UROKA CAPSULES

Indications

• Benign prostatic hyperplasia

Dosage

Adults: 500 micrograms daily, with treatment review at 3–6 months and then every 6–12 months.

Mechanism of action

Dutasteride binds to both type I and type II isoenzymes of 5α-reductase, forming a stable complex that inhibits the conversion of testosterone to DHT. DHT is a key hormone in prostate development and growth, and by reducing its levels by more than 90%, dutasteride alleviates symptoms of BPH and improves urinary flow.

Pharmacodynamics

Dutasteride exhibits a dose-dependent reduction in circulating DHT levels, with maximum effects observed within 1-2 weeks after initial administration. Clinical studies have shown that median serum DHT concentrations were reduced by 85% and 90% after 1 and 2 weeks of daily dosing with 0.5 mg, respectively. Continuous administration of dutasteride maintains DHT levels suppressed in the majority of patients, and it may also lead to decreased serum prostate-specific antigen (PSA) levels in patients with prostate cancer.

Pharmacokinetics

Dutasteride is well absorbed after oral administration, with a peak plasma concentration typically reached within 1-2 hours. The drug has a long half-life, allowing for once-daily dosing. It is extensively metabolized in the liver, primarily by CYP3A4 and CYP3A5 enzymes, leading to the formation of several metabolites. The elimination half-life is approximately 5 weeks, which supports the need for regular follow-up and dose adjustment based on clinical response.

Contra-indications

• History of micturition syncope
• History of postural hypotension

Adverse effects

• Abdominal pain
• Anxiety
• Angioedema
• Arrhythmias
• Asthenia
• Chest pain
• Constipation
• Cough
• Depression
• Dizziness
• Diarrhoea
• Drowsiness
• Fatigue
• Gastrointestinal disturbances
• Hyperhidrosis
• Insomnia
• Myalgia
• Nasal congestion
• Nausea
• Oedema
• Palpitations
• Paraesthesia
• Postural hypotension
• Sexual dysfunction
• Skin reactions
• Syncope
• Vomiting
• Weight gain

Interactions

• Cobicistat increases exposure
• Idelalisib increases exposure
• Clarithromycin increases exposure
• Crizotinib unknown effect on exposure
• Imatinib unknown effect on exposure
• Letermovir unknown effect on exposure
• Nilotinib unknown effect on exposure
• Terazosin may increase risk of hypotension

Precautions

• Caution in elderly patients
• Caution in patients with history of prostate cancer
• Monitor for signs of hypotension and syncope
• Consider lower initial dose in patients with autonomic neuropathy

Pregnancy

Dutasteride is contraindicated in pregnancy due to potential harm to a male fetus.

Breast-feeding

Manufacturer advises avoiding use during breastfeeding due to potential for effects on the infant.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Dutasteride 0.5 mg capsules

Mechanism of action

The 5α-reductase is a nuclear-bound steroid intracellular enzyme primarily located in the prostatic stromal cell that converts the androgen testosterone into the more active metabolite, 5α-dihydrotestosterone (DHT). DHT is considered to be the primary androgen playing a role in the initial development and subsequent enlargement of the prostate gland. It serves as the hormonal mediator for the hyperplasia upon accumulation within the prostate gland. DHT displays a higher affinity towards androgen receptors in the prostate gland compared to testosterone and by acting on the androgen receptors, DHT modulates genes that are responsible for cell proliferation. Responsible for the synthesis of approximately one-third of circulating DHT, type I 5α-reductase is predominant in the sebaceous glands of most regions of skin, including the scalp, and liver. The type II 5a-reductase isozyme is primarily found in the prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two-thirds of circulating DHT. Due to its dual inhibition of both isoenzymes of 5α-reductase, dutasteride causes a near-complete suppression of DHT. Compared to a 70% reduction of serum DHT levels caused by [finasteride], a near-complete suppression of serum DHT-more than 90% is seen with dutasteride. By forming a stable complex with both type I and type II 5α-reductase, dutasteride inhibits its enzymatic action of converting testosterone to 5α-dihydrotestosterone (DHT), which is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. It is proposed that DHT is the principal androgen responsible for prostatic growth in later life-normal masculinization of the external genitalia and maturation of the prostate gland during development-thus reducing the serum DHT levels results in reduced prostatic volume and increased epithelial apoptosis. Dutasteride is a competitive and specific inhibitor of both Type I and Type II 5α-reductase isoenzymes and when evaluated under _in vitro_ and _in vivo_ conditions, the dissociation of the drug from the drug-enzyme complex is reported to be extremely slow. Dutasteride does not bind to the human androgen receptor.

Pharmacodynamics

Dutasteride is a synthetic 4-azasteroid compound that selectively inhibits both the type I and type II isoforms of steroid 5α-reductase, an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone (DHT). Dutasteride works by reducing the levels of circulating DHT. It was also shown to reduce the size of the prostate gland, improve urinary flow, and symptoms of benign prostatic hyperplasia alone or in combination with tamsulosin. The effect of the reduction of DHT by dutasteride is dose-dependent, with the maximum effect observed within 1-2 weeks following initial administration. After 1 and 2 weeks of daily dosing with dutasteride 0.5 mg, median serum DHT concentrations were reduced by 85% and 90%, respectively. The serum concentrations of DHT were maintained to be decreased by more than 90% in 85% of patients following 1 years' administration of oral dutasteride 0.5 mg/day. As evident from the clinical studies, dutasteride may also cause decreases in serum PSA in the presence of prostate cancer.