Sildenafil Citrate

What it is and how it works

Mechanism of Action Sildenafil is an inhibitor of cGMP specific phosphodiesterase type-5 (PDE-5) in the smooth muscle of the pulmonary vasculature, where PDE-5 is responsible for degradation of cGMP. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation. In patients with PAH, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation. Studies in vitro have shown that sildenafil is selective for PDE-5.

Indications

Sildenafil tablets are indicated for the treatment of pulmonary arterial hypertension (WHO Group I) in adults to improve exercise ability and delay clinical worsening. The delay in clinical worsening was demonstrated when sildenafil tablets were added to background epoprostenol therapy [ see Clinical Studies ]. Studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with New York Heart Association (NYHA) Functional Class II-III symptoms and idiopathic etiology (71%) or associated with connective tissue disease (CTD) (25%). Limitation of Use: Adding sildenafil to bosentan therapy does not result in any beneficial effect on exercise capacity [ see Clinical Studies ]. Sildenafil is a phosphodiesterase-5 (PDE-5) inhibitor indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening. Studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with NYHA Functional Class II-III symptoms.

Dosage and administration (summary)

Tablet: 20 mg three times a day, 4-6 hours apart Sildenafil Tablets The recommended dose of sildenafil tablets is 20 mg three times a day. Administer sildenafil tablets doses 4-6 hours apart. In the clinical trial no greater efficacy was achieved with the use of higher doses. Treatment with doses higher than 20 mg three times a day is not recommended.

Contraindications

Sildenafil tablets are contraindicated in patients with: • Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [ see Warnings and Precautions ]. • Concomitant use of riociguat, a guanylate cyclase stimulator. PDE-5 inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat. • Known hypersensitivity to sildenafil or any component of the tablet.

Warnings and precautions

• Increased mortality with increasing doses in pediatric patients. Not recommended for use in pediatric patients. • Vasodilation effects may be more common in patients with hypotension or on antihypertensive therapy. • Use in pulmonary veno-occlusive disease may cause pulmonary edema and is not recommended. • Hearing or visual impairment: Seek medical attention if sudden decrease or loss of vision or hearing occurs. ( 5.5 , 5.6 ) • Pulmonary hypertension secondary to sickle cell disease: Sildenafil may cause serious vaso-occlusive crises.

Pregnancy

Pregnancy Risk Summary Limited published data from randomized controlled trials, case-controlled trials, and case series do not report a clear association with sildenafil and major birth defects, miscarriage, or adverse maternal or fetal outcomes when sildenafil is used during pregnancy.

Storage and supply

Sildenafil tablets, USP are supplied as white to off-white, film-coated, round tablets containing sildenafil citrate equivalent to the nominally indicated amount of sildenafil as follows: Sildenafil Tablets Package Configuration Strength NDC Debossing on Tablet Bottle of 30 Tablets 20 mg 76420-061-30 repackaged from NDC 33342-121-10 “C 89” Bottle o…

Source: Sildenafil (Sildenafil) — US FDA prescribing information, 2022-08-31, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.