PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Other Agents for Tuberculosis

    DEA CLASS

    Rx

    DESCRIPTION

    Antimycobacterial agent; considered a first-line agent in the treatment of susceptible M. tuberculosis organisms. Appears to be more effective and less toxic than other antitubercular agents.

    COMMON BRAND NAMES

    Nydrazid

    HOW SUPPLIED

    Isoniazid Oral Sol: 5mL, 50mg
    Isoniazid Oral Tab: 100mg, 300mg
    Isoniazid/Nydrazid Intramuscular Inj Sol: 1mL, 100mg

    DOSAGE & INDICATIONS

    For the treatment of drug-susceptible tuberculosis infection as part of combination therapy.
    For the treatment of drug-susceptible tuberculosis infection in persons without HIV as part of combination therapy.
    Oral dosage
    Adults

    5 mg/kg/dose (Max: 300 mg/dose) PO once daily or 5 days/week, or alternatively, 15 mg/kg/dose (Max: 900 mg/dose) PO 3 days/week or twice weekly.[44180] [61094] 15 mg/kg/dose (Max: 900 mg/dose) PO once weekly in combination with rifapentine may be considered in rare circumstances.[61094] Daily dosing is preferred and is defined as 5- or 7 days/week.[61094] [65619] Isoniazid is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[61094] [65619] 

    Infants, Children, and Adolescents

    10 to 15 mg/kg/dose (Max: 300 mg/dose) PO once daily or 5 days/week, or alternatively, 20 to 40 mg/kg/dose (Max: 900 mg/dose) PO 3 days/week or twice weekly.[44180] [61094] [63245] Daily dosing is preferred and is defined as 5- or 7 days/week.[61094] [65619] Isoniazid is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[61094] [65619]

    Neonates†

    10 to 15 mg/kg/dose PO once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Daily dosing is preferred and is defined as 5- or 7 days/week.[61094] [65619] Isoniazid is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[53484] [53485] [61095] [63245] [65675]

    Intravenous† or Intramuscular dosage
    Adults

    5 mg/kg/dose (Max: 300 mg/dose) IV or IM once daily or 5 days/week, or alternatively, 15 mg/kg/dose (Max: 900 mg/dose) IV or IM 3 days/week or twice weekly.[42734] [61094] 15 mg/kg/dose (Max: 900 mg/dose) IV or IM once weekly in combination with rifapentine may be considered in rare circumstances.[61094] Daily dosing is preferred and is defined as 5- or 7 days/week.[61094] [65619] Isoniazid is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[61094] [65619]

    Infants, Children, and Adolescents

    10 to 15 mg/kg/dose (Max: 300 mg/dose) IV or IM once daily or 5 days/week, or alternatively, 20 to 40 mg/kg/dose (Max: 900 mg/dose) IV or IM 3 days/week or twice weekly. Daily dosing is preferred and is defined as 5- or 7 days/week.[61094] [65619] Isoniazid is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement. 

    Neonates†

    10 to 15 mg/kg/dose IV or IM once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Isoniazid is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[53484] 

    For the treatment of drug-susceptible tuberculosis infection in persons with HIV as part of combination therapy.
    Oral dosage
    Adults

    5 mg/kg/dose (Max: 300 mg/dose) PO once daily or 5 days/week. Daily dosing is defined as 5- or 7 days/week. Isoniazid is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.  

    Infants, Children, and Adolescents

    10 to 15 mg/kg/dose (Max: 300 mg/dose) PO once daily or 5 days/week.   Daily dosing is defined as 5- or 7 days/week. Isoniazid is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.  

    Neonates†

    10 to 15 mg/kg/dose PO once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Isoniazid is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[53484] 

    Intravenous† or Intramuscular dosage
    Adults

    5 mg/kg/dose (Max: 300 mg/dose) IV or IM once daily or 5 days/week.[34362] [42734] [61094] Daily dosing is defined as 5- or 7 days/week.[61094] Isoniazid is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.[34362] [61094] [65619]

    Infants, Children, and Adolescents

    10 to 15 mg/kg/dose (Max: 300 mg/dose) IV or IM once daily or 5 days/week.     Daily dosing is defined as 5- or 7 days/week. Isoniazid is generally recommended throughout the intensive and continuation phases of treatment as first-line therapy; duration is dependent on the site of involvement.  

