- UROGENITAL DRUGS
- Urogenital drugs
- Pharmaceutical Form : Film coated tablets
- Composition : Vardenafil Hcl 10 mg/Tab
- Active Substance : Vardenafil Hcl
Mechanism of Action:
Vardenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5).
The inhibition of PDE5 enhances erectile function by increasing the amount of cyclic guanosine monophosphate (cGMP).
The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection.
Absorption: Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%.
Distribution: The mean steady-state volume of distribution (Vss) for vardenafil is 208 L, indicating extensive tissue distribution.
Metabolism: Vardenafil is metabolized predominantly by the hepatic enzyme CYP3A4, with contribution from the CYP3A5 and CYP2C isoforms.
Excretion: The total body clearance of vardenafil is 56 L/h, vardenafil is excreted as metabolites predominantly in the feces (approximately 91-95% of administered oral dose) and to a lesser extent in the urine (approximately 2-6% of administered oral dose).
VARI STRONG is indicated for the treatment of erectile dysfunction (impotence).
Nitrates: Administration of VARI STRONG with nitrates (either regularly and/or intermittently) and nitric oxide donors is contraindicated.
phosphodiesterase type 5 inhibitors ( PDE5 inhibitors) may potentiate the hypotensive effects of nitrates. A suitable time interval following VARI STRONG dosing for the safe administration of nitrates or nitric oxide donors has not been determined.
Hypersensitivity: VARI STRONG is contraindicated for patients with a known hypersensitivity to any component of the tablet.
The chance of having a side effect is described by the following categories:
-Indigestion – Feeling sick (nausea)
-Dizziness – Blocked or runny nose
-Sensitivity of the skin to sunlight -High or low blood pressure
-Back or muscle pain – Effects on vision
-Bloodshot or watery eyes – Rash
-Effect in results of blood tests to check liver function
-Increase in blood of a muscle enzyme (creatine phosphokinase)
-Fast heart beat or pounding heart
-Increase pressure in the eye (glaucoma)
-Prolonged or painful erections
-Effects on the heart (such as angina)
-Swelling inside the throat
-Temporary loss of memory (such as transient global amnesia)
Partial, sudden, temporary or permanent decrease or loss of vision in one or both eyes has been experienced by patients.
Sudden decrease or loss of hearing has been reported.
General: Physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. In men for whom sexual activity is not recommended because of their underlying cardiovascular status, any treatment for erectile dysfunction, including VARI STRONG, generally should not be used.
Left Ventricular Outflow Obstruction:
Patients with left ventricular outflow obstruction, e.g., aortic stenosis and idiopathic hypertrophic subaortic stenosis, can be sensitive to the action of vasodilators including Type 5 phosphodiesterase inhibitors.
Blood Pressure Effects:
VARI STRONG has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers. Prior to prescribing VARI STRONG, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects.
There have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds, including vardenafil. In the event that an erection persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.
Drug and Food Interactions
Some medicines may be affected by VARI STRONG or vice versa. These medicines include:
-ketoconazole and itraconazole, (used to treat fungal infections) A 5-mg VARI STRONG dose should not be exceeded when used in combination with 200 mg once daily ketoconazole. A single 2.5 mg dose of VARI STRONG should not be exceeded in a 24-hour period when used in combination with ketoconazole 400 mg daily
-erythromycin (an antibiotic) It is recommended not to exceed a single 5 mg dose of VARI STRONG in a 24-hour period when used in combination with erythromycin
-alpha-blockers, medicines used to treat an enlarged prostate (BPH) or high blood pressure. Examples of alpha-blockers are terazosin, tamsulosin and prazosin. VARI STRONG can be used together with an alpha blocker if treatment with an alpha blocker is stable.
-HIV Protease Inhibitors: Concomitant administration with ritonavir or indinavir substantially increases plasma concentrations of vardenafil.
- Indinavir (800 mg t.i.d.). It is recommended not to exceed a single 2.5 mg VARI STRONG dose in a 24-hour period when used in combination with Indinavir.
