Vardenafil Drug Interactions
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Vardenafil Drug Interactions
Vardenafil is primarily metabolized via cytochrome P450 (CYP)isoforms, predominatly CYP 3A4 and to a lesser extend CYP 2C9 and CYP 3A5. Therefore, inhibitors of these isoenzymes may reduce the clearance of vardenafil. [1]
Increase concentration or Toxic Effect: Level Four
Nitrates Consistent with its known effects on the nitric oxide/cGMP pathway, sildenafil was shown to potentiate the hypotensive effects of nitrates and therefore its use in patients who are using organic nitrates (either regularly and/or intermittently) in any form is therefore contraindicated.[1] [2]
Increase concentration or Toxic Effect: Level Three
CYP 3A4 Inhibitors May decrease the metabolism of PDE5 inhibitors via CYP isoenzymes resulting in an increase in PDE5-induced adverse effects; hypotension, dyspepsia, headache, visual changes, and priapism. If coadminstrated, monitor for adverse events.[1]
- Protease inhibitors:
- Indinavir dosed at 800 mg tid in combination with vardenafil 10 mg resulted in a 16-fold, 7-fold, and 2-fold increase in the AUC, Cmax, and t1/2 of vardenafil, respectively. Therefore, it is recommended that the dose of vardenafil not to exceed 2.5 mg in a 24-hour period when used in combination with indinavir.[1]
- Ritonavir dosed at 600 mg bid in combination with vardenafil 5 mg resulted in a 49-fold and 13-fold increase in the AUC and Cmax of vardenafil, respectively. Ritonavir also significantly prolonged the t1/2 of vardenafil to 26 hours. Therefore it is recommended that the dose of vardenafil not to exceed 2.5 mg in a 72-hour period when used in combination with ritonavir.[1]
- Antifugal Agents(Imidazole) Imidazoles are potent inhibitors of CYP 3A4. Monitor for toxic effects of PDE5 inhibitors if an imidazole derivative is initiated and or dosage increased.[3] Ketoconazole dosed at 200 mg once daily in combination with vardenafil 5 mg resulted in a 10-fold and 4-fold increase in AUC and Cmax of vardenafil in healthy male subjects, respectively. Therefore, it is recommended that the dose of vardenafil not to exceed 5 mg when used in combination with 200 mg once daily ketoconazole. If the dose of ketoconazole is 400mg once daily, a single 2.5 mg dose of vardenafil should not be exceeded in a 24-hour period when used in combination.[1]
- Marcolide Antibiotics Erythromycin dosed at 500 mg tid and a single 5 mg dose vardenafil resulted in a 4-fold and 3-fold increase AUC and Cmax in healthy male subjects, respectively. Therefore, it is recommended that the dose of vardenafil to not exceed 5 mg in a 24-hour period when used in combination with erythromycin. This interaction appears likely with clarithromycin and telithromycin, but does not appear likely with azithromycin.[1]
Alpha1-Blockers Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of alpha1-blockers. The adverse clinical effects observed during concomitant administration is likely due to additive vasodilating effects.[4] [5] Coadminstration of an alpha 1 blockers (chronic and/or stable) with a single dose of a PDE5 inhibitors results in mild reductions in blood pressure and with generally mild symptoms; dizziness and lightheadedness.[5] However, symptomatic hypotension (systolic BP <85 mmHg) have been reported. This interaction appears more likely with doxazosin and terazosin than tamsulosin.[6]
Increase concentration or Toxic Effect: Level Two
Grapefruit Juice May inhibit the metabolism of CYP3A4 substrates. Monitor for increase adverse events.[1]
Decrease Concentration: Level Three
High-Fat Meals Two food-effect studies found that when vardenafil was adminstered with a high-fat meal, it caused a reduction in Cmax by 18 to 50%.[1]
Decrease Concentration: Level Two
CYP 3A4 Inducers May increase the metabolism of PDE5 inhibitors. Monitor for decrease effects during concomitant therapy.
Protease Inhibitors:
- Ritonavir: Concomitant administration of 5 mg of vardenafil with 600mg of ritonavir bid, resulted in a decrease in the Cmax and AUC of ritonavir by approximately 20%.[1]
- Indinavir: Concomitant adminstration of 10 mg of vardenafil with 800mg of indinavir tid, resulted in a decrease in the Cmax and AUC of indinavir by 40% and 30%, respectively.[1]
Back to Vardenafil
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Levitra® [Package Insert]. West Haven, CT: Bayer Pharmaceuticals Corporation, 2005.
- ↑ Kloner RA. Hutter AM. Emmick JT. Mitchell MI. Denne J. Jackson G. Time course of the interaction between tadalafil and nitrates. Journal of the American College of Cardiology. 42(10):1855-60, 2003 Nov 19.
- ↑ Galatti L. Fioravanti A. Salvo F. Polimeni G. Giustini SE. Interaction between tadalafil and itraconazole. Annals of Pharmacotherapy. 39(1):200, 2005 Jan.
- ↑ De Rose AF, Giglio M, Traverso P, et al. Combined oral therapy with sildenafil and doxazosin for the treatment of non-organic erectile dysfunction refractory to sildenafil monotherapy. Int J Impot Res 2002;14:50—3.
- ↑ 5.0 5.1 Kloner RA. Jackson G. Emmick JT. Mitchell MI. Bedding A. Warner MR. Pereira A. Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men. Journal of Urology. 172(5 Pt 1):1935-40, 2004 Nov.
- ↑ Auerbach SM. Gittelman M. Mazzu A. Cihon F. Sundaresan P. White WB. Simultaneous administration of vardenafil and tamsulosin does not induce clinically significant hypotension in patients with benign prostatic hyperplasia. Urology. 64(5):998-1003; discussion 1003-4, 2004 Nov.
