In patients with a tendency to bleeding and with an exacerbation of peptic ulcer disease, the drug should be prescribed only after assessing the benefit-risk ratio.
- Levitra Use in pregnancy and children
- The drug is not indicated for use in women.
Levitra Side Effects
- Adverse reactions (HP) reported in connection with the use of Levitra® are shown in the table. In each group, undesirable effects are presented in order of decreasing severity. Frequency is defined as "very often (≥1/10)", "often (≥1/100 to <1/10)", "infrequently (≥1/1 000 to <1/100)", "rarely (≥1/10 000 to <1/1 000)", "very rarely (<1/10 000)".
- HP, which were recorded only during post-marketing observations and the frequency of which could not be estimated, are designated as "frequency unknown".
- Post-marketing observations: cerebral hemorrhages, transient ischemic attack, unstable angina, ventricular arrhythmia when used simultaneously with other drugs of this group.
- The frequency is unknown: visual defect, hematuria, hemospermia, hemorrhage in the penis.
- HP detected in patients in all clinical trials|worldwide, including those considered drug-related in ≥ 0.1% of patients or rare and serious in their nature.
Description of individual adverse reactions
There have been reported cases of myocardial infarction associated with vardenafil intake and sexual activity, but it has not been established whether the occurrence of this disease is directly related to the use of vardenafil, sexual activity, concomitant diseases or a combination of these factors.
There are rare reports of cases of non-arteritic anterior ischemic optic neuropathy (NPINZN), leading to visual impairment (including persistent vision loss), associated with the use of PDE-5 inhibitors, including Levitra® in patients, many of whom have concomitant risk factors for the development of NPINZN, such as anatomical defect optic disc, age over 50 years, diabetes mellitus, hypertension, coronary heart disease, hyperlipidemia and smoking. It has not been established whether the development of NSAID is directly related to the use of PDE-5 inhibitors, with the patient's concomitant vascular risk factors and anatomical defects, a combination of these factors or other causes.
In two observational cross-sectional studies, the risk of developing NPINZN was assessed when taking drugs of the PDE-5 inhibitor class. The results indicate an approximately twofold increase in the risk of developing NPINZN. However, the causal relationship between the use of the PDE-5 inhibitor and the NPINZN has not been confirmed.
Cases of visual impairment, including temporary or permanent loss of vision, have been reported, which are associated with taking PDE-5 inhibitors, including Levitra®. It has not been established whether these cases are directly related to the use of PDE-5 inhibitors, or with concomitant vascular risk factors or other causes.
There have been few cases of sudden deafness or hearing loss when using drugs from the group of PDE-5 inhibitors, including Levitra®. It has not been established whether these cases are directly related to the use of Levitra®, concomitant risk factors for hearing loss, a combination of these factors or other causes.
- Vardenafil is metabolized mainly with the participation of liver enzymes of the cytochrome P450 (CYP) system, namely, isoforms 3A4, as well as with some participation of isoforms CYP3A5 and CYP2C. Inhibitors of these enzymes may reduce the clearance of vardenafil.
- Cimetidine (400 mg 2 times a day): a non-specific cytochrome P450 inhibitor does not affect the value of the parameters of the ACC and Cmax of Levitra® (20 mg) with their simultaneous use.
- Erythromycin (500 mg 3 times a day): an inhibitor of CYP 3A4 causing a 4-fold (300%) increase in the index of ACC and a 3-fold (200%) increase in the Cmax of Levitra® (5 mg).
- Ketoconazole (200 mg): as a potent inhibitor of CYP 3A4, ketoconazole causes a 10-fold increase (900%) in PPK and a 4-fold increase (300%) in the Cmax of Levitra® (5 mg).
- With the combined use of Levitra® (10 mg) and the HIV protease inhibitor indinavir (800 mg 3 times a day), there is a 16-fold (1500%) increase in PPK and a 7-fold (600%) increase in the Cmax of vardenafil. 24 hours after administration, the concentration of vardenafil in plasma is approximately 4% of its Cmax.
- Ritonavir (600 mg 2 times a day): increases the Cmax of Levitra® (5 mg) by 13 times and its total daily index PPK by 49 times. The interaction is due to the fact that ritonavir, being a powerful inhibitor of CYP3A4 and CYP2C9, blocks the hepatic metabolism of Levitra®. Ritonavir significantly lengthens the T1/2 of vardenafil (up to 25.7 hours).
With the combined use of Levitra® with erythromycin, ketoconazole, itraconazole, clarithromycin, indinavir and ritonavir (potential CYP3A4 inhibitors), a significant increase in the concentration of vardenafil in blood plasma can be expected. Levitra® is contraindicated when used concomitantly with moderately active or potent CYP3A4 inhibitors, such as erythromycin, ketoconazole (at a dose of more than 200 mg), itraconazole (at a dose of more than 200 mg), clarithromycin, indinavir and ritonavir.
Nitrates, nitric oxide donors
Taking Levitra® (10 mg) for a period of 24 hours to 1 hour before taking nitroglycerin (0.4 mg sublingually) does not cause an increase in its hypotensive effect. At a dose of 20 mg 1-4 hours before the use of nitrates (0.4 mg sublingually), Levitra® enhances their hypotensive effect, but if prescribed 24 hours in advance, there is no increase in the hypotensive effect.
Nicorandil is an activator of potassium channels and contains a nitro group in its composition. The presence of a nitro group in the composition of nicorandil causes a high probability of its interaction with vardenafil. However, there is insufficient information about the potential hypotensive effects of vardenafil when used concomitantly with nitrates. In this regard, this combination is contraindicated.
Since it is known that alpha-blockers cause a decrease in blood pressure, especially postural hypotension and fainting, the issue of interaction of alpha-blockers and Levitra® when used together has been carefully studied.
Hypotension, in some cases symptomatic, has been reported in a significant number of subjects after simultaneous administration of Levitra®, in film-coated tablets, by normotensive volunteers with simultaneous forced increase to high doses of alpha-blockers tamsulosin or terazosin for 14 days or less.
When taking Levitra®, film-coated tablets in doses of 5, 10 and 20 mg against the background of continuous tamsulosin therapy, no clinically significant additional decrease in maximum blood pressure was observed. When taking Levitra®, film-coated tablets of 5 mg, simultaneously with 0.4 mg of tamsulosin, 2 out of 21 patients had systolic pressure in the standing position < 85 mmHg. When taking Levitra®, in film-coated tablets, 6 hours after taking tamsulosin, 2 out of 21 patients had systolic pressure in the standing position < 85 mmHg.
Levitra®, film-coated tablets, 5 mg or 10 mg were used 4 hours after taking alfuzosin. The four-hour interval was chosen in order to achieve maximum potential interaction. After taking Levitra® 4 hours after taking alfuzosin, there was no clinically significant maximum additional decrease in blood pressure within 10 hours after taking Levitra®. In two patients, after taking Levitra® at a dose of 5 and 10 mg, there was a decrease in systolic blood pressure in the standing position compared to the baseline level by more than 30 mm Hg. There were no cases of a decrease in systolic blood pressure in the standing position below 85 mm Hg. in this study, there were no cases of a decrease in systolic blood pressure in the standing position below 85 mm Hg. Two patients reported dizziness after taking Levitra® at a dose of 5 mg. One patient reported dizziness after taking 10 mg of Levitra® and one patient reported dizziness after taking a placebo.