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    Combinations for Tuberculosis

    BOXED WARNING

    Alcoholism, anticoagulant therapy, Black patients, females, hepatic disease, hepatitis, hepatotoxicity, Hispanic patients, jaundice, malnutrition, vitamin K deficiency

    Isoniazid is associated with a risk for serious hepatotoxicity, manifesting as isoniazid-induced hepatitis. Isoniazid is contraindicated in patients who develop severe hypersensitivity reactions, including drug-induced hepatitis; previous isoniazid-associated hepatic injury; severe adverse reactions to isoniazid such as drug fever, chills, arthritis; and acute hepatic disease of any etiology, including jaundice. Transient increases in liver function tests (LFTs), particularly transaminases, have occurred during isoniazid treatment. In rare instances, hyperbilirubinuria, jaundice, and fatal hepatitis have been reported. Use isoniazid with caution in patients with chronic hepatic disease (e.g., alcoholism, cirrhosis, or chronic hepatitis). Increased age, injection substance abuse, and alcohol consumption have been associated with a higher risk of developing isoniazid-induced hepatotoxicity. Older adults (over the age of 35 years, and especially those 50 years or older) are at increased risk of developing hepatic toxicity as compared to patients younger than 20 years. Carefully monitor older patients. Rates of isoniazid-induced hepatitis are 4-fold higher in persons who drink alcohol daily compared to those who do not drink alcohol. The risk of fatal isoniazid-associated hepatitis appears to be increased among females, particularly female Black patients and female Hispanic patients. An increased risk may also be associated with the postpartum period. Obtain baseline LFTs and perform a monthly symptom assessment and exam in all patients. Periodically monitor LFTs during isoniazid treatment in persons whose pretreatment LFTs were abnormal (i.e., more than 3-times the upper limit of normal), in persons who are 35 years or older, and in women, including those who are pregnant or within 3 months of delivery, or in other patients as clinically indicated. Advise patients to immediately report signs or symptoms consistent with liver damage or other adverse effects, which include unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and feet, persistent fatigue, weakness or fever for more than 3 days, and/or abdominal tenderness, especially right upper quadrant discomfort. If these symptoms appear or if signs suggestive of hepatic damage are detected, discontinue isoniazid promptly, since continued use of the drug in these cases has been reported to cause a more severe form of hepatotoxicity. Consider discontinuation of isoniazid if serum transaminases rise more than 3 times the upper limit of normal. Initiate alternative tuberculosis treatment in patients who develop hepatitis. If isoniazid therapy must be restarted, do so only after symptoms and lab abnormalities have cleared. Start therapy in very small and gradually increasing doses; stop therapy immediately if there is any indication of recurrent hepatotoxicity. In patients with acute hepatic disease, delay preventative treatment. [42734] [44180] Use rifampin in patients with hepatic disease only in cases of necessity and then under strict medical supervision. In these patients, carefully monitor liver function before therapy and then every 2 to 4 weeks during therapy. If signs of hepatic damage occur or worsen, discontinue rifampin. Severe hepatic dysfunction or hepatotoxicity, including fatalities, were reported in patients with hepatic disease and in patients taking rifampin with other hepatotoxic agents. Additionally, rifampin may cause vitamin K-dependent coagulation disorders and bleeding. Monitor coagulation tests during rifampin treatment (e.g., prothrombin time and other coagulation tests) in patients at risk of vitamin K deficiency, such as patients with chronic hepatic disease or malnutrition or those on prolonged antibacterial drugs or anticoagulant therapy. Consider supplementation with vitamin K when appropriate and discontinuation of rifampin if abnormal coagulation tests and/or bleeding occur.[30314] [42451] Most combination therapy for active TB disease includes more than 1 agent that may contribute to hepatotoxicity.[61094]

    DEA CLASS

    Rx

    DESCRIPTION

    Oral combination antitubercular agent
    Used to treat pulmonary tuberculosis in patients already receiving a fixed dosage regimen; simplified regimen may promote adherence
    Monitor liver enzymes due to potential fatal hepatitis and hepatic dysfunction

    COMMON BRAND NAMES

    Rifamate

    HOW SUPPLIED

    Rifamate Oral Cap: 150-300mg

    DOSAGE & INDICATIONS

    For the treatment of drug-susceptible tuberculosis infection as part of combination therapy in patients already on a fixed-dose regimen.
    Oral dosage (capsules containing 150 mg of isoniazid and 300 mg of rifampin)
    Adults

    2 capsules (300 mg isoniazid; 600 mg rifampin) PO once daily. Isoniazid and rifampin are generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.  

    Adolescents 15 to 17 years

    2 capsules (300 mg isoniazid; 600 mg rifampin) PO once daily. Isoniazid and rifampin are generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.  

    MAXIMUM DOSAGE

    Adults

    2 capsules/day PO.

    Geriatric

    2 capsules/day PO.

    Adolescents

    15 to 17 years: 2 capsules/day PO.
    13 to 14 years: Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    The manufacturer of the isoniazid; rifampin combination product does not provide recommendations for patients with hepatic dysfunction. However, isoniazid is not recommended for use in patients with acute hepatic disease and should be used cautiously and potentially at lower starting doses for patients with chronic hepatic disease ; therefore, the fixed dosage combination product should likely not be used in patients with hepatic impairment.

    Renal Impairment

    The manufacturer of the isoniazid; rifampin combination product does not provide recommendations for patients with renal dysfunction. However, dosage adjustments are recommended for the individual drug components ; therefore, the fixed dosage combination product should likely not be used in patients with renal impairment.

    ADMINISTRATION

     
    Directly observed therapy (DOT) is recommended for adolescents and adults living with HIV.[34362] [61094]
    Concomitant pyridoxine is recommended in any patient at risk for neuropathy (e.g., persons living with HIV, diabetes, alcoholism, nutritional deficiency, chronic renal failure, advanced age).

    Oral Administration
    Oral Solid Formulations

    Take capsules on an empty stomach, at least 1 hour before or 2 hours after a meal.

    STORAGE

    IsonaRif:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a dry place
    Rifamate:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a dry place

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D. Rifampin has been reported to alter vitamin D metabolism. Reduced concentrations of circulating 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D have been accompanied by reduced serum calcium and phosphate, and elevated parathyroid hormone.

    Rifamycin hypersensitivity

    Isoniazid; rifampin is contraindicated in patients with known isoniazid hypersensitivity, rifampin hypersensitivity, rifamycin hypersensitivity, or hypersensitivity to any component of isoniazid; rifampin. Symptoms of renal dysfunction may also be associated with hypersensitivity reactions and usually occur during intermittent or interrupted rifampin therapy. Monitor patients receiving isoniazid; rifampin for signs and symptoms of hypersensitivity reactions; discontinue treatment and institute appropriate therapy if a reaction occurs.[30314] [42451]

    Alcoholism, anticoagulant therapy, Black patients, females, hepatic disease, hepatitis, hepatotoxicity, Hispanic patients, jaundice, malnutrition, vitamin K deficiency

    Isoniazid is associated with a risk for serious hepatotoxicity, manifesting as isoniazid-induced hepatitis. Isoniazid is contraindicated in patients who develop severe hypersensitivity reactions, including drug-induced hepatitis; previous isoniazid-associated hepatic injury; severe adverse reactions to isoniazid such as drug fever, chills, arthritis; and acute hepatic disease of any etiology, including jaundice. Transient increases in liver function tests (LFTs), particularly transaminases, have occurred during isoniazid treatment. In rare instances, hyperbilirubinuria, jaundice, and fatal hepatitis have been reported. Use isoniazid with caution in patients with chronic hepatic disease (e.g., alcoholism, cirrhosis, or chronic hepatitis). Increased age, injection substance abuse, and alcohol consumption have been associated with a higher risk of developing isoniazid-induced hepatotoxicity. Older adults (over the age of 35 years, and especially those 50 years or older) are at increased risk of developing hepatic toxicity as compared to patients younger than 20 years. Carefully monitor older patients. Rates of isoniazid-induced hepatitis are 4-fold higher in persons who drink alcohol daily compared to those who do not drink alcohol. The risk of fatal isoniazid-associated hepatitis appears to be increased among females, particularly female Black patients and female Hispanic patients. An increased risk may also be associated with the postpartum period. Obtain baseline LFTs and perform a monthly symptom assessment and exam in all patients. Periodically monitor LFTs during isoniazid treatment in persons whose pretreatment LFTs were abnormal (i.e., more than 3-times the upper limit of normal), in persons who are 35 years or older, and in women, including those who are pregnant or within 3 months of delivery, or in other patients as clinically indicated. Advise patients to immediately report signs or symptoms consistent with liver damage or other adverse effects, which include unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and feet, persistent fatigue, weakness or fever for more than 3 days, and/or abdominal tenderness, especially right upper quadrant discomfort. If these symptoms appear or if signs suggestive of hepatic damage are detected, discontinue isoniazid promptly, since continued use of the drug in these cases has been reported to cause a more severe form of hepatotoxicity. Consider discontinuation of isoniazid if serum transaminases rise more than 3 times the upper limit of normal. Initiate alternative tuberculosis treatment in patients who develop hepatitis. If isoniazid therapy must be restarted, do so only after symptoms and lab abnormalities have cleared. Start therapy in very small and gradually increasing doses; stop therapy immediately if there is any indication of recurrent hepatotoxicity. In patients with acute hepatic disease, delay preventative treatment. [42734] [44180] Use rifampin in patients with hepatic disease only in cases of necessity and then under strict medical supervision. In these patients, carefully monitor liver function before therapy and then every 2 to 4 weeks during therapy. If signs of hepatic damage occur or worsen, discontinue rifampin. Severe hepatic dysfunction or hepatotoxicity, including fatalities, were reported in patients with hepatic disease and in patients taking rifampin with other hepatotoxic agents. Additionally, rifampin may cause vitamin K-dependent coagulation disorders and bleeding. Monitor coagulation tests during rifampin treatment (e.g., prothrombin time and other coagulation tests) in patients at risk of vitamin K deficiency, such as patients with chronic hepatic disease or malnutrition or those on prolonged antibacterial drugs or anticoagulant therapy. Consider supplementation with vitamin K when appropriate and discontinuation of rifampin if abnormal coagulation tests and/or bleeding occur.[30314] [42451] Most combination therapy for active TB disease includes more than 1 agent that may contribute to hepatotoxicity.[61094]

    Acquired immunodeficiency syndrome (AIDS), diabetes mellitus, human immunodeficiency virus (HIV) infection, peripheral neuropathy

    Do not treat persons with tuberculosis (TB) and human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS) with intermittent (i.e., once weekly, twice weekly, or 3 days/week) TB treatment regimens to avoid recurrent disease and the emergence of drug resistance.[34361] [34362] [61094] Isoniazid can cause peripheral neuropathy due to pyridoxine antagonism or increased excretion of pyridoxine. Carefully monitor isoniazid use in patients with peripheral neuropathy or conditions predisposing to neuropathy. Persons with HIV, diabetes mellitus, alcoholism, malnutrition, chronic kidney disease, and advanced age may be predisposed to developing this complication. Concomitant pyridoxine is recommended in any patient receiving isoniazid and at risk for peripheral neuropathy.[34361] [34362]  [42734] [44180] [61094] Use isoniazid; rifampin with caution in patients with a history of diabetes mellitus, as diabetes management may be more difficult.

    Renal disease, renal failure, renal impairment

    Carefully monitor isoniazid use in patients with severe renal impairment or renal failure, which is a condition predisposing to neuropathy. Isoniazid can cause peripheral neuropathy due to pyridoxine antagonism or increased excretion of pyridoxine. Persons with chronic renal disease may be predisposed to developing this complication. Concomitant pyridoxine is recommended in any patient receiving isoniazid and at risk for peripheral neuropathy.[42734] [44180] [61094]

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including rifampin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

    Contact lenses

    Rifampin may produce a discoloration (i.e., yellow, orange, red, brown) of the teeth, urine, sweat, tears, and sputum. Soft contact lenses may become permanently stained due to rifampin therapy.

    Laboratory test interference

    Rifampin may cause laboratory test interference. Cross-reactivity and false-positive urine screening tests for opioids have been reported in patients receiving rifampin when utilizing the KIMS (Kinetic Interaction of Microparticles in Solution) testing method (e.g., Abuscreen Online opioids assay). Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish rifampin from opioids. Rifampin has been shown to inhibit standard microbiological assays for serum folate and vitamin B12; consider alternate assays. Transient abnormalities in liver function tests and reduced biliary excretion of contrast media used for visualization of the gallbladder have also been observed; therefore, perform these tests before the morning dose of rifampin.

    Serious rash

    Cases of serious rash, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, have been reported with rifampin. If symptoms or signs of severe cutaneous adverse reactions develop, discontinue rifampin immediately and institute appropriate therapy.

    Gout

    Isoniazid is contraindicated in patients with acute gout.

