Viagra interactions are important, as some drugs may influence the effect and metabolism of this drug used for erectile dysfunction treatment.
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- The metabolism of Viagra mainly occurs in the liver under the influence of isoenzymes CYP3A4 (the major route) and CYP2C9, so inhibitors of these isoenzymes may reduce Viagra (Sildenafil) clearance, and inducers, respectively, increase Viagra (Sildenafil) clearance.
- The combined use of CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine) and this ED drug may reduce Sildenafil clearance.
- Cimetidine (at the dose of 800 mg), being a nonspecific CYP3A4 inhibitor, causes an increase of Sildenafil concentration in plasma by 56%, when taken with Sildenafil.
- Generic Viagra in combination with erythromycin – a specific CYP3A4 inhibitor (at erythromycin dose 500 mg 2 times/day for 5 days) – increases Sildenafil AUC by 182% due to constant erythromycin concentration in blood.
- Simultaneous use of this drug (at the dose 100 mg) and Saquinavir (at the dose of 1200 mg 3 times/day) – an HIV protease inhibitor and CYP3A4 inhibitor, provokes Sildenafil Cmax in blood increase by 140% and Sildenafil AUC increase by 210% due to the constant Saquinavir concentration in blood. Viagra pills produce no effect on the pharmacokinetic parameters of Saquinavir.
- Strong isoenzyme CYP3A4 inhibitors, such as ketoconazole or itraconazole may cause pronounced changes in the pharmacokinetics of the ED drug.
- Simultaneous use of Sildenafil (at the dose of 100 mg) and ritonavir (at the dose of 500 mg, 2 times / day) – a HIV protease inhibitor and a potent inhibitor of P450 isozymes – increases the Sildenafil Cmax by 300 % (4 times) and AUC by 1000% (11 times) due to the constant ritonavir concentration in blood. In 24 hours Sildenafil concentration in plasma concentration is approximately 200 ng/ml (at a single Sildenafil administration 5 ng/ml).
- If Viagra is used at the recommended doses by patients taking strong CYP3A4 inhibitors, Sildenafil Cmax is less than 200 nM, and the drug is well tolerated.
- A single dose of Antacid (hydroxide/magnesium aluminum hydroxide) does not affect the bioavailability of the ED medication.
- Studies involving healthy volunteers have shown that the simultaneous use of antagonists of endothelin receptor, bosentan (isoenzyme CYP2C9, CYP2C19, CYP3A4 inductor (moderate), in the equal concentration (125 mg, 2 times/day) and Sildenafil in the equal concentration (80 mg 3 times/day) provokes a decrease on Sildenafil AUC and Cmax by 62.6% and 52.4%, respectively. The increased bosentan AUC and Cmax by 49.8% and 42%, respectively.
- The simultaneous use Sildenafil with strong isoenzyme CYP3A4 inducers, such as rifampicin, can reduce Sildenafil concentration in plasma.
Isoenzyme CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 isoenzyme (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and thiazide diuretics, ACE inhibitors and calcium antagonists produce no effect on Viagra pharmacokinetics. - Simultaneous administration of azithromycin (500 mg/day for 3 days) does not affect Sildenafil AUC, Cmax and Tmax, constant elimination rate and its main circulating metabolite.
Effects of Viagra on other drugs
- Viagra from Canadian Pharmacy is a weak inhibitor of isoenzyme P450 cytochrome system – 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4. When taking the recommended dosage, Sildenafil Cmax makes about 1 micromolar, so Sildenafil unlikely may affect the clearance of these isoenzymes substrates.
- Excessive use of the ED drug from Canadian Health and Care Mall increases the hypotensive effects of nitrates, as well as when used under acute indications. In this regard, use of Viagra with nitrates or nitric oxide donators is contraindicated.
- Simultaneous use of an alpha-blocker Doxazosin (4 mg and 8 mg) and Sildenafil (25 mg, 50 mg, and 100 mg) in patients with benign prostatic hyperplasia with stable hemodynamics the average additional reduction in systolic/diastolic blood pressure in the supine position made 7 / 7 pt.ct. mm, 5.9 mm Hg and 8/4 mm rt.ct. respectively, in a standing position – 6/6 mm pt.ct., 11/4 mm pt.ct. and 4/5 mmHg respectively. There were rare cases of symptomatic postural hypotension, manifested in the form of dizziness (without fainting) in these patients. Certain sensitive patients treated with alpha-blockers may develop symptomatic hypotension with the simultaneous use of the ED remedy.
- Signs of significant Viagra interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP2C9, are not revealed.
- Sildenafil produces no effect on the pharmacokinetic parameters of HIV protease inhibitors, such as saquinavir and ritonavir – CYP3A4 substrates.
- Simultaneous use of the drug for men at equilibrium (80 mg 3 times/day) results in the increased bosentan AUC and Cmax (125 mg, 2 times/day) by 49.8% and 42%, respectively.
- The dosage 50 mg causes an additional increase of bleeding time when combined with aspirin at a dose of 150 mg.
- Sildenafil does not intensify the hypotensive effect of ethanol in healthy volunteers at the maximum ethanol level in blood 0.08% (80 mg/dl).
- Patients with signs of hypertension had no interaction with simultaneous use of Sildenafil and amlodipine. The average additional reduction in blood pressure in the supine position makes 8 mm Hg (Systolic) and 7 mm Hg (Diastolic).
- Simultaneous use of Viagra in combination with antihypertensive drugs does not cause additional side effects.
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