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VEGA
F. Ctd. Tab (50 mg / 100mg)
COMPOSITION:
Each film coated tablet contains : sildenafil 50-ma ( as citrate )
PROPERTIES:
The physiological mechanism of erection o1 the penis involves release of nitric oxide (NO) in the corpus cavernosum
during sexual stimulation NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic
guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing
inflow of blood.
Sildenafil has no direct relaxant effect on isolated human corpus cavernosum. but enhances the effect of nitric oxide
INO) by inhibiting phosphodiesterase type 5 (PDE5).which is responsible for degradation of cGMP in Ihe corpus
cavemosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased
levels of cGMP in the corpus cavernosum. resulting in smooth muscle relaxation and inflow of blood to the corpus
cavernosum Sildenafil at recommended doses has no effect in the absence of sexual stimulation
Studies in vitro nave shown that sildenafil is selective for PDE5 Its effect is more potent on PDE5 than on other known
phosphodiesterases (>80-fold tor PDE1, > 1,000-fold tor PDE2, PDE3. and PDE4). The approximately 4000-fold
selectivity for PDE5 versus PDE3 is important because that PDE is involved in control of cardiac contractility. Sildenafil
is only about 10 fold as potent for PDE5 compared to PDE6 an enzyme found in the retina: this lower selectivity is
thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels
PHARMACOKINETICS AND METABOLISM: ^aariawve.s
Sildenafil is rapidly absorbed after oral administration, with absolute bioavailabilily of about 40% It is eliminated
predominantly by hepatic metabolism (mainly cylochrome P450 3A4) and is converted to an active metabolite with
properties similar to the parent, sildenafil. Both sildenafil and the metabolite have terminal half-lives of about 4 hours
Absorption and distribution: sildenafil is rapidly absorbed Maximum observed plasma concentrations are reached
within 30 to 120 minutes (median 60 minutes) of oral dosing in the lasted state When Sildenalil is taken with a high fat
meal, the rate of absorption is reduced, with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 29%
The mean steady state volume of distribution (Vss) lor sildenafil is 105 I. indicating distribution into the tissues.
Stidenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins
Protein binding is independent of total drug concentrations.
Based upon measurements of Sildenafil in semen of healthy volunteers 90 minutes after dosing less than 0.001% of
the administered dose may appear in the semen of patients
Metabolism and Excretion: Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route)
hepatic microsomal isoenzymes The major circulating metabolite results from N-desmethylation of sildenafil and is
itself further metabolized. This metabolite has a selectivity profile similar to sildenafil and an in vitro potency for PDE5
approximately 50% of the parent drug Plasma concentrations of this metabolite are approximately 40% of those seen
for sildenafil. so that the metabotite accounts for about 20°'o of sildenafil's pharmacologic effects.
After either oral or intravenous administration, sildenatil is excreted as metabolites predominantly in the feces
(approximately 80% of administered oral dose), and to a lesser extent in the urine (approximately 13% of administered
oral dose)
Pharmacokinetic in Special Populations
Geriatrics: Healthy elderly volunteers (65 years or over) had a reduced clearance of sUdenalil. 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
mpairment, the pharmacokinetics of a single oral dose of sildenafil (.50 mg) were not altered, in volunteers with severe
(CLcr = <30 mL/min) renal impairment, sildenafil clearance was reduced, resulting in approximately doubling of AUC
and Cmax compared to age-matched volunteers with no renal impairment
Hepatic insufficiency: In volunteers with hepatic cirrhosis sildenafil clearance was reduced, resulting in increases in
AUC (84%) and C max (47%) compared to age-matched volunteers with no hepatic impairment.
Pregnants, Nursing mothers, Children: Sildenafil is contraindicated in infants, children and women
INDICATION AND USAGE
Sildenafil is indicated for the treatment of erectile dysfunction The studies that established benefits demonstrated
improvements in success rates for sexual intercourse compared with placebo
CONTRAINDICATIONS
Use of sildenafil is contraindicated in patients with a Known hypersensitivity to any components of the tablet
Consistent with its known effects on the nitric oxide/cGMP/ pathway, sildenafil was shown to potentiate the hypotensive
effects of nitrates, and its administration to patients who are concurrently using organic nitrates in any form is therefore
contraindicated,
PRECAUTIONS
A thorough medical history and physical examination should be undertaken to diagnose erectile dysfunction, determine
potential underlying causes, and identify appropriate treatment.