    Geriatric

    Carefully monitor isoniazid use in patients older than 35 years. Isoniazid can cause peripheral neuropathy due to pyridoxine antagonism or increased excretion of pyridoxine. Carefully monitor isoniazid use in patients with conditions predisposing to neuropathy. Geriatric patients may be predisposed to developing this complication. Concomitant pyridoxine is recommended in any patient receiving isoniazid and at risk for peripheral neuropathy.[42734] [44180] [61094] Also, the frequency of progressive liver damage increases with age. It is rare in persons under 20 years, but occurs in up to 2.3% of those older than 50 years. Use rifampin with caution in geriatric patients.  The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    Pregnancy

    Use isoniazid; rifampin during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies of isoniazid; rifampin in pregnant women. Extensive use of isoniazid during pregnancy has indicated that although the drug readily crosses the placental barrier, isoniazid is not teratogenic even when given during the first 4 months of gestation. Reports have suggested that isoniazid-induced hepatitis may be increased by the administration of isoniazid to a pregnant woman in the third trimester or the immediate postpartum period. Careful clinical and/or laboratory monitoring for hepatitis is warranted. All pregnant women taking isoniazid should receive pyridoxine supplementation; pregnancy may increase the risk for drug-induced neuropathy. Additionally, rifampin does not appear to be teratogenic in humans. However, when given during the last few weeks of pregnancy, rifampin can cause postnatal hemorrhages in the mother and infant; vitamin K therapy may be indicated.[30314] [42451] [42734] [61094]

    Breast-feeding

    Isoniazid and rifampin are excreted into breast milk. FDA-approved labeling recommends discontinuing breast-feeding or isoniazid; rifampin, taking into consideration the importance of the drug to the mother.[42451] [42734] However, guidelines encourage breast-feeding for women who are noninfectious and taking first-line tuberculosis agents, such as isoniazid and rifampin, as the small concentrations of these drugs measured in breast milk have not been reported to produce toxic effects in the nursing infant. Pyridoxine supplementation is recommended for the mother and breast-feeding infant.[61094]

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / Incidence not known
    optic atrophy / Delayed / Incidence not known
    optic neuritis / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    hepatic failure / Delayed / Incidence not known
    hepatotoxicity / Delayed / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    intracranial bleeding / Delayed / Incidence not known
    sideroblastic anemia / Delayed / Incidence not known
    porphyria / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    pemphigus / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    vasculitis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known
    thrombotic microangiopathy / Delayed / Incidence not known
    hemolytic-uremic syndrome / Delayed / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known

    Moderate

    elevated hepatic enzymes / Delayed / 10.0-20.0
    hepatitis / Delayed / 0-2.3
    myopathy / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    encephalopathy / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    confusion / Early / Incidence not known
    psychosis / Early / Incidence not known
    memory impairment / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    hyperuricemia / Delayed / Incidence not known
    hemolysis / Early / Incidence not known
    hematuria / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    eosinophilia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    wheezing / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    neutropenia / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    palpitations / Early / Incidence not known
    bone pain / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    metabolic acidosis / Delayed / Incidence not known
    vitamin D deficiency / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    interstitial lung disease / Delayed / Incidence not known
    pneumonitis / Delayed / Incidence not known