- Ritonavir (600 mg b.i.d.). it is recommended not to exceed a single 2.5 mg VARI STRONG dose in a 72-hour period when used in combination with ritonavir
-Other CYP3A4 inhibitors: other CYP3A4 inhibitors, including grapefruit juice would likely increase vardenafil exposure.
-Nifedipine: Vardenafil 20 mg, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the relative bioavailability or maximum concentration of nifedipine. And Nifedipine did not alter the plasma levels of VARI STRONG
-Alcohol: Alcohol and vardenafil plasma levels were not altered when dosed simultaneously.
-Aspirin: VARI STRONG did not potentiate the increase in bleeding time caused by aspirin.
For most patients, the recommended starting dose of VARI STRONG is 10 mg, taken orally approximately 60 minutes before sexual activity. The dose may be increased to a maximum recommended dose of 20 mg or decreased to 5 mg based on efficacy and side effects. The maximum recommended dosing frequency is once per day. VARI STRONG can be taken with or without food. Sexual stimulation is required for a response to treatment.
Geriatrics: A starting dose of 5 mg VARI STRONG should be considered in patients >/= 65 years of age.
Hepatic Impairment: For patients with mild hepatic impairment, no dose adjustment of VARI STRONG is required. Vardenafil clearance is reduced in patients with moderate hepatic impairment, and a starting dose of 5 mg VARI STRONG is recommended. The maximum dose in patients with moderate hepatic impairment should not exceed 10 mg. VARI STRONG has not been evaluated in patients with severe hepatic impairment
Renal Impairment: For patients with mild, moderate, or severe renal impairment, no dose adjustment is required. VARI STRONG has not been evaluated in patients on renal dialysis.
Signs of overdosage (120 mg dose) are reversible back pain/myalgia and /or “abnormal vision.”
In cases of overdose, standard supportive measures should be taken as required. Renal dialysis is not expected to accelerate clearance because vardenafil is highly bound to plasma proteins and is not significantly eliminated in the urine.
Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. Phosphodiesterase Type 5 (PDE5) inhibitors, including VARI STRONG and alpha-adrenergic blocking agents are both vasodilators with blood-pressure lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. In some patients, concomitant use of these two drug classes can lower blood pressure significantly leading to symptomatic hypotension (e.g., fainting).
Consideration should be given to the following:
-Patients should be stable on alpha-blocker therapy prior to initiating a PDE5 inhibitor. Patients who demonstrate hemodynamic instability on alpha-blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of PDE5 inhibitors.
-In those patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest recommended starting dose.
-In those patients already taking an optimized dose of PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure in patients taking a PDE5 inhibitor.
-Safety of combined use of PDE5 inhibitors and alpha-blockers may be affected by other variables, including intravascular volume depletion and other anti-hypertensive drugs.
A starting dose of 5 mg is recommended for patients with moderate hepatic impairment and the maximum dose should not exceed 10 mg, and. Vardenafil has not been evaluated in patients with severe hepatic impairment.
Congenital or Acquired QT Prolongation
Patients taking Class 1A (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medications or those with congenital QT prolongation, should avoid using VARI STRONG.
Vardenafil pharmacokinetics have not been evaluated in patients requiring renal dialysis.
General: vardenafil alone in doses up to 20 mg does not prolong the bleeding time. Therefore VARI STRONG should be administered to these patients after careful benefit-risk assessment.
Treatment for erectile dysfunction should generally be used with caution by patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease) or by patients who have conditions that may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).
The use of VARI STRONG with other treatments for erectile dysfunction is not recommended.
Pregnancy, Nursing Mothers and Pediatric Use
VARI STRONG is not indicated for use in women, newborns, or children. It is not known if vardenafil is excreted in human breast milk.
Pregnancy Category B: There are no adequate and well-controlled trials of vardenafil in pregnant women.
Elderly males age 65 years and older have higher vardenafil plasma concentrations than younger males (18-45 years), due to increased vardenafil concentrations in the elderly, a starting dose of 5 mg VARI STRONG should be considered in patients >/= 65 years of age.
Storage Conditions: Store at temperature between (15 – 30) ˚c
VARI STRONG 5 – 10 – 20
4 film coated tablets
10 film coated tablets