News - Part 34

What’s new

Nov-25-2008

This is the first clinical study in which a stopwatch approach was used to measure accurately the duration of erection as it pertains to successful intercourse during PDE5 inhibitor therapy. Results demonstrate that treatment with vardenafil (Levitra) is associated with an increased duration of erection and restoration of erectile function compared with placebo.

Dosage

Sep-22-2008

Dosage and Administration

It is recommended to take an oral dose of LEVITRA 25 mins to 1 hour before engaging in sexual acts. 10 mg is the advsed starting dose for LEVITRA. A patient can commence with sex acts as early as 15 minutes post taking LEVITRA and as late as 4-5 hours.

It is advised not to take more than one LEVITRA dose per day.

Take LEVITRA with or without eating.

In order to gain a natural response to the treatment, sexual excitement is required.

Dose Range

LEVITRA can be administered in as small a dose as 5 mg and as large a dose as 20 mg weighing heavily on effectiveness of the drug and tolerability of the patient. It is ill-advised to take more than 20 mg of LEVITRA per day.

Vardenafil’s plasma levels can expect a boost if taken with potent cytochrome P450 (CYP) inhibitors, ritonavir, itraconazole, indinavir, ketoconazole. If LEVITRA use is to be combined with erythromycin, ketoconazol, or itraconazole the maximum dose of LEVITRA should not be more than 5 mg as concomitant use not only up efficacy but also increases incidents of adverse reactions. Avoid using LEVITRA with HIV protease inhibitors indinavir or ritonavir.

Dose adjustment is not needed for Elderly (65 years and older) patients.

Vardenafil is not to be used in Children (16 years and younger).

Hepatic Impairment

Patients possessing mild hepatic impairment (Child-Pugh A) do not require a dose adjustment.

Patients possessing moderate hepatic impairment (Child-Pugh B) require a lowered clearence for Vardenafil. They are to be started with a dose of 5 mg then, based on tolerability and efficacy, their dose can gradually be raised up to 20 mg.

Patients with severe hepatic impairment (Child-Pugh C) should refrain from using vardenafil, as the pharmacokinetics of vardenafil in patients needing dialysis has yet to be studied.

Renal Impairment

Patients with renal impairment do not require a dose adjsutment, whether it be mild (CLcr> 50-80 ml/min), moderate (CLcr> 30-50 ml/min), or even severe (CLcr> 30ml/min) impairment.

Patients requiring dialysis should refrain from using vardenafil, as the pharmacokinetics of vardenafil in patients in this condition has yet to be studied.

Over-Dosage

Doses of vardenafil as large as 80 mg per day were administered during a single dose volunteer study. For the most part, there were no heavy adverse reactions to even the highest tested dosage (80 mg/day). Studying 40 mg per day for more than a month confirmed this fact.

Though it could not be attributed to muscle or neurological toxicity, 40 mg, twice per day, induced serious back pain in some cases.

Take the required standard supportive measures in case of overdose on generic vardenafil. Vardenafil is intensely bound to plasma proteins and is not greatly disposed of through urine, so it is not expected that renal dialysis will accelerate clearance.

Glibenclamide

The relative bioavailability of glibenclamide was not affected with 3.5 mg of glibenclamide was co-administered with 20mg of vardenafil (there was no effect on glibenclamide’s AUC or Cmax).

Warfarin

The co-administration of warfarin with vardenafil did not effect vardenafil’s pharmacokinetics. When 25 mg of warfarin was co-administered with 20 mg of vardenafil no pharmacokinetic or pharmacodynamic (prothrombin time and clotting factor II, VII and X) interactions were identified.

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CYP 3A4 Inhibitors

Using the CYP 3A4 inhibitors itraconazole and ritonavir with vardenafil will most likely be responsible for plasma levels similar to indinavir and ketoconazole (In Demonstrated Interactions). High plasma levels will not only increase effectiveness but increase occasions of adverse events. Never take more than a 5 mg dose of vardenafil when combining it with the use of itraconazole, ketaconazole, and erythromycin. It is advised to avoid combination use of the HIV protease inhibitors indinavir or ritonavir with canadian vardenafil.