    Mild

    vomiting / Early / 1.0-10.0
    anorexia / Delayed / 1.0-10.0
    flatulence / Early / 1.0-10.0
    nausea / Early / 1.0-10.0
    menstrual irregularity / Delayed / 1.0-10.0
    diarrhea / Early / 10.0
    dyspepsia / Early / 10.0
    pyrosis (heartburn) / Early / 10.0
    drowsiness / Early / Incidence not known
    fatigue / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    weakness / Early / Incidence not known
    headache / Early / Incidence not known
    purpura / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    chills / Rapid / Incidence not known
    rash / Early / Incidence not known
    maculopapular rash / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    syncope / Early / Incidence not known
    flushing / Rapid / Incidence not known
    fever / Early / Incidence not known
    cough / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known
    tooth discoloration / Delayed / Incidence not known
    contact lens discoloration / Delayed / Incidence not known
    urine discoloration / Early / Incidence not known
    vitamin B6 deficiency / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Major) When possible, avoid concurrent use of dolutegravir with rifampin in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with rifampin. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and rifampin is an inducer of CYP3A4.
    Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Rifampin can accelerate the metabolism of zidovudine, causing a decrease in AUC of approximately 50%. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required.
    Abemaciclib: (Major) Avoid coadministration of rifampin with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
    Abiraterone: (Major) Avoid the concomitant use of abiraterone and rifampin. If rifampin must be coadministered with abiraterone, increase the abiraterone dosing frequency to twice daily (i.e., 1,000 mg once daily to 1,000 mg twice daily). Reduce the dose back to the previous dose and frequency when rifampin is discontinued. Abiraterone is a substrate of CYP3A4; rifampin is a strong inducer of CYP3A4. Concomitant use may result in decreased concentrations of abiraterone resulting in reduced efficacy. In a drug interaction study, administration of abiraterone with rifampin decreased exposure of abiraterone by 55%.
    Abrocitinib: (Major) Avoid coadministration of abrocitinib with rifampin as the combined exposure of abrocitinib and its 2 active metabolites may be decreased, resulting in reduced therapeutic effect. Abrocitinib is a CYP2C9 substrate and rifampin is a strong CYP2C9 inducer.
    Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and rifampin. If coadministration cannot be avoided, increase the acalabrutinib dose to 200 mg PO twice daily. Decreased acalabrutinib exposure occurred in a drug interaction study. Acalabrutinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. In healthy subjects, the Cmax and AUC values of acalabrutinib were decreased by 68% and 77%, respectively, when acalabrutinib was coadministered with rifampin 600 mg/day for 9 days.
    Acetaminophen: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Aspirin, ASA; Caffeine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Acetaminophen; Caffeine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Concomitant use of dihydrocodeine with isoniazid may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Isoniazid is a weak inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Acetaminophen; Chlorpheniramine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Codeine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Concomitant use of codeine with isoniazid may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. isoniazid is a weak inhibitor of CYP3A4. (Moderate) Concomitant use of codeine with rifampin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifampin is a strong CYP3A4 inducer.
    Acetaminophen; Dextromethorphan: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dextromethorphan; Doxylamine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Diphenhydramine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Guaifenesin; Phenylephrine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Hydrocodone: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Acetaminophen; Oxycodone: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Major) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression, sedation, and serotonin syndrome if concurrent use of isoniazid is necessary. If isoniazid is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system like isoniazid has resulted in serotonin syndrome. In addition, oxycodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If isoniazid is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of oxycodone as needed. If rifampin is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Acetaminophen; Pamabrom; Pyrilamine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Pentazocine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Propoxyphene: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetaminophen; Pseudoephedrine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents.
    Acetohexamide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Afatinib: (Major) Increase the daily dose of afatinib by 10 mg as tolerated if the concomitant use with rifampin is necessary; resume the previous dose of afatinib 2 to 3 days after discontinuation of rifampin. Afatinib is a P-glycoprotein (P-gp) substrate and rifampin is a P-gp inducer; coadministration may decrease plasma concentrations of afatinib. Pre-treatment with rifampin decreased afatinib exposure by 34%.
    Aldesleukin, IL-2: (Moderate) Aldesleukin, IL-2 is associated with serious adverse reactions affecting many organ systems, including hepatotoxicity. Agents known to cause hepatotoxicity can add to the hepatic impairment produced by aldesleukin. Drugs with known risks of hepatotoxicity include, but are not limited to: isoniazid, INH. In addition, reduced hepatic function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs
    Alendronate; Cholecalciferol: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of cholecalciferol, Vitamin D3. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of cholecalciferol, Vitamin D3 may be required.
    Alfentanil: (Major) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression, sedation, serotonin syndrome and hypertension if concurrent use of isoniazid is necessary. If isoniazid is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Isoniazid has MAOI activity. Severe and unpredictable potentiation of MAOIs has been reported rarely with alfentanil. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma). Monitor for hypertension and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension if alfentanil is administered to patients who have received MAO inhibitors within 14 days. In addition, alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If isoniazid is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with rifamycins is necessary. If the rifamycin is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of CYP3A4 inducers like rifamycins with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
    Aliskiren; Amlodipine: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Aliskiren; Valsartan: (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
    Alogliptin; Pioglitazone: (Minor) Concomitant administration of rifampin with pioglitazone resulted in a decrease in the AUC of pioglitazone. Patients receiving rifampin with pioglitazone should be monitored for changes in glycemic control; dosage adjustments may be necessary.
    Alosetron: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as isoniazid, INH, however, this interaction has not been studied.
    Alpelisib: (Major) Avoid coadministration of alpelisib with rifampin due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
    Alprazolam: (Major) Avoid coadministration of alprazolam and isoniazid due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with isoniazid, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and isoniazid is a weak CYP3A4 inhibitor. Coadministration with another weak CYP3A4 inhibitor increased alprazolam maximum concentration by 82%, decreased clearance by 42%, and increased half-life by 16%. (Moderate) Monitor for reduced efficacy of alprazolam and signs of benzodiazepine withdrawal if coadministration with rifampin is necessary. Alprazolam is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease alprazolam concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Altretamine: (Minor) Altretamine undergoes significant metabolism by the cytochrome P450 system. Rifampin is known to induce CYP450 enzymes. In theory, co-administration may increase the rate of altretamine metabolism thus decreasing altretamine effect; one study in mice has suggested that hepatic enzyme induction antagonizes antitumor activity of altretamine.
    Aluminum Hydroxide: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of aminosalicylate sodium, aminosalicylic acid and isoniazid, INH. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs may be used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. When administered as a rapidly available formulation at a dose of 12 g, aminosalicylic acid has been reported to produce a 20% reduction in the acetylation of isoniazid, INH, especially in rapid acetylators. However, the INH serum concentrations, half-lives, and excretion in fast acetylators still remained half of those noted in slow acetylators, with or without aminosalicylic acid. The effect is dose related and has not been studied in the delayed-release preparation (i.e. delayed-release granules) of aminosalicylic acid. Lower serum concentrations observed with the delayed release aminosalicylic acid products should result in a reduced effect on the acetylation of INH. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program. (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifampin and aminosalicylate sodium, aminosalicylic acid. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs may be used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Aminosalicylic acid has previously been reported to block the absorption of rifampin; however, this was due to an excipient not included in the aminosalicylic acid granules. Oral administration of a solution of both agents showed full absorption of each product. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Amiodarone: (Major) Certain rifamycins, including rifampin, rifabutin, and rifapentine, may induce CYP3A4 metabolism of amiodarone, resulting in decreased serum concentrations of amiodarone and its active metabolite (desethylamiodarone) and potential decreased efficacy. A possible drug interaction has been reported with rifampin and amiodarone in one patient receiving therapy with ICD and amiodarone for history of atrial and ventricular arrhythmias; this patient had evidence of reduced serum amiodarone and metabolite levels, loss of antiarrhythmic efficacy, and required hospitalization.
    Amitriptyline: (Major) Due to the risk of serotonin syndrome, concurrent use of amitriptyline and medications with MAO-like activity, such as isoniazid, INH, should be avoided if possible. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO and may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, amitriptyline and concurrent serotonergic agents should be discontinued. (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Amlodipine: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Atorvastatin: (Moderate) Coadministration of atorvastatin with rifampin may result in variable decreases in atorvastatin exposures, with the potential for reduced antilipemic efficacy. If concomitant use of these drugs is required, atorvastatin and rifampin should be simultaneously administered. Atorvastatin is a CYP3A4 and OATP1B1 substrate. Rifampin is a strong CYP3A4 inducer and OATP1B1 inhibitor. As a result of the dual interaction mechanisms, delayed administration of atorvastatin after rifampin administration has been associated with a significant reduction in atorvastatin plasma concentrations. To evaluate this interaction, monitor serum lipid concentrations during coadministration. (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Benazepril: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Celecoxib: (Moderate) Rifampin has been reported to induce the hepatic metabolism of celecoxib via cytochrome P450 2C9. It is possible that patients treated with celecoxib and rifampin may have a reduced response to celecoxib. (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Olmesartan: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Valsartan: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers. (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of calcium-channel blockers. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers. (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Major) Clarithromycin is a substrate and inhibitor of CYP3A4, and rifampin is an inducer of CYP3A4. As compared with the plasma concentration obtained with clarithromycin 500 mg twice daily as monotherapy, the clarithromycin plasma concentration was reduced by 87% when rifampin 600 mg daily was coadministered. Specifically, as monotherapy, the mean serum clarithromycin concentration was 5.4 +/- 2.1 mcg/ml. The mean serum clarithromycin concentration was 0.7 +/- 0.6 mcg/ml when given in combination with rifampin. The mean serum concentrations of 14-OH clarithromycin were similar between the two groups. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
    Amprenavir: (Contraindicated) Concurrent treatment with rifampin and amprenavir is contraindicated. Rifampin decreases amprenavir AUC by 82% and Cmin concentrations by 92%. Coadministration of amprenavir and rifampin may lead to loss of virologic response and possible resistance to amprenavir or to the class of protease inhibitors.
    Anagrelide: (Moderate) Anagrelide is partially metabolized by CYP1A2. Coadministration of anagrelide with drugs that induce CYP1A2, including rifampin, could theoretically increase the elimination of anagrelide and decrease the efficacy of anagrelide. Patients should be monitored for changes in efficacy if anagrelide is coadministered with rifampin.
    Antacids: (Moderate) Concomitant use of antacids and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.
    Apixaban: (Major) Avoid the concomitant administration of apixaban and drugs that are both strong inducers of CYP3A4 and P-gp, such as rifampin. Concomitant administration of apixaban and rifampin results in decreased exposure to apixaban and an increase in the risk of stroke.
    Apremilast: (Major) The coadministration of apremilast and rifampin is not recommended. Apremilast is metabolized primarily by CYP3A4, with minor metabolism by CYP1A2 and CYP2D6. Rifampin is a strong CYP3A4 inducer and also induces CYP1A2 and CYP2D6. Coadministration of rifampin (600 mg daily for 15 days) with a single dose of apremilast resulted in a decrease in apremilast AUC and Cmax by 72% and 43%, respectively. This reduction in systemic exposure may result in a loss of efficacy of apremilast.
    Aprepitant, Fosaprepitant: (Major) Avoid the concurrent use of rifampin with aprepitant due to substantially decreased exposure of aprepitant. If these drugs must be coadministered, monitor for a decrease in the efficacy of aprepitant. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Rifampin is a strong CYP3A4 inducer and aprepitant is a CYP3A4 substrate. When a single dose of aprepitant (375 mg, or 3 times the maximum recommended dose) was administered on day 9 of a 14-day rifampin regimen, the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased by 3-fold.
    Aripiprazole: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when a potent CYP3A4 inducer, such as rifampin, is added to aripiprazole therapy with subsequent adjustments based upon clinical response. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is discontinued, the aripiprazole dose in adults should be reduced to the original dose over 1 to 2 weeks. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving Aristada with a strong CYP3A4 inducer, no dosage adjustment is necessary for the 662 mg, 882 mg, or 1,064 mg dose; increase the 441 mg dose to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. (Moderate) Administering aripiprazole with isoniazid may result in elevated aripiprazole plasma concentrations. Aripiprazole is a substrate of CYP3A4 and isoniazid is a weak CYP3A inhibitor. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP3A4 inhibitor.
    Armodafinil: (Major) Armodafinil is partially metabolized via CYP3A4/5 isoenzymes. Drugs that exhibit significant induction of the CYP3A4 isoenzyme, such as rifampin, may potentially increase the metabolism of armodafinil. Decreased serum levels of armodafinil could potentially result in decreased efficacy of the drug.
    Artemether; Lumefantrine: (Contraindicated) Concomitant use of rifampin and artemether; lumefantrine is contraindicated. Rifampin is a potent inducer of CYP3A4 and both components of artemether; lumefantrine are substrates of this isoenzyme; therefore, coadministration may lead to decreased artemether; lumefantrine concentrations and possible reduction in antimalarial activity. Coadministration in 6 HIV and tuberculosis co-infected adults caused reductions in the AUC of artemether, dihydroartemisinin (metabolite of artemether), and lumefantrine by 89%, 85%, and 68%, respectively. (Moderate) Administering artemether with isoniazid may result in elevated artemether plasma concentrations. Concomitant use warrants caution due to the potential for increased side effects, including increased potentiation of QT prolongation. Artemether is a substrate of CYP3A; isoniazid is a weak CYP3A inhibitor. (Moderate) Administering lumefantrine with isoniazid may result in elevated lumefantrine plasma concentrations. Concomitant use warrants caution due to the potential for increased side effects, including increased potentiation of QT prolongation. Lumefantrine is a substrate of CYP3A; isoniazid is a weak CYP3A inhibitor.
    Artesunate: (Moderate) Monitor for a decrease in antimalarial efficacy if artesunate is coadministered with rifampin. Coadministration may decrease the exposure of the active metabolite of artesunate, dihydroartemisinin (DHA). DHA is a UGT substrate, and rifampin is a strong UGT inducer.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Moderate) It may be necessary to adjust the dosage of butalbital if given concurrently with rifampin. Rifampin may induce the metabolism of butalbital; coadministration may result in decreased butalbital plasma concentrations. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Moderate) Concomitant use of codeine with isoniazid may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. isoniazid is a weak inhibitor of CYP3A4. (Moderate) Concomitant use of codeine with rifampin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifampin is a strong CYP3A4 inducer. (Moderate) It may be necessary to adjust the dosage of butalbital if given concurrently with rifampin. Rifampin may induce the metabolism of butalbital; coadministration may result in decreased butalbital plasma concentrations. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Aspirin, ASA; Caffeine: (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Moderate) Concomitant use of dihydrocodeine with isoniazid may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Isoniazid is a weak inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Aspirin, ASA; Carisoprodol: (Minor) Carisoprodol is metabolized via CYP2C19. The formation of meprobamate (active metabolite of carisoprodol) is catalyzed by CYP2C19. If carisoprodol is combined with an inducer of CYP2C19 such as rifampin, the potential exists for increased metabolism of carisoprodol. Theoretically, carisoprodol plasma concentrations could be decreased, and meprobamate (active metabolite) plasma concentrations could be increased. The clinical significance of this interaction is unknown.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with isoniazid may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. isoniazid is a weak inhibitor of CYP3A4. (Moderate) Concomitant use of codeine with rifampin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifampin is a strong CYP3A4 inducer. (Minor) Carisoprodol is metabolized via CYP2C19. The formation of meprobamate (active metabolite of carisoprodol) is catalyzed by CYP2C19. If carisoprodol is combined with an inducer of CYP2C19 such as rifampin, the potential exists for increased metabolism of carisoprodol. Theoretically, carisoprodol plasma concentrations could be decreased, and meprobamate (active metabolite) plasma concentrations could be increased. The clinical significance of this interaction is unknown.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Concomitant use of sodium bicarbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of sodium bicarbonate.
