Interactions : אינטראקציות

4.5.    Interaction with other medicinal products and other forms of interaction

Concomitant use contraindicated (see section 4.3)

Saint John’s Wort: Decrease in the active metabolite of irinotecan, SN-38, plasma levels. In a small pharmacokinetic study (n=5), in which irinotecan 350 mg/m2 was co-administered with St. John's Wort (Hypericum perforatum) 900 mg, a 42% decrease in the active metabolite of irinotecan, SN-38, plasma concentrations was observed. As a result, St. John's Wort should not be administered with irinotecan.

Live attenuated vaccines (e.g. yellow fever vaccine): Risk of generalised reaction to vaccines, possibly fatal. Concomitant use is contraindicated during treatment with irinotecan and for 6 months following discontinuation of chemotherapy. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.

Concomitant use not recommended (see section 4.4)

Concurrent administration of irinotecan with a strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) may alter the metabolism of irinotecan and should be avoided (see section 4.4): 
Strong CYP3A4 and/or UGT1A1 inducing medicinal products: (e.g., rifampicin, carbamazepine, phenobarbital, phenytoin or apalutamide):
Risk of reduced exposure to irinotecan, SN-38 and SN-38 glucuronide and reduced pharmacodynamic effects. Several studies have shown that concomitant administration of CYP3A4-inducing anticonvulsant medicinal products leads to reduced exposure to irinotecan, SN-38 and SN-38 glucuronide and reduced pharmacodynamic effects. The effects of such anticonvulsant medicinal products were reflected by a decrease in AUC of SN-38 and SN-38G by 50% or more. In addition to induction of CYP3A4 enzymes, enhanced glucuronidation and enhanced biliary excretion may play a role in reducing exposure to irinotecan and its metabolites. Additionally with phenytoin: Risk of exacerbation of convulsions resulting from the decrease of phenytoin digestive absorption by cytotoxic medicinal products.

Strong CYP3A4 inhibitors: (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, protease inhibitors, clarithromycine, erythromycine, telithromycine):
A study has shown that the co-administration of ketoconazole resulted in a decrease in the AUC of APC of 87% and in an increase in the AUC of SN-38 of 109% in comparison to irinotecan given alone.
UGT1A1 inhibitors (e.g., atazanavir, ketoconazole, regorafenib):
Risk to increase systemic exposure to SN-38, the active metabolite of irinotecan. Physicians should take this into consideration if the combination is unavoidable.

Other CYP3A4 inhibitors (e.g., crizotinib, idelalisib):
Risk of increase in irinotecan toxicity, due to a decrease in irinotecan metabolism by crizotinib or idelalisib.

Caution for use

Vitamin K antagonists: Increased risk of haemorrhage and thrombotic events in tumoral diseases. If vitamin K antagonist are indicated, an increased frequency in the monitoring of INR (International Normalised Ratio) is required.

Concomitant use to take into consideration

Immunodepressant agents: (e.g., ciclosporine, tacrolimus): Excessive immunosuppression with risk of lymphoproliferation.

Neuromuscular blocking agents: Interaction between irinotecan and neuromuscular blocking agents cannot be ruled out. Since Irinotecan HCl Seacross 20 mg/ml has anticholinesterase activity, medicinal products with anticholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium and the neuromuscular blockade of non-depolarising medicinal products may be antagonised.

Other combinations

5-fluorouracil/folinic acid: Co-administration of 5-fluorouracil/folinic acid in the combination regimen does not change the pharmacokinetics of irinotecan.


Bevacizumab: Results from a dedicated drug-drug interaction trial demonstrated no significant effect of bevacizumab on the pharmacokinetics of irinotecan and its active metabolite SN-38. However, this does not preclude any increase of toxicities due to their pharmacological properties.

Cetuximab: There is no evidence that the safety profile of irinotecan is influenced by cetuximab or vice versa.

Antineoplastic agents (including flucytosine as a prodrug for 5-fluorouracil): Adverse effects of irinotecan, such as myelosuppression, may be exacerbated by other antineoplastic agents having a similar adverse-effect profile.