Sildenafil 100mg

Sildenafil may potentiate the hypotensive effects of organic nitrates, and is therefore contraindicated in patients receiving such drugs. Concomitant administration of Sildenafil with drugs that inhibit the cytochrome P450 isoenzyme CYP3A4, such as cimetidine, erythromycin, itraconazole, ketoconazole, and HIV-protease inhibitors may reduce Sildenafil clearance necessitating a reduction in dosage. However, plasma concentrations of Sildenafil are significantly increased by ritonavir, requiring even greater dosage reduction, and it is therefore strongly recommended that these two drugs are not given together.

  • Antivirals: Rises in Sildenafil concentrations following concomitant administration of saquinavir or ritonavir were consistent with inhibition of metabolism mediated by the cytochrome P450 isoenzyme CYP3A4. The larger increases seen with ritonavir may be due to its additional inhibition of the isoenzyme CYP2C9. Death following myocardial infarction has been reported in a 47-year-old patient who took Sildenafil 25mg concomitantly with ritonavir and saquinavir.
  • Nitrates: Administration of Sildenafil 50mg to patients receiving isosorbide mononitrate, or sublingual administration of glyceryl trinitrate 1 hour after Sildenafil, resulted in substantially greater decreases in blood pressure than when the nitrate was administered alone in 2 crossover studies in patients with angina. Treatment-related adverse effects were reported in 8 of 16 patients who took Sildenafil with isosorbide mononitrate and 3 of 15 who received Sildenafil with glyceryl trinitrate. The authors confirmed that Sildenafil should not be taken concomitantly with nitrates.

Effects of Sildenafil on other medicinal products: In vitro studies: Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50>150µM). Given Sildenafil peak plasma concentrations of approximately 1 µM after recommended doses, it is unlikely that Sildenafil will alter the clearance of substrates of these isoenzymes.

In vitro studies: No significant interactions were shown with Tolbutamide (250mg) or warfarin (40mg), both of which are metabolized by CYP2C9.

  • Sildenafil (50mg) did not potentiate the increase in bleeding time caused by aspirin (150mg).
  • Sildenafil (50mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08%.

No interaction was seen when Sildenafil (100mg) was co-administered with amlodipine in hypertensive patients. The mean additional reduction on supine blood pressure (systolic-8mmHg, diastolic-7mmHg) was of a similar magnitude to that seen when Sildenafil was administered alone to healthy volunteers.

Analysis of the safety database has shown no difference in the side effect profile in patients taking Sildenafil with and without anti-hypertensive medication.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINE

No studies on the effects on the ability to drive and use machines have been performed. As dizziness and altered vision were reported in clinical trials with Sildenafil, patients should be aware of how they react to Sildenafil, before driving or operating machinery.

  • Women: Sildenafil is not indicated in pregnant women.
  • Pediatrics: Sildenafil is not indicated in children.
  • Pregnancy: There are no adequate and well controlled studies of Sildenafil in pregnant women. Sildenafil is not indicated in pregnant women.
  • Lactation: Sildenafil is not indicated in nursing mothers.

ADVERSE EFFECTS

Sildenafil citrate was administered to over 3700 patients (aged 19-87 years) during clinical trials worldwide; over 550 patients were treated for a period longer than one year. In placebo controlled clinical studies the discontinuation rate due to adverse events for Sildenafil citrate (2.5%) was not significantly different from placebo (2.3%). The adverse events were generally transient and mild to moderate in nature. In case of oral jelly preparation patient is expected to report similar adverse effects like those occurring with the other oral dosage forms.

Adverse effects most commonly reported from Sildenafil are headache, flushing, and dyspepsia. There may be visual disturbances, dizziness, and nasal congestion. Other adverse effects reported included diarrhea, muscle pain, skin rashes, and urinary- or respiratory-tract infection. Priapism has also occurred. There have also been reports of serious cardiovascular events, including sudden cardiac death, associated with the use of Sildenafil.

Effects on the cardiovascular system:

There has been considerable uncertainty about the potential cardiovascular risk associated with Sildenafil treatment. Minor effects associated with vasodilation, such as headache and flushing are relatively common, but in patients without pre-existing cardiovascular risk factors the risk of serious cardiovascular events associated with the drug appears to be low. However, there has been a report of myocardial infarction in a patient without apparent risk factors that patients with erectile dysfunction are mostly over 65 years of age and are more likely to have risk factors predisposing them to cardiovascular disease.

Effects on eyes: A bluish tinge or haze to vision and some increased light sensitivity has been reported by a significant percentage of patients taking Sildenafil, with the percentage of reports increasing with increasing dose. The visual symptoms usually peak after 1 to 2 hours following ingestion and resolve about 3 to 4 hours later.

The following events occurred in < 2% of patients in controlled clinical trials; a causal relationship to Sildenafil in uncertain. Reported events include those with a plausible relation to drug use, omitted are minor events and reports too imprecise to be meaningful.

  • Body as whole: face edema, photosensitivity reaction, shock, asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain, and accidental injury.
  • Cardiovascular: Angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram, cardiomyopathy
  • Digestive: Vomitting, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, liver functions test abnormal, rectal hemorrhage, gingivitis
  • Hemic and Lymphatic: Anemia and leucopenia

Metabolic and nutritional: Thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia Musculoskeletal: Arthritis, arthrosis, myalgia, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis

  • Nervous: Ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, somnolence, abnormal dreams, refluxes decreased, hypesthesia
  • Respiratory: Asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, and cough increased
  • Skin and appendages: Urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis
  • Special senses: Mydriasis, conjunctivitis, photophobia, tinnitus, eye pain, deafness, ear pain, eye hemorrhage, cataract, dry eyes
  • Urogenital: Cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema and anorgasmia

OVERDOSAGE

In single dose volunteer studies of doses up to 800mg, adverse reactions were similar to those seen at lower doses, but the incidence rates and severities were increased. Doses of 200mg did not result in increased efficacy but the incidence of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, altered vision) was increased.

In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance as Sildenafil is highly bound to plasma proteins and not eliminated in the urine.