    Aspirin, ASA; Omeprazole: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Aspirin, ASA; Oxycodone: (Major) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression, sedation, and serotonin syndrome if concurrent use of isoniazid is necessary. If isoniazid is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system like isoniazid has resulted in serotonin syndrome. In addition, oxycodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If isoniazid is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of oxycodone as needed. If rifampin is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Aspirin, ASA; Pravastatin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
    Atazanavir: (Contraindicated) Atazanavir is contraindicated for use with rifampin. Rifampin induces CYP isoenzymes, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Atazanavir; Cobicistat: (Contraindicated) Atazanavir is contraindicated for use with rifampin. Rifampin induces CYP isoenzymes, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Moderate) Caution is warranted when cobicistat is administered with isoniazid, INH as there is a potential for elevated cobicistat concentrations. Isoniazid is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4.
    Atogepant: (Major) Use an atogepant dose of 30 or 60 mg PO once daily if coadministered with rifampin. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer resulted in a 60% reduction in atogepant exposure and a 30% reduction in atogepant peak concentration.
    Atomoxetine: (Contraindicated) The use of atomoxetine with monoamine oxidase inhibitors (MAOIs) is contraindicated. Isoniazid (INH) possesses weak MAO-inhibiting activity. Atomoxetine is one of the selective norepinephrine reuptake inhibitors. Since norepinephrine is deaminated by monoamine oxidase, administration of drugs that inhibit this enzyme concurrently with atomoxetine can lead to serious reactions. These reactions may include confusion, seizures, and severe hypertension as well as less severe symptoms. Atomoxetine should not be taken with any MAOI, or within 2 weeks after discontinuing a MAOI and vice versa.
    Atorvastatin: (Moderate) Coadministration of atorvastatin with rifampin may result in variable decreases in atorvastatin exposures, with the potential for reduced antilipemic efficacy. If concomitant use of these drugs is required, atorvastatin and rifampin should be simultaneously administered. Atorvastatin is a CYP3A4 and OATP1B1 substrate. Rifampin is a strong CYP3A4 inducer and OATP1B1 inhibitor. As a result of the dual interaction mechanisms, delayed administration of atorvastatin after rifampin administration has been associated with a significant reduction in atorvastatin plasma concentrations. To evaluate this interaction, monitor serum lipid concentrations during coadministration.
    Atorvastatin; Ezetimibe: (Moderate) Coadministration of atorvastatin with rifampin may result in variable decreases in atorvastatin exposures, with the potential for reduced antilipemic efficacy. If concomitant use of these drugs is required, atorvastatin and rifampin should be simultaneously administered. Atorvastatin is a CYP3A4 and OATP1B1 substrate. Rifampin is a strong CYP3A4 inducer and OATP1B1 inhibitor. As a result of the dual interaction mechanisms, delayed administration of atorvastatin after rifampin administration has been associated with a significant reduction in atorvastatin plasma concentrations. To evaluate this interaction, monitor serum lipid concentrations during coadministration.
    Atovaquone: (Major) The administration of rifampin with atovaquone is not recommended, as rifampin is known to reduce atovaquone levels by 52%. In a small study of HIV-positive subjects, concomitant administration of oral rifampin with atovaquone suspension lead to a substantial decrease in average steady-state plasma atovaquone concentrations and a simultaneous increase in average steady-state plasma rifampin concentrations. The half-life of atovaquone decreased from 82 hours (without rifampin) to 50 hours during rifampin administration. Other rifamycins, (e.g.; rifapentine) may exert similar effects on atovaquone pharmacokinetics, but data are not available.
    Atovaquone; Proguanil: (Major) The administration of rifampin with atovaquone is not recommended, as rifampin is known to reduce atovaquone levels by 52%. In a small study of HIV-positive subjects, concomitant administration of oral rifampin with atovaquone suspension lead to a substantial decrease in average steady-state plasma atovaquone concentrations and a simultaneous increase in average steady-state plasma rifampin concentrations. The half-life of atovaquone decreased from 82 hours (without rifampin) to 50 hours during rifampin administration. Other rifamycins, (e.g.; rifapentine) may exert similar effects on atovaquone pharmacokinetics, but data are not available.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of methylene blue and drugs that possess MAOI-like activity (e.g., isoniazid, INH) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving serotonergic agents such as selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clompiramine. It is not known if patients receiving intravenous methylene blue with other serotonergic psychiatric agents are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Avacopan: (Major) Avoid concomitant use of avacopan and rifampin due to the risk of decreased avacopan exposure which may reduce its efficacy. Avacopan is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use decreased avacopan overall exposure by 93%.
    Avanafil: (Minor) Avanafil is primarily metabolized by CYP3A4, and although no studies have been performed, concomitant administration of CYP3A4 inducers, such as rifampin, may decrease avanafil plasma levels. Concomitant use is not recommended.
    Avapritinib: (Major) Avoid coadministration of avapritinib with rifampin due to the risk of a decrease in the efficacy of avapritinib. Avapritinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the AUC and Cmax of avapritinib by 92% and 74%, respectively.
    Avatrombopag: (Major) In patients with chronic immune thrombocytopenia (ITP), increase the starting dose of avatrombopag to 40 mg PO once daily when used concomitantly with rifampin. In patients starting rifampin while receiving avatrombopag, monitor platelet counts and adjust the avatrombopag dose as necessary. Dosage adjustments are not required for patients with chronic liver disease. Avatrombopag is a CYP2C9 and CYP3A4 substrate, and dual moderate or strong inducers such as rifampin decrease avatrombopag exposure, which may reduce efficacy.
    Axitinib: (Major) Avoid coadministration of axitinib with rifampin due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Axitinib is a CYP3A4/5 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin significantly decreased the plasma exposure of axitinib in healthy volunteers.
    Bacillus Calmette-Guerin Vaccine, BCG: (Major) Postpone instillation of BCG if the patient is receiving antibiotics, such as isoniazid. Urinary concentrations of isoniazid could interfere with the therapeutic effectiveness of BCG. (Major) Urinary concentrations of rifampin could interfere with the therapeutic effectiveness of BCG. Postpone instillation of BCG if the patient is receiving antibiotics.
    Bedaquiline: (Major) Avoid concurrent use of bedaquiline with rifamycins (e.g., rifampin, rifapentine, and rifabutin). Rifamycins may induce the CYP3A4 metabolism of bedaquiline, resulting in decreased bedaquiline systemic exposure (AUC) and possibly reduced therapeutic effect. One study found bedaquiline AUC decreased by 52% when administered concurrently with rifampin 600 mg PO daily for 21 days.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) It may be necessary to adjust the dosage of phenobarbital if given concurrently with rifampin. Rifampin may induce the metabolism of phenobarbital; coadministration may result in decreased phenobarbital plasma concentrations. Phenobarbital is a CYP29 and CYP2C19 substrate, and rifampin is an inducer of these enzymes.
    Belumosudil: (Major) Increase the dosage of belumosudil to 200 mg PO twice daily when coadministered with rifampin. Belumosudil is a CYP3A4 substrate and rifampin is a strong CYP3A inducer; concomitant use resulted in decreased belumosudil exposure in a drug interaction study. Decreased belumosudil exposure may lead to reduced belumosudil efficacy. Coadministration with rifampin decreased belumosudil exposure by 72% in healthy subjects.
    Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of isoniazid with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and isoniazid is a CYP2C19 inhibitor.
    Bendamustine: (Major) Consider the use of an alternative therapy if rifampin treatment is needed in patients receiving bendamustine. Rifampin may decrease bendamustine exposure, which may result in decreased efficacy. Bendamustine is a CYP1A2 substrate and rifampin is a CYP1A2 inducer.
    Benzhydrocodone; Acetaminophen: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Concurrent use of benzhydrocodone with isoniazid may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of isoniazid in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Isoniazid is an inhibitor of CYP3A4. (Moderate) Concurrent use of benzhydrocodone with rifampin may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If concomitant use is necessary, consider increasing the benzhydrocodone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Discontinuation of rifampin may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If rifampin is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Rifampin is a strong inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of methylene blue and drugs that possess MAOI-like activity (e.g., isoniazid, INH) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving serotonergic agents such as selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clompiramine. It is not known if patients receiving intravenous methylene blue with other serotonergic psychiatric agents are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Bepridil: (Major) Rifampin may induce the CYP3A4 metabolism of calcium-channel blockers and thereby reduce their oral bioavailability. The dosage requirements of bepridil may be increased in patients receiving concurrent enzyme inducers.
    Berotralstat: (Major) Avoid coadministration of berotralstat with rifampin. Concurrent use may decrease berotralstat exposure, leading to reduced efficacy. Berotralstat is a P-gp substrate and rifampin is a P-gp inducer.
    Betrixaban: (Major) Avoid the concomitant administration of betrixaban and rifampin. Concomitant administration of betrixaban and rifampin results in decreased plasma concentrations of betrixaban that may be insufficient to achieve the intended therapeutic effect. Betrixaban is a P-glycoprotein (P-gp) substrate and rifampin is a P-gp inducer.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concomitant use of bictegravir and rifampin is contraindicated due to the potential for decreased bictegravir plasma concentrations which may result in the loss of therapeutic efficacy and development of resistance. Bictegravir is a substrate of CYP3A4; rifampin is a potent inducer of this isoenzyme. In drug interactions studies, coadministration of rifampin and bictegravir decreased the mean AUC of bictegravir by approximately 75%.
    Boceprevir: (Contraindicated) The potential for boceprevir treatment failure exists when boceprevir is administered with rifampin; concurrent use is contraindicated. Rifampin is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations and impaired virologic response.
    Bortezomib: (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of bortezomib.
    Bosentan: (Major) Concomitant administration of a single dose of rifampin (a known inducer of CYP2C9 and CYP3A4) and bosentan in normal volunteers has resulted in increased mean bosentan serum concentrations (trough) by 6-fold; however, coadministration of rifampin with bosentan decreases bosentan serum concentrations at steady-state by about 60%. The effect of bosentan on rifampin serum concentrations has not been assessed. When concomitant use is justified after weighing the risks and benefits, the manufacturer recommends monitoring LFTs weekly for the first 4 weeks, and then to follow routine recommendations for monitoring LFTs during bosentan therapy.
    Bosutinib: (Major) Avoid the concomitant use of bosutinib, a CYP3A4 substrate, and rifampin, a strong CYP3A4 inducer, as a large decrease in bosutinib plasma exposure may occur. In a cross-over trial in 24 healthy volunteers, the Cmax and AUC values of bosutinib were decreased by 86% and 94%, respectively, following a single oral dose of bosutinib 500 mg administered after 6 days of oral rifampin 600 mg/day.
    Brentuximab vedotin: (Moderate) Concomitant administration of brentuximab vedotin and rifampin decreased the exposure of monomethyl auristatin E (MMAE), one of the 3 components released from brentuximab vedotin, by approximately 46%. MMAE is a CYP3A4 substrate and rifampin is a potent CYP3A4 inducer; therefore, the efficacy of brentuximab may be reduced.
    Brexpiprazole: (Major) Because brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be doubled over 1 to 2 weeks when a strong CYP3A4 inducer, such as rifampin, is added to brexpiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in brexpiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the brexpiprazole dose should be reduced to the original level over 1 to 2 weeks.
    Brigatinib: (Major) Avoid coadministration of brigatinib with rifampin due to decreased plasma exposure to brigatinib, which may result in decreased efficacy. Brigatinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased the AUC and Cmax of brigatinib by 80% and 60%, respectively.
    Brivaracetam: (Major) Co-administration of brivaracetam with rifampin decreases brivaracetam plasma concentrations by 45%, likely because of CYP2C19 induction. When metabolized, brivaracetam undergoes hydroxylation that is mediated by CYP2C19. The dose of brivaracetam should be increased by up to 100% in patients in patients taking concomitant rifampin.
    Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and rifampin are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; rifampin is a strong inducer of CYP3A4.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and isoniazid may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; isoniazid inhibits CYP3A4. (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of lidocaine,
    Buprenorphine: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with rifamycins is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If the rifamycin is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and rifamycins are CYP3A4 inducers.
    Buprenorphine; Naloxone: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with rifamycins is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If the rifamycin is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and rifamycins are CYP3A4 inducers.
    Bupropion: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours.
    Bupropion; Naltrexone: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours.
    Buspirone: (Major) Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as rifampin, may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. An in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect.
    Butalbital; Acetaminophen: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) It may be necessary to adjust the dosage of butalbital if given concurrently with rifampin. Rifampin may induce the metabolism of butalbital; coadministration may result in decreased butalbital plasma concentrations.
    Butalbital; Acetaminophen; Caffeine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) It may be necessary to adjust the dosage of butalbital if given concurrently with rifampin. Rifampin may induce the metabolism of butalbital; coadministration may result in decreased butalbital plasma concentrations. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity. (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Moderate) Concomitant use of acetaminophen with rifampin may increase the known risk of hepatotoxicity in relation to each drug. Severe hepatic dysfunction including fatalities were reported in patients taking rifampin with other hepatotoxic agents. (Moderate) Concomitant use of codeine with isoniazid may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. isoniazid is a weak inhibitor of CYP3A4. (Moderate) Concomitant use of codeine with rifampin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifampin is a strong CYP3A4 inducer. (Moderate) It may be necessary to adjust the dosage of butalbital if given concurrently with rifampin. Rifampin may induce the metabolism of butalbital; coadministration may result in decreased butalbital plasma concentrations. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Cabotegravir: (Contraindicated) Coadministration of cabotegravir and rifampin is contraindicated due to the potential for significant decreases in the plasma concentrations of cabotegravir, which may result in potential loss of virologic response and development of resistance. Cabotegravir is a substrate for UGT1A1 and UGT1A9; rifampin is an inducer of UGT. Coadministration with rifampin decreased cabotegravir exposure by 59%.
    Cabotegravir; Rilpivirine: (Contraindicated) Coadministration of cabotegravir and rifampin is contraindicated due to the potential for significant decreases in the plasma concentrations of cabotegravir, which may result in potential loss of virologic response and development of resistance. Cabotegravir is a substrate for UGT1A1 and UGT1A9; rifampin is an inducer of UGT. Coadministration with rifampin decreased cabotegravir exposure by 59%. (Contraindicated) Concurrent use of rifampin and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifampin is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
    Cabozantinib: (Major) Avoid coadministration of cabozantinib with rifampin due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with rifampin 2 to 3 days after discontinuation of rifampin. Cabozantinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased single-dose cabozantinib exposure by 77%.
    Caffeine: (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Caffeine; Sodium Benzoate: (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Calcium Carbonate: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium Carbonate; Risedronate: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium Carbonate; Simethicone: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Calcium; Vitamin D: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate. (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of cholecalciferol, Vitamin D3. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of cholecalciferol, Vitamin D3 may be required.
