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Drug Interactions between Clolar and Ifex

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

ifosfamide clofarabine

Applies to: Ifex (ifosfamide) and Clolar (clofarabine)

GENERALLY AVOID: Coadministration of clofarabine with other nephrotoxic agents may increase the risk of renal impairment due to additive effects on the kidney. Moreover, renal impairment secondary to the use of these agents may reduce the clearance of clofarabine, which is primarily eliminated by renal excretion. This may increase the risk of other adverse effects such as nausea, vomiting, stomatitis, hypertension, hypotension, myelosuppression, hemorrhage, and hepatotoxicity. In clinical trials for clofarabine, grade 3 or 4 elevations in creatinine occurred in 8% of patients, and acute renal failure was reported in 3% at grade 3 and 2% at grade 4. Hematuria was observed in 13% of patients overall. Patients with infection, sepsis, or tumor lysis syndrome may be at increased risk of renal toxicity during treatment with clofarabine.

MANAGEMENT: Drugs that are potentially nephrotoxic (e.g., aminoglycosides; polypeptide, glycopeptide, and polymyxin antibiotics; amphotericin B; aminosalicylates; antiviral/antiretroviral agents such as acyclovir, adefovir, cidofovir, foscarnet, ganciclovir, and tenofovir; antineoplastics such as aldesleukin, carboplatin, cisplatin, ifosfamide, streptozocin, and high intravenous dosages of methotrexate; chelating agents such as deferasirox, deferoxamine, edetate disodium, and edetate calcium disodium; immunosuppressants such as cyclosporine, everolimus, sirolimus, and tacrolimus; intravenous bisphosphonates; intravenous pentamidine; high dosages and/or chronic use of nonsteroidal anti-inflammatory agents; gallium nitrate; lithium; penicillamine) should be avoided during the 5 days of clofarabine administration if possible. Renal function should be evaluated prior to and during therapy, and administration discontinued immediately if substantial increases (e.g., grade 3 or higher) in creatinine are noted. Clofarabine therapy should be reinstated when the patient is stable and renal function has returned to baseline, generally with a 25% dose reduction.

References

  1. "Product Information. Clolar (clofarabine)." sanofi-aventis (2005):

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Drug and food interactions

Moderate

ifosfamide food

Applies to: Ifex (ifosfamide)

GENERALLY AVOID: Grapefruit and/or grapefruit juice may reduce the efficacy of ifosfamide, whose anticancer effect is dependent on its activation to the 4-hydroxyifosfamide metabolite via CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4 metabolism by certain compounds present in grapefruit. There are no data available about the effects of grapefruit on ifosfamide. However, in a small study, 8 patients with incurable malignancies received ifosfamide 3 g/m2 by infusion with the potent CYP450 3A4 inhibitor ketoconazole 200 mg orally twice daily for 4 days starting 1 day before the ifosfamide infusion. Ketoconazole decreased the clearance of ifosfamide by 11%, decreased systemic exposure (AUC) of the active metabolite 4-hydroxyifosfamide by 30%, and increased the AUC of the inactive but potentially neurotoxic metabolite 2-dechloroethylifosfamide by 23%, as compared to control. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

GENERALLY AVOID: Alcohol may potentiate the neurotoxic effects of ifosfamide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, ifosfamide therapy may cause gastrointestinal disorders and alcohol consumption may increase nausea and vomiting.

MANAGEMENT: Given the potential for reduced efficacy of ifosfamide and increased risk of neurotoxicity and nephrotoxicity it may be advisable for patients to avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with ifosfamide. In addition, patients receiving ifosfamide should be warned of the increased risk of neurotoxicity, nausea and vomiting when used in combination with alcohol. Patients should avoid or limit the consumption of alcohol during treatment with ifosfamide.

References

  1. "Product Information. Ifosfamide (ifosfamide)." Hikma USA (formerly West-Ward Pharmaceutical Corporation) (2019):
  2. Kerbusch T, jansen rlh, mathot raa, huitema adr, Jansen RNM, Rijswijk REN, Beijen JH "Modulation of the cytochrome P450-mediated metabolism of ifosfamide by ketoconazole and rifampin" Clin Pharmacol and Therapeutic 70 (2001): 132-141
  3. "Product Information. Ifex (ifosfamide)." Baxter Pharmaceutical Products, Inc (2018):
  4. "Product Information. Holoxan (iFOSFamide)." Baxter Healthcare Pty Ltd (2018):
  5. "Product Information. Ifosfamide (ifosfamide)." Baxter Healthcare Ltd (2022):
  6. "Product Information. Ifex (ifosfamide)." Baxter Corporation (2018):
View all 6 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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