Irinocan 40/Irinocan 100 Drug Interactions

Interaction between Irinotecan and neuromuscular blocking agents cannot be ruled out. Since Irinotecan Hydrochloride Trihydrate Injection has anticholinesterase activity, drugs with anticholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium and the neuromuscular blockade of non depolarising drugs may be antagonized.
Several studies have shown that concomitant administration of CYP3A inducing anticonvulsant drugs (e.g., carbamazepine, phenobarbital or phenytoin) leads to reduced exposure to Irinotecan, SN-38 and SN-38 glucuronide and reduced Pharmacodynamic effects. The effects of such anticonvulsant drugs were reflected by a decrease in AUC of SN-38 and SN-38G by 50% or more. In addition to induction of Cytochrome P450 3A enzymes, enhanced glucuronidation and enhanced biliary excretion may play a role in reducing exposure to Irinotecan and its metabolites.
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.
Caution should be exercised in patients concurrently taking drugs known to inhibit (e.g., ketoconazole) or induce (e.g., rifampicin, carbamazepine, phenobarbital or phenytoin) drug metabolism by cytochrome P450 3A4. Concurrent administration of Irinotecan with an inhibitor/inducer of this metabolic pathway may alter the metabolism of Irinotecan and should be avoided.
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.
St. John's Wort decreases SN-38 plasma levels. As a result, St. John's Wort should not be administered with Irinotecan.
Co administration of 5 fluorouracil/folinic acid in the combination regimen does not change the pharmacokinetics of Irinotecan.
Co administration of atazanavir sulfate, a CYP3A4 and UGT1A1 inhibitor, has the potential to increase systemic exposure to SN-38, the active metabolite of Irinotecan. Physicians should take this into consideration when co administering these drugs.
Interactions common to all cytotoxic: The use of anticoagulants is common due to increased risk of thrombotic events in tumoural diseases. If vitamin K antagonist anticoagulants are indicated, an increased frequency in the monitoring of INR (International Normalized Ratio) is required due to their narrow therapeutic index, the high intra individual variability of blood thrombogenicity and the possibility of interaction between oral anticoagulants and anticancer chemotherapy.
Concomitant use contraindicated: Yellow fever vaccine: risk of fatal generalised reaction to vaccines.
Concomitant use not recommended: Live attenuated vaccines (except yellow fever): risk of systemic, possible fatal disease (e.g. infections). This risk is increased in subjects who are already immune suppressed by their underlying disease.
Use an inactivated vaccine where this exists (poliomyelitis).
Phenytoin: Risk of exacerbation of convulsions resulting from the decrease of phenytoin digestive absorption by cytotoxic drug or risk of toxicity enhancement due to increased hepatic metabolism by phenytoin.
Concomitant use to take into consideration: Ciclosporine, Tacrolimus: Excessive immunosuppression with risk of lymphoproliferation.
There is no evidence that the safety profile of Irinotecan is influenced by Cetuximab or vice versa.
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.