Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
Planned co administration or sequential administration of other substances or treatments that could increase the likelihood or severity of toxic effects (by means of pharmacodynamic or pharmacokinetic interactions) requires careful individual assessment of the expected benefit and the risks. Patients receiving such combinations must be monitored closely for signs of toxicity to permit timely intervention.
Patients being treated with ifosfamide and agents that reduce its activation should be monitored for a potential reduction of therapeutic effectiveness and the need for dose adjustment.
Increased haematotoxicity and/or immunosuppression may result from a combined effect of ifosfamide and, for example:
– ACE inhibitors: ACE inhibitors can cause leukopenia.
– Carboplatin
– Cisplatin
– Natalizumab
Increased cardiotoxicity may result from a combined effect of ifosfamide and, for example: – Anthracyclines
– Irradiation of the cardiac region
Increased pulmonary toxicity may result from a combined effect of ifosfamide and, for example:
– Amiodarone
– G-CSF, GM-CSF (granulocyte colonystimulating factor, granulocyte macrophage colony- stimulating factor)
Increased nephrotoxicity may result from a combined effect of ifosfamide and, for example: – Acyclovir
– Aminoglycosides
– Amphotericin B
– Carboplatin
– Cisplatin
An increased risk of developing haemorrhagic cystitis may result from a combined effect of ifosfamide and, for example:
– Busulfan
– Irradiation of the bladder
Additive CNS effects may result from a combined effect of ifosfamide and, for example: – Antiemetics
– Antihistamines
– Narcotics
– Sedatives
Inducers of human hepatic and extrahepatic microsomal enzymes (e.g.,cytochrome P450 enzymes):
The potential for increased formation of metabolites responsible for cytotoxicity and other toxicities (depending on the enzymes induced) must be considered in case of prior or concomitant treatment with, for example:
– Carbamazepine
– Corticosteroids
– Rifampin
– Phenobarbital
– Phenytoin
– St. John's Wort
See also aprepitant below.
Inhibitors of CYP 3A4: Reduced activation and metabolism of ifosfamide may alter the effectiveness of ifosfamide treatment. Inhibition of CYP 3A4 can also lead to increased formation of an ifosfamide metabolite associated with CNS and nephrotoxicity. CYP 3A4 inhibitors include:
– Ketoconazole
– Fluconazole
– Itraconazole
– Sorafenib
See also aprepitant below.
Aprepitant: Reports suggest increased ifosfamide neurotoxicity in patients receiving antiemetic prophylaxis with aprepitant, which is both an inducer and a moderate inhibitor of CYP 3A4.
Docetaxel: Increased gastrointestinal toxicity has been reported when ifosfamide was administered before docetaxel infusion.
Coumarin derivatives: Increased INR (increased international normalized ratio) has been reported in patients receiving ifosfamide and warfarin.
Vaccines: The immunosuppressive effects of ifosfamide can be expected to reduce the response to vaccination. Use of live vaccines may lead to vaccine induced infection.
Tamoxifen: Concomitant use of tamoxifen and chemotherapy may increase the risk of thromboembolic complications.
Cisplatin: Cisplatin-induced hearing loss can be exacerbated by concurrent ifosfamide therapy (see also interactions above).
Irinotecan: Formation of the active metabolite of irinotecan may be reduced when irinotecan is administered with ifosfamide.
Alcohol: In some patients, alcohol may increase ifosfamide-induced nausea and vomiting.
Concurrent administration of antidiabetic agents, such as sulfonylureas and ifosfamide may enhance the hypoglycaemic effects of the former drugs.
Theoretical interactions of ifosfamide and allopurinol resulting in an increased severity of bone marrow depression.