    Neonates†

    10 to 15 mg/kg/dose IV or IM once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Isoniazid is generally recommended throughout the intensive and continuation phases of treatment for a minimum of 8 months as first-line therapy.[53484] [53485] [61095] [63245] [65675]

    For the treatment of drug-resistant tuberculosis infection as part of combination therapy.
    Oral dosage
    Adults

    5 to 15 mg/kg/dose PO once daily. High-dose isoniazid can be considered despite low-level isoniazid resistance but not with high-level isoniazid resistance.[34362] [65465] [65620] [65645] The FDA-approved dose is 5 mg/kg/dose (Max: 300 mg/dose) PO once daily or 15 mg/kg/dose (Max: 900 mg/dose) PO 3 days/week or twice weekly.[44180]

    Infants, Children, and Adolescents

    15 to 20 mg/kg/dose PO once daily. High-dose isoniazid can be considered despite low-level isoniazid resistance but not with high-level isoniazid resistance. The FDA-approved dose is 10 to 15 mg/kg/dose (Max: 300 mg/dose) PO once daily or 20 to 40 mg/kg/dose (Max: 900 mg/dose) PO 3 days/week or twice weekly.

    Intravenous† or Intramuscular dosage
    Adults

    5 to 15 mg/kg/dose IV or IM once daily. High-dose isoniazid can be considered despite low-level isoniazid resistance but not with high-level isoniazid resistance. The FDA-approved dose is 5 mg/kg/dose (Max: 300 mg/dose) IM once daily or 15 mg/kg/dose (Max: 900 mg/dose) IM 3 days/week or twice weekly.

    Infants, Children, and Adolescents

    15 to 20 mg/kg/dose IV or IM once daily. High-dose isoniazid can be considered despite low-level isoniazid resistance but not with high-level isoniazid resistance. The FDA-approved dose is 10 to 15 mg/kg/dose (Max: 300 mg/dose) IM once daily or 20 to 40 mg/kg/dose (Max: 900 mg/dose) IM 3 days/week or twice weekly.

    For tuberculosis prophylaxis or latent tuberculosis infection (LTBI).
    For tuberculosis prophylaxis or LTBI in combination with rifapentine.
    Oral dosage
    Adults

    15 mg/kg/dose (Max: 900 mg/dose) PO once weekly for 3 months.

    Children and Adolescents 12 to 17 years

    15 mg/kg/dose (Max: 900 mg/dose) PO once weekly for 3 months. 

    Children 2 to 11 years

    25 mg/kg/dose (Max: 900 mg/dose) PO once weekly for 3 months.

    Intramuscular dosage
    Adults

    15 mg/kg/dose (Max: 900 mg/dose) IM once weekly for 3 months.

    Children and Adolescents 12 to 17 years

    15 mg/kg/dose (Max: 900 mg/dose) IM once weekly for 3 months. 

    Children 2 to 11 years

    25 mg/kg/dose (Max: 900 mg/dose) IM once weekly for 3 months. 

    For tuberculosis prophylaxis or LTBI in combination with rifampin.
    Oral dosage
    Adults

    5 mg/kg/dose (Max: 300 mg/dose) PO once daily for 3 to 4 months.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose (Max: 300 mg/dose) PO once daily for 3 to 4 months.

    Intramuscular dosage
    Adults

    5 mg/kg/dose (Max: 300 mg/dose) IM once daily for 3 to 4 months.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose (Max: 300 mg/dose) IM once daily for 3 to 4 months.

    For tuberculosis prophylaxis or LTBI as monotherapy.
    Oral dosage
    Adults

    5 mg/kg/dose (Max: 300 mg/dose) PO once daily or 15 mg/kg/dose (Max: 900 mg/dose) PO twice weekly for 6 to 9 months. 

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose (Max: 300 mg/dose) PO once daily or 20 to 40 mg/kg/dose (Max: 900 mg/dose) PO twice weekly for 6 to 9 months.   