    Canagliflozin: (Moderate) Monitor for decreased efficacy of canagliflozin if coadministration with rifampin is necessary. In patients taking rifampin who have an eGFR of 60 mL/min/1.73 m2 or greater and are currently tolerating a canagliflozin dose of 100 mg once daily, increase the dose of canagliflozin to 200 mg (taken as two 100 mg tablets) once daily. In patients who are tolerating canagliflozin to 200 mg and who require additional glycemic control, the dose may be increased to 300 mg once daily. In patients taking rifampin who have an eGFR less than 60 mL/min/1.73 m2, and are currently tolerating a canagliflozin dose of 100 mg once daily, increase the dose of canagliflozin to 200 mg (taken as two 100 mg tablets) once daily. Consider other antihyperglycemic therapy in patients who require additional glycemic control. Coadministration of canagliflozin with rifampin, a nonselective inducer of several UGT enzymes, including UGT1A9, UGT2B4, decreased canagliflozin AUC by 51%. This decrease in exposure to canagliflozin may decrease efficacy.
    Canagliflozin; Metformin: (Moderate) Monitor for decreased efficacy of canagliflozin if coadministration with rifampin is necessary. In patients taking rifampin who have an eGFR of 60 mL/min/1.73 m2 or greater and are currently tolerating a canagliflozin dose of 100 mg once daily, increase the dose of canagliflozin to 200 mg (taken as two 100 mg tablets) once daily. In patients who are tolerating canagliflozin to 200 mg and who require additional glycemic control, the dose may be increased to 300 mg once daily. In patients taking rifampin who have an eGFR less than 60 mL/min/1.73 m2, and are currently tolerating a canagliflozin dose of 100 mg once daily, increase the dose of canagliflozin to 200 mg (taken as two 100 mg tablets) once daily. Consider other antihyperglycemic therapy in patients who require additional glycemic control. Coadministration of canagliflozin with rifampin, a nonselective inducer of several UGT enzymes, including UGT1A9, UGT2B4, decreased canagliflozin AUC by 51%. This decrease in exposure to canagliflozin may decrease efficacy.
    Capmatinib: (Major) Avoid coadministration of capmatinib and rifampin due to the risk of decreased capmatinib exposure, which may reduce its efficacy. Capmatinib is a CYP3A substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased capmatinib exposure by 67%.
    Capreomycin: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and any of the rifamycins could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered. (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and isoniazid, INH could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Carbamazepine: (Major) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of carbamazepine. Carbamazepine dosages may need to be adjusted while the patient is receiving rifampin. (Moderate) Isoniazid is known to increase carbamazepine exposure. Measure carbamazepine concentrations prior to coadministration with isoniazid. Monitor for evidence of carbamazepine toxicity during concurrent use and adjust the carbamazepine dose as necessary.
    Carbidopa: (Major) There was a 5% incidence of generalized polyneuropathy during clinical trial evaluation of carbidopa; levodopa enteral suspension (Duopa). The manufacturer recommends an initial evaluation for signs and symptoms of peripheral neuropathy, and periodic monitoring for peripheral neuropathy during treatment with Duopa, particularly in patients receiving other medications that are associated with neuropathy. Isoniazid, INH can cause peripheral neuropathy due to pyridoxine antagonism or increased excretion of pyridoxine. In addition, concomitant use of carbidopa; levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity, such as isoniazid, INH, can result in hypertensive crisis or unstable blood pressure changes. Simultaneous use of these agents or combination products containing isoniazid (e.g., isoniazid, INH; pyrazinamide, PZA; rifampin or isoniazid, INH; rifampin) should be avoided if possible.
    Carbidopa; Levodopa: (Major) Concurrent use of levodopa with drugs that have MAOI-type activity, such as isoniazid, INH should be avoided if possible. Levodopa, a catecholamine precursor, can lead to a relative catecholamine (e.g., dopamine, norepinephrine, and epinephrine) excess when combined with a MAOI. Hypertension and other adverse cardiovascular effects can occur. (Major) There was a 5% incidence of generalized polyneuropathy during clinical trial evaluation of carbidopa; levodopa enteral suspension (Duopa). The manufacturer recommends an initial evaluation for signs and symptoms of peripheral neuropathy, and periodic monitoring for peripheral neuropathy during treatment with Duopa, particularly in patients receiving other medications that are associated with neuropathy. Isoniazid, INH can cause peripheral neuropathy due to pyridoxine antagonism or increased excretion of pyridoxine. In addition, concomitant use of carbidopa; levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity, such as isoniazid, INH, can result in hypertensive crisis or unstable blood pressure changes. Simultaneous use of these agents or combination products containing isoniazid (e.g., isoniazid, INH; pyrazinamide, PZA; rifampin or isoniazid, INH; rifampin) should be avoided if possible.
    Carbidopa; Levodopa; Entacapone: (Major) Concurrent use of levodopa with drugs that have MAOI-type activity, such as isoniazid, INH should be avoided if possible. Levodopa, a catecholamine precursor, can lead to a relative catecholamine (e.g., dopamine, norepinephrine, and epinephrine) excess when combined with a MAOI. Hypertension and other adverse cardiovascular effects can occur. (Major) There was a 5% incidence of generalized polyneuropathy during clinical trial evaluation of carbidopa; levodopa enteral suspension (Duopa). The manufacturer recommends an initial evaluation for signs and symptoms of peripheral neuropathy, and periodic monitoring for peripheral neuropathy during treatment with Duopa, particularly in patients receiving other medications that are associated with neuropathy. Isoniazid, INH can cause peripheral neuropathy due to pyridoxine antagonism or increased excretion of pyridoxine. In addition, concomitant use of carbidopa; levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity, such as isoniazid, INH, can result in hypertensive crisis or unstable blood pressure changes. Simultaneous use of these agents or combination products containing isoniazid (e.g., isoniazid, INH; pyrazinamide, PZA; rifampin or isoniazid, INH; rifampin) should be avoided if possible. (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation or intestinal beta-glucuronidation such as rifampin. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Concurrent use of cariprazine with CYP3A4 inducers, such as rifabutin or rifampin, has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear.
    Carisoprodol: (Minor) Carisoprodol is metabolized via CYP2C19. The formation of meprobamate (active metabolite of carisoprodol) is catalyzed by CYP2C19. If carisoprodol is combined with an inducer of CYP2C19 such as rifampin, the potential exists for increased metabolism of carisoprodol. Theoretically, carisoprodol plasma concentrations could be decreased, and meprobamate (active metabolite) plasma concentrations could be increased. The clinical significance of this interaction is unknown.
    Carvedilol: (Moderate) Concurrent use of carvedilol and rifampin may result in decreased carvedilol concentrations and reduced beta-blocker efficacy. Dosage must be individualized to the patient's response and tolerance. Monitor for signs of altered carvedilol response. During drug interaction studies, rifampin decreased the Cmax and AUC of carvedilol by approximately 70%. Carvedilol is metabolized primarily by CYP2D6 and CYP2C9; rifampin is a known CYP450 hepatic enzyme inducer.
    Caspofungin: (Major) Dose caspofungin as 70 mg IV once daily for adult patients and 70 mg/m2 (Max: 70 mg/day) IV once daily for pediatric patients when coadministered with rifampin. Coadministration of caspofungin with CYP450 enzyme inducers, such as rifampin, may reduce the plasma concentrations of caspofungin. Rifampin has been shown to decrease caspofungin trough concentrations by 30%.
    Cefazolin: (Moderate) Avoid coadministration of rifampin and cefazolin in patients at increased risk of bleeding. If no alternative treatment options are available, closely monitor prothrombin time and other coagulation tests, and administer vitamin K as indicated. Postmarketing reports suggest that concomitant administration of high doses of rifampin and cefazolin may prolong the prothrombin time, leading to severe vitamin K-dependent coagulation disorders that may be life-threatening or fatal.
    Celecoxib: (Moderate) Rifampin has been reported to induce the hepatic metabolism of celecoxib via cytochrome P450 2C9. It is possible that patients treated with celecoxib and rifampin may have a reduced response to celecoxib.
    Celecoxib; Tramadol: (Major) Use tramadol cautiously, if at all, in patients also receiving a MAOI or a drug with MAO-inhibiting activity such as isoniazid, INH. International recommendations contraindicate the concurrent use of tramadol and MAOIs or the use of tramadol within 14 days of discontinuing MAOI therapy. An increased risk of seizures and serotonin syndrome exists in patients receiving tramadol and MAOIs concurrently. Postmarketing reports of serotonin syndrome with use of tramadol and MAOIs and alpha-2-adrenergic blockers exist. If concomitant treatment of tramadol with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised, especially during treatment initiation and dose increases. (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with rifampin is necessary; consider increasing the dose of tramadol as needed. If rifampin is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. (Moderate) Rifampin has been reported to induce the hepatic metabolism of celecoxib via cytochrome P450 2C9. It is possible that patients treated with celecoxib and rifampin may have a reduced response to celecoxib.
    Ceritinib: (Major) Avoid concomitant use of ceritinib with rifampin as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased ceritinib exposure by 70%.
    Chloramphenicol: (Moderate) It may be necessary to adjust the dosage of chloramphenicol if given concurrently with rifampin. Rifampin may induce the metabolism of chloramphenicol; coadministration may result in decreased chloramphenicol plasma concentrations.
    Chlordiazepoxide: (Moderate) Several hepatic inducers, such as rifampin, can theoretically increase the clearance of benzodiazpines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Chlordiazepoxide; Amitriptyline: (Major) Due to the risk of serotonin syndrome, concurrent use of amitriptyline and medications with MAO-like activity, such as isoniazid, INH, should be avoided if possible. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO and may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, amitriptyline and concurrent serotonergic agents should be discontinued. (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations. (Moderate) Several hepatic inducers, such as rifampin, can theoretically increase the clearance of benzodiazpines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Chlordiazepoxide; Clidinium: (Moderate) Several hepatic inducers, such as rifampin, can theoretically increase the clearance of benzodiazpines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Chloroquine: (Moderate) Monitor patients more frequently for signs of reduced chloroquine effects if administered with rifampin. Coadministration may decrease the exposure of chloroquine. Chloroquine may be a CYP3A4 substrate in vitro, and rifampin is a strong CYP3A4 inducer.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with isoniazid may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. isoniazid is a weak inhibitor of CYP3A4. (Moderate) Concomitant use of codeine with rifampin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifampin is a strong CYP3A4 inducer.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with isoniazid may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Isoniazid is a weak inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with isoniazid may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Isoniazid is a weak inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpropamide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Cilostazol: (Major) Decrease cilostazol dose to one-half of the recommended dosage when coadministered with isoniazid. Coadministration may increase cilostazol serum concentrations and increase the risk for adverse reactions. Cilostazol is a CYP2C19 substrate; isoniazid is a moderate CYP2C19 inhibitor. Coadministration of another CYP2C19 inhibitor did not significantly affect the metabolism of cilostazol, but the systemic exposure to 3,4-dehydro-cilostazol was increased by 69%.
    Ciprofloxacin: (Moderate) It may be necessary to adjust the dosage of ciprofloxacin if given concurrently with rifampin. Rifampin may induce the metabolism of ciprofloxacin; coadministration may result in decreased ciprofloxacin plasma concentrations. Ciprofloxacin and rifampin have been used concomitantly in some cases for the treatment of MRSA.
    Cisapride: (Major) Post-marketing surveillance reports have documented QT prolongation and ventricular arrhythmias, including torsade de pointes and death, when known and potent inhibitors of CYP3A4 are coadministered with cisapride. Isoniazid, INH may have the potential to inhibit the metabolism of cisapride through CYP3A4 and thus, should not be used with cisapride. (Moderate) Cisapride is metabolized by the hepatic cytochrome P450 enzyme system, specifically the CYP3A4 isoenzyme. Inducers of CYP3A4, such as rifampin, may increase the clearance of cisapride.
    Citalopram: (Major) The maximum adult dose of citalopram should not exceed 20 mg/day with isoniazid, INH, which inhibits CYP2C19. Concurrent use of isoniazid and citalopram, an SSRI, should be approached with caution. Coadministration of isoniazid, INH and citalopram may result in increased risk of QT prolongation from increased citalopram exposure. Isoniazid is also chemically related to iproniazid, a drug that was known to possess monoamine oxidase (MAO) inhibiting activity, and INH may produce clinical symptoms consistent with serotonergic excess when combined with citalopram, including serotonin syndrome. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be implemented. (Moderate) Monitor for decreased efficacy of citalopram if coadministration with rifampin is necessary. Citalopram is a substrate of CYP3A4 and CYP2C19 and rifampin is a moderate to strong CYP2C19 inducer and strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer did not affect citalopram plasma concentrations, but increased clearance of citalopram with strong CYP3A4 inducers is possible.
    Clarithromycin: (Major) Clarithromycin is a substrate and inhibitor of CYP3A4, and rifampin is an inducer of CYP3A4. As compared with the plasma concentration obtained with clarithromycin 500 mg twice daily as monotherapy, the clarithromycin plasma concentration was reduced by 87% when rifampin 600 mg daily was coadministered. Specifically, as monotherapy, the mean serum clarithromycin concentration was 5.4 +/- 2.1 mcg/ml. The mean serum clarithromycin concentration was 0.7 +/- 0.6 mcg/ml when given in combination with rifampin. The mean serum concentrations of 14-OH clarithromycin were similar between the two groups. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
    Clindamycin: (Moderate) Monitor for loss of clindamycin efficacy with coadministration of rifampin as concurrent use may decrease clindamycin exposure. Clindamycin is a CYP3A4 substrate; rifampin is a strong inducer of CYP3A4.
    Clobazam: (Moderate) A dosage reduction of clobazam may be necessary during co-administration of isoniazid, INH. Metabolism of N-desmethylclobazam, the active metabolite of clobazam, occurs primarily through CYP2C19 and isoniazid is an inhibitor of CYP2C19. Extrapolation from pharmacogenomic data indicates that concurrent use of clobazam with moderate or potent inhibitors of CYP2C19 may result in up to a 5-fold increase in exposure to N-desmethylclobazam. Adverse effects, such as sedation, lethargy, ataxia, or insomnia may be potentiated.
    Clomipramine: (Major) Due to the risk of serotonin syndrome, concurrent use of tricyclic antidepressants and medications with MAO-like activity, such as isoniazid, INH, should be avoided if possible. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO and may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, clomipramine and concurrent serotonergic agents should be discontinued. (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Clonazepam: (Moderate) Isoniazid, INH can decrease the hepatic oxidative metabolism of clonazepam if administered concomitantly. Monitor for signs of an exaggerated response to clonazepam if isoniazid is used concomitantly. (Moderate) Monitor patients for a change in clonazepam dosage requirements when starting or stopping concomitant rifampin. Clonazepam concentration decreases of approximately 38% have been reported when clonazepam is used with strong CYP3A4 inducers. Clonazepam is a CYP3A4 substrate. Rifampin is a strong CYP3A4 inducer.
    Clopidogrel: (Major) Avoid concomitant use of clopidogrel and rifampin due to the risk of bleeding. Concomitant use results in increased plasma concentrations of clopidogrel's active metabolite and an increase in platelet inhibition. Clopidogrel is primarily metabolized to its active metabolite by CYP2C19; rifampin is a strong CYP2C19 inducer. (Moderate) Monitor for reduced clopidogrel efficacy during concomitant use of isoniazid. Clopidogrel is primarily metabolized to its active metabolite by CYP2C19; isoniazid is a CYP2C19 inhibitor.
    Clorazepate: (Major) Rifampin, a hepatic inducer can theoretically increase the clearance of benzodiazpines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations. (Moderate) Administering clorazepate with isoniazid may result in elevated clorazepate plasma concentrations. If these drugs are used together, closely monitor for signs of adverse events. Clorazepate is a pro-drug converted to N-desmethyldiazepam in the GI tract; N-desmethyldiazepam is metabolized by 2C19 and 3A4. Isoniazid is a CYP3A and CYP2C19 inhibitor.
    Clozapine: (Major) Coadministration of clozapine, a CYP3A4 substrate, with a potent inducer of CYP3A4, such as rifampin, is not recommended. If coadministration is necessary, monitor for decreased effectiveness of clozapine and consider increasing the clozapine dose if necessary. If the inducer is discontinued, reduce the clozapine dose based on clinical response. Rifampin may also increase the metabolism of clozapine through induction of CYP1A2. (Moderate) Consider a clozapine dose reduction if coadministered with isoniazid and monitor for adverse reactions. If isoniazid is discontinued, monitor for lack of clozapine effect and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is partially metabolized by CYP3A4. isoniazid is a weak CYP3A4 inhibitor.
    Cobicistat: (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Moderate) Caution is warranted when cobicistat is administered with isoniazid, INH as there is a potential for elevated cobicistat concentrations. Isoniazid is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4.
    Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with rifampin due to decreased cobimetinib efficacy. Cobimetinib is a CYP3A substrate in vitro; rifampin is a strong inducer of CYP3A. Based on simulations, cobimetinib exposure would decrease by 83% when coadministered with a strong CYP3A inducer.
    Codeine: (Moderate) Concomitant use of codeine with isoniazid may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. isoniazid is a weak inhibitor of CYP3A4. (Moderate) Concomitant use of codeine with rifampin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifampin is a strong CYP3A4 inducer.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with isoniazid may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. isoniazid is a weak inhibitor of CYP3A4. (Moderate) Concomitant use of codeine with rifampin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifampin is a strong CYP3A4 inducer.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with isoniazid may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. isoniazid is a weak inhibitor of CYP3A4. (Moderate) Concomitant use of codeine with rifampin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifampin is a strong CYP3A4 inducer.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with isoniazid may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. isoniazid is a weak inhibitor of CYP3A4. (Moderate) Concomitant use of codeine with rifampin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifampin is a strong CYP3A4 inducer.
    Codeine; Promethazine: (Moderate) Concomitant use of codeine with isoniazid may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. isoniazid is a weak inhibitor of CYP3A4. (Moderate) Concomitant use of codeine with rifampin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifampin is a strong CYP3A4 inducer.
    Colchicine: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with isoniazid is necessary, especially in patients with renal or hepatic impairment. Isoniazid is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    COMT inhibitors: (Major) Patients should generally not receive COMT inhibitors in combination with agents that have some non-selective MAO inhibiting activity like isoniazid. It is recommended that at least 14 days should elapse between the discontinuation of a non-selective MAOI and the use of a COMT inhibitor to avoid potential interactions. Monoamine oxidase and catechol-O-methyltransferase are the 2 major enzymes involved in the metabolism of catecholamines. It is possible that the combination of a COMT inhibitor and a non-selective MAOI would result in inhibition of the majority of pathways responsible for normal catecholamine metabolism.
    Conjugated Estrogens; Bazedoxifene: (Major) Bazedoxifene undergoes metabolism by UGT enzymes in the intestinal tract and liver. The metabolism of bazedoxifene may be increased by concomitant use of substances known to induce UGTs, such as rifampin. A reduction in bazedoxifene exposure may be associated with an increase risk of endometrial hyperplasia. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. In addition, in vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as rifampin, may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Patients taking these hormones may need to be monitored for reduced clinical effect while on rifampin, with dose adjustments made based on clinical efficacy.
    Conjugated Estrogens; Medroxyprogesterone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Copanlisib: (Major) Avoid the concomitant use of copanlisib and rifampin; decreased copanlisib exposure occurred in a drug interaction study. Copanlisib is a substrate of CYP3A and P-glycoprotein (P-gp); rifampin is a strong CYP3A inducer and also induces P-gp. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of rifampin 600 mg/day in a drug interaction study in patients with cancer.
    Crizotinib: (Major) Avoid coadministration of crizotinib with rifampin due to decreased plasma concentrations of crizotinib, which may result in decreased efficacy. Crizotinib is primarily metabolized by CYP3A and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the crizotinib AUC and Cmax at steady state by 84% and 79%, respectively.
    Cycloserine: (Moderate) Concomitant administration of isoniazid, INH and cycloserine has resulted in adverse CNS effects. Dizziness and/or drowsiness occurred more frequently in patients receiving both drugs than in patients receiving cycloserine alone.
    Cyclosporine: (Moderate) Closely monitor cyclosporine concentrations and adjust the dose of cyclosporine as appropriate if coadministration with rifamycins is necessary. Concurrent use may decrease cyclosporine exposure resulting in decreased efficacy. Cyclosporine is extensively metabolized by CYP3A4 and has a narrow therapeutic index; rifamycins are CYP3A4 inducers. (Minor) Cyclosporine is a CYP3A4 substrate. Coadministration with a CYP3A4 inhibitor, such as isoniazid, may decrease the metabolism and clearance of cyclosporine, resulting in increased serum concentrations and, thus, potentially causing cyclosporine toxicity (e.g., nephrotoxicity, hepatotoxicity, or seizures). Reduced cyclosporine dosage requirements may be needed. Conversely, if isoniazid is discontinued, cyclosporine concentrations could decrease. Monitor serum cyclosporine concentrations carefully if isoniazid is used concomitantly and upon discontinuation.
    Dabigatran: (Major) In general, avoid coadministration of dabigatran with P-gp inducers, such as rifampin. Concomitant administration of 600 mg rifampin for 7 days followed by a single dose of dabigatran decreased dabigatran AUC and Cmax by 66% and 67%, respectively. Dabigatran exposure returned to normal 7 days after cessation of rifampin therapy.
    Daclatasvir: (Contraindicated) Concomitant use of daclatasvir with rifampin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration reduces systemic exposes to daclatasvir by 79%. Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
    Dapagliflozin; Saxagliptin: (Minor) Coadministration of saxagliptin and rifampin decreased the maximum serum saxagliptin concentration by 53% and the systemic exposure by 76%. As expected, the maximum serum concentration of the saxagliptin active metabolite was increased by 39%; no significant change in the systemic exposure was noted. Saxagliptin dose adjustment is not advised when coadministered with rifampin, as the plasma dipeptidyl peptidase-4 activity over a 24-hour period was unaffected.
    Dapsone: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with rifampin is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and rifampin is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with rifampin decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
    Darifenacin: (Moderate) Monitor for decreased efficacy of darifenacin if coadministration with rifamycins is necessary; coadministration may result in decreased plasma concentrations of darifenacin. Rifamycins are CYP3A4 inducers and darifenacin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of darifenacin.
    Darolutamide: (Major) Avoid coadministration of darolutamide with rifampin due to the risk of decreased darolutamide plasma concentrations which may decrease efficacy. Rifampin is a P-glycoprotein (P-gp) inducer and a strong inducer of CYP3A4; darolutamide is a CYP3A4 substrate. Concomitant use with rifampin decreased the mean AUC and Cmax of darolutamide by 72% and 52%, respectively.
    Darunavir: (Contraindicated) Darunavir is contraindicated for use with rifampin. Rifampin induces CYP3A4, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Moderate) Isoniazid, INH is a CYP3A4 inhibitor, and serum concentrations of darunavir, a CYP3A4 substrate, may increase with coadministration. Coadminister these drugs with caution due to the potential for darunavir toxicity.
    Darunavir; Cobicistat: (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Contraindicated) Darunavir is contraindicated for use with rifampin. Rifampin induces CYP3A4, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Moderate) Caution is warranted when cobicistat is administered with isoniazid, INH as there is a potential for elevated cobicistat concentrations. Isoniazid is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4. (Moderate) Isoniazid, INH is a CYP3A4 inhibitor, and serum concentrations of darunavir, a CYP3A4 substrate, may increase with coadministration. Coadminister these drugs with caution due to the potential for darunavir toxicity.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Contraindicated) Darunavir is contraindicated for use with rifampin. Rifampin induces CYP3A4, thereby decreasing the plasma concentrations and AUC of most protease inhibitors by roughly 90% and leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Moderate) Caution is warranted when cobicistat is administered with isoniazid, INH as there is a potential for elevated cobicistat concentrations. Isoniazid is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4. (Moderate) Isoniazid, INH is a CYP3A4 inhibitor, and serum concentrations of darunavir, a CYP3A4 substrate, may increase with coadministration. Coadminister these drugs with caution due to the potential for darunavir toxicity.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) Coadministration of rifampin and ritonavir results in markedly decreased ritonavir concentrations; HIV treatment failure and virologic resistance would be expected. Rifampin (300 or 600 mg daily for 10 days) decreases the AUC and Cmax of ritonavir (500 mg every 12 hours for 20 days) by 35% and 25%, respectively. Coadministration may lead to loss of virologic response if ritonavir is the sole protease inhibitor and increase the risk of hepatotoxicity. The DHHS/NIH HIV Treatment Guidelines recommend ritonavir and rifampin should not be coadministered and suggest the consideration of alternative antimycobacterial agents, such as rifabutin. However, CDC guidelines suggest no change in ritonavir or rifampin dose when the drugs are coadministered, but this appears to only be in the setting of low-dose ritonavir (i.e., 100 mg or 200 mg twice daily) used to 'boost' concentrations of other protease inhibitors. In this setting it would be less likely to produce adverse events than higher ritonavir doses; however, a net CYP3A4 induction still results when used with rifampin. (Contraindicated) Concomitant use of dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir with rifampin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to dasabuvir, ombitasvir, paritaprevir and ritonavir. Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4; dasabuvir (minor), paritaprevir and ritonavir are substrates of this isoenzyme. Rifampin also induces CYP2D6 and CYP2C8, enzymes partially responsible for the metabolism of ritonavir and dasabuvir, respectively. In addition, rifampin induces the drug transporter proteins P-glycoprotein (P-gp) and UGT; dasabuvir, ombitasvir, paritaprevir and ritonavir are substrates for P-gp, while dasabuvir, ombitasvir and paritaprevir are also substrates of UGT. (Contraindicated) Concomitant use of dasabuvir; ombitasvir; paritaprevir; ritonavir with rifampin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to dasabuvir, ombitasvir, paritaprevir and ritonavir. Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4; dasabuvir (minor), paritaprevir and ritonavir are substrates of this isoenzyme. Rifampin also induces CYP2D6 and CYP2C8, enzymes partially responsible for the metabolism of ritonavir and dasabuvir, respectively. In addition, rifampin induces the drug transporter proteins P-glycoprotein (P-gp) and UGT; dasabuvir, ombitasvir, paritaprevir and ritonavir are substrates for P-gp, while dasabuvir, ombitasvir and paritaprevir are also substrates of UGT.
    Dasatinib: (Major) Avoid coadministration of dasatinib and rifampin due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to rifampin with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Concurrent use of rifampin decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Deferasirox: (Major) Deferasirox undergoes UGT metabolism, and rifampin is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Avoid the concomitant use of rifampin and deferasirox if possible. If rifampin and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications.
    Deflazacort: (Major) Avoid concomitant use of deflazacort and rifampin. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; rifampin is a strong inducer of CYP3A4. Administration of deflazacort with multiple doses of rifampin resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
    Delavirdine: (Contraindicated) Rifampin decreases delavirdine concentrations by 97%. Do not administer delavirdine with rifampin because of the potential for subtherapeutic antiretroviral activity and the subsequent possibility for the development of resistant mutations of HIV.
    Desipramine: (Major) Due to the risk of serotonin syndrome, concurrent use of tricyclic antidepressants and medications with MAO-like activity, such as isoniazid, INH, should be avoided if possible. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO and may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, desipramine and concurrent serotonergic agents should be discontinued. (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Desogestrel; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Desvenlafaxine: (Moderate) Due to the risk of serotonin syndrome, concurrent use of desvenlafaxine and medications with MAO-like activity, such as isoniazid, INH, should be approached with caution. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO and may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess when combined with serotonin norepinephrine reuptake inhibitors (SNRIs). If serotonin syndrome is suspected, duloxetine and concurrent serotonergic agents should be discontinued.
    Dexamethasone: (Moderate) Monitor for decreased efficacy of dexamethasone if coadministration with rifampin is necessary; consider increasing the dose of dexamethasone if clinically appropriate. Dexamethasone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Dexlansoprazole: (Major) Avoid coadministration of dexlansoprazole with rifampin due to the risk of decreased dexlansoprazole plasma concentrations which may decrease efficacy. Dexlansoprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Dextromethorphan; Quinidine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
    Diazepam: (Major) Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4, one of the pathways responsible for the hepatic metabolism of diazepam. Patients receiving rifampin may require higher doses of diazepam to achieve the desired clinical effect. (Moderate) Concurrent use of isoniazid, INH and diazepam can increase serum concentrations of diazepam due to alterations in the half-life and clearance of diazepam. Patients should be observed for signs of altered diazepam effects if isoniazid therapy is initiated or discontinued.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and isoniazid, INH together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Dienogest; Estradiol valerate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Digoxin: (Moderate) It appears that rifampin decreases serum concentrations of digoxin by inducing intestinal P-glycoprotein and decreasing the oral bioavailability of digoxin by 30.1%. The Cmax and AUC of digoxin were decreased by 43% and 58%, respectively. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of rifampin. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with isoniazid may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of isoniazid could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Isoniazid is a weak inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Diltiazem: (Major) Avoid coadministration of diltiazem and rifampin due to decreased plasma concentrations of diltiazem. Coadministration with rifampin lowered diltiazem plasma concentrations to undetectable. Diltiazem is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Disopyramide: (Major) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of disopyramide. Patients should be monitored for loss of disopyramide activity if rifampin is added. In addition, disopyramide doses may need to be reduced if rifampin is stopped and disopyramide therapy is continued. Serum disopyramide concentrations should be monitored closely if hepatic enzyme inducers are either added or discontinued during disopyramide therapy. (Moderate) Caution should be used when isoniazid is coadministered with disopyramide; monitor clinical response and serum disopyramide concentrations. CYP3A4 inhibitors, such as isoniazid, may increase serum plasma concentrations of disopyramide, a CYP3A4 substrate.
    Disulfiram: (Minor) Concomitant administration of isoniazid, INH and disulfiram has resulted in adverse CNS effects, including psychosis and coordination difficulties, in a limited number of patients. Data appears to be limited to one report; the incidence of the interaction is uncertain, but apparently quite small. Two-thirds of the group in this report did not experience an interaction, and in another report, 200 additional patients did not experience an interaction. Concurrent use need not be avoided, although patient response should be monitored and, if necessary, the disulfiram dose reduced, or treatment withdrawn.
    Docetaxel: (Major) Avoid coadministration of docetaxel with rifampin due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Dofetilide: (Moderate) Monitor for an increase in dofetilide-related adverse reactions, including QT prolongation, if coadministration with isoniazid is necessary. Isoniazid is a weak CYP3A4 inhibitor. Dofetilide is a minor CYP3A4 substrate; however, because there is a linear relationship between dofetilide plasma concentration and QTc, concomitant administration of CYP3A4 inhibitors may increase the risk of arrhythmia (torsade de pointes).
    Dolasetron: (Moderate) Blood concentrations of hydrodolasetron, the active metabolite of dolasetron, may be decreased when dolasetron is administered concomitantly with rifampin, a potent inducer of cytochrome P450.
    Dolutegravir: (Major) When possible, avoid concurrent use of dolutegravir with rifampin in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with rifampin. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and rifampin is an inducer of CYP3A4.
    Dolutegravir; Lamivudine: (Major) When possible, avoid concurrent use of dolutegravir with rifampin in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with rifampin. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and rifampin is an inducer of CYP3A4.
    Dolutegravir; Rilpivirine: (Contraindicated) Concurrent use of rifampin and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifampin is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine. (Major) When possible, avoid concurrent use of dolutegravir with rifampin in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with rifampin. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and rifampin is an inducer of CYP3A4.
    Donepezil: (Moderate) Monitor for decreased efficacy of donepezil if coadministration with rifampin is necessary. Donepezil is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Inducers of CYP3A4 could increase the rate of elimination of donepezil.
    Donepezil; Memantine: (Moderate) Monitor for decreased efficacy of donepezil if coadministration with rifampin is necessary. Donepezil is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Inducers of CYP3A4 could increase the rate of elimination of donepezil.
    Doravirine: (Contraindicated) Concurrent administration of doravirine and rifampin is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Contraindicated) Concurrent administration of doravirine and rifampin is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
