A suitable time interval following LEVITRA dosing for the safe administration of nitrates or nitric oxide donors has not been determined. WARNINGS Cardiovascular effects 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 LEVITRA, generally should not be used.

Left Ventricular Outflow Obstruction: Patients with left ventricular outflow obstruction, e. While this normally would be expected to be of little consequence in most patients, prior to prescribing LEVITRA, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects.

Concomitant administration with ritonavir or indinavir substantially increases plasma concentrations of vardenafil. Patients taking indinavir, saquinavir, atazanavir or other potent CYP3A4 inhibitors such as clarithromycin, ketoconazole mg daily, or itraconazole mg daily should not exceed a dose of LEVITRA 2. Other 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. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated.

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 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.

Vardenafil has not been evaluated in patients with severe hepatic impairment Child-Pugh C. These observations should be considered in clinical decisions when prescribing LEVITRA to patients with known history of QT prolongation or patients who are taking medications known to prolong the QT interval. Patients taking Class 1A e. Vardenafil pharmacokinetics have not been evaluated in patients requiring renal dialysis. General: In humans, vardenafil alone in doses up to 20 mg does not prolong the bleeding time.

There is no clinical evidence of any additive prolongation of the bleeding time when vardenafil is administered with aspirin. Vardenafil has not been administered to patients with bleeding disorders or significant active peptic ulceration. Therefore, the use of such combinations is not recommended.

Patients should be counseled that concomitant use of LEVITRA with nitrates could cause blood pressure to suddenly drop to an unsafe level, resulting in dizziness, syncope, or even heart attack or stroke.

Physicians should inform their patients that in some patients concomitant use of PDE5 inhibitors, including LEVITRA, with alpha-blockers can lower blood pressure significantly leading to symptomatic hypotension e. Patients should be advised of the possible occurrence of symptoms related to postural hypotension and appropriate countermeasures.

Patients should be advised to contact the prescribing physician if other anti-hypertensive drugs or new medications that may interact with LEVITRA are prescribed by another healthcare provider. Patients should be advised to contact their healthcare provider for dose modification if they are not satisfied with the quality of their sexual performance with LEVITRA or in the case of an unwanted effect.

Patients should be advised to contact the prescribing physician if new medications that may interact with LEVITRA are prescribed by another healthcare provider. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy NAIONa cause of decreased vision, including permanent loss of vision, that has been reported rarely post-marketing in temporal association with the use of all PDE5 inhibitors.

It is not possible to determine whether these events were related directly to the use of PDE5 inhibitors or to other factors. Physicians should discuss with patients the potential cardiac risk of sexual activity for patients with preexisting cardiovascular risk factors. Counseling of patients about protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus HIVshould be considered.

Physicians should inform patients that there have been rare reports of prolonged erections greater than 4 hours and priapism painful erections greater than 6 hours in duration for LEVITRA and this class of compounds. In vivo studies: Cytochrome P Inhibitors Cimetidine mg b. Erythromycin mg t. Since higher doses of ketoconazole mg daily may result in higher increases in Cmax and AUC, a single 2. It is recommended not to exceed a single 2. Ritonavir mg b.

The interaction is a consequence of blocking hepatic metabolism of vardenafil by ritonavir, a highly potent CYP3A4 inhibitor, which also inhibits CYP2C9.

Ritonavir significantly prolonged the half-life of vardenafil to 26 hours. Consequently, it is recommended not to exceed a single 2. Other CYP3A4 inhibitors: Although specific interactions have not been studied, other CYP3A4 inhibitors, including grapefruit juice would likely increase vardenafil exposure.

Other Drug Interactions: No pharmacokinetic interactions were observed between vardenafil and the following drugs: glyburide, warfarin, digoxin, Maalox, and ranitidine. In the warfarin study, vardenafil had no effect on the prothrombin time or other pharmacodynamic parameters.

The most potent inhibitory activity was observed for vardenafil metabolite M1, which had a Ki of 1. In vivo studies: Nitrates: The blood pressure lowering effects of sublingual levitra 20 mg 0. Nifedipine: Vardenafil 20 mg, levitra 20 mg co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the relative bioavailability AUC or maximum concentration Cmax of nifedipine, a drug that is metabolized via CYP3A4.

Alpha-blockers: Blood levitra 20 mg effects in patients on stable alpha-blocker treatment: Two clinical pharmacology studies were conducted in patients with benign prostatic hyperplasia BPH on stable-dose alpha-blocker treatment for at least four weeks. Study 1: This study was designed to evaluate the effect of 5 mg vardenafil compared to placebo when administered to BPH patients on chronic alpha-blocker therapy in two separate cohorts: tamsulosin 0. The design was a randomized, double blind, cross-over study with four treatments: vardenafil 5 mg or placebo administered simultaneously with the alpha-blocker and vardenafil 5 mg or placebo administered 6 hours after the alpha-blocker.

Blood pressure and pulse were evaluated over the 6-hour interval after vardenafil dosing. For BP results see Table 2. Hypotension was not observed when vardenafil 5 mg and terazosin were administered 6 hours apart. There were no severe adverse events related to hypotension reported during the study. There were no cases of syncope.