sildenafil-citrate and Drug-Overdose

To review special safety topics associated with sildenafil and to document the tolerability of 50- and 100-mg doses, overall and by age, in men with erectile dysfunction (ED).. Data were collated from 67 double-blind placebo-controlled (DBPC) trials (> 14,000 men) conducted by the manufacturer and from the manufacturer's postmarketing safety database (39,277 patients). The DBPC data were stratified by dose, starting dose and age (> or = 65 and > or = 75 years). Special safety topics included cardiovascular risk, priapism, non-arteritic anterior ischaemic optic neuropathy (NAION), impaired renal and hepatic function, drug interactions (i.e. nitrates, cytochrome P3A4 inhibitors, other ED therapies and alpha-blockers) and incorrect use.. Sildenafil was well tolerated at a dose of 50 or 100 mg in men with ED, overall, in those aged > or = 65 years, and in those aged > or = 75 years. Analyses of the databases did not reveal any causal link between sildenafil and cardiovascular events, or any new safety risks relating to cardiovascular events, priapism, NAION, hearing loss or drug interactions. In the small number of men with moderate impairment of renal function or hepatic function who were treated with sildenafil in DBPC trials, the safety profile was similar to that in men with no impairment of renal or hepatic function. Overdose with sildenafil was rare in the ED population. No new safety issues, emerging trends or adverse reactions were identified in conjunction with overdose, dependence, abuse or misuse.. This collated review confirms generally the good tolerability and established safety profile of sildenafil 50 and 100 mg in men with ED and reveals no new safety issues.

Topics: Aged; Cardiovascular Diseases; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Drug Overdose; Erectile Dysfunction; Hearing Disorders; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Priapism; Product Surveillance, Postmarketing; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Treatment Outcome

A fatal case of sildenafil citrate (Viagra) overdosage is presented. The deceased was a 56-year old male found dead at home, with a past history of diabetes mellitus, hypertension, chronic alcoholism, anxio-depressive disorders, and erectile dysfunction. The main autopsy findings were cardiomegaly (650 g) with dilated cardiomyopathy, diffuse coronary atherosclerosis with no sign of acute ischaemic disease, and extensive fibrosis of the myocardium, especially affecting the cardiac conducting tissue. As measured by HPLC/MS, sildenafil concentration in postrmortem blood (6.27 microg/mL) exceeded at least four times the highest therapeutic levels previously reported. The results are discussed in the light of the literature about the cardiovascular side effects of sildenafil, with special emphasis on the recently evidenced arrhythmogenic potential of the drug. This is the first report of a fatality caused by sildenafil overdosage.

Topics: Alcoholism; Autopsy; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Diabetes Complications; Drug Overdose; Fatal Outcome; Humans; Male; Mass Spectrometry; Middle Aged; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Adult; Alcoholic Beverages; Chromatography, High Pressure Liquid; Drug Contamination; Drug Overdose; Homosexuality, Male; Humans; Illicit Drugs; Male; Sexual Partners; Sildenafil Citrate; Sodium Oxybate; Tandem Mass Spectrometry

The phosphodiesterase type 5 inhibitor, sildenafil, is not generally known for its use as a self-poisoning drug. However, intoxication cases with lethal outcome have been described. The case presented here is of a 56-year-old man who claimed to have undertaken an unsuccessful suicide attempt by mono-ingestion of 65 tablets of 100 mg sildenafil. He arrived at the emergency department 24 h after intake with severe vomiting and symptoms of blurred vision. Clinical examination revealed no priapism. Of note was a sinus tachycardia of 100 bpm without signs of hypotension. To quantify the sildenafil concentration in serum, an high-performance liquid chromatography photo-diode array method was developed and validated according to European Medicines Agency guidelines. The intoxicated patient had a serum concentration of 22.2 µg/mL sildenafil, at the time of presentation, which is far above the therapeutic peak concentration. The serum concentration further declined to 9.2 and 2.3 µg/mL, respectively, 5 and 14 h later, revealing a biological half-life of 4.2 h. To the best of our knowledge, this patient took the highest sildenafil dose, which resulted in the highest serum concentration, ever reported. In this subject, sildenafil showed good tolerability because few symptoms occurred and only moderate supportive therapy was needed for full recovery without sequelae.

Topics: Chromatography, High Pressure Liquid; Drug Overdose; Half-Life; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Substance Abuse Detection; Suicide, Attempted

Sildenafil is used for the treatment of erectile dysfunction and is helping millions of men around the world to achieve and maintain a long lasting erection. Fifty healthy male rabbits (Oryctolagus cuniculus) were used in the present study and exposed daily to sildenafil (0, 1, 3, 6, 9 mg/kg) for 5 days per week for 7 weeks to investigate the biochemical changes and alterations in the hepatic tissues induced by this drug overdosing. In comparison with respective control rabbits, sildenafil overdoses elevated significantly (p-value<0.05, ANOVA test) alanine aminotransferase (ALT), aspartate aminotransferase (AST), testosterone, follicular stimulating hormone and total protein, while creatinine and urea were lowered with no significant alteration was observed in uric acid and luteinizing hormone concentration. Also sildenafil provoked hepatocytes nuclear alterations, necrosis, hydropic degeneration, bile duct hyperplasia, Kupffer cells hyperplasia, inflammatory cells infiltration, hepatic vessels congestion and evident partial depletion of glycogen content. The results show that subchronic exposure to sildenafil overdoses exhibits significant biochemical and alterations in the hepatic tissues that might affect the functions of the liver and other vital organs.

