Sildenafil

Treatment of pulmonary arterial HTN (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening.

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.

Special Populations: Patients with hepatic or renal impairment (creatinine clearance <30 mL/min): 25 mg.

Hypersensitivity.Organic nitrates in any form, either regularly/intermittently, because of the greater risk of hypotension.

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

Not recommended in children. Vasodilatory effects may adversely affect patients with resting hypotension (BP <90/50), fluid depletion, severe left ventricular outflow obstruction, or autonomic dysfunction. Not recommended with pulmonary veno-occlusive disease (PVOD); consider possibility of associated PVOD if signs of pulmonary edema occur. Safety not known in patients with bleeding disorders or active peptic ulceration. Non-arteritic anterior ischemic optic neuropathy (NAION) reported; seek immediate medical attention if sudden loss of vision in one or both eyes occurs. Caution with previous NAION in one eye and with retinitis pigmentosa. Cases of sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness, reported. Caution in patients with anatomical penile deformation (eg, angulation, cavernal fibrosis, Peyronie's disease) or with predisposition to priapism (eg, sickle cell anemia, multiple myeloma, leukemia). Penile tissue damage and permanent loss of potency may result if priapism is not immediately treated. Vaso-occlusive crises requiring hospitalization reported in patients with pulmonary HTN secondary to sickle cell disease. Caution in elderly. (Inj) Used as continued treatment in patients currently taking tab/susp and who are temporarily unable to take PO medication.

Headache,dyspepsia,edema, epistaxis, diarrhea, insomnia, flushing, pyrexia,myalgia, rhinitis, respiratory tract infection, angina pectoris, AV block, migraine, syncope,erythema, tachycardia, postural hypotension, MI, cerebral thrombosis, cardiac arrest, nasal congestion, paraesthesia, tremor, depression, herpes simplex, skin ulcer, oesophagitis, abnormal LFT, rectal haemorrhage, hypoglycaemic reaction, arthritis, deafness, retinal vascular disease, photosensitivity, accidental fall.

Overdose: Should be managed by standard supportive care.

See Contraindications. Vasodilatory effects may adversely affect patients on antihypertensive therapy; monitor BP when given with antihypertensives. Reports of epistaxis with oral vitamin K antagonists. Retinal and eye hemorrhage reported with anticoagulants. Avoid with other PDE5 inhibitors (eg, Viagra). Not recommended with ritonavir and other potent CYP3A inhibitors. Increased clearance with CYP3A and CYP2C9 inducers. Decreased clearance with CYP3A and CYP2C9 inhibitors. Expected to cause substantial decrease in plasma levels with potent CYP3A inducers. Reduced clearance with mild/moderate CYP3A inhibitors and β-blockers. Increased exposure with CYP3A inhibitors (except for potent inhibitors eg, ketoconazole, itraconazole, and ritonavir). Increased clearance with mild CYP3A inducers. Slight decrease of sildenafil exposure with epoprostenol. Infrequent reports of patients who experienced symptomatic postural hypotension when given with α-blocker doxazosin. Additional reduction of supine BP with oral amlodipine reported.

Potentially Fatal: May potentiate hypotensive effects of of organic nitrates and nicorandil.

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. increases cGMP within pulmonary vascular smooth muscle cells resulting in vasodilation of pulmonary vascular bed and, to a lesser degree, vasodilation in the systemic circulation.
Absorption: Rapidly absorbed after oral admin. Bioavailability: about 40%.
Distribution: Widely distributed. Plasma protein binding: 96%.
Metabolism: Metabolised in the liver mainly by CYP3A4 and CYP2C9.
Excretion: Excreted as metabolites mainly in the faeces. 

B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.