    Neonates†

    10 to 15 mg/kg/dose PO once daily for 3 to 4 months, then perform a tuberculin skin test (TST). If TST is negative and the mother has good response to treatment, discontinue isoniazid. If TST is positive and active disease is excluded, continue for a total of 9 months. Isoniazid is recommended for neonates of mothers who have tuberculosis disease when congenital tuberculosis is excluded.[63245]

    Intramuscular dosage
    Adults

    5 mg/kg/dose (Max: 300 mg/dose) IM once daily or 15 mg/kg/dose (Max: 900 mg/dose) IM twice weekly for 6 to 9 months. 

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose (Max: 300 mg/dose) IM once daily or 20 to 40 mg/kg/dose (Max: 900 mg/dose) IM twice weekly for 6 to 9 months.  

    Neonates†

    10 to 15 mg/kg/dose IM once daily for 3 to 4 months, then perform a tuberculin skin test (TST). If TST is negative and the mother has good response to treatment, discontinue isoniazid. If TST is positive and active disease is excluded, continue for a total of 9 months. Isoniazid is recommended for neonates of mothers who have tuberculosis disease when congenital tuberculosis is excluded.[63245]

    MAXIMUM DOSAGE

    Adults

    5 mg/kg/dose (Max: 300 mg/dose) PO/IV/IM once daily or 5 days/week or 15 mg/kg/dose (Max: 900 mg/dose) PO/IV/IM 3 days/week or twice weekly. 15 mg/kg/dose (Max: 900 mg) PO/IV/IM once daily or once weekly has been used off-label.

    Geriatric

    5 mg/kg/dose (Max: 300 mg/dose) PO/IV/IM once daily or 5 days/week or 15 mg/kg/dose (Max: 900 mg/dose) PO/IV/IM 3 days/week or twice weekly. 15 mg/kg/dose (Max: 900 mg) PO/IV/IM once daily or once weekly has been used off-label.

    Adolescents

    15 mg/kg/dose (Max: 300 mg/dose) PO/IV/IM once daily or 5 days/week or 40 mg/kg/dose (Max: 900 mg/dose) PO/IV/IM 3 days/week or twice weekly. 20 mg/kg/dose PO/IV/IM once daily or 15 mg/kg/dose (Max: 900 mg/dose) PO/IM once weekly have been used off-label.

    Children

    12 years: 15 mg/kg/dose (Max: 300 mg/dose) PO/IV/IM once daily or 5 days/week or 40 mg/kg/dose (Max: 900 mg/dose) PO/IV/IM 3 days/week or twice weekly. 20 mg/kg/dose PO/IV/IM once daily or 15 mg/kg/dose (Max: 900 mg/dose) PO/IM once weekly have been used off-label.
    2 to 11 years: 15 mg/kg/dose (Max: 300 mg/dose) PO/IV/IM once daily or 5 days/week or 40 mg/kg/dose (Max: 900 mg/dose) PO/IV/IM 3 days/week or twice weekly. 20 mg/kg/dose PO/IV/IM once daily and 25 mg/kg/dose (Max: 900 mg/dose) PO/IM once weekly have been used off-label.
    1 year: 15 mg/kg/dose PO/IV/IM once daily or 5 days/week or 40 mg/kg/dose PO/IV/IM 3 days/week or twice weekly. 20 mg/kg/dose PO/IV/IM once daily has been used off-label.

    Infants

    15 mg/kg/dose PO/IV/IM once daily or 5 days/week or 40 mg/kg/dose PO/IV/IM 3 days/week or twice weekly. 20 mg/kg/dose PO/IV/IM once daily has been used off-label.

    Neonates

    Safety and efficacy have not been established. 15 mg/kg/day PO/IV/IM has been used off-label.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Use isoniazid with caution in patients with chronic hepatic disease. Delay preventive therapy in persons with acute hepatic disease.

