Products
The 5alpha-reductase inhibitor dutasteride and the alpha-blocker tamsulosin are commercially available as a fixed combination in the form of capsules (Duodart, generics). The drug has been approved in many countries since 2010.
Structure and properties
Dutasteride (C27H30F6N2O2, Mr = 528.5 g/mol) is a 4-azasteroid and structurally closely related to finasteride. It exists as a white to pale yellow powder that is insoluble in water. Tamsulosin (C20H28N2O5S, Mr = 408.51 g/mol) exists as tamsulosin hydrochloride, a white crystalline powder that is sparingly soluble in water. Only the -(-)-isomer is used clinically. Tamsulosin is a methoxybenzenesulfonamide and is not one of the quinazoline derivatives such as terazosin and alfuzosin.
Effects
Dutasteride (ATC G04CB02) is a selective, potent, dual, and competitive inhibitor of 5α-reductase, which converts testosterone to 5α-dihydrotestosterone. 5α-Dihydrotestosterone represents an important growth stimulus for prostate enlargement. Dutasteride reduces prostate size, relieves symptoms, and improves urinary flow. It has a long half-life of 3 to 5 weeks. Tamsulosin (ATC G04CA02) binds competitively to postsynaptic α1-adrenoreceptors as an antagonist, relaxing prostate and urethral smooth muscle. This increases urinary flow, improves urination and filling symptoms. The effects occur quickly, within hours to days, compared to dutasteride. On the other hand, tamsulosin has no effect on the size of the prostate.
Indications
As combination therapy for the treatment of moderate to severe symptoms of benign prostatic hyperplasia (BPH).
Dosage
According to the SmPC. Capsules are taken once daily, always at the same time of day, within 30 minutes after a meal and with a glass of water. Fasting administration is not recommended.
Contraindications
- Hypersensitivity
- Orthostatic hypotension in the patient history.
- Severe liver dysfunction
- Women, children and adolescents
Due to fertility damaging properties, pregnant women should not come into contact with the active substance dutasteride (e.g. defective capsules). Full precautions can be found in the drug information leaflet.
Adverse effects
The most common possible adverse effects include impotence, ejaculatory dysfunction (eg, retrograde ejaculation), breast enlargement (gynecomastia), breast tenderness, dizziness, and decreased libido.