Nitrates/Nitric Oxide Donors

Data concerning the potential hypotensive effects of vardenafil when combined with use of nitrates is limited. Concomitant use is contraindicated due to experience with patients suffering clinically significant hypotension with co-administration of other PDE5 inhibitors. (In CONTRAINDICATIONS).

Avoid using nitrates until no less than 24 hours (~5 half-lives), after the last time you have taken vardenafil. If you have been using concomitant drugs, like CYP3A4 inhibitors, which injure the metabolism of drug vardenafil, you should observe an extended wash out period.

Antihypertensive Agents

Information concerning the combined use of antihypertensive agents ant vardenafil is limited. Notable effects of ACE-inhibitors, diuretics, or beta-blockers on vardenafil’s pharmacokinetics were not uncovered by population pharmacokinetic investigations of phase III data. The potential for additive hypotensive effects still remains so, until more is know about the combination, use cautions when co-administering antihypertensive agents with vardenafil (levitra).

Demonstrated Interactions

Erythromycin

Fit voluteers experience a increase of 4-fold vardenafil AUC and 3-fold in Cmax when vardenafil (5 mg) was taken with a CYP3A4 inhibitor called Erythromycin 500 mg t.i.d.. Never take more than a 5 mg dose of vardenafil when combining it with the use of generic erythromycin.

Ketoconazole

Fit voluteers experience a increase of 10-fold vardenafil AUC and 4-fold in Cmax when vardenafil pills (5 mg) was taken with a CYP3A4 inhibitor called Ketoconazole 200 mg. Never take more than a 5 mg dose of canadian vardenafil when combining it with the use of generic ketoconazole.

Indinavir

10 mg of vardenafil was administered along witn 800 mg t.i.d. of the HIV protease inhibitor indinavir. The result was a 7-fold increase in vardenafil Cmax and 16-fold increase in vardenafil AUC. Vardenafil plasma level were about 4% of the maximum Cmax 24 hours after the drugs were administered. It is highly advised to avoid this combination. Never take more than a 5 mg dose of vardenafil drug when combining it with the use of indinavir.

Precautions

Sep-22-2008

Precautions

Cardiovascular Disease

There is some element of cardiac risk involved in sexual activity, therefore physicians must take a look their patients cardiovascular condition before prescribing erectile dysfunction treatment.

Other Pre-existing Medical Conditions

Patients with anatomically deforming penis conditions (like cavernosal fibrosis, angulation, or Peyronie’s disease) or with condition that might induce priapism (like leukemia, sickle cell anemia, or multiple myeloma) must use agents for treating erectile dysfunction carefully.

Using a combination of vardenafil drugs with other erectile dysfunction treatments (this includes other PDE5 inhibitors) has yet to be studied and is therefore ill-advised.

Patients with significant active peptic ulceration or other bleeding disorders have not yet been given vardenafil therefore should not be given vardenafil until after a serious benefit-risk assessment. Vardenafil medication has no effect on human bleeding time, alone or with aspirin. Human platelets from in vitro studies showed that platelet aggregation caused by various types of platelet agonists was not inhibited by vardenafil. Studies observed a small concentration-dependent improvement of the antiaggregatory effect fo sodium nitroprusside, a nitric oxide donor, with super-therapeutic concentrations of generic vardenafil. Though combining heparin and vardenafil has yet to be studied in humans, it did not effect the bleeding time in rats.

Use with Alpha-Blockers

Some patients may experience symptomatic hypotension with the conjoined use of alpha-blockers and vardenafil. Conjoining alpha-blockers with vardenafil is ill-advised until more is known about such a combination.

Use with Potent CYP 3A4 Inhibitors

Expect a notable increase in vardenafil plasma levels with the conjoined use of the potent cytochrome P450 3A4 (CYP 3A4) inhibitors, ritovavir, ketoconazole, indinavir, or itraconazole. Not only will higher levels of plasma increase effectiveness but it will also increase the occurance of conflicting events. If being combined with the usage of erythromycin, ketoconazole, and itraconazole, vardenafil’s dose should not exceed a maximum of 5 mg. Do not use vardenafil with the HIV protease inhibitors ritonavir or indinavir. (See INTERACTION WITH DRUGS).

Ability to Drive and Use Machines

Before driving or operating machinery patients should take note of their reactions to vardenafil.

