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Drug Interactions between asciminib and Seldane

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

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Interactions between your drugs

Moderate

terfenadine asciminib

Applies to: Seldane (terfenadine) and asciminib

MONITOR: It is uncertain whether asciminib causes clinically significant prolongation of the QT interval of the electrocardiogram. In clinical studies, prolongation of the Fridericia-corrected QT interval (QTcF) was reported in 3 of 356 (0.8%) of patients, with one report of QTcF greater than 500 msec together with more than 60 msec QTcF increase from baseline. Asciminib is not reported to prolong the corrected QT (QTc) interval by greater than 20 msec at the maximum recommended clinical dosage (200 mg twice daily); however, a prolongation of up to 10 msec cannot be excluded. 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, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Some authorities recommend caution and clinical monitoring when asciminib is used with drugs that are known to cause QT interval prolongation. An ECG should be obtained at baseline and during treatment as clinically indicated, particularly in patients with a history of cardiac arrhythmias, uncontrolled or significant cardiac disease (including bradycardia), or congenital or family history of long QT syndrome. Serum electrolytes, including potassium and magnesium should also be corrected prior to starting asciminib therapy and monitored during treatment as clinically indicated. Patients should be advised to seek prompt medical attention if they experience symptoms that indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

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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Drug and food interactions

Major

terfenadine food

Applies to: Seldane (terfenadine)

CONTRAINDICATED: The consumption of grapefruit juice has been associated with significantly increased plasma concentrations of terfenadine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. Terfenadine in high serum levels has been associated with prolongation of the QT interval and development of torsade de pointes, a potentially fatal ventricular arrhythmia.

MANAGEMENT: Due to the risk of cardiotoxicity, patients receiving the drug should be advised to avoid consumption of grapefruit products. Loratadine, cetirizine, and fexofenadine may be safer alternatives in patients who may have trouble adhering to the dietary restriction.

References

  1. Honig PK, Woosley RL, Zamani K, Conner DP, Cantilena LR Jr (1992) "Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin." Clin Pharmacol Ther, 52, p. 231-8
  2. Zimmermann M, Duruz H, Guinand O, et al. (1992) "Torsades de Pointes after treatment with terfenadine and ketoconazole." Eur Heart J, 13, p. 1002-3
  3. Mathews DR, McNutt B, Okerholm R, et al. (1991) "Torsades de pointes occurring in association with terfenadine use." JAMA, 266, p. 2375-6
  4. Monahan BP, Ferguson CL, Killeavy ES, et al. (1990) "Torsades de pointes occurring in association with terfenadine use." JAMA, 264, p. 2788-90
  5. Honig PK, Wortham DC, Zamani K, et al. (1993) "Terfenadine-ketoconazole interaction: pharmacokinetic and electrocardiographic consequences." JAMA, 269, p. 1513-8
  6. Pohjola-Sintonen S, Viitasalo M, Toivonene L, Neuvonen P (1993) "Torsades de pointes after terfenadine-itraconazole interaction." BMJ, 306, p. 186
  7. Cortese LM, Bjornson DC (1992) "Potential interaction between terfenadine and macrolide antibiotics." Clin Pharm, 11, p. 675
  8. Paris DG, Parente TF, Bruschetta HR, Guzman E, Niarchos AP (1994) "Torsades-de-pointes induced by erythromycin and terfenadine." Am J Emerg Med, 12, p. 636-8
  9. Zechnich AD, Haxby DG (1996) "Drug interactions associated with terfenadine and related nonsedating antihistamines." West J Med, 164, p. 68-9
  10. Honig PK, Wortham DC, Lazarev A, Cantilena LR (1996) "Grapefruit juice alters the systemic bioavailability and cardiac repolarization of terfenadine in poor metabolizers of terfenadine." J Clin Pharmacol, 36, p. 345-51
  11. Woosley RL (1996) "Cardiac actions of antihistamines." Annu Rev Pharmacol Toxicol, 36, p. 233-52
  12. Benton RE, Honig PK, Zamani K, Cantilena LR, Woosley RL (1996) "Grapefruit juice alters terfenadine pharmacokinetics resulting in prolongation of repolarization on the electrocardiogram." Clin Pharmacol Ther, 59, p. 383-8
  13. Hsieh MH, Chen SA, Chiang CE, et al. (1996) "Drug-induced torsades de pointes in one patient with congenital long QT syndrome." Int J Cardiol, 54, p. 85-8
  14. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  15. Rau SE, Bend JR, Arnold JMO, Tran LT, Spence JD, Bailey DG (1997) "Grapefruit juice terfenadine single-dose interaction: Magnitude, mechanism, and relevance." Clin Pharmacol Ther, 61, p. 401-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
View all 17 references

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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-

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.


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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.