    Doxepin: (Major) Due to the risk of serotonin syndrome, concurrent use of tricyclic antidepressants and medications with MAO-like activity, such as isoniazid, INH, should be avoided if possible. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO and may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Pharmacokinetic interactions are also possible. Doxepin is primarily metabolized by CYP2C19 and CYP2D6, and use of isoniazid, a potent inhibitor of CYP2C19, may result in increased doxepin plasma concentrations and subsequent adverse reactions. (Moderate) It may be necessary to adjust the dosage of tricyclic antidepressants if given concurrently with rifampin. Rifampin may induce the metabolism of tricyclic antidepressants; coadministration may result in decreased tricyclic antidepressant plasma concentrations.
    Doxercalciferol: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as rifampin, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol. (Moderate) Cytochrome P450 enzyme inhibitors, such as isoniazid, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Doxorubicin Liposomal: (Major) Avoid coadministration of isoniazid with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Isoniazid is a weak CYP3A4 inhibitor and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions. (Major) Rifampin is a potent CYP3A4 inducer, a moderate inducer of P-glycoprotein (P-gp), and a mild inducer of CYP2D6. Doxorubicin is a major substrate of CYP3A4, P-gp, and CYP2D6. Inducers of CYP3A4, CYP2D6, and/or P-gp may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of rifampin and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy.
    Doxorubicin: (Major) Avoid coadministration of isoniazid with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Isoniazid is a weak CYP3A4 inhibitor and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions. (Major) Rifampin is a potent CYP3A4 inducer, a moderate inducer of P-glycoprotein (P-gp), and a mild inducer of CYP2D6. Doxorubicin is a major substrate of CYP3A4, P-gp, and CYP2D6. Inducers of CYP3A4, CYP2D6, and/or P-gp may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of rifampin and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy.
    Doxycycline: (Major) Although doxycycline is not appreciably metabolized by the liver, concomitant use of rifampin has been shown to substantially increase doxycycline clearance. It is possible that extrahepatic sites of metabolism (e.g., intestinal mucosa) may be involved since P-450 cytochrome enzymes have been identified in areas such as adrenal cortex, intestinal mucosa, and kidney. A similar effect on doxycycline clearance and half-life has been noted for carbamazepine, pentobarbital, phenobarbital, phenytoin, and primidone. It is likely that all barbiturates exert the same effect on doxycycline pharmacokinetics. The possibility of antibiotic failure should also be considered whenever these enzyme inducers are used with doxycycline.
    Dronabinol: (Moderate) Use caution if coadministration of dronabinol with isoniazid, INH is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a 3A4 substrate; isoniazid is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. (Moderate) Use caution if coadministration of dronabinol with rifampin is necessary, and monitor for a decrease in the efficacy of dronabinol. Concomitant use may result in decreased plasma concentrations of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; rifampin is a strong inducer of CYP3A4 and a moderate CYP2C9 inducer.
    Dronedarone: (Major) Avoid coadministration of dronedarone with rifampin due to the potential for decreased dronedarone exposure and efficacy. Dronedarone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin significantly decreased dronedarone exposure.
    Drospirenone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Drospirenone; Estetrol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Drospirenone; Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Drospirenone; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Duloxetine: (Moderate) Due to the risk of serotonin syndrome, concurrent use of duloxetine and medications with MAO-like activity, such as isoniazid, INH, should be approached with caution. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO and may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess when combined with serotonin norepinephrine reuptake inhibitors (SNRIs). If serotonin syndrome is suspected, duloxetine and concurrent serotonergic agents should be discontinued.
    Duvelisib: (Major) Avoid coadministration of duvelisib with rifampin. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; rifampin is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with rifampin for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
    Edoxaban: (Major) Coadministration of edoxaban and rifampin should be avoided. Edoxaban is a P-glycoprotein (P-gp) substrate; rifampin is a strong inducer of P-gp. Coadminsitration decreases the serum concentration of edoxaban; reduced serum concentrations of edoxaban are expected to result in decreased efficacy of the anticoagulant.
    Efavirenz: (Major) When efavirenz and rifampin are coadministered, decreased efavirenz concentrations are seen and decreased antiretroviral efficacy is expected. These drugs may be coadministered to patients weighing 50 kg or more if the efavirenz dose is increased to 800 mg PO daily. A small study evaluated this interaction by administering the drugs (both at 600 mg PO daily x 7 days) to 12 subjects, and found decreased mean efavirenz Cmax, AUC, and Cmin of 20%, 26%, and 32%. Of note, reduced efavirenz metabolism is seen in patients with genetic polymorphisms of cytochrome P450 2B6 (primarily in patients of African, Asian, and Hispanic descent). Increasing the dose in these patients can result in a significant increase in efavirenz toxicity; some patients may even require lower doses.
    Efavirenz; Emtricitabine; Tenofovir: (Major) When efavirenz and rifampin are coadministered, decreased efavirenz concentrations are seen and decreased antiretroviral efficacy is expected. These drugs may be coadministered to patients weighing 50 kg or more if the efavirenz dose is increased to 800 mg PO daily. A small study evaluated this interaction by administering the drugs (both at 600 mg PO daily x 7 days) to 12 subjects, and found decreased mean efavirenz Cmax, AUC, and Cmin of 20%, 26%, and 32%. Of note, reduced efavirenz metabolism is seen in patients with genetic polymorphisms of cytochrome P450 2B6 (primarily in patients of African, Asian, and Hispanic descent). Increasing the dose in these patients can result in a significant increase in efavirenz toxicity; some patients may even require lower doses.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) When efavirenz and rifampin are coadministered, decreased efavirenz concentrations are seen and decreased antiretroviral efficacy is expected. These drugs may be coadministered to patients weighing 50 kg or more if the efavirenz dose is increased to 800 mg PO daily. A small study evaluated this interaction by administering the drugs (both at 600 mg PO daily x 7 days) to 12 subjects, and found decreased mean efavirenz Cmax, AUC, and Cmin of 20%, 26%, and 32%. Of note, reduced efavirenz metabolism is seen in patients with genetic polymorphisms of cytochrome P450 2B6 (primarily in patients of African, Asian, and Hispanic descent). Increasing the dose in these patients can result in a significant increase in efavirenz toxicity; some patients may even require lower doses.
    Elagolix: (Contraindicated) The use of rifampin with elagolix is contraindicated. Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as rifampin increase exposure to elagolix. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. During drug interaction studies, a single dose of rifampin increased the mean AUC of elagolix by 5.58-fold. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. While induction of CYP3A by rifampin may also occur, particularly with continued use, it appears that elagolix is more influenced by the OATP1B1 activity of rifampin as AUC remained elevated by a mean of 1.65-fold with continued use of rifampin.
    Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) The use of rifampin with elagolix is contraindicated. Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as rifampin increase exposure to elagolix. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. During drug interaction studies, a single dose of rifampin increased the mean AUC of elagolix by 5.58-fold. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. While induction of CYP3A by rifampin may also occur, particularly with continued use, it appears that elagolix is more influenced by the OATP1B1 activity of rifampin as AUC remained elevated by a mean of 1.65-fold with continued use of rifampin. (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Elbasvir; Grazoprevir: (Contraindicated) Concurrent administration of elbasvir; grazoprevir with rifampin is contraindicated. Rifampin is a strong CYP3A inducer, while both elbasvir and grazoprevir are substrates of CYP3A. Use of these drugs together is expected to significantly decrease the plasma concentrations of both elbasvir and grazoprevir, and may result in decreased virologic response.
    Elexacaftor; tezacaftor; ivacaftor: (Major) Coadministration of elexacaftor; tezacaftor; ivacaftor with rifampin is not recommended as concurrent use may decrease exposure of elexacaftor; tezacaftor; ivacaftor. Elexacaftor, tezacaftor, and ivacaftor are CYP3A4 substrates (ivacaftor is a sensitive CYP3A4 substrate). Coadministration of rifampin, a strong CYP3A4 inducer, significantly decreased ivacaftor exposure by 89%; elexacaftor and tezacaftor exposures are expected to also decrease during coadministration of strong CYP3A4 inducers. (Major) Coadministration of ivacaftor with rifampin is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin significantly decreased ivacaftor exposure by approximately 9-fold. (Major) Do not administer tezacaftor; ivacaftor and rifampin together; coadministration may reduce the efficacy of tezacaftor; ivacaftor. Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by the concomitant use of rifampin, a strong CYP3A inducer; both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate). Coadministration of ivacaftor with rifampin decreased ivacaftor exposure 89%.
    Eliglustat: (Major) Coadministration of eliglustat and rifampin significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6 (EMs, IMs, PMs). Rifampin is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. During clinical trials, systemic exposures (Cmax and AUC) of eliglustat decreased by approximately 90% in EMs and IMs after coadministration of eliglustat 127 mg PO twice daily with rifampin 600 mg PO once daily. Of note, the only FDA-approved dose of eliglustat is 84 mg. Additionally, systemic exposures decreased by approximately 95% after coadministration of eliglustat 84 mg PO twice daily with rifampin 600 mg PO once daily in PMs. (Major) In poor CYP2D6 metabolizers (PMs), coadministration of isoniazid and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Isoniazid ia a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients.
    Eltrombopag: (Major) Eltrombopag is metabolized by CYP1A2 and CYP2C8. The significance of administering inducers of CYP1A2 and CYP2C8, such as rifampin, on the systemic exposure of eltrombopag has not been established. Additionally, eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as rifampin, may exhibit an increase in systemic exposure if coadministered with eltrombopag. Monitor patients for a decrease in the efficacy of eltrombopag and for an increase in adverse reactions of rifampin if these drugs are coadministered.
    Eluxadoline: (Major) When administered concurrently with rifampin, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); rifampin is an inhibitor of OATP. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
    Elvitegravir: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with elvitegravir, a CYP3A4 substrate, is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with elvitegravir, a CYP3A4 substrate, is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Moderate) Caution is warranted when cobicistat is administered with isoniazid, INH as there is a potential for elevated cobicistat concentrations. Isoniazid is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Coadministration of rifampin with cobicistat is contraindicated. Rifampin induces CYP3A4; cobicistat is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of cobicistat and of the simultaneously administered protease inhibitors (atazanavir or darunavir), leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with elvitegravir, a CYP3A4 substrate, is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Moderate) Caution is warranted when cobicistat is administered with isoniazid, INH as there is a potential for elevated cobicistat concentrations. Isoniazid is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4.
    Empagliflozin; Linagliptin: (Major) Concomitant use of linagliptin with rifampin is not recommended due to the potential for decreased linagliptin serum concentrations and loss of efficacy. Linagliptin is a substrate of hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); rifampin is a strong inducer of CYP3A4 and an inducer of P-gp. In drug interaction studies, rifampin decreased the mean AUC and Cmax of linagliptin by 40% and 44%, respectively. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended.
    Empagliflozin; Linagliptin; Metformin: (Major) Concomitant use of linagliptin with rifampin is not recommended due to the potential for decreased linagliptin serum concentrations and loss of efficacy. Linagliptin is a substrate of hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); rifampin is a strong inducer of CYP3A4 and an inducer of P-gp. In drug interaction studies, rifampin decreased the mean AUC and Cmax of linagliptin by 40% and 44%, respectively. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Concurrent use of rifampin and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifampin is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Contraindicated) Concurrent use of rifampin and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifampin is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
    Enalapril, Enalaprilat: (Moderate) Concomitant use of rifampin and enalapril may result in decreased concentrations of enalaprilat, the active metabolite of enalapril. Dosage adjustments of enalapril may be required.
    Enalapril; Felodipine: (Major) The metabolism of felodipine may be increased by rifampin, an enzyme inducer. (Moderate) Concomitant use of rifampin and enalapril may result in decreased concentrations of enalaprilat, the active metabolite of enalapril. Dosage adjustments of enalapril may be required.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of rifampin and enalapril may result in decreased concentrations of enalaprilat, the active metabolite of enalapril. Dosage adjustments of enalapril may be required.
    Encorafenib: (Major) Avoid coadministration of encorafenib and rifampin due to decreased encorafenib exposure and potential loss of efficacy. Encorafenib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration with CYP3A4 inducers has not been studied with encorafenib; however, in clinical trials, steady-state encorafenib exposures were lower than encorafenib exposures after the first dose, suggesting CYP3A4 auto-induction.
    Enflurane: (Major) Anesthetic requirements may be increased for enflurane with concomitant use of isoniazid, INH. The cytochrome P450 (CYP) 2E1 isoenzyme appears to be a predominant enzyme responsible for human oxidative enflurane metabolism. Isoniazid, INH has been shown to induce CYP2E1. Additionally, the concurrent use of enflurane and isoniazid may increase the risk of hepatotoxicity. (Moderate) Caution is advised with the concomitant use of enflurane and rifampin as concurrent use may increase the risk of hepatotoxicity.
    Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation or intestinal beta-glucuronidation such as rifampin. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
    Entrectinib: (Major) Avoid coadministration of entrectinib with rifampin due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased the entrectinib AUC by 77% in a drug interaction study.
    Enzalutamide: (Major) Avoid coadministration of enzalutamide with rifampin if possible due to the risk of decreased enzalutamide plasma concentrations. If concomitant use is unavoidable, increase the dose of enzalutamide from 160 mg to 240 mg PO once daily. If rifampin is discontinued, resume the dose of enzalutamide used prior to initiation of rifampin. Enzalutamide is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the composite AUC of enzalutamide plus N-desmethyl enzalutamide by 37%.
    Eravacycline: (Major) Increase the dose of eravacycline to 1.5 mg/kg IV every 12 hours when coadministered with a strong CYP3A4 inducer, such as rifampin. Concomitant use of strong CYP3A4 inducers decreases the exposure of eravacycline, which may reduce its efficacy. When eravacycline was administered with rifampin, the eravacycline AUC was decreased by 35% and its clearance was increased by 54%.
    Erdafitinib: (Major) Avoid the concomitant use of erdafitinib and rifampin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 and CYP2C9 substrate; rifampin is a strong CYP3A4 and CYP2C9 inducer. Simulations suggested that rifampin may significantly decrease erdafitinib Cmax and AUC.
    Ergotamine; Caffeine: (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
    Erlotinib: (Major) Avoid coadministration of erlotinib with rifampin if possible due to the risk of decreased erlotinib efficacy. If concomitant use is unavoidable, increase the dose of erlotinib in 50 mg increments at 2-week intervals as tolerated (maximum dose, 450 mg). Erlotinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased erlotinib exposure by 58% to 80%.
    Erythromycin: (Major) Caution is warranted with the concomitant use of erythromycin and rifampin as this may result in reduced erythromycin Cmax and increased clearance. Coadministration of oral erythromycin 500 mg and rifampin 600 mg to healthy patients led to a reduced erythromycin maximum serum concentration (Cmax) and an increased clearance. Specifically, as monotherapy, the median erythromycin Cmax was 1.34 mg/L (range, 0.4 to 3.16), and the median apparent oral clearance was 96 L/hour (range, 37 to 250). In combination with rifampin, the median erythromycin Cmax was 0.72 mg/L (range, 0.06 to 1.66), and the median apparent oral clearance was 197 L/hour (range, 102 to 2015).
    Erythromycin; Sulfisoxazole: (Major) Caution is warranted with the concomitant use of erythromycin and rifampin as this may result in reduced erythromycin Cmax and increased clearance. Coadministration of oral erythromycin 500 mg and rifampin 600 mg to healthy patients led to a reduced erythromycin maximum serum concentration (Cmax) and an increased clearance. Specifically, as monotherapy, the median erythromycin Cmax was 1.34 mg/L (range, 0.4 to 3.16), and the median apparent oral clearance was 96 L/hour (range, 37 to 250). In combination with rifampin, the median erythromycin Cmax was 0.72 mg/L (range, 0.06 to 1.66), and the median apparent oral clearance was 197 L/hour (range, 102 to 2015).
    Escitalopram: (Moderate) Concurrent use of isoniazid and selective serotonin reuptake inhibitors (SSRIs), such as escitalopram, should be approached with caution. Isoniazid is chemically related to iproniazid, a drug that was known to possess monoamine oxidase (MAO) inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Isoniazid may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess when combined with escitalopram, including serotonin syndrome. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be implemented. (Moderate) Escitalopram is metabolized by CYP3A4. Rifampin can induce the metabolism of escitalopram via induction of CYP3A4. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking rifampin.