Carcinogenesis/Mutagenesis

Cheap Vardenafil was administers orally in doses up to 75 mg/kg/day to male rates and 25 mg/kg/day to female rats also in drinking water to mice at 150 mg/kg/day to males and 193 mg/kg/day and displayed no carcinogenic activity. Systematic exposure (AUC) to vardenafil was associated with the maximum dose in the studies: 25 (mice) or ~300 (rats) multiplied by that expected in a man taking a daily vardenafil dose of 20mg. When tested for gene mutation (forward mutations in Chinese hamsters V79 cells in vitro and reverse mutations in bacterial cells) or chromosomal damage (mouse micronucleus tested in vivo and Chinese hamsters V79 cells in vitro) vardenafil was found to be non-genotoxic.

Impairment of Fertility

Sperm morphology, motility, nor a variety or parameters that indicate the function of male reproduction were affected, in an individual clinical trial, after a single oral dose of 20 mg of vardenafil. A maximum of 0.0002% of the given dose appeared in patients semen when measurements were taken of vardenafil in the semen of healthy patients 90 mins post dosing.

Male and female rats issued an oral dose of 100 mg/kg/day had no effects on fertility, reproductive performance, or reproductive organ morphology (systematic exposure is greater than 200 times that expected at a dose of 20 mg, the maximum recommended, based on AUC).

Use in Pregnancy (Category B3)

Generic Vardenafil should not be used by women.

Vardenafil (Levitra) and/or its metabolites has seen to cross the placenta and issued to the fetus, according to rat studies. Neither pregnant rats or rabbits, issued vardenafil in oral doses up to 18 mg/kg/day, displayed signs of teratogenicity or embryofetal toxicity. Systematic exposure to vardenafil 7 (rabbit) or 125 (rat) times more than what’s expected at 20 mg, the maximum advised dose, were associated with these doses, based on AUC. Both rats and rabbits experienced increased embryonic resorptions, maternal toxicity, and delayed fetal development when taking higher doses.

Delayed physical development and postnatal pup mortality was a direct result of giving rats a 60 mg/kg/day dose of vardenafil throughout lactation and in late gestation. Systematic exposure ~28 times that expected in a human being 20 mg vardenafil, maximum advised dose, was associated with the “no-effect-dose” of 8 mg/kg/day.

Canadian Vardenafil has not been tested and studied in pregnant women.

Use in Lactation

Vardenafil should not be used by women.

The milk of lactating rats experiences an excretion of vardenafil and/or its metabolites up to 19 times more than the parallel maternal plasma concentration. Rats given an oral vardenafil dose of 60 mg/kg/day during lactation and gestation periods suffered increases in delayed physical development and prenatal and postnatal mortality to offspring.

Human data regarding vardenafil excretion in breast milk or the safty of infants exposed to vardenafil has not been collected.

Contraindications

Sep-22-2008

Contraindications

Vardenafil’s contraindications are found in patients who are known to be highly sensitive any of the drugs ingredients, active or inactive.

Canadian Vardenafil and Nitrates must not be used together. Using drugs vardenafil with nitric oxide donors, organic nitrites, or organic nitrate is contraindicated, whether it is used occasionally of regularly. A list of other drugs than must not be used together with vardenafil (Levitra), though not a complete list, are: isosorbide salts, amyl nitrite, glyceryl trinitrate (spray, tablets, patches, and injection) sodium nitroprusside, organic nitrates (any form), and nicorandil. In line with the common effect of PDE inhibition on nitric oxide and cGMP, pathway, PDE5 inhibitors may cause encourage the hypotensive nitriate effects.

As warned in PRECAUTIONS, men use cardiovascular condition makes sex a health risk are contraindicated for vardenafil drug. Men with erectile dysfunction should have themselves checked for any cardiovascular complications they may not be aware of prior too taking generic vardenafil.

The use of vardenafil is contraindicated for patients with the following health conditions as the effects of vardenafil has yet to be studied in such situations: uncontrolled hypertension, unstable angina, myocardial infraction, resting or orthostatic hypotension (systolic blood pressure less than 90 mmHg), cardiac ischaemia (except stable angina), stroke, uncontrolled arrhythmia, life threatening arrhythmia in the past 6 months, on dialysis for end-stage renal disease, severe hepatic impairment, and known hereditary degenerating retinal complications like reinitis pigmentosa.

 

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