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Drug Interactions between cephalexin and Kisqali Femara Co-Pack

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

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Interactions between your drugs

Moderate

letrozole ribociclib

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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ribociclib is added to or withdrawn from therapy.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

Drug and food interactions

Moderate

ribociclib food

Applies to: Kisqali Femara Co-Pack (letrozole / 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)
  1. (2017) "Product Information. Kisqali (ribociclib)." Novartis Pharmaceuticals
Moderate

cephalexin food

Applies to: cephalexin

ADJUST DOSING INTERVAL: Oral products containing zinc such as mineral supplements and multivitamins may interfere with the gastrointestinal absorption of cephalexin, ceftibuten or cephradine. In one pharmacokinetic study (n=12), concurrent administration of zinc sulfate (250 mg, single oral dose) and cephalexin (500 mg, single oral dose) decreased cephalexin maximum concentration (Cmax) and systemic exposure (AUC; 0-inf) by 31.05% and 27.4%, respectively. However, in the same study, when zinc sulfate was administered 3 hours after the cephalexin dose, no significant alteration in cephalexin pharmacokinetics were observed.

MANAGEMENT: Oral medications or mineral supplements that contain zinc are recommended to be administered at least 3 hours after the cephalexin, ceftibuten or cephradine dose.

References (3)
  1. Ding Y, Jia Y, Li F, et al. (2011) "The Effect of Staggered Administration of Zinc Sulfate on the Pharmacokinetics of Oral Cephalexin*" Br J Clin Pharmacol, 73, p. 422-7
  2. World Health Organization (2020) WHO Public Assessment Reports (WHOPARs) https://extranet.who.int/pqweb/medicines/prequalification-reports/whopars
  3. Okamura M, Terada t, KatsuraT, Saito H, Inui K (2003) "Inhibitory effect of zinc on PEPT1-mediated transport of glycylsarcosine and beta-lactam antibiotics in human intestinal cell line Caco-2" Pharm Res, 20, p. 1389-93

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

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