The most commonly reported adverse reactions were headache, flushing and dyspepsia. Others include dizziness, vomiting, diarrhea, hypotension, tachycardia syncope, epistaxis, nasal congestion, hypersensitivity reactions (including skin rash), eye pain, red eyes/bloodshot eyes, muscle/back pain and prolonged erection and/or priapism. The adverse events were generally transient and mild to moderate in nature. Other adverse effects include urinary tract infection, cerebrovascular hemorrhage and transient ischemic attacks.
In fixed-dose studies, the incidence of some adverse effects increased with dose. The nature of the adverse effects in flexible-dose studies, which more closely reflect the recommended dosage regimen was similar to that for fixed-dose studies. At doses above the recommended range, adverse events were similar to those detailed previously but generally were reported more frequently.
Special Patient Groups: Healthy elderly volunteers (≥65 years) had a reduced clearance of Sildenafil, with free plasma concentrations approximately 40% greater than those seen in healthy younger volunteers (18-45 years). A pooled analysis of a large number of studies showed that age had no clinically important effect on the incidence of adverse effects.
Toxicology: No evidence of drug-related carcinogenicity was seen in a 24-month study in rats subjected to doses of up to 42x the maximum recommended human dose (MRHD) on a mg/kg basis and approximately 5x the MRHD on a mg/m2 basis. In an 18 to 21-month study in mice subjected to doses up to 21x the MRHD on a mg/kg basis (approximately 2x the MRHD on a mg/m2 basis), bacterial and in vivo mutagenicity tests were negative. There was no effect on sperm motility or morphology after single 100-mg oral doses of Sildenafil in healthy volunteers. No teratogenic effects, impairment of fertility or adverse effects on peri-/postnatal development were found in reproduction studies in animal studies (on rats and rabbits) following oral administration of Sildenafil.