Elonza-100 Drug Interactions

Effects of other medicinal products on Sildenafil: 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 and inducers of these isoenzymes, may increase Sildenafil clearance. Efficacy of Sildenafil should be closely monitored in patients using concomitant potent CYP3A4 inducers, such as Carbamazepine, Phenytoin, Phenobarbital, St. John's wort and Rifampicin. This is consistent with Ritonavir's marked effects on a broad range of P450 substrates. Based on these pharmacokinetic results co-administration of Ritonavir is contraindicated in pulmonary arterial hypertension patients. Sildenafil had no effect on Saquimavir pharmacokinetics. Potent CYP3A4 inhibitors such as Ketoconazole and Itraconzaole would be expected to have effects similar to Ritonavir. CYP3A4 inhibitors of intermediate potency (e.g. Clarithromycin, Telithromycin and Nefazodone) are expected to have an effect in between that of Ritonavir and CYP3A4 inhibitors of medium potency (e.g. Saquinavir/Erythromycin) a seven-fold increase in exposure is assumed. Therefore dose adjustments are recommended when using CYP3A4 inhibitors of intermediate potency.
The population pharmacokinetic analysis in pulmonary arterial hypertension patients suggested that co-administration of beta-blockers in combination with CYP3A4 substrates might result in an additional increase in Sildenafil exposure compared with administration of CYP3A4 substrates alone. Grapefruit juice is a weak inhibitor of CYP3A4 gut wall metabolism and may give rise to modest increases in plasma levels of Sildenafil. Single doses of antacid (Magnesium hydroxide/Aluminum hydroxide) did not affect the bioavailability of Sildenafil. Co-administration of oral contraceptives (Ethinyloestradiol 30 mg and Levonorgestrel 150 mg) did not affect the pharmacokinetics of Sildenafil. Nicorandil is a hybrid of potassium channel activator and nitrate. Due to the nitrate component, it has the potential to have serious interaction with Sildenafil. No significant interactions were shown when Sildenafil (50 mg) was co-administered with Tolbutamide (250 mg) or Warfarin (40 mg), both of which are metabolized by CYP2C9. Sildenafil had no significant effect on Atorvastatin exposure (AUC increased 11%, suggesting that Sildenafil does not have a clinically relevant effect on CYP3A4. No interactions were observed between Sildenafil (100 mg single dose) and Acenocoumarol. Sildenafil (100 mg single dose) did not affect the steady state pharmacokinetics of the HIV protease inhibitor Saquinavir, which is a CYP3A4 substrate/ inhibitor. Consistent with its known effects on the nitric oxide/ cGMP pathway, Sildenafil was shown to potentiate the hypotensive effects of nitrates in any form is therefore contraindicated; Sildenafil had no clinically significant impact on the plasma levels of oral contraceptives (Ethinyloestradiol 30 mg and Levonorgestrel 150 mg).