There is a degree of cardiac risk associated with sexual activity; therefore, physicians may wish to consider the
cardiovascular status of their patients prior to initiating any treatment tor erectile dysfunction.
Agents for the treatment of erectile dysfunction should be used wuth caution with anatomical deformation of the 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 with other treatments for erectile dysfunction have not been studied.
Therefore, the use of such combinations is not recommended.
Sildenafi) has no effect on bleeding time 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). There is no safety
information on the administration of sildenan) to patients with bleeding disorders or active peptic ulceration. Therefore,
sildenafil should be administered with caution to these patients.
A minority of patients with the inherited condition retinitis pigmentosa have genetic disorders of retinal phosphodieste
rases. There is no safety information on the administration of sildenafil to patients with retinitis pigmentosa. therefore,
sildenatil should be administered with caution to these patients.
Drug Interactions
Effects of Other Drugs on Sildenafil
Population data from patients in clinical thals did Indicate a reduction in sildenafil clearance when it was co-administered
with CYP3A4 inhibitors (such as ketoconazole, erythromyciniJ) cimetidine). It can be expected that concomitant
administration of CYP3A4 inducers, such as fitampin. will decrease plasma levels of sildenafil,
Single doses of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil
Pharmacokinetic data from patients in clinical trials showed no effect on sildenafil pharmacokinetics of CYP2C9
inhibitors (such as totbutamide, warfarin}, CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic
antidepressants), thiazide and related diuretics, ACE inhibitors, and calcium channel blockers,
Effects of Sildenafil on Other Drugs
No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolized by
Sildenafit (50 mg) did not potentiate the Increase in bleeding time caused by aspirin (150 mg).
No interaction was seen when sildenafil was co-administered with amiodipine in hypertensive patients.
SIDE EFFECTS
When sildenafil was taken as recommended (on an as-needed basis) the following adverse events were reported:
Headache16 %, Flushing 10%, Dyspepsia 7 %. Nasal Congestion 4 %. Urinary Tract Infection 3 %, Abnormal Vision 3%,
Diarrhea 3 %, Dizziness 2 %. Rash 2 %,
Other adverse reactions occurred at rate of >2% such as respiratory tract Infection, back pain. flu syndrome and
arthralgia.
Sildenafil caused some rare cases such as: allergic reaction, face edema, photosensitlvity reaction, migraine.
tachycardia, angina pectoris. palpitation, heart failure, abnormal electrocardiogram, glossitis, stomatitis, vomiting,
anemia, leukopenla. thirst, gout, arthritis, myalgia, neuralgia, paresthesia,tremor,vertigo, depression, dyspenea.
laryngitis, pharyngitis, pruritis. dermatitis, nocturia, urinary frequency, urinary incontinence, genital edema
In studies with healthy volunteers of single doses up to 800 mg. adverse events were similar to those seen at lower
doses but incidence rates were 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 it is not eliminated in the urine
DOSAGE AND ADMINISTRATION
For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity
However, VEGA may be taken anywhere from 4 hours to 0.5 hour before sexual activity Based on effectiveness and
toleration, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg,
The maximum recommended dosing frequency is once per day The following factors are associated with increased
plasma levels of sildenafil: age >65 (40% increase in AUC), hepatic impairment (e.g. cirrhosis, 80%) severe renal
impairment (creatinine clearance <30mL/min. 100%). and concomitant use of potent cytochrome P450 3A4 inhibitors
(erythromycin, ketoconazole, itraconazole, 200%). Since higher plasma levels may increase both the efficacy and
incidence of adverse events, a starting dose of 25 mg shouTd be considered in these patients.
VEGA was shown to potentiate the hypotensive effects of nitrates and its administration in patients who use nitric oxide
donors or nitrates in any form is therefore contraindicated.
PACKAGES
A pack contains 4 film - coated tablets.50 mg / 1OOmg. -
IMPORTANT NOTES
Keep in cool and dry place out of reach of children
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