Bal Pharma


ECE Pharma


Full Prescribing Info
Sildenafil citrate.
Each SEREGRA 50 mg film-coated tablet contains: Sildenafil Citrate equivalent to Sildenafil 50 mg.
Each SEREGRA 100 mg film-coated tablet contains: Sildenafil Citrate equivalent to Sildenafil 100 mg.
Sildenafil citrate is a white to off-white crystalline powder with a solubility or 3.5 mg/mL in water and a molecular weight of 666.7.
Sildenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Sildenafil tablets are formulated as blue, diamond-shaped film coated tablets equivalent to 50 mg and 100 mg of Sildenafil for oral administration.
Pharmacology: Pharmacodynamics: Mechanism of Action: Sildenafil restores impaired erectile function by increasing blood flow to the penis, in response to sexual stimulation. Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but enhances the relaxant effect of nitric oxide (NO) on this tissue. When the NO/cGMP pathway is activated, during sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP, producing smooth muscle relaxation in the corpus cavernosum allowing the inflow of blood. Sildenafil at recommended doses has no effect in the absence or sexual stimulation.
Pharmacokinetics: Absorption: Sildenafil is rapidly absorbed after oral administration. Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) or oral dosing in the fasted state. The mean absolute oral bioavailability is 41% (range 25-63%). After oral dosing of sildenafil AUC and Cmax increase in proportion with dose over the recommended dose range (25-100 mg), When sildenafil is taken with food, the rate or absorption is reduced with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 2.9%.
Distribution: The mean steady state volume of distribution (Vd) for sildenafil is 105 l, indicating distribution into the tissues. After a single oral dose of 100 mg, the mean maximum total plasma concentration of sildenafil is approximately 440 ng/ml (CV 40%). Since sildenafil (and its major circulating N-desmethyl metabolite) is 96% bound to plasma proteins, this results in the mean maximum free plasma concentration for sildenafil of 18 ng/ml (38 nM). Protein binding is independent of total drug concentrations.
Metabolism: Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes. The major circulating metabolite results from N-demethylation of sildenafil.
This metabolite has a phosphodiesterase selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% that of the parent drug. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil. The N-desmethyl metabolite is further metabolised, with a terminal half life of approximately 4 h.
Elimination: The total body clearance of sildenafil is 41 l/h with a resultant terminal phase half life of 3-5 h. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the faeces approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of administered oral dose).
Pharmacokinetics in Special Patient Groups: Elderly: Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, with free plasma concentrations approximately 40% greater than those seen in healthy younger volunteers (18-45 years).
Renal Insufficiency: In volunteers with mild (Clcr=50-80 mL/min) and moderate (Clcr=30-49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of Sildenafil were not altered. In volunteers with severe (Clcr <30 mL/min) renal impairment, sildenafil clearance was reduced, resulting in increases in AUC (100%) and Cmax (88%) compared to age-matched volunteers with no renal impairment.
Hepatic Insufficiency: In volunteers with hepatic cirrhosis (Child-Pugh A and B) sildenafil clearance was reduced, resulting in increases in AUC (84%) and Cmax (47%) compared to age-matched volunteers with no hepatic impairment.
Sildenafil is indicated for the management of erectile dysfunction.
Dosage/Direction for Use
It is given orally as the citrate although doses are expressed in terms of the base; 14 mg of sildenafil citrate is equivalent to about 10 mg of sildenafil.
In erectile dysfunction the usual dose is equivalent to sildenafil 50 mg about one hour before sexual intercourse. The dose may be increased or decreased depending on response. The maximum recommended dose is 100 mg, and sildenafil should not be taken more than once in 24 hours.
An initial dose of no more than 25 mg daily is advised in patients taking sildenafil with inhibitors of cytochrome P450 isoenzyme CYP3A4; the dose should not exceed 25 mg every 48 hours if given with ritonavir-boosted HIV-protease inhibitors, although such combination is best avoided entirely.
In patients stabilised on alpha blocker therapy, an initial dose of sildenafil 25 mg should be considered.
To improve exercise ability in pulmonary arterial hypertension, sildenafil is given orally in a dose of 20 mg three times daily. The dose may need adjustment to account for drug interactions (see Interactions) although licensed product information suggests that in these patients no adjustment is required when sildenafil is given with erythromycin or saquinavir. It also suggests that no adjustment is generally needed for pulmonary hypertension patients with renal or hepatic impairment, although patients with severe hepatic impairment (Child-Pugh category C) have not been studied.
