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Drug Interactions between cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide and isoniazid / rifampin

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 / rifampin and isoniazid / 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 tenofovir

Applies to: isoniazid / rifampin and cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide

RifAMPin may significantly reduce the blood levels of tenofovir from certain preparations, which may make it less effective in treating your condition. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring 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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Major

rifAMPin cobicistat

Applies to: isoniazid / rifampin and cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide

Using cobicistat together with rifAMPin is not recommended. Combining these medications may decrease the blood levels of cobicistat, which may reduce its effectiveness in treating HIV infection. Your doctor may be able to prescribe alternatives that do not interact. 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 elvitegravir

Applies to: isoniazid / rifampin and cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide

Using elvitegravir together with rifAMPin is not recommended. Combining these medications may significantly decrease the blood levels of elvitegravir, which may reduce its effectiveness in treating HIV infection. Your doctor may be able to prescribe alternatives that do not interact. 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 tenofovir

Applies to: isoniazid / rifampin and cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide

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 emtricitabine

Applies to: isoniazid / rifampin and cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide

Consumer information for this interaction is not currently available.

MONITOR: Coadministration of rifampin with agents known to induce hepatotoxicity may potentiate the risk of liver injury. There are various possible mechanisms related to rifampin-associated hepatotoxicity described in product labeling and medical literature, however no consensus has been made. These include increased mitochondrial oxidative stress, apoptotic liver cell injury (in rodent studies), the development of cholestasis, hepatic lipid accumulation, and elevated toxic metabolites caused by rifampin-mediated induction of cytochrome P450 enzymes. Cases of drug-induced liver injury (including fatal cases) have been reported within the first few days to months following rifampin treatment initiation. Additional data suggests that 1-2% of patients receiving rifampin monotherapy for tuberculosis prophylaxis experience hepatotoxicity. The severity of hepatotoxicity from rifampin ranges from asymptomatic elevations in liver enzymes, jaundice and/or hyperbilirubinemia, and symptomatic self-limiting hepatitis to fulminant liver failure and death. In most cases, liver function recovers upon on discontinuation of rifampin treatment, however, progression to acute liver failure requiring liver transplantation is possible. Known risk factors that may predispose the patient to rifampin related hepatotoxicity include: coadministration with other hepatotoxic agents, alcoholism, existing liver disease, malnutrition, extensive liver tuberculosis, liver adenocarcinoma and biliary tract neoplasm. Clinical data have been reported with concurrent use of rifampin with other antituberculosis agents (e.g. isoniazid, pyrazinamide), acetaminophen, antiretroviral agents (e.g., saquinavir/ritonavir) and halothane. Data with other hepatotoxic agents are limited.

MANAGEMENT: Caution and close clinical monitoring should be considered if rifampin is coadministered with other hepatotoxic medications. In addition, the manufacturer recommends patients with impaired liver function only be given rifampin in cases of necessity and then under strict medical supervision. Some authorities consider rifampin treatment in patients with existing liver injury contraindicated (Canada). In cases where coadministration of rifampin with hepatotoxic agents is required, careful monitoring of liver function, especially ALT and AST, should be done prior to therapy and then every 2 to 4 weeks during therapy. If hepatic damage is suspected, rifampin should be immediately discontinued. Furthermore, if hepatitis is attributed to rifampin in patients with tuberculosis, alternative agents should be considered. Patients should be instructed to contact their physician immediately if they experience symptoms such as itching, weakness, loss of appetite, nausea, vomiting, abdominal pain, yellowing of the eyes or skin or dark urine.

References

  1. Tostmann A, Boeree MJ, Aarnoutse RE, De Lange WCM, Van Der Ven AJAM, Dekhuijzen R "Antituberculosis drug-induced hepatotoxicity: concise up-to-date review https://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2007.05207.x" (2024):
  2. "Product Information. Rifampin (rifAMPin)." Akorn Inc (2022):
  3. "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc (2022):
  4. "Product Information. Rifadin (rifampicin)." Sanofi (2023):
  5. "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd (2024):
  6. Zhuang X, Li L, liu t, zhang r, Yang P, Wang X, et al. "Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1037814/full" (2024):
  7. "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc. (2019):
View all 7 references
Moderate

isoniazid emtricitabine

Applies to: isoniazid / rifampin and cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide

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

tenofovir cobicistat

Applies to: cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide and cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide

Using cobicistat together with tenofovir can increase the effects of tenofovir, which can cause new or worse kidney problems. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. 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

emtricitabine cobicistat

Applies to: cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide and cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide

Cobicistat is a medication used to boost the effects of some medications that treat HIV infection. However, using cobicistat together with other HIV medications, such as emtricitabine, may alter the blood levels and effects of both medications. Using emtricitabine with cobicistat may reduce or increase blood levels of cobicistat. Reduced blood levels of cobicistat may make cobicistat less effective and may cause overall HIV treatment to be less effective. Cobicistat may increase blood levels of emtricitabine which may increase the risk of side effects. Talk to your doctor or pharmacist if you have any questions on how to use these medications properly. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. 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 / 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 / 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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Moderate

elvitegravir food

Applies to: cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide

Food significantly increases the absorption of elvitegravir. You should take each dose of elvitegravir with a meal. Taking it on an empty stomach may lead to inadequate blood levels and reduced effectiveness of the medication in treating HIV infection.

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Minor

tenofovir food

Applies to: cobicistat / elvitegravir / emtricitabine / tenofovir alafenamide

Information for this minor interaction is available on the professional version.

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.