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Drug Interactions between letrozole / ribociclib and Promacta

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: letrozole / ribociclib and 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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ribociclib is added to or withdrawn from therapy.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

  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
View all 9 references

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Moderate

eltrombopag ribociclib

Applies to: Promacta (eltrombopag) and letrozole / ribociclib

MONITOR: Coadministration with ribociclib may increase the plasma concentrations and pharmacologic effects of drugs that are substrates of breast cancer resistance protein (BCRP), organic cation transporter-2 (OCT-2), multidrug and toxin extrusion 1 (MATE1), and/or bile salt efflux pump (BSEP) transporters. The proposed mechanism, based on in vitro data, is decreased clearance due to ribociclib-mediated inhibition of these transport proteins at clinically relevant concentrations.

MANAGEMENT: Caution is advised if ribociclib is used concomitantly with drugs that are substrates of BCRP, OCT-2, MATE1, and/or BSEP transport proteins, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever ribociclib is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2017) "Product Information. Kisqali (ribociclib)." Novartis Pharmaceuticals

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Drug and food interactions

Moderate

eltrombopag food

Applies to: Promacta (eltrombopag)

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of eltrombopag. In healthy volunteers, a standard high-fat breakfast significantly decreased plasma eltrombopag peak plasma concentration (Cmax) by 65% and systemic exposure (AUC) by 59% and delayed Tmax by one hour. The calcium content of this meal may have also contributed to this decrease in exposure. In another study, adult subjects administered a single 25 mg dose of eltrombopag for oral suspension with a high-calcium, moderate-fat, moderate-calorie meal exhibited a 79% decrease in Cmax and 75% decrease in AUC of eltrombopag. Administration of eltrombopag 2 hours after the high-calcium meal decreased eltrombopag Cmax by 48% and AUC by 47%, while administration 2 hours before the high-calcium meal decreased eltrombopag Cmax by 14% and AUC by 20%.

ADJUST DOSING INTERVAL: Polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc can significantly reduce the gastrointestinal absorption of eltrombopag due to chelation. In one clinical trial, administration of a single 75 mg dose of eltrombopag with an antacid containing 1524 mg aluminum hydroxide and 1425 mg magnesium carbonate resulted in an approximately 70% decrease in eltrombopag Cmax and AUC.

MANAGEMENT: Eltrombopag should be taken on an empty stomach one hour before or two hours after a meal. Additionally, eltrombopag should be taken at least 2 hours before or 4 hours after any products that contain polyvalent cations such as antacids, mineral supplements, dairy products, and fortified juices.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2008) "Product Information. Promacta (eltrombopag)." GlaxoSmithKline

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Moderate

ribociclib food

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

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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.

See also

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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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