Interactions with Other Medicaments and Other Forms of Interaction:
Effects of other drugs on ZEAGRA
In vitro studies:
Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance.
In vivo studies:
Cimetidine (800 mg), a non-specific CYP3A4 inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with ZEAGRA (50 mg) to healthy volunteers.
Population pharmacokinetic analysis of clinical trial data indicated a reduction in sildenafil clearance when co-administered with CYP3A4 inhibitors (such as itraconazole, ketoconazole, erythromycin, and cimetidine). However, zeagra.net there was no increased incidence of adverse events in these patients.
Single doses of antacid (magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability of ZEAGRA.
Population pharmacokinetic analysis showed no effect of concomitant medication on sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, loop and potassium sparing diuretics, ACE inhibitors, calcium channel blockers, beta-adrenoreceptor antagonists or inducers of CYP450 metabolism (such as rifampicin, barbiturates).
Effects of ZEAGRA on other medicines
In vitro studies:
Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 >150 microM). Given sildenafil peak plasma concentrations of approximately 1 microM after recommended doses, it is unlikely that ZEAGRA will alter the clearance of substrates of these isoenzymes.
In vivo studies:
No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolised by CYP2C9.
ZEAGRA (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg).
ZEAGRA (50 mg) did not potentiate the hypotensive effects of alcohol in healthy volunteers with mean maximum blood alcohol levels of 80 mg/dL.
No interaction was seen when ZEAGRA (100 mg) was co-administered with amlodipine in hypertensive patients. The mean additive reduction on supine blood pressure (systolic, 8 mmHg; diastolic, 7 mmHg) was of a similar magnitude to that seen when ZEAGRA was administered alone to healthy volunteers (see Pharmacodynamic properties).
Analysis of the safety database showed no difference in the side effect profile in patients taking ZEAGRA with and without anti-hypertensive medication.
ZEAGRA was shown to potentiate the hypotensive effect of acute and chronic nitrates. Therefore, use of nitrates or nitric oxide donors with ZEAGRA is contraindicated (see Contraindications).
Health care professionals are encouraged to report any unexpected and/or serious adverse events associated with the use of ZEAGRA to Pfizer Laboratories .
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
In studies with healthy volunteers, of single doses up to 800 mg, adverse events were similar to those seen at lower doses but incidence rates were increased.
In cases of overdose, supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and not eliminated in the urine.
Effects of other drugs on ZEAGRA
In vitro studies:
Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance.
In vivo studies:
Cimetidine (800 mg), a non-specific CYP3A4 inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with ZEAGRA (50 mg) to healthy volunteers.
Population pharmacokinetic analysis of clinical trial data indicated a reduction in sildenafil clearance when co-administered with CYP3A4 inhibitors (such as itraconazole, ketoconazole, erythromycin, and cimetidine). However, zeagra.net there was no increased incidence of adverse events in these patients.
Single doses of antacid (magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability of ZEAGRA.
Population pharmacokinetic analysis showed no effect of concomitant medication on sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, loop and potassium sparing diuretics, ACE inhibitors, calcium channel blockers, beta-adrenoreceptor antagonists or inducers of CYP450 metabolism (such as rifampicin, barbiturates).
Effects of ZEAGRA on other medicines
In vitro studies:
Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 >150 microM). Given sildenafil peak plasma concentrations of approximately 1 microM after recommended doses, it is unlikely that ZEAGRA will alter the clearance of substrates of these isoenzymes.
In vivo studies:
No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolised by CYP2C9.
ZEAGRA (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg).
ZEAGRA (50 mg) did not potentiate the hypotensive effects of alcohol in healthy volunteers with mean maximum blood alcohol levels of 80 mg/dL.
No interaction was seen when ZEAGRA (100 mg) was co-administered with amlodipine in hypertensive patients. The mean additive reduction on supine blood pressure (systolic, 8 mmHg; diastolic, 7 mmHg) was of a similar magnitude to that seen when ZEAGRA was administered alone to healthy volunteers (see Pharmacodynamic properties).
Analysis of the safety database showed no difference in the side effect profile in patients taking ZEAGRA with and without anti-hypertensive medication.
ZEAGRA was shown to potentiate the hypotensive effect of acute and chronic nitrates. Therefore, use of nitrates or nitric oxide donors with ZEAGRA is contraindicated (see Contraindications).
Health care professionals are encouraged to report any unexpected and/or serious adverse events associated with the use of ZEAGRA to Pfizer Laboratories .
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
In studies with healthy volunteers, of single doses up to 800 mg, adverse events were similar to those seen at lower doses but incidence rates were increased.
In cases of overdose, supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and not eliminated in the urine.