Zydena Drug Interactions

Drugs that affect the serum concentration of Zydena: in vitro studies: Zydena was metabolized principally by CYP450 3A4. Thus, CYP450 3A4 inhibitors may increase plasma concentration of Zydena. In human, ketoconazole, itraconazole, ritonavir, indinavir, cimetidine, erythromycin and grapefruit juice are typical CYP450 3A4 inhibitors.
in vitro studies: In healthy adults, the concomitant use of ketoconazole (400 mg) with Zydena (100 mg) increased the AUC and C_max of Zydena (100 mg) approximately twice (212%) and approximately 0.8 times (85%), respectively, compared to the AUC and C_max of Zydena (100 mg) monotherapy.
Although specific interaction has not been studied, when concomitantly used with inhibitors of CYP450 3A4 such as itraconazole, cimetidine, erythromycin, and grapefruit juice, the systemic exposure of Zydena is expected to be increased. Therefore, it should be co-administered with caution.
In PDE5 inhibitors, when co-administered with potent CYP450 3A4 inhibitors such as HIV protease inhibitors indinavir or ritonavir, a significant increase in systemic exposure of the drug has been reported. Therefore, co-administration is not recommended.
In addition, CYP450 3A4 metabolism inducers such as dexamethasone, rifampicin and some antiepileptic drugs (phenytoin, phenobarbital, carbamazepine) promote the metabolism of Zydena. Therefore, when co-administered, a decrease in plasma concentration of Zydena is expected.
When alcohol (0.6 g/kg, mean maximum plasma concentration 0.088%) was co-administered with Zydena (200 mg), Zydena did not augment the effects of alcohol on blood pressure and heart rate, and the pharmacokinetics of the drug also did not change. However, because both Zydena and alcohol has slight vasodilating effects, the blood pressure lowering effect may be augmented when administered in combination. Therefore, doctors should inform the patient that symptoms such as increased heart rate, decreased blood pressure, dizziness, headache and orthostatic symptoms may occur when a large amount of alcohol is co-administered with Zydena.
In a pharmacokinetic study of Zydena 200 mg and Dapoxetine 60 mg co-administration in healthy subjects, the AUC was compared with the AUC of separate administration. The two drugs did not affect each other, and the C_max of Zydena and Dapoxetine decreased by approximately 13.6% and 16.3%, respectively. Such changes of Zydena were not considered clinically significant.
In an experiment with rats, nitroglycerin (2.5 mg/kg, intravenous administration of a single dose) did not have a significant effect on the pharmacokinetics of Zydena (30 mg/kg, orally). However, because Zydena has antihypertensive effects by vasodilatation, co-administration of nitroglycerin is not recommended.
In an experiment with rats, as amlodipine besylate (5 mg/kg, orally for 3 days) has antihypertensive effects by vasodilation, the blood pressure may decrease due to amlodipine. Therefore, medical judgment is needed in concomitant use.
In a clinical study in which Zydena (200 mg) and selective alpha-1 blockers were concomitantly administered in 28 healthy adults, orthostatic systolic blood pressure, on average, was reduced by 4 mmHg at most. With concomitant use, orthostatic systolic blood pressure was reduced to less than 85 mmHg in four patients but without symptoms of hypotension. Although there has not been a clinical study on the concomitant use of Zydena and alpha-blockers in patients, as Zydena and alpha-blockers present equal vasodilating effects, patients should be warned about the possibility of a decrease in blood pressure.
When administered in combination with alpha-blockers, PDE5 inhibitors including Zydena may cause hypotension in some patients. Therefore, combination therapy of the two agents should be initiated at the minimum recommended doses in stable patients. Gradual increase of the alpha-blocker dosage may be associated with decreased blood pressure when administered with PDE5 inhibitors.
Co-administration of PDE5 inhibitors and alpha-blockers may affect its safety by other factors such as a decrease in the amount of blood or anti-hypertensives.
In an experiment with rats, oral administration of omeprazole (30 mg/kg) for about one week followed by oral administration of Zydena (30 mg/kg) resulted in approximately 30% and 37% increase in the maximum plasma concentration and AUC, respectively.
The effect of Zydena on other drugs: In in vitro studies, Zydena showed the IC50 of more than 200 μM in all CYP450 isoform 1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 except 2D6 (IC50 67.7 μmol/L). Considering that the maximum plasma concentration of the drug was 2.2 μmol/L after administration of the recommended dose, it is unlikely that Zydena would affect the clearance rate of these isoforms.