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Drug Interactions between asciminib and tinidazole

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

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Interactions between your drugs

Moderate

tinidazole asciminib

Applies to: tinidazole and asciminib

MONITOR: Coadministration with asciminib may increase the plasma concentrations of drugs that are primarily metabolized by the CYP450 3A4 isoenzyme. The mechanism is reduced clearance due to inhibition of CYP450 3A4 by asciminib. When midazolam, a sensitive CYP450 3A4 substrate, was coadministered with asciminib 40 mg twice daily, midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 11% and 28%, respectively. Likewise, the Cmax and AUC of midazolam increased by 17% and 24%, respectively, following coadministration with asciminib at 80 mg once daily, but increased by 58% and 88%, respectively, following coadministration with asciminib at 200 mg twice daily. These results suggest weak inhibition of CYP450 3A4 by asciminib.

MANAGEMENT: Caution is advised when asciminib is used concomitantly with drugs that are substrates of CYP450 3A4, 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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever asciminib is added to or withdrawn from therapy.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 closely monitoring for the development of adverse reactions in patients receiving asciminib therapy at 80 mg total daily dose with certain CYP450 3A4 substrates where minimal concentration changes may lead to serious or life-threatening toxicities, and avoiding coadministration of these drugs with 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 weak CYP450 3A4 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

tinidazole food

Applies to: tinidazole

GENERALLY AVOID: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.

MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction and instructed to avoid alcoholic beverages and products containing alcohol or propylene glycol while using oral, intravenous, or vaginal preparations of a nitroimidazole. Alcoholic beverages should not be consumed for up to 3 days after completion of systemic nitroimidazole therapy.

References

  1. Giannini AJ, DeFrance DT (1983) "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol, 20, p. 509-15
  2. Alexander I (1985) "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract, 39, p. 292-3
  3. Harries DP, Teale KF, Sunderland G (1990) "Metronidazole and alcohol: potential problems." Scott Med J, 35, p. 179-80
  4. Edwards DL, Fink PC, Van Dyke PO (1986) "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm, 5, p. 999-1000
  5. (2002) "Product Information. Flagyl (metronidazole)." Searle
  6. Williams CS, Woodcock KR (2000) "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother, 34, p. 255-7
  7. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP (2002) "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother, 36, p. 971-4
  8. Krulewitch CJ (2003) "An unexpected adverse drug effect." J Midwifery Womens Health, 48, p. 67-8
  9. (2004) "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc
View all 9 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-

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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.