ach ml of ONIVYDE contains 0.144 mmol (3.31 mg) sodium. This needs to be taken into consideration by patients on a controlled sodium diet.
4.5 Interaction with other medicinal products and other forms of interaction
Information about drug interactions with ONIVYDE is referenced from the published scientific literature for nonliposomal irinotecan.
Interaction affecting the use of ONIVYDE
Strong CYP3A4 inducers
Patients receiving concomitant non-liposomal irinotecan and CYP3A4 enzyme-inducing anticonvulsants phenytoin, phenobarbital or carbamazepine have substantially reduced exposure to irinotecan (AUC reduction by 12% with St John's wort, 57%-79% with phenytoin, phenobarbital, or carbamazepine) and SN-38 (AUC reduction by 42% with St John's wort, 36%-92% with phenytoin phenobarbital, or carbamazepine). Therefore, co-administration of ONIVYDE with inducers of CYP3A4 may reduce systemic exposure of ONIVYDE.
Strong CYP3A4 inhibitors and UGT1A1 inhibitors
Patients receiving concomitant non-liposomal irinotecan and ketoconazole, a CYP3A4 and UGT1A1 inhibitor, have increased SN-38 exposure by 109%. Therefore, co-administration of ONIVYDE with other inhibitors of CYP3A4 (e.g. grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) may increase systemic exposure of ONIVYDE. Based on the drug interaction of non-liposomal irinotecan and ketoconazole, co-administration of ONIVYDE with other inhibitors of UGT1A1 (e.g. atazanavir, gemfibrozil, indinavir) may also increase systemic exposure of ONIVYDE.
Co-administration of ONIVYDE+5-FU/LV does not alter the pharmacokinetics of ONIVYDE based on the population pharmacokinetic analysis.
No interaction of ONIVYDE (liposomal irinotecan) with other medicinal products is known.
4.6 Fertility, pregnancy and lactation
Women of childbearing potential / contraception in males and females
Women of childbearing potential should use effective contraception during ONIVYDE treatment and 1 month thereafter. Males should use condoms during ONIVYDE treatment and 4 months thereafter.
Pregnancy
There are no adequate data on the use of ONIVYDE in pregnant women. ONIVYDE can cause harm to the foetus when administered to the pregnant woman, as the main ingredient irinotecan has been shown to be embryotoxic and teratogenic in animals (see section 5.3). Therefore, based on results from animal studies and the mechanism of action of irinotecan, ONIVYDE should not be used during pregnancy unless clearly necessary. If ONIVYDE is used during pregnancy or if the patient becomes pregnant while receiving therapy, the patient should be informed about the potential hazard to the foetus.
Breast-feeding
It is unknown whether ONIVYDE or its metabolites are excreted into human milk. Because of the potential for serious adverse reactions of ONIVYDE in breast-feeding infants, ONIVYDE is contraindicated during breast-feeding (see section 4.3). Patients should not breast-feed until one month after the last dose.
Fertility
There are no data on the impact of ONIVYDE on human fertility. Non-liposomal irinotecan was shown to cause atrophy of male and female reproductive organs after multiple daily irinotecan doses in animals (see section 5.3).
4.7 Effects on ability to drive and use machines
ONIVYDE has moderate influence on the ability to drive and use machines. During treatment patients s |
