DBL Vincristine Sulfate Drug Interactions

Anti-gout Agents: Allopurinol may increase the incidence of cytotoxic induced bone-marrow depression. The mechanism for this potentiation has not been fully classified.
Dosage adjustment of anti-gout agents (eg. allopurinol, colchicine, probenecid or sulfinpyrazone) may be necessary to control hyperuricaemia and gout, since vincristine may raise the concentration of blood uric acid.
Drugs Acting on the Peripheral Nervous System: The neurotoxicity of vincristine may be additive with that of asparaginase (see Dosage & Administration), isoniazid and other medicines acting on the peripheral nervous system.
Doxorubicin: The concurrent use of doxorubicin with vincristine and prednisone may produce increased myelosuppression; it is recommended that the combination be avoided.
Methotrexate: Vincristine appears to increase the cellular uptake of methotrexate by malignant cells and this principle has been applied in high-dose methotrexate therapy. The clinical importance of this interaction is not known however, it has also been reported that a 2.5-fold increase of methotrexate levels in CSF occurred when vincristine was given 23 hours after high dose methotrexate therapy was initiated. The effect lasted approximately 3 hours.
Vaccines: Because normal defense mechanisms may be suppressed by vincristine sulfate therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, and may increase adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine. The patient's antibody response to killed virus may also be decreased. Immunisation of a patient who is receiving or who has received vincristine should be undertaken only with extreme caution after careful review of the patient's haematologic status and only with the knowledge and consent of the physician managing the vincristine therapy. The interval between discontinuation of medications that cause immune suppression and restoration of the patient's ability to respond to the vaccine depends on many factors; estimates vary from 3 months to 1 year.
Oral Quinolones: Due to decreased absorption of the antimicrobial agent, the antimicrobial effect of oral quinolones (ciprofloxacin, norfloxacin and ofloxacin) may be decreased by administration of vincristine.
Phenytoin: The simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included vincristine sulfate has been reported to reduce blood levels of the anticonvulsant and to increase seizure activity. Dosage adjustment should be based on serial blood level monitoring. The contribution of vincristine sulfate to this interaction is not certain. The interaction may result from reduced absorption of phenytoin and an increase in the rate of its metabolism and elimination.
Nifedipine: Nifedipine decreases the clearance of vincristine.
CYP 3A4 Inhibitors/Inducers: Vincristine should be administered cautiously with drugs which inhibit or induce the cytochrome P450 isoenzyme CYP3A, as these drugs may decrease vincristine metabolism, thereby increasing its toxicity. Concurrent administration with itraconazole or fluconazole (known inhibitors of this metabolic pathway) have been reported to cause an earlier onset and/or increased severity of neuromuscular side effects. This interaction is presumed to be related to inhibition of vincristine metabolism. Inducers like St. John's wort should be given cautiously.
Digoxin: Cancer chemotherapy and radiation therapy may result in decreased absorption of the digitalis glycosides digoxin and B-acetyldigoxin administered in tablet forms. Serial monitoring of digoxin blood levels before, during and after chemotherapy should be initiated so that any necessary dosage adjustment can be made.
Voriconazole: Although not studied in vitro or in vivo, voriconazole may increase the plasma concentrations of vinca alkaloids including vincristine sulfate and lead to neurotoxicity. Therefore, it is recommended that dose adjustment of vincristine sulfate be considered.
Mitomycin: Concurrent administration of mitomycin with vincristine may increase the incidence of acute shortness of breath and severe bronchospasm (see Precautions).
Ototoxic Drugs: Vincristine should be used with extreme caution with potentially ototoxic drugs such as the platinum-containing antineoplastic agents, as temporary or permanent hearing impairment has been reported in patients receiving vinca alkaloids (see Adverse Reactions).
Bleomycin: Thromboembolism or Raynaud's syndrome may occur if bleomycin is used with vinca alkaloids and other agents such as cisplatin or etoposide (see Adverse Reactions).
Radiation Therapy: When chemotherapy is being given in conjunction with radiation therapy the use of vincristine should be delayed until radiation therapy has been completed.