    Esomeprazole: (Major) Avoid coadministration of esomeprazole with rifampin due to the risk of decreased esomeprazole plasma concentrations which may decrease efficacy. Esomeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Minor) Isoniazid, INH may inhibit the CYP2C19 isoenzyme, leading to increased plasma levels of drugs that are substrates for the CYP2C19 isoenzyme, such as esomeprazole.
    Estradiol Cypionate; Medroxyprogesterone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Estradiol; Levonorgestrel: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Estradiol; Norethindrone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Estradiol; Norgestimate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Estradiol; Progesterone: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Estrogens affected by CYP3A inducers: (Major) Women taking both estrogens and rifamycins should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed rifamycins. In some cases, it may be advisable for patients to change to non-hormonal methods of birth control during rifamycin therapy. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of rifamycins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on rifamycins, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and rifamycins are a CYP3A4 inducers. Concurrent administration may increase estrogen elimination.
    Eszopiclone: (Moderate) Monitor for decreased efficacy of eszopiclone if coadministration with rifampin is necessary. Eszopiclone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased racemic zopiclone exposure by 80%; a similar effect would be expected with eszopiclone.
    Ethambutol: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of ethambutol and isoniazid, INH. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program. (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifampin and ethambutol. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Ethanol: (Major) Daily consumption of alcohol increases the risk of isoniazid, INH-induced hepatitis and can increase the clearance of INH. Isoniazid should be discontinued if signs or symptoms of hepatitis, such as fatigue, weakness, malaise, nausea/vomiting, anorexia, or serum aminotransferase concentrations greater than three times the upper limit of normal, become evident. Isoniazid may possess enough MAO inhibiting activity to produce clinical symptoms when combined with the ingestion of tyramine-containing beverages. Some ethanol-based products also contain tyramine including some beers (including reduced-alcohol and ethanol-free beer); wines (red); sherry; hard liquor; or liqueurs. Patients should be counseled to avoid alcohol-containing beverages while taking isoniazid. (Major) Rifampin is associated with dose-related hepatoxicity. Daily use of alcohol while receiving rifampin increases the risk of drug-induced hepatitis. Liver-function tests should be conducted prior to and every 2-4 weeks during treatment in patients who consume alcohol routinely while receiving rifampin therapy. (Major) Rifampin is associated with dose-related hepatoxicity. Daily use of ethanol while receiving rifampin increases the risk of drug-induced hepatitis. Liver-function tests should be conducted prior to and every 2-4 weeks during treatment in patients who consume ethanol routinely while receiving rifampin therapy.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Ethinyl Estradiol; Norelgestromin: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Ethinyl Estradiol; Norethindrone Acetate: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Ethinyl Estradiol; Norgestrel: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Ethionamide: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of ethionamide and isoniazid, INH. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs may be used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Also, concomitant administration of isoniazid, INH and ethionamide may cause a temporary increase in serum concentrations of isoniazid. Carefully monitor patients for adverse effects of isoniazid. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program. (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifampin and ethionamide. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs may be used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Ethotoin: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of ethotoin. Dosages of ethotoin may need to be adjusted while the patient is receiving rifampin.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Etonogestrel: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Etonogestrel; Ethinyl Estradiol: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer.
    Etravirine: (Major) Etravirine should not be coadministered with rifampin, a potent inducer of CYP450 enzymes, as significant decreases in etravirine plasma concentrations and, thus, loss of therapeutic effect could occur.
    Everolimus: (Major) Avoid coadministration of everolimus with rifampin due to the risk of decreased efficacy of everolimus. If concomitant use is unavoidable, coadministration requires a dose increase for some indications and close monitoring for others. For oncology indications and tuberous sclerosis complex (TSC)-associated renal angiomyolipoma, double the daily dose using increments of 5 mg or less; multiple increments may be required. For patients with TSC-associated subependymal giant cell astrocytoma (SEGA) and TSC-associated partial-onset seizures, assess the everolimus whole blood trough concentration 2 weeks after initiation of rifampin and adjust the dose as necessary to remain in the recommended therapeutic range. Also closely monitor everolimus whole blood trough concentrations in patients receiving everolimus for either kidney or liver transplant and adjust the dose as necessary to remain in the recommended therapeutic range. Everolimus is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the Cmax and AUC of everolimus by 58% and 63%, respectively. For indications where everolimus trough concentrations are monitored, the addition of a second strong CYP3A4 inducer in a patient already receiving treatment with a strong CYP3A4 inducer may not require additional dose modification.
    Exemestane: (Major) If coadministration of exemestane with rifampin is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased exemestane exposure by 54%.
    Ezetimibe; Simvastatin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of simvastatin. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered.
    Fedratinib: (Major) Avoid coadministration of fedratinib with isoniazid as concurrent use may increase fedratinib exposure. Fedratinib is a substrate of both CYP3A4 and CYP2C19; isoniazid is an inhibitor of both CYP3A4 and CYP2C19. The coadministration of fedratinib with agents that are both a CYP3A4 and CYP2C19 inhibitor has not been evaluated. (Major) Avoid coadministration of fedratinib with rifampin as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of fedratinib with rifampin decreased the overall exposure of fedratinib by 81%.
    Felodipine: (Major) The metabolism of felodipine may be increased by rifampin, an enzyme inducer.
    Fenfluramine: (Moderate) Consider an increase in fenfluramine dosage if coadministered with rifampin. Concurrent use may decrease fenfluramine plasma concentrations, which may lower its efficacy. Fenfluramine is a CYP2B6 and CYP1A2 substrate and rifampin is a strong CYP2B6 and CYP1A2 inducer.
    Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. If isoniazid is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If isoniazid is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl. (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of rifampin is necessary. If rifampin is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like rifampin with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
    Fexofenadine: (Minor) Rifampin may decrease plasma concentrations of fexofenadine and potentially reduce its antihistaminic effects. Although the therapeutic range of fexofenadine is broad, monitor for potential decreased therapeutic effects of fexofenadine if rifampin is initiated.
    Fexofenadine; Pseudoephedrine: (Minor) Rifampin may decrease plasma concentrations of fexofenadine and potentially reduce its antihistaminic effects. Although the therapeutic range of fexofenadine is broad, monitor for potential decreased therapeutic effects of fexofenadine if rifampin is initiated.
    Finerenone: (Major) Avoid concurrent use of finerenone and rifampin due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased overall exposure to finerenone by 90%. (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or isoniazid; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and isoniazid is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased overall exposure to finerenone by 21%.
    Flibanserin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and rifampin, a strong CYP3A4 inducer, is not recommended. In a study of 24 healthy female subjects, rifampin 600 mg once daily for 7 days prior to administration of 100 mg flibanserin significantly decreased flibanserin exposure by 95%. (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including isoniazid, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
    Fluconazole: (Moderate) Rifampin is a potent enzyme inducer and can increase the metabolism of fluconazole. Administration of fluconazole 200 mg PO after 15 days of rifampin 600 mg PO daily to 8 healthy male volunteers resulted in a significant decrease in fluconazole AUC and a significant increase in fluconazole apparent oral clearance. The AUC was reduced by about 23% and the apparent oral clearance was increased by about 32%. Fluconazole half-life decreased from approximately 33 hours to approximately 27 hours. The dose of fluconazole may need to be increased in patients also receiving rifampin to assure adequate fluconazole plasma concentrations. Although available data are inconclusive, rifabutin may be less likely than rifampin to interact with fluconazole in this manner.
    Fluoxetine: (Major) Concurrent use of isoniazid and selective serotonin reuptake inhibitors (SSRIs) should be avoided if possible. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Isoniazid may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess when combined with SSRIs. Concurrent use of SSRIs and MAOIs may lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If combination therapy is necessary, patients should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Flurazepam: (Major) Rifamycins are hepatic inducers and can theoretically increase the clearance of benzodiazpines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Fluvastatin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors. Monitor serum lipid concentrations during coadministration of rifampin with fluvastatin.
    Fluvoxamine: (Major) Concurrent use of isoniazid and selective serotonin reuptake inhibitors (SSRIs) should be avoided if possible. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Isoniazid may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess when combined with SSRIs. Concurrent use of SSRIs and MAOIs may lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If combination therpay is necessary, patients should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Food: (Moderate) Isoniazid may possess enough MAO inhibiting activity to produce clinical symptoms when combined with the ingestion of histamine and tyramine-containing foods. Reactions reported include headache, palpitations, flushing, nausea/vomiting, and pruritus; increased blood pressure may occur if the food contains high tyramine content. (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with isoniazid, INH. Isoniazid is an inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with isoniazid, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be reduced. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile. (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with rifampin. Rifampin is an inducer of CYP2C9 and CYP3A4, two isoenzymes responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with rifampin, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be increased. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Fosamprenavir: (Contraindicated) Fosamprenavir is contraindicated for use in combination with rifampin. Rifampin decreases fosamprenavir Cmax, AUC, and Cmin by 70%, 82%, and 92%, respectively. Coadministration of fosamprenavir and rifampin may lead to loss of virologic response and possible resistance to fosamprenavir or to the class of protease inhibitors.
    Fosphenytoin: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of fosphenytoin. Dosages of fosphenytoin may need to be adjusted while the patient is receiving rifampin. (Moderate) The metabolism of phenytoin or fosphenytoin is inhibited by isoniazid, INH, resulting in possible phenytoin intoxication. Monitoring is recommended for signs of toxicity such as ataxia, nystagmus, mental impairment, involuntary muscular movements, and seizures. Conversely, a decrease in clinical response to phenytoin or fosphenytoin may occur following withdrawal of INH.
    Fostamatinib: (Major) Avoid the concomitant use of fostamatinib with rifampin. Concomitant use of fostamatinib with a strong CYP3A4 inducer decreases exposure to the major active metabolite, R406. R406 is extensively metabolized by CYP3A4; rifampin is a strong CYP3A4 inducer. Concomitant use of fostamatinib with rifampin decreased R406 AUC by 75% and Cmax by 59%.
    Fostemsavir: (Contraindicated) Concomitant use of fostemsavir and rifampin is contraindicated. Use of these drugs together significantly decreases the plasma concentrations of temsavir, the active moiety of fostemsavir, thereby increasing the risk for HIV treatment failure or development of viral resistance. Temsavir is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
    Gefitinib: (Major) Increase the dose of gefitinib to 500 mg PO once daily if coadministration with rifampin is necessary. If rifampin is discontinued, gefitinib at a dose of 250 mg once daily may be resumed 7 days later. Gefitinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin reduced gefitinib exposure by 83%.
    Gemfibrozil: (Moderate) Coadministration may result in an increase in rifampin exposure. A dose reduction of rifampin may be required if used concomitantly with gemfibrozil. Use rifampin and gemfibrozil together with caution. Rifampin is a substrate of the OATP1B1 transporter. Gemfibrozil inhibits OATP1B1.
    Gilteritinib: (Major) Avoid coadministration of gilteritinib and rifampin due to the potential for decreased gilteritinib exposure and risk of decreased efficacy. Gilteritinib is a P-gp and CYP3A4 substrate; rifampin is a combined P-gp and strong CYP3A4 inducer. Coadministration with rifampin decreased the gilteritinib AUC by 70% in a drug interaction study
    Glasdegib: (Major) Avoid coadministration of glasdegib and rifampin due to the potential for decreased glasdegib exposure and risk of decreased efficacy. Glasdegib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the glasdegib AUC by 70% in a drug interaction study.
    Glecaprevir; Pibrentasvir: (Contraindicated) Coadministration of glecaprevir with rifampin is contraindicated due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate for CYP3A4 and P-glycoprotein (P-gp); rifampin is a CYP3A4 and P-gp inducer. Coadministration decreases the plasma concentrations of glecaprevir by 88%. (Contraindicated) Coadministration of pibrentasvir with rifampin is contraindicated due to the potential loss of efficacy of pibrentasvir. Pibrentasvir is a substrate for P-glycoprotein (P-gp); rifampin is an inducer of P-gp. Coadministration decreases the plasma concentrations of pibrentasvir by 87%.
    Glimepiride: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Glimepiride; Rosiglitazone: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers. (Minor) The coadministration of rifampin and rosiglitazone may decrease the concentration of rosiglitazone. This interaction is most likely due to rifampin's inhibition of the CYP2C8 and, to a lesser extent, CYP2C9 isozymes. Use caution if rifampin and rosiglitazone are to be coadministered, as decreased rosiglitazone efficacy may be seen. Blood glucose concentrations should be monitored and possible dose adjustments of rosiglitazone may need to be made.
    Glipizide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Glipizide; Metformin: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Glyburide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Glyburide; Metformin: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
    Green Tea: (Major) Patients should not receive COMT-inhibitors like green tea in combination with agents with non-selective MAO inhibiting activity like isoniazid. As is recommended with other COMT inhibitors, 14 days should lapse between the discontinuation of nonselective MAOIs and the use of green tea. Monoamine oxidase and catechol-O-methyltransferase are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the combination of green tea and a non-selective MAOI would result in inhibition of the majority of pathways responsible for normal catecholamine metabolism and an increase in adverse effects.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Guanfacine: (Major) Rifampin may significantly decrease guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, doubling the recommended dose of guanfacine should be considered; if rifampin is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. Upon rifampin discontinuation, decrease the guanfacine ER dosage back to the recommended dose over 1 to 2 weeks. Specific recommendations for immediate-release (IR) guanfacine are not available. Guanfacine is primarily metabolized by CYP3A4, and rifampin is a strong CYP3A4 inducer.
    Haloperidol: (Major) Limited data suggest that rifampin, a potent CYP inducer, can increase the metabolism and/or reduce the bioavailability of haloperidol. In one small study (n=12), plasma levels of haloperidol were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale (BPRS) were increased from baseline during concurrent use of rifampin. Discontinuation of rifampin has resulted in a mean 3.3-fold increase in haloperidol concentrations in some instances. Haloperidol dosage adjustments should be made as needed when rifampin is added or discontinued. Prolonged use of CYP inducers such as rifampin in patients receiving haloperidol has resulted in significant reductions in haloperidol plasma concentrations. (Moderate) Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4, such as isoniazid. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 may increase the risk of adverse effects, including QT prolongation. Monitor for adverse events when these medications are coadministered.
    Halothane: (Major) Anesthetic requirements may be increased for halothane with concomitant use of isoniazid, INH. The cytochrome P450 (CYP) 2E1 isoenzyme appears to be a predominant enzyme responsible for human oxidative halothane metabolism. Isoniazid, INH has been shown to induce CYP2E1. Additionally, the concurrent use of halothane and isoniazid may increase the risk of hepatotoxicity. (Major) Avoid concomitant use of rifampin and halothane. Concurrent use may increase the potential for hepatotoxicity.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with rifampin can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If rifampin is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isoniazid is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isoniazid is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
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