General Information

Entadfi is a combination of finasteride, a 5α-reductase inhibitor, and tadalafil, a phosphodiesterase 5 (PDE5) inhibitor.

Entadfi is specifically indicated to initiate treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate for up to 26 weeks.

Entadfi is supplied as a capsule for oral administration. The recommended dosage of Entadfi is one capsule (containing finasteride 5 mg and tadalafil 5 mg) orally once daily at approximately the same time every day for up to 26 weeks. Take Entadfi on an empty stomach.

Mechanism of Action

Finasteride: The development and enlargement of the prostate gland is dependent on the potent androgen, 5αdihydrotestosterone (DHT). Type II 5α-reductase metabolizes testosterone to DHT in the prostate gland, liver and skin. DHT induces androgenic effects by binding to androgen receptors in the cell nuclei of these organs. Finasteride is a competitive and specific inhibitor of Type II 5α-reductase with which it slowly forms a stable enzyme complex. Turnover from this complex is extremely slow (t½ ~ 30 days). This has been demonstrated both in vivo and in vitro. Finasteride has no affinity for the androgen receptor. In man, the 5α-reduced steroid metabolites in blood and urine are decreased after administration of finasteride.

Tadalafil: The mechanism for reducing BPH symptoms has not been established. Studies in vitro have demonstrated that tadalafil is a selective inhibitor of phosphodiesterase 5 (PDE5). PDE5 is found in the smooth muscle of the corpus cavernosum, prostate, and bladder as well as in vascular and visceral smooth muscle, skeletal muscle, urethra, platelets, kidney, lung, cerebellum, heart, liver, testis, seminal vesicle, and pancreas.

Side Effects

Adverse effects associated with the use of finasteride monotherapy may include, but are not limited to, the following:

• impotence
• decreased libido
• decreased volume of ejaculate
• breast enlargement
• breast tenderness
• rash

Adverse effects associated with the use of tadalafil may include, but are not limited to, the following:

• headache
• dyspepsia
• back pain
• myalgia
• nasal congestion
• flushing
• pain in limb

Clinical Trial Results

The efficacy of Entadfi is based on an adequate and well-controlled study of tadalafil co-administered with finasteride.

Tadalafil for once daily use initiated together with finasteride was shown to be effective in treating the signs and symptoms of BPH in men with an enlarged prostate (>30 cc) for up to 26 weeks. A double-blinded, parallel-design study of 26 weeks duration randomized 696 men to initiate either tadalafil 5 mg with finasteride 5 mg or placebo with finasteride 5 mg. The study population had a mean age of 64 years (range 46-86). Patients with multiple co-morbid conditions such as erectile dysfunction, diabetes mellitus, hypertension, and other cardiovascular disease were included. Tadalafil and finasteride administered together demonstrated statistically significant improvement in the signs and symptoms of BPH compared to placebo with finasteride, as measured by the total symptom score (IPSS) at 12 weeks, the primary study endpoint. Key secondary endpoints demonstrated improvement in total IPSS starting at the first scheduled observation at week 4 (tadalafil -4.0, placebo -2.3: p<.001) and the score remained decreased through 26 weeks (tadalafil -5.5, placebo -4.5; p=.022). However, the magnitude of the treatment difference between placebo/finasteride and tadalafil/finasteride decreased from 1.7 points at Week 4 to 1.0 point at Week 26. The incremental benefit of Entadfi beyond 26 weeks is unknown.