Sildenafil

Indications

Sildenafil is used for: Erectile dysfunction, Pulmonary arterial hypertension

Adult Dose

Oral Erectile dysfunction Adult: 50 mg about 1 hr before sexual intercourse. May adjust dose depending on penile response. Max: 100 mg/dose and not to be taken > once in 24 hr. Elderly: >65 yr: Lower initial dose at 25 mg. Hepatic impairment: Initially, 25 mg. Pulmonary Arterial Hypertension 20 mg 3 times daily, administered 4-6 hours apart

Child Dose

Renal Dose

Renal impairment: CrCl (ml/min) Dosage Recommendation <30 Initially, 25 mg.

Administration

May be taken with or without food.

Contra Indications

Hypersensitivity. Patients concurrently or intermittently using organic nitrates in any form.

Precautions

Caution when used in patients with anatomical deformation of penis or conditions that may predispose them to priapism (e.g. sickle cell anaemia, myeloma, or leukaemia). Mild, transient, dose-related impairment of colour discrimination (blue/green) may occur. Hepatic or severe renal impairment, bleeding disorders, active peptic ulceration, hypotension, recent history of stroke, MI, arrhythmias, unstable angina, heart failure or retinal disorders. May cause sudden loss or decrease in hearing.

Pregnancy-Lactation

Pregnancy 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; there are risks to mother and fetus from untreated pulmonary arterial hypertension Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death Lactation Limited published data from a case report describe presence of sildenafil and its active metabolite in human milk; there is insufficient information about effects of sildenafil on breastfed infant and no information on effects of sildenafil on milk production; limited clinical data during lactation preclude a clear determination of risk of drug to an infant during lactation

Interactions

Inhibitors of CYP3A4 such as cimetidine and erythromycin are likely to reduce sildenafil clearance. CYP3A4 inducers such as rifampicin may decrease the plasma concentrations of sildenafil. Symptomatic hypotension when used with beta-blockers. Plasma concentrations are increased by ritonavir. Potentially Fatal: May potentiate hypotensive effects of of organic nitrates and nicorandil.

Adverse Effects

Side effects of Sildenafil : >10% Headache (7-16%) 1-10% Flushing (4-10%), Epistaxis (8%), Dyspepsia (4-8%), Insomnia (6%), Erythema (5%), Diarrhea (4%), Dizziness (2%), Skin rash (2%)

Mechanism of Action

Sildenafil inhibits phosphodiesterase type-5 (PDE5) which is responsible for cGMP degradation in the corpus cavernosum. Inhibition of PDE5 increases cGMP levels in the corpus cavernosum which results in smooth muscle relaxation and inflow of blood to the corpus cavernosum.