Tadalafil / Phentolamine Mesylate Capsules

Tadalafil

Tadalafil is a selective phosphodiesterase (PDE) type 5 inhibitor similar to sildenafil and vardenafil. It is administered orally for the treatment of male erectile dysfunction (ED), pulmonary arterial hypertension (PAH), benign prostatic hypertrophy (BPH), or the concurrent treatment of erectile dysfunction and BPH. Tadalafil does not inhibit prostaglandins as do some agents for treating impotence (e.g., alprostadil). Unlike sildenafil, visual disturbances have not been reported with tadalafil, which is more selective for PDE5 than for PDE6 present in the retina. The duration of action of tadalafil for the treatment of ED (up to 36 hours) appears to be longer than that of sildenafil and vardenafil. Because PDE inhibitors promote erection only in the presence of sexual stimulation, the longer duration of action of tadalafil allows for more spontaneity in sexual activity. According to ED treatment guidelines, oral phosphodiesterase type 5 inhibitors (PDE5 inhibitor) are considered first-line therapy.1 Tadalafil was in phase II trials for the treatment of female sexual dysfunction, however, further investigation was discontinued. FDA approval was granted November 2003 for treatment of male erectile dysfunction (ED), and in January 2008, approval was granted for once daily use without regard to timing of sexual activity. Tadalafil (Adcirca) was FDA approved for the treatment of pulmonary arterial hypertension (PAH) in May 2009. In clinical studies of patients with pulmonary arterial hypertension (PAH), tadalafil-treated patients experienced improved exercise capacity and less clinical worsening compared to placebo. In October 2011, tadalafil received FDA approval for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) and for the concurrent treatment of erectile dysfunction and BPH.

Phentolamine Mesylate

Phentolamine is an alpha-adrenergic receptor antagonist. Phentolamine is similar in action to phenoxybenzamine but is administered parenterally and has a shorter duration of action. Approved uses of phentolamine include diagnosis of pheochromocytoma and treatment of hypertension in pheochromocytoma, prevention of tissue necrosis after norepinephrine extravasation, and reversal of soft tissue anesthesia.23 Phentolamine also has been used to treat hypertensive crisis associated with monoamine oxidase inhibitor (MAOI) therapy and in combination with papaverine to treat erectile dysfunction (ED).1 According to ED treatment guidelines, oral phosphodiesterase type 5 (PDE5) inhibitors are considered first-line therapy.1 Second-line treatment options include intracavernous injection and intra-urethral therapy. Intracavernous injection therapy is the most effective nonsurgical treatment for ED, with predictable and sustained response. However, it is invasive and carries notable side-effects including priapism and penile fibrosis.1 Phentolamine injection is contraindicated for use in patients with any coronary artery disease due to cardiac stimulating effects and corresponding increase in myocardial oxygen demand. Phentolamine was FDA-approved in 1952.