Use in the Elderly and in Patients with Impaired Renal or Hepatic Function: Elderly (65 years or over), hepatic impairment and severe renal impairment (creatinine clearance <30 mL/min) are associated with higher plasma levels which may increase both the efficacy and incidence of adverse events. A starting dose of 25 mg should be considered in these patients.
Use in Women and Children: Sildenafil is not indicated for use in women and children.
The symptoms of overdose are similar to that of adverse effects with increase in incidence rates and severities. 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 it is not eliminated in the urine.
Sildenafil is contraindicated in patients with a known hypersensitivity to any component of the tablets.
Sildenafil was shown to potentiate the hypotensive effects of nitrates, either regularly and/or intermittently, in any form is therefore contraindicated.
There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatment for erectile dysfunction, including Sildenafil, should not be generally used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. Sildenafil has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg. While this normally would be expected to be of little consequence in most patients, prior to prescribing Sildenafil, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects, especially in combination with sexual activity.
Patients with the following underlying conditions can be particularly sensitive to the actions of vasodilators including Sildenafil - those with left ventricular outflow obstruction (e.g. aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely Impaired autonomic control of blood pressure. There is no controlled clinical data on the safety or efficacy of Sildenafil in the following groups; if prescribed, this should be done with caution.
Patients who have suffered a myocardial Infarction, stroke, or life-threatening arrhythmia within the last 6 months; Patients with resting hypotension (BP <90/50) or hypertension (BP >170/110); Patients with cardiac failure or coronary artery disease causing unstable angina; Patients with retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases); Patients with sickle cell or related anemias.
Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently.
In the event of an erection that persists longer than 11 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.
Special Precautions
General: The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment. Before prescribing Sildenafil, it is important to note the following - caution is advised when Phosphodiesterase Type 5 (PDE5) inhibitors (including Sildenafil) is co-administered with alpha-blockers as both are vasodilators with blood pressure lowering effects which in some patients could lead to symptomatic hypotension (e.g. dizziness, lightheadedness, fainting). Sildenafil has systemic vasodilatory properties and may augment the blood pressure lowering effect of other antihypertensive medications.
The safety and efficacy of combinations of Sildenafil with other treatments for erectile dysfunction have not been studied. Therefore the use of such combinations is not recommended. Sildenafil has no effect on bleeding time, including during co-administration with aspirin. In vitro studies with human platelets indicate that sildenafil potentiates the anti-aggregatory effect of sodium nitroprusside (a nitric oxide donor). There is no safety Information on the administration of Sildenafil to patients with bleeding disorders or active peptic ulceration. Therefore Sildenafil should be administered with caution to these patients.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Sildenafil was not carcinogenic when administered to rats for 24 months. Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity. There was no impairment of fertility in rats given sildenafil up to 60 mg/kg/day.
Pregnancy, Nursing Mothers and Pediatric Use: Sildenafil is not indicated for use in newborns, children, or 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.
Adverse Reactions
Headache, flushing, dyspepsia, nasal congestion, urinary tract infection, blurred vision, diarrhea, dizziness, rash are the common adverse effects in patients using Sildenafil tablets.
Cardiovascular: angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram, cardiomyopathy.
Digestive: vomiting. glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, liver function tests abnormal, rectal hemorrhage, gingivitis, hemorrhage, gingivitis.
Hemic and lymphatic: anemia and leukopenia.
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, reflexes decreased, hypesthesia.
Respiratory: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased.
Skin and Appendages: urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis.
Special Senses: sudden decrease or loss of hearing, mydriasis, conjunctivitis, photophobia, tinnitus, eye pain, ear pain, eye hemorrhage, cataract, dry eyes.
Urogenital: cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema and anorgasmia.
Drug Interactions
Sildenafil metabolism is principally mediated by the cytochrome P4S0 (CYP) isoforms 3A4 (major route) and 2C9 (minor route).
Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and Inducers of these isoenzymes may increase sildenafil clearance.
Although the interaction between other protease inhibitors and sildenafil has not been studied, their concomitant use is expected to increase sildenafil levels.
No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolized by CYP2C9.
Sildenafil does not potentiate the increase in bleeding time caused by aspirin (150 mg). Sildenafil does not potentiate the hypotensive effect of alcohol. Sildenafil does not affect the steady state pharmacokinetics of the HIV protease inhibitor, saquinavir and ritonavir, both of which are metabolized by CYP2C9. No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolized by CYP2C9.
Store at temperatures not exceeding 30°C. Protect from light,
ATC Classification
G04BE03 - sildenafil ; Belongs to the class of drugs used in erectile dysfunction.
FC tab 50 mg x 4's. 100 mg x 4's.
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