General
The evaluation of erectiledysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment.
Before prescribing sildenafil citrate, it is important to note the following:
– Patients on multipleantihypertensive medications were included in the pivotal clinical trials for sildenafil citrate. In a separate drug interaction study, when amlodipine, 5 mg or 10 mg, and sildenafil citrate, 100 mg were orally administered concomitantly to hypertensive patients mean additional blood pressurereduction of 8 mmHg systolic and 7 mmHg diastolic were noted. Controlled studies of drug interactions between sildenafil citrate and other antihypertensive medications have not been performed.
The safety of sildenafil citrate is unknown in patients with bleeding disorders and patients with active peptic ulceration.
Vegarpi should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie’s disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).
The safety and efficacy of combinations of sildenafil citrate with other treatments for erectiledysfunction have not been studied. Therefore, the use of such combinations is not recommended.
In humans, sildenafil citrate has no effect on bleedingtime when taken alone or with aspirin. In vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside (a nitric oxide donor). The combination of heparin and sildenafil citrate had an additiveeffect on bleedingtime in the anesthetized rabbit, but this interaction has not been studied in humans.
Information for the Patient
Physicians should discuss with patients the contraindication of sildenafil citrate with regular and/or intermittent use of organic nitrates. Physicians should discuss with patients the potentialcardiacrisk of sexual activity in patients with preexisting cardiovascularrisk factors. Patients who experience symptoms (e.g., angina pectoris, dizziness, nausea) upon initiation of sexual activity should be advised to refrain from further activity and should discuss the episode with their physician. Physicians should warn patients that prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of sildenafil citrate. In the event of an erection that persists longer than 4 hours, the patient should seek immediatemedical assistance. If priapism is not treated immediately, penile tissue damage and permanentloss of potency may result. The use of sildenafil citrate offers no protection against sexually transmitted diseases. Counseling of patients about the protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), may be considered.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Sildenafil was not carcinogenic when administered to rats for 24 months at a dose resulting in total systemicdrugexposure (AUCs) for unbound sildenafil and its major metabolite of 29- and 42-times, for male and female rats, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 100 mg. Sildenafil was not carcinogenic when administered to mice for 18-21 months at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.6 times the MRHD on a mg/m2 basis.
Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mousemicronucleus assays to detect clastogenicity.
There was no impairment of fertility in rats given sildenafil up to 60 mg/kg/day for 36 days to females and 102 days to males, a dose producing an AUCvalue of more than 25 times the humanmale AUC.
There was no effect on sperm motility or morphology after single 100 mg oral doses of sildenafil citrate in healthy volunteers.
Pregnancy, Nursing Mothers, and Pediatric Use
Sildenafil citrate is not indicated for use in newborns, children, or women.
Pregnancy Category B: No evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits which received up to 200 mg/kg/day during organogenesis. These doses represent, respectively, about 20 and 40 times the MRHD on a mg/m2 basis in a 50 kg subject. In the rat pre- and postnataldevelopment study, the no observed adverse effect dose was 30 mg/kg/day given for 36 days. In nonpregnant rat the AUC at this dose was about 20 times human AUC. There are no adequate and well-controlled studies of sildenafil in pregnant women.
Geriatric Use
Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil. Since higher plasma levels may increase both the efficacy and incidence of adverse events, a starting dose of 25 mg should be considered.