Skip to main content

Drug Interactions between ifosfamide and ribociclib

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

ifosfamide ribociclib

Applies to: ifosfamide and ribociclib

MONITOR: Coadministration with ribociclib may increase the plasma concentrations and pharmacologic effects of drugs that are substrates of CYP450 3A4. The proposed mechanism is decreased clearance due to ribociclib-mediated inhibition of CYP450 3A4 metabolism. In healthy study subjects, administration of midazolam, a sensitive CYP450 3A4 substrate, with multiple 400 mg daily doses of ribociclib increased the midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) by 2.1-fold and 3.8-fold, respectively, compared to midazolam administered alone. When given at a clinically relevant dose of 600 mg daily, ribociclib is predicted to increase midazolam Cmax and AUC by 2.4-fold and 5.2-fold, respectively.

MANAGEMENT: Caution is advised when ribociclib is used concomitantly with drugs that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ribociclib is added to or withdrawn from therapy.

References

  1. Zhou XJ, Zhou-Pan XR, Gauthier T, Placidi M, Maurel P, Rahmani R "Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions." Biochem Pharmacol 45 (1993): 853-61
  2. Trivier JM, Libersa C, Belloc C, Lhermitte M "Amiodarone N-deethylation in human liver microsomes: involvement of cytochrome P450 3A enzymes (first report)." Life Sci 52 (1993): pl91-6
  3. Rawden HC, Kokwaro GO, Ward SA, Edwards G "Relative contribution of cytochromes P-450 and flavin-containing monoxygenases to the metabolism of albendazole by human liver microsomes." Br J Clin Pharmacol 49 (2000): 313-22
  4. DSouza DL, Levasseur LM, Nezamis J, Robbins DK, Simms L, Koch KM "Effect of alosetron on the pharmacokinetics of alprazolam." J Clin Pharmacol 41 (2001): 452-4
  5. Katoh M, Nakajima M, Yamazaki H, Yokoi T "Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transport." Eur J Pharm Sci 12 (2001): 505-13
  6. Kane GC, Lipsky JJ "Drug-grapefruit juice interactions." Mayo Clin Proc 75 (2000): 933-42
  7. Yu DK "The contribution of P-glycoprotein to pharmacokinetic drug-drug interactions." J Clin Pharmacol 39 (1999): 1203-11
  8. Nagy J, Schipper HG, Koopmans RP, Butter JJ, van Boxtel CJ, Kager PA "Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability." Am J Trop Med Hyg 66 (2002): 260-3
  9. "Product Information. Kisqali (ribociclib)." Novartis Pharmaceuticals (2017):
View all 9 references

Switch to consumer interaction data

Drug and food interactions

Moderate

ifosfamide food

Applies to: 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

Switch to consumer interaction data

Moderate

ribociclib food

Applies to: ribociclib

GENERALLY AVOID: Pomegranates and grapefruit may increase the systemic exposure to ribociclib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Increased exposure to ribociclib may increase the risk of adverse effects such as infections, neutropenia, leukopenia, anemia, thrombocytopenia, anorexia, nausea, vomiting, diarrhea, stomatitis, alopecia, fatigue, headache, and abnormal liver function may be increased.

MANAGEMENT: Patients receiving ribociclib should avoid consumption of pomegranates or pomegranate juice and grapefruit or grapefruit juice during treatment.

References

  1. "Product Information. Kisqali (ribociclib)." Novartis Pharmaceuticals (2017):

Switch to consumer interaction data

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.

See also

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer