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Drug Interactions between asciminib and losartan

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

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Interactions between your drugs

Moderate

losartan asciminib

Applies to: losartan and asciminib

MONITOR: Coadministration with asciminib may increase the plasma concentrations of drugs that are primarily metabolized by the CYP450 2C9 isoenzyme. The mechanism is reduced clearance due to inhibition of CYP450 2C9 by asciminib. When warfarin, a probe substrate for CYP450 2C9, was coadministered with asciminib 40 mg twice daily, peak plasma concentration (Cmax) and systemic exposure (AUC) for the biologically more active S(-) enantiomer of warfarin increased by 8% and 41%, respectively. Likewise, the Cmax and AUC of S(-) warfarin increased by 4% and 52%, respectively, following coadministration with asciminib at 80 mg once daily, but increased by 7% and 314%, respectively, following coadministration with asciminib at 200 mg twice daily. These results suggest weak inhibition of CYP450 2C9 by asciminib at the lower dosages and moderate inhibition at the highest dosage.

MANAGEMENT: Caution is advised when asciminib is used concomitantly with drugs that are substrates of CYP450 2C9, particularly sensitive substrates or those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever asciminib is added to or withdrawn from therapy. The prescribing information recommends avoiding concomitant use of asciminib with sensitive CYP450 2C9 substrates or certain substrates where minimal concentration changes may lead to serious or life-threatening toxicities. If treatment with CYP450 2C9 substrate(s) is required, closely monitor for the development of adverse reactions and reduce dosage(s) as necessary in patients receiving asciminib therapy at 80 mg total daily dose. Consider alternative therapy with non-CYP450 2C9 substrates in patients receiving asciminib at the maximum recommended dosage of 200 mg twice daily. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration of a moderate CYP450 2C9 inhibitor like asciminib and for any dosage adjustments that may be required.

References

  1. (2021) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals

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Drug and food interactions

Moderate

losartan food

Applies to: losartan

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

MONITOR: Grapefruit juice may modestly decrease and delay the conversion of losartan to its active metabolite, E3174. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who regularly consume grapefruits and grapefruit juice should be monitored for altered efficacy of losartan. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.

References

  1. (2001) "Product Information. Cozaar (losartan)." Merck & Co., Inc
  2. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
  3. Ray K, Dorman S, Watson R (1999) "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction." J Hum Hypertens, 13, p. 717-20

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Moderate

asciminib food

Applies to: asciminib

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of asciminib. When a single 40 mg dose of asciminib was administered with a low-fat meal (400 calories; 25% fat) in healthy volunteers, asciminib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 35% and 30%, respectively, compared to asciminib administered in the fasted state. Administration with a high-fat meal (1000 calories; 50% fat) decreased the Cmax and AUC of asciminib by 68% and 62%, respectively.

MANAGEMENT: To ensure adequate asciminib exposures, food consumption should be avoided for at least 2 hours before and 1 hour after taking asciminib.

References

  1. (2021) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals
  2. (2022) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals UK Ltd, Scemblix 20 mg film-

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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.

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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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