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Drug Interactions between amoxicillin and isoniazid

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

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Interactions between your drugs

No interactions were found between amoxicillin and isoniazid. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.

amoxicillin

A total of 40 drugs are known to interact with amoxicillin.

isoniazid

A total of 675 drugs are known to interact with isoniazid.

Drug and food interactions

Moderate

isoniazid food

Applies to: isoniazid

GENERALLY AVOID: Concurrent use of isoniazid (INH) in patients who ingest alcohol daily may result in an increased incidence of both hepatotoxicity and peripheral neuropathy. The increase in hepatotoxicity may be due to an additive risk as both alcohol and INH are individually associated with this adverse reaction. INH-associated hepatotoxicity is believed to be due to an accumulation of toxic metabolites and may also be partly immune mediated, though the exact mechanisms are not universally agreed upon. INH is metabolized by N-acetyltransferase and CYP450 2E1. The rate of acetylation is genetically determined and generally classified as slow or rapid. Slow acetylators have been identified by some studies as having a higher risk of hepatotoxicity; therefore, this interaction may be more significant for patients who fall into this category. Other studies have postulated that alcohol-mediated CYP450 2E1 induction may play a role, as this isoenzyme is involved in INH metabolism and may be responsible for producing hepatotoxic metabolites. However, available literature is conflicting. The labeling for some INH products lists daily alcohol use or chronic alcoholism as a risk factor for hepatitis, but not all studies have found a significant association between alcohol use and INH-induced hepatotoxicity. Additionally, INH and alcohol are both associated with pyridoxine (B6) deficiency, which may increase the risk of peripheral neuropathy.

GENERALLY AVOID: Concomitant administration of isoniazid (INH) with foods containing tyramine and/or histamine may increase the risk of symptoms relating to tyramine- and/or histamine toxicity (e.g., headache, diaphoresis, flushing, palpitations, and hypotension). The proposed mechanism is INH-mediated inhibition of monoamine oxidase (MAO) and diamine oxidase (DAO), enzymes responsible for the metabolism of tyramine and histamine, respectively. Some authors have suggested that the reactions observed are mainly due to INH's effects on DAO instead of MAO or the amounts of histamine instead of tyramine present in the food. A Japanese case report recorded an example in 8 out of 25 patients on the tuberculosis ward who developed an accidental histamine poisoning after ingesting a fish paste (saury). Patients developed allergy-like symptoms, which started between 20 minutes and 2 hours after ingesting the food. A high-level of histamine (32 mg/100 g of fish) was confirmed in the saury paste and all 8 patients were both on INH and had reduced MAO concentrations. The 17 remaining patients were not on INH (n=5) or reported not eating the saury paste (n=12).

ADJUST DOSING INTERVAL: Administration with food significantly reduces oral isoniazid (INH) absorption, increasing the risk of therapeutic failure or resistance. The mechanism is unknown. Pharmacokinetic studies completed in both healthy volunteers (n=14) and tuberculosis patients (n=20 treatment-naive patients during days 1 to 3 of treatment) have resulted in almost doubling the time to reach INH's maximum concentration (tmax) and a reduction in isoniazid's maximum concentration (Cmax) of 42%-51% in patients who consumed high-fat or high-carbohydrate meals prior to INH treatment.

MANAGEMENT: The manufacturer of oral forms of isoniazid (INH) recommends administration on an empty stomach (i.e., 30 minutes before or 2 hours after meals). Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and INH concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with INH. Concomitant pyridoxine (B6) administration is also recommended to reduce the risk of peripheral neuropathy, with some authorities suggesting a dose of at least 10 mg/day. Patients should be advised to avoid foods containing tyramine (e.g., aged cheese, cured meats such as sausages and salami, fava beans, sauerkraut, soy sauce, beer, or red wine) or histamine (e.g., skipjack, tuna, mackerel, salmon) during treatment with isoniazid. Consultation of product labeling for combination products containing isoniazid and/or relevant guidelines may be helpful for more specific recommendations.

References

  1. Smith CK, Durack DT "Isoniazid and reaction to cheese." Ann Intern Med 88 (1978): 520-1
  2. Dimartini A "Isoniazid, tricyclics and the ''cheese reaction''." Int Clin Psychopharmacol 10 (1995): 197-8
  3. Uragoda CG, Kottegoda SR "Adverse reactions to isoniazid on ingestion of fish with a high histamine content." Tubercle 58 (1977): 83-9
  4. Self TH, Chrisman CR, Baciewicz AM, Bronze MS "Isoniazid drug and food interactions." Am J Med Sci 317 (1999): 304-11
  5. "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India) 2 (2021):
  6. "Product Information. Isoniazid (isoniazid)." Chartwell RX, LLC. (2023):
  7. "Product Information. Isoniazid (Arrotex) (isoniazid)." Arrotex Pharmaceuticals Pty Ltd (2023):
  8. "Product Information. Isoniazid (isoniazid)." RPH Pharmaceuticals AB (2023):
  9. Saukkonen JJ, Cohn DL, Jasmer RM, et al. "An official ATS statement: hepatotoxicity of antituberculosis therapy." Am J Respir Crit Care Med 174 (2006): 935-52
  10. Bouazzi OE, Hammi S, Bourkadi JE, et al. "First line anti-tuberculosis induced hepatotoxicity: incidence and risk factors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326068/" (2024):
  11. Wang P, Pradhan K, Zhong XB, Ma X "Isoniazid metabolism and hepatoxicity." Acta Pharm Sin B 6 (2016): 384-92
  12. Saktiawati AM, Sturkenboom MG, Stienstra Y, et al. "Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment naive TB patients: a randomized cross-over trial." J Antimicrob Chemother 71 (2016): 703-10
  13. Hahn JA, Ngabirano C, Fatch R, et al. "Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use." AIDS 37 (2023): 1535-43
  14. Huang YS, Chern HD, Su WJ, et al. "Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis." Hepatology 37 (2003): 924-30
  15. Sousou JM, Griffith EM, Marsalisi C, Reddy P "Pyridoxine deficiency and neurologic dysfunction: an unlikely association. https://www.cureus.com/articles/188310-pyridoxine-deficiency-and-neurologic-dysfunction-an-unlikely-association?score_article=true#!/" (2024):
  16. Miki M, Ishikawa T, Okayama H "An outbreak of histamine poisoning after ingestion of the ground saury paste in eight patients taking isoniazid in tuberculous ward." Intern Med 44 (2005): 1133-6
  17. "Product Information. Isotamine (isoniazid)." Bausch Health, Canada Inc. (2021):
View all 17 references

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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.