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Drug Interactions between isoniazid / pyrazinamide / rifampin and Zuplenz

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

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Interactions between your drugs

Major

rifAMPin isoniazid

Applies to: isoniazid / pyrazinamide / rifampin and isoniazid / pyrazinamide / rifampin

Using isoniazid together with rifAMPin can cause serious side effects that may affect your liver. Call your doctor immediately if you experience a fever, chills, joint pain or swelling, excessive tiredness or weakness, unusual bleeding or bruising, skin rash or itching, loss of appetite, nausea, vomiting, or yellowing of the skin or the whites of your eyes. If your doctor does prescribe these medications together, you may need a dose adjustment or special tests to safely take both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Major

rifAMPin pyrazinamide

Applies to: isoniazid / pyrazinamide / rifampin and isoniazid / pyrazinamide / rifampin

Ask your doctor before using rifAMPin together with pyrazinamide. This can cause damage to the liver. Liver function and drug levels in the blood may be monitored with blood tests during treatment. Call your doctor if you experience fever, rash, loss of appetite, nausea, vomiting, fatigue, right upper abdominal pain, dark urine, and jaundice. You may need a dose adjustment or special tests to safely take both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Moderate

isoniazid pyrazinamide

Applies to: isoniazid / pyrazinamide / rifampin and isoniazid / pyrazinamide / rifampin

Consumer information for this interaction is not currently available.

MONITOR: Coadministration of isoniazid (INH) with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. 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 INH's acetylation is genetically determined and generally classified as slow or rapid, with slow acetylators characterized by a relative lack of N-acetyltransferase. While the rate of acetylation does not significantly alter INH's effectiveness, it can lead to higher blood levels of INH and an increase of adverse reactions. In addition, INH is an in vitro inhibitor of several CYP450 isoenzymes (2C9, 2C19, 2E1, and 3A4). Coadministration of hepatotoxic drugs eliminated by one or more of these pathways may lead to elevated concentrations of the concomitant drug and increase the risk of hepatotoxicity. Most of the INH-associated hepatitis cases occur during the first 3 months of treatment, but may occur at any time and have been reported to be severe or even fatal. INH is reported in medical literature to cause clinically apparent acute liver injury with jaundice in 0.5% to 1% and fatality in 0.05% to 0.1% of recipients. A United States Public Health Service Surveillance Study of 13,838 people taking INH reported 8 deaths among 174 cases of hepatitis. Risk factors for INH related liver injury may include: age > 35 years, female gender, postpartum period, daily consumption of alcohol, injection drug user, slow acetylator phenotype, malnutrition, HIV infection, pre-existing liver disease, extra-pulmonary tuberculosis, and concomitant use of hepatotoxic medications. Clinical data have been reported with concurrent use of acetaminophen, alcohol, carbamazepine, phenobarbital, phenytoin, and rifampin.

MANAGEMENT: Coadministration of isoniazid (INH) with other hepatotoxic medications should be done with caution and close clinical monitoring. Some authorities recommend avoiding concurrent use when possible. If coadministration is needed, baseline and monthly liver function testing as well as monthly interviewing of the patient to check for signs and symptoms of adverse effects is recommended. More frequent testing may be advisable in patients at increased risk of INH-associated liver injury. Some manufacturers of INH recommend strongly considering its discontinuation if serum aminotransferase concentrations (AST or SGOT, ALT or SGPT) exceed 3 to 5 times the upper limit of normal. Patients should be counseled to immediately report signs or symptoms consistent with liver damage and notified that prodromal symptoms usually consist of fatigue, weakness, malaise, anorexia, nausea, and/or vomiting. If hepatic damage is suspected, INH should be immediately discontinued as continuation may lead to more severe damage. If hepatitis is attributed to INH in patients with tuberculosis, alternative drugs should be used. However, if INH must be used, it should only be resumed after the patient's symptoms and laboratory abnormalities have cleared. It should also be restarted in very small, gradually increasing doses and immediately withdrawn if there is any indication of recurrent liver involvement. Consultation with product labeling and relevant guidelines is advisable.

References

  1. "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India) 2 (2021):
  2. "Product Information. Isoniazid (isoniazid)." Chartwell RX, LLC. (2023):
  3. "Product Information. Isoniazid (Arrotex) (isoniazid)." Arrotex Pharmaceuticals Pty Ltd (2023):
  4. "Product Information. Isoniazid (isoniazid)." RPH Pharmaceuticals AB (2023):
  5. 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
  6. 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):
  7. Metushi I, Uetrecht J, Phillips E "Mechanism of isoniazid-induced hepatotoxicity: then and now." Br J Clin Pharmacol 81 (2016): 1030-6
  8. National Institute of Diabetes and Digestive and Kidney Diseases "LiverTox: clinical and research information on drug-induced liver injury [internet]. Isoniazid. https://www.ncbi.nlm.nih.gov/books/NBK548754/" (2024):
  9. "Product Information. Isotamine (isoniazid)." Bausch Health, Canada Inc. (2021):
View all 9 references
Moderate

rifAMPin ondansetron

Applies to: isoniazid / pyrazinamide / rifampin and Zuplenz (ondansetron)

Using rifAMPin together with ondansetron may decrease the effects of ondansetron. Contact your doctor if your condition changes. If your doctor does prescribe these medications together, you may need a dose adjustment or special test to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Drug and food interactions

Moderate

rifAMPin food

Applies to: isoniazid / pyrazinamide / rifampin

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 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 rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

References

  1. "Product Information. Rifampin (rifAMPin)." Akorn Inc (2022):
  2. "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc (2022):
  3. "Product Information. Rifadin (rifampicin)." Sanofi (2023):
  4. "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd (2024):
  5. Peloquin CA, Namdar R, Singleton MD, Nix DE "Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids https://pubmed.ncbi.nlm.nih.gov/9925057/" (2024):
  6. "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc. (2019):
View all 6 references
Moderate

isoniazid food

Applies to: isoniazid / pyrazinamide / rifampin

Food decreases the levels of isoniazid in your body. Take isoniazid on an empty stomach at least 1 hour before or 2 hours after a meal. This will make it easier for your body to absorb the medication. If nausea occurs, ask your doctor if you can take isoniazid with food. Avoid alcohol while taking isoniazid. Alcohol may increase the risk of damage to the liver during isoniazid treatment. Alcohol can also cause isoniazid side effects to get worse. Contact your doctor if you experience flushing, chills, headache, nausea, vomiting, and diarrhea.

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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

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