Topics: Animals; Bile Ducts; Biomarkers; Chemical and Drug Induced Liver Injury; Drug Overdose; Hyperplasia; Kupffer Cells; Liver; Liver Function Tests; Male; Necrosis; Phosphodiesterase 5 Inhibitors; Rabbits; Risk Assessment; Sildenafil Citrate; Time Factors; Toxicity Tests

Topics: Drug Overdose; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Rhabdomyolysis; Sildenafil Citrate; Sulfones; Treatment Outcome; Visual Perception

Twenty adult male rabbits (Oryctolagus cuniculus) received sildenafil (0, 1, 3, 6, 9 mg/kg/day) for 4 weeks to investigate the testicular histological alterations induced by overdoses of this drug. Exposure to overdoses of sildenafil had provoked tubular and interstitial histological alterations. Abnormality in the germinal epithelium of the seminiferous tubules included spermatocytes karyopyknosis, spermatocytes degeneration, desquamation, spermatid giant cells and arrest of spermatogenesis. Additionally, increased Leydig cells cellularity, tubular degeneration, thickening of the interstitium were also observed. The encountered histological findings indicate that chronic exposure to sildenafil overdoses produces significant morphological and histological alterations in the testes which finally might lead to complete arrest of spermatogenesis.

Topics: Animals; Drug Overdose; Leydig Cells; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Rabbits; Seminiferous Tubules; Sildenafil Citrate; Sulfones; Testis

We report on a case of combined nonarteritic anterior ischemic optic neuropathy (NAAION) and cilioretinal artery occlusion resulting from misuse of sildenafil citrate (Viagra Pfizer Pharmaceuticals, New York, NY).. This is an observational case report.. A 54-year-old white man developed blindness in his left eye after an overdose of Viagra. He was examined and fully evaluated.. Ocular examinations revealed a left relative afferent pupillary defect and a left combined NAAION and obstruction of the ipsilateral cilioretinal artery.. Although ocular side-effects of Viagra are rare, they are potentially blinding. Patients should be warned about the side-effects and against misuse of this agent.

Topics: Blindness; Drug Overdose; Humans; Male; Middle Aged; Optic Neuropathy, Ischemic; Piperazines; Purines; Retinal Artery Occlusion; Sildenafil Citrate; Sulfones

Topics: Cardiovascular Diseases; Cause of Death; Drug Overdose; Humans; Male; Middle Aged; Piperazines; Product Surveillance, Postmarketing; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Adult; Drug Overdose; Female; Humans; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Suicide, Attempted; Sulfones

Sildenafil (Viagra) has been developed as a drug to help male impotence. It has a direct effect on the vasculature of the corpus cavernosum. A case of spontaneous intracerebral haemorrhage (ICH) following the illicit use of Viagra is reported. A discussion of drug-induced ICH is included.

Topics: Adult; Cerebral Hemorrhage; Drug Overdose; Fatal Outcome; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tomography, X-Ray Computed

Sildenafil is indicated for the treatment of male erectile dysfunction. It has been used successfully in males to remediate problems associated with impaired neural and/or hemodynamic response to sexual stimulation. Sildenafil is a cyclic guanosine-specific phosphodiesterase type 5 inhibitor that prevents the metabolism of cyclic guanosine which produces arterial smooth muscle relaxation within the corpora cavernosa of the penis and ultimately enhances penile tumescence. Inherent to its pharmacology, sildenafil produces mild decreases in systolic and diastolic blood pressure and an array of minimal side effects due to the inhibition of other types of phosphodiesterase. Drug interactions involving the concurrent use of sildenafil with nitrates and nitrites are well-documented and can produce profound hypotension leading to decreased coronary perfusion and myocardial infarction. Sildenafil is metabolized primarily by cytochrome P450 3A4, and inhibitors of this enzyme (e.g., macrolide antibiotics, antifungals, cimetidine) may increase sildenafil serum concentrations and lead to enhanced pharmacological and toxicological effects. The antiviral protease inhibitors have been demonstrated to inhibit first-pass metabolism and increase serum concentrations and half-life of sildenafil.. Previously unpublished data from the American Association of Poison Control Centers Toxic Exposure Surveillance System indicate that unintentional pediatric exposures to sildenafil are unlikely to be associated with adverse effects. Adults may experience effects similar to those identified in the preclinical trials. This may be due to larger doses in this population, preexisting cardiovascular pathology, or the concomitant use of contraindicated medications.

Topics: Adolescent; Adult; Child; Child, Preschool; Drug Interactions; Drug Overdose; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Poison Control Centers; Purines; Sildenafil Citrate; Sulfones