Skip to main content

Drug Interactions between letrozole / ribociclib and pazopanib

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

PAZOPanib ribociclib

Applies to: pazopanib and letrozole / ribociclib

GENERALLY AVOID: Ribociclib can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MONITOR CLOSELY: 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: Coadministration of ribociclib with other drugs that can prolong the QT interval and are substrates of CYP450 3A4, particularly those with a narrow therapeutic range, should generally be avoided. Since the magnitude of QT prolongation may increase with increasing plasma concentrations of these drugs, caution and close clinical monitoring are recommended if concomitant use with these drugs is unavoidable. 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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ribociclib is added to or withdrawn from therapy.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. (2003) "Product Information. Uroxatral (alfuzosin)." sanofi-aventis
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  4. Cerner Multum, Inc. "Australian Product Information."
  5. EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852
  6. Abbas R, Hug BA, Leister C, Sonnichsen D (2012) "A randomized, crossover, placebo- and moxifloxacin-controlled study to evaluate the effects of bosutinib (SKI-606), a dual Src/Abl tyrosine kinase inhibitor, on cardiac repolarization in healthy adult subjects." Int J Cancer, 131, Epub
  7. (2017) "Product Information. Kisqali (ribociclib)." Novartis Pharmaceuticals
View all 7 references

Switch to consumer interaction data

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

Switch to consumer interaction data

Drug and food interactions

Major

PAZOPanib food

Applies to: pazopanib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pazopanib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of pazopanib. The mechanism of interaction is unknown. Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in peak plasma concentration (Cmax) and systemic exposure (AUC).

MANAGEMENT: Patients treated with pazopanib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Pazopanib should be administered at least one hour before or two hours after a meal.

References

  1. (2009) "Product Information. Votrient (pazopanib)." GlaxoSmithKline

Switch to consumer interaction data

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

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