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Drug Interactions between Kisqali Femara Co-Pack and tolvaptan

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

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Interactions between your drugs

Major

tolvaptan ribociclib

Applies to: tolvaptan and Kisqali Femara Co-Pack (letrozole / ribociclib)

GENERALLY AVOID: Coadministration with moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of tolvaptan. According to the prescribing information, tolvaptan is extensively metabolized in the liver almost exclusively by CYP450 3A4. Tolvaptan peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 80% and 200%, respectively, when the moderate CYP450 3A4 inhibitor fluconazole was given in a 400 mg dose one day prior and a 200 mg dose concomitantly with tolvaptan.

MANAGEMENT: Concomitant use of tolvaptan with moderate CYP450 3A4 inhibitors should generally be avoided. A 50% reduction of the total daily tolvaptan dosage is recommended when used in the treatment of adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD), along with close monitoring of serum sodium and volume status. The prescribing information for both the specific tolvaptan product and the concomitant medication should be consulted for more detailed guidance.

References (6)
  1. (2022) "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc
  2. (2019) "Product Information. Samsca (tolvaptan)." Otsuka Canada Pharmaceutical Inc
  3. (2021) "Product Information. Samsca (tolvaptan)." Otsuka Australia Pharmaceutical Pty Ltd
  4. (2022) "Product Information. Jynarque (tolvaptan)." Otsuka American Pharmaceuticals Inc
  5. (2019) "Product Information. Jinarc (tolvaptan)." Otsuka Pharmaceutical Co Ltd
  6. (2022) "Product Information. Jinarc (tolvaptan)." Otsuka Australia Pharmaceutical Pty Ltd
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

tolvaptan food

Applies to: tolvaptan

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of tolvaptan. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration of tolvaptan with grapefruit juice resulted in a 1.8-fold increase in tolvaptan systemic exposure. The clinical significance is unknown, although increased pharmacologic effects may be expected. Too rapid correction of hyponatremia increases the risk of osmotic demyelination syndrome, which is associated with dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death.

MANAGEMENT: Patients treated with tolvaptan should avoid consumption of grapefruits and grapefruit juice.

References (1)
  1. (2009) "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc
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

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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