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Drug Interaction Report

13 potential interactions and/or warnings found for the following 5 drugs:

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Interactions between your drugs

Major

rifAMPin isoniazid

Applies to: rifampin, isoniazid

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: rifampin, pyrazinamide

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

rifAMPin ethambutol

Applies to: rifampin, ethambutol

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.

Moderate

ethambutol isoniazid

Applies to: ethambutol, isoniazid

Using ethambutol together with isoniazid may increase the risk of nerve damage, which is a potential side effect of both medications. 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. Let your doctor know if you develop weakness, numbness, pain, burning, or tingling in your hands, feet, or limbs. 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

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.

Moderate

rifAMPin escitalopram

Applies to: rifampin, Lexapro (escitalopram)

RifAMPin may reduce the blood levels and effects of escitalopram. Contact your doctor if your symptoms worsen or your condition changes during treatment with these medications. 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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Moderate

isoniazid escitalopram

Applies to: isoniazid, Lexapro (escitalopram)

Isoniazid may increase the blood levels and effects of escitalopram. You may have an increased risk of developing side effects, including irregular heart rhythm and a rare but serious condition called the serotonin syndrome, which may include symptoms such as confusion, hallucination, seizure, extreme changes in blood pressure, increased heart rate, fever, excessive sweating, shivering or shaking, blurred vision, muscle spasm or stiffness, tremor, incoordination, stomach cramp, nausea, vomiting, and diarrhea. You should contact your doctor immediately if you experience these symptoms while taking the medications. 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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No other interactions were found between your selected drugs. However, this does not necessarily mean no other interactions exist. Always consult your healthcare provider.

Drug and food interactions

Moderate

rifAMPin food

Applies to: 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.

Moderate

isoniazid food

Applies to: isoniazid

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

escitalopram food

Applies to: Lexapro (escitalopram)

Alcohol can increase the nervous system side effects of escitalopram such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with escitalopram. Do not use more than the recommended dose of escitalopram, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. Talk to your doctor or pharmacist if you have any questions or concerns.

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Anti-infectives

Therapeutic duplication

The recommended maximum number of medicines in the 'anti-infectives' category to be taken concurrently is usually three. Your list includes four medicines belonging to the 'anti-infectives' category:

  • ethambutol
  • isoniazid
  • pyrazinamide
  • rifampin

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

Duplication

Antituberculosis agents

Therapeutic duplication

The recommended maximum number of medicines in the 'antituberculosis agents' category to be taken concurrently is usually three. Your list includes four medicines belonging to the 'antituberculosis agents' category:

  • ethambutol
  • isoniazid
  • pyrazinamide
  • rifampin

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

Duplication

Miscellaneous antituberculosis agents

Therapeutic duplication

The recommended maximum number of medicines in the 'miscellaneous antituberculosis agents' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'miscellaneous antituberculosis agents' category:

  • ethambutol
  • pyrazinamide

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.


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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.

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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.