Combodart is the first treatment in the UK that combines the benefits of two recommended monotherapies for BPH. Dutasteride delays progression of the disease by inhibiting the production of the male hormone dihydrotestosterone (DHT) that stimulates prostate growth, whilst tamsulosin provides rapid symptom relief by reducing smooth muscle tone in the prostate and bladder neck.

 

BPH is a prevalent condition in the UK affecting an estimated 3.2 million men (one in three men over the age of 50 years) and this number is expected to increase with the growing elderly population.4,5 Men frequently experience problematic symptoms for a considerable period of time before they seek medical help, believing it is just part of the natural ageing process.

 

BPH is the non-cancerous enlargement of the prostate gland, which occurs in men as they age, due to an increase in DHT. This leads to the narrowing of the urethra and bladder obstruction, which is characterised by a range of clinical symptoms including a more frequent or sudden urge to urinate, needing to wake to pass urine in the night, weak or poor urinary stream and hesitancy/intermittency when passing urine.6 If left untreated, BPH may result in serious long-term complications such as the sudden and total inability to pass urine (acute urinary retention requiring hospitalisation), or BPH-related surgery.

 

Combodart received marketing authorisation in the UK in May 2010 based on the 4-year CombAT trial results, which demonstrated that combined treatment with dutasteride and tamsulosin significantly reduced the risk of AUR or BPH-related surgery by 66% compared with tamsulosin alone (p<0.001). It was also shown that combination therapy significantly reduced the risk of BPH disease progression by 44% compared with tamsulosin and 31% compared with dutasteride alone.7 Results from the CombAT trial showed that the therapy was generally well tolerated during the 4-year study and the common adverse events reported were consistent with previous experience of using each component as stand-alone treatments. Patients prescribed Combodart should take one single capsule, once a day after food.

首个固定剂量的联合治疗药物Combodart在苏格兰获批用于治疗良性前列腺增生

Combodart是首个固定剂量的同时含有5α还原酶抑制剂度他雄胺（0.5mg）和α-阻滞剂盐酸坦索罗辛（0.4mg）的联合治疗药物，适用于治疗中重度良性前列腺增生（BPH），以及降低急性尿潴留（AUR）和BPH相关手术的风险
制造商：
葛兰素史克制药公司

类药物：
I及II型5α-还原酶抑制剂+α1A受体阻滞剂。

活性成分（补）：
度他雄胺为0.5mg，盐酸坦索罗辛0.4mg;上限。

适应症（补）：
良性前列腺增生症（BPH）。

 

Manufacturer:
GlaxoSmithKline Pharmaceuticals
Pharmacological Class:
Type I and II 5α-reductase inhibitor + α1A-blocker.
Active Ingredient(s):
Dutasteride 0.5mg, tamsulosin HCl 0.4mg; caps.
      
Indication(s):
Benign prostatic hyperplasia (BPH).
Pharmacology:
The development and enlargement of the prostate gland is largely controlled by the androgen, dihydrotestosterone. It is formed by the conversion of testosterone through the action of the enzyme steroid 5α-reductase. The type 2 isoform of this enzyme is primarily active in reproductive tissues, while the type 1 also works in the skin and the liver. Dutasteride is a selective inhibitor of both type 1 and type 2
5α-reductase. By inhibiting the formation of dihydrotestosterone, dutasteride reduces prostate enlargement.
Smooth muscle tone is controlled by the sympathetic nervous systemviastimulation of α&#8321;-adrenergic receptors. Most (70%)oftheα&#8321;adrenergicreceptors in the prostate are of the type α1A subtype. Tamsulosin is anα1A-antagonist that is selective for those receptors. It improves urine flow rates and reduces the symptoms of BPH by relaxing the smooth musculature in the bladder neck and prostate.
Dutasteride is metabolized by CYP3A4 and CYP3A5, and tamsulosin is metabolized mainly by CYP3A4 and CYP2D6. In making decisions regarding drug therapy, potential interactions with other drugs that affect these metabolic enzymes should be considered.

Clinical Trials:
A 4-year, multicenter, randomized, double-blind study investigated the efficacy of dutasteride + tamsulosin compared to either drug alone in relieving the symptoms of BPH. The primary efficacy endpoint for this parallel group study was based on the change in the International Prostate Symptom Score (IPSS). The results of this study indicated that coadministration therapy (dutasteride 0.5mg/day +tamsulosin HCl 0.4mg/day) was statistically superior to each of the monotherapy treatments in reducing the symptom scoreatmonth24.Also,coadministration of both drugs was superior to monotherapy in increasing maximum urine flow rates. Prostate volume was reduced by both dual therapy and monotherapy with dutasteride, but not for tamsulosin.
Legal Classification:
Rx
Adults:
Swallow whole. Take &frac12; hour after same meal each day. 1 capsule daily.
Children:
Not recommended.
Contraindication(s):
Not for use in children or women. Pregnantwomenandthoseofchildbearingpotential should avoid handling capsules. Pregnancy (Cat.X). Nursing mothers.

Warnings/Precautions:
Rule out prostate cancer. Monitor prostate specific antigen (PSA) values (set new baseline PSA after 3–6 months of treatment); double PSA levels to compare with normal values. Monitor for prostate cancer, obstructive uropathy. Syncope. End-stage renal disease. Severe hepatic impairment.
Cataract surgery (intraoperative floppy iris syndrome possible). Poor metabolizers (low CYP2D6 activity). Sulfa allergy. Avoid donating blood until at least 6 months after last dose.Interaction(s):Concomitant strong inhibitors of CYP3A4 (eg,ketoconazole): not recommended; caution with strong CYP2D6 inhibitors (eg, paroxetine). Do not use with other alpha-blockers. Potentiated by cimetidine. Dutasteride may be potentiated by moderate CYP3A4/5 inhibitors(eg,diltiazem,erythromycin). Tamsulosin may be potentiated by a concomitant combination of CYP3A4 and CYP2D6 inhibitors (eg, terbinafine). Caution with PDE-5 inhibitors (may increase orthostatic hypotension). Monitor warfarin.
Adverse Reaction(s):
Ejaculation disorders, impotence, decreased libido, dizziness, breast disorders, orthostatic hypotension and/or syncope; rare: priapism.

How Supplied:
Caps—30, 90

Last Updated:
9/9/2010