Precaution: Males treated with dutasteride should not donate blood until at least 6 months after their last dose to prevent the risk of administering dutasteride to a pregnant female through transfusion. Dutasteride can be detected in serum for 4-6 months after therapy ends.

Spermatogenesis and Fertility:

• Precaution: Dutasteride may cause inhibition of spermatogenesis, oligospermia, decreased sperm motility, and decreased semen volume. The clinical significance of these effects on male fertility is not fully known, but they should be considered when assessing fertility in men undergoing treatment with dutasteride. Studies have shown reductions in total sperm count and semen volume, with partial recovery after discontinuation. However, some individuals may experience significant reductions in sperm count.

Pregnancy:

• Contraindicated Use: Dutasteride is contraindicated in females of childbearing potential due to its ability to inhibit the conversion of testosterone to dihydrotestosterone (DHT), which can cause severe abnormalities in the external genitalia of a male fetus.
• Handling Precautions: Pregnant women or those trying to conceive should avoid handling dutasteride capsules. The drug can be absorbed through the skin, leading to potential fetal exposure. If a leaking capsule is handled, the area should be washed with soap and water immediately.
• Exposure Through Semen: Dutasteride is secreted into male semen, but the amount available for vaginal absorption is estimated to be less than 100 times the concentration needed to cause fetal abnormalities in animal studies. Additionally, the drug is over 96% protein-bound in semen, which may further reduce vaginal absorption.

Breastfeeding:

• Contraindicated Use: Dutasteride is not indicated for use in women of childbearing potential and is contraindicated during breastfeeding.
• Excretion in Breast Milk: It is unknown whether dutasteride is excreted in human milk, and therefore, the effects on a breastfeeding infant cannot be determined.

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.