Table 2.

Summary of the common drug interactions between supportive care and anticancer agents in pediatric oncology and recommendations for alternative agents

Supportive Care Agent	Chemotherapy Agent	Outcome and Mechanism of Interaction	Alternatives	Ref
Phenytoin, Carbamazepine, Phenobarbital,	Anthracyclines, Cyclophosphamide, Ifosfamide, Epipodophyllotoxins, Tyrosine kinase inhibitors, Vinca alkaloids	Decreased effectiveness of chemotherapy agent through induction of CYP450 that catabolize anticancer agents	Use non-enzyme inducing anticonvulsants	19–22
Valproic acid (VPA)	Cisplatin	Increased cisplatin hematologic toxicity	- Use non-enzyme inhibiting anticonvulsants	23,24
	Methotrexate	Decreased absorption of VPA	- Monitor valproic acid serum concentration	23
Aprepitant	Anthracyclines, Epipodophyllotoxins, Cyclophosphamide, Ifosfamide, Dexamethasone, Tyrosine kinase inhibitors,Thiotepa	Increased toxicity of the chemotherapy agent through CYP450 inhibition	Use alternative antiemetic	26,27,29
Proton pump inhibitors	Methotrexate	Decreased methotrexate excretion via transporter inhibition	- Use ranitidine or sucralfate	37
	Tyrosine kinase inhibitors (except imatinib)	Decreased absorption of the chemotherapy agent by decreasing gastric pH	- Separate drug administration by 3–4 hours	47
Azole antifungals	Anthracyclines, Busulfan, Calcineurin inhibitors, Epipodophyllotoxins, Tyrosine kinase inhibitors, Vinca alkaloids	Increased toxicity through inhibition of CYP450 catabolism of active anticancer drugs	Use echinocandin antifungals or amphotericin B formulations	12,48–51,62
Amphotericin B	Cisplatin, High-dose methotrexate	Decreased excretion of renally cleared anticancer drug due to amphotericin nephrotoxicity	Use echinocandin antifungals	56
Penicillins	Methotrexate	Interference with tubular excretion of methotrexate	Consider an alternative non-penicillin antibiotic	43,57
TMP/SMX	Methotrexate	Delayed clearance of methotrexate	Some institutions hold TMP/SMX; others do not	59,60
NSAIDs	Methotrexate	Decreased excretion of methotrexate	Avoid NSAIDs, use opioids for pain if needed	42,63,64
Acyclovir (high dose)	Cisplatin, High-dose methotrexate	Additive nephrotoxicity	Do not combine if possible	41
Sargramostim, filgrastim	Vinca alkaloids	Severe atypical neuropathy	Some institutions hold factor support; others do	65
St. John’s Wort	Anthracyclines, Calcineurin inhibitors, Epipodophyllotoxins, Tyrosine kinase inhibitors, Vinca alkaloids	Decreased effectiveness of chemotherapy agent through induction of CYP450 induction	Avoid the use of St. John’s Wort during chemotherapy	66

Abbreviations: VPA, valproic acid; trimethoprim-sulfamethoxazole (TMP/SMX); NSAIDs, non-steroidal anti-inflammatory drugs.