DUODART

What it is

DUODART is a capsule containing 500 micrograms of dutasteride and 400 micrograms of tamsulosin hydrochloride. Dutasteride–tamsulosin is a combination of two drugs with complementary mechanisms of action: dutasteride, a dual 5 alpha-reductase inhibitor, and tamsulosin hydrochloride, an antagonist of alpha-1a adrenoreceptors. Dutasteride inhibits both type 1 and type 2, 5 alpha-reductase isoenzymes, which are responsible for the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT), the androgen primarily responsible for hyperplasia of glandular prostatic tissue. Tamsulosin inhibits alpha-1a adrenergic receptors in the stromal prostatic smooth muscle and bladder neck, with approximately 75% of the alpha-1 receptors in the prostate being of the alpha-1a subtype.

Approved indications

— Management of moderate to severe symptomatic benign prostatic hyperplasia.

Dosing overview

The recommended dose of DUODART is one capsule (dutasteride 500 micrograms / tamsulosin 400 micrograms) taken orally approximately 30 minutes after the same meal each day. The capsules should be swallowed whole and not chewed or opened. DUODART should not be taken on an empty stomach as this may increase the potential for cardiovascular related adverse events such as orthostatic hypotension.

Key safety warnings

In a 4-year study of over 8,000 men aged 50 to 75, there was a higher incidence of Gleason 8 to 10 prostate cancers in the dutasteride group (0.9%) compared to the placebo group (0.6%). Men taking dutasteride should be regularly evaluated for prostate cancer risk including PSA testing. Digital rectal examination and other evaluations for prostate cancer should be performed prior to initiating therapy and periodically thereafter. Dutasteride causes a decrease in mean serum PSA levels by approximately 50% after 6 months of treatment, and patients receiving DUODART should have a new PSA baseline established after 6 months of treatment. Orthostatic hypotension can occur in patients treated with tamsulosin, which in rare cases can result in syncope. Patients beginning treatment with DUODART should be cautioned to sit or lie down at the first signs of orthostatic hypotension (dizziness and vertigo) until the symptoms have resolved and should avoid situations where injury could result should these symptoms occur. Caution is advised when alpha adrenergic blocking agents including tamsulosin are co-administered with phosphodiesterase type 5 inhibitor (PDE5) inhibitors, as both are vasodilators that can lower blood pressure and concomitant use can potentially cause symptomatic hypotension. Intraoperative Floppy Iris Syndrome (IFIS), a variant of small pupil syndrome, has been observed during cataract surgery in some patients treated with alpha-1 adrenergic blockers including tamsulosin. This syndrome is characterised by a flaccid iris that billows as a result of intraoperative irrigation currents, prolapse of the iris toward the phacoemulsification incisions, and progressive intraoperative miosis, and may increase the risk of eye complications during and after operation. Men being treated with any dutasteride-containing products should not donate blood until at least 6 months have passed following their last dose, to prevent administration of dutasteride to a pregnant female transfusion recipient.

Contraindications

DUODART is contraindicated in patients with known hypersensitivity to dutasteride, other 5 alpha-reductase inhibitors, tamsulosin hydrochloride or any component of the preparation; women and children; patients with a history of orthostatic hypotension; patients with severe hepatic impairment (Child–Pugh scores greater than 9); patients with severe renal impairment (creatinine clearance less than 10 mL/min); and combination with another alpha-1 adrenergic blocker.

PBS listing

DUODART 500/400 (dutasteride 500 microgram and tamsulosin hydrochloride 400 microgram modified release capsule) was first listed on the ARTG on 28 October 2010.

Regulatory history

DUODART was registered on the Australian Register of Therapeutic Goods (ARTG 162530) on 28 October 2010.