    Renal Impairment

    Carefully monitor isoniazid use in patients with severe renal dysfunction.[44180] Guidelines recommend no dosage adjustment with any degree of renal dysfunction.[32569] [61094] [65645]
     
    Intermittent hemodialysis
    Isoniazid is 50% to 100% dialyzable. Dose after hemodialysis on dialysis days.[32569] [61094]
     
    Peritoneal dialysis
    No dosage adjustment needed.[32569]
     
    Continuous renal replacement therapy (CRRT)†NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.[42303]
     
    No dosage adjustment needed.[32569]

    ADMINISTRATION

     
    Directly observed therapy (DOT) is recommended for all children as well as adolescents and adults with HIV and any regimen consisting of intermittent therapy.[34361] [34362] [44180] [61094] [63245]
    Concomitant pyridoxine is recommended for any patient at risk for neuropathy (e.g., persons with HIV, diabetes, alcoholism, nutritional deficiency, chronic renal failure, advanced age).[34362] [44180] [61094]

    Oral Administration

    Do not administer with food.
    Glucose or lactose decreases isoniazid absorption.

    Oral Solid Formulations

    Tablets may be crushed in foods containing low glucose, such as sugar-free pudding.
    Do not store crushed tablets mixed in food for later use.[61094]

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    NOTE: Isoniazid is not FDA-approved for intravenous administration.
     
    Dilution
    Dilute dose in 25 mL 0.9% Sodium Chloride Injection.
     
    Intermittent IV Push†
    Administer as slow bolus over 5 minutes.
    Do not infuse with other drugs through a shared IV line.

    Intramuscular Administration

    Inject deeply into a large muscle (e.g., ventrogluteal, anterolateral thigh, or deltoid). The deltoid and ventrogluteal areas should be reserved for adults and older children.[65648] [65650] [65651]
    In general, the American Academy of Pediatrics suggests the following volume limits for intramuscular administration of medications: [60486]
    0.5 mL per injection for small infants
    1 mL per injection for larger infants
    2 mL per injection for school-aged children
    3 mL per injection for adolescents

    STORAGE

    Generic:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Nydrazid:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Alcoholism, Black patients, females, hepatic disease, hepatitis, hepatotoxicity, Hispanic patients, jaundice

    Isoniazid is associated with a risk for serious hepatotoxicity, manifesting as INH-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. Most combination therapy for active TB disease includes more than 1 agent that may contribute to hepatotoxicity.[42734] [44180] [61094]

    Acquired immunodeficiency syndrome (AIDS), diabetes mellitus, human immunodeficiency virus (HIV) infection, malnutrition, 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]

    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]

    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.

    Pregnancy

    Use isoniazid during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies of isoniazid 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.

    Breast-feeding

    Isoniazid is excreted into breast milk. Encourage breast-feeding for women who are noninfectious and taking first-line tuberculosis agents, such as isoniazid, 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.[42734] [61094]

    ADVERSE REACTIONS

    Severe

    lupus-like symptoms / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    optic neuritis / Delayed / Incidence not known
    optic atrophy / Delayed / Incidence not known
    sideroblastic anemia / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    interstitial nephritis / Delayed / Incidence not known

    Moderate

    elevated hepatic enzymes / Delayed / 10.0-20.0
    hepatitis / Delayed / 0-2.3
    metabolic acidosis / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    memory impairment / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    encephalopathy / Delayed / Incidence not known
    psychosis / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    palpitations / Early / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    dyspnea / Early / Incidence not known
    neutropenia / Delayed / Incidence not known
    vitamin D deficiency / Delayed / Incidence not known

    Mild

    gynecomastia / Delayed / Incidence not known
    vomiting / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    nausea / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    maculopapular rash / Early / Incidence not known
    purpura / Delayed / Incidence not known
    chills / Rapid / Incidence not known
    cough / Delayed / Incidence not known
    syncope / Early / Incidence not known
    skin irritation / Early / Incidence not known
    injection site reaction / Rapid / Incidence not known
    myalgia / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    fever / Early / Incidence not known
    rash / Early / Incidence not known
    vitamin B6 deficiency / Delayed / Incidence not known

    DRUG INTERACTIONS

    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.
    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.
    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.
    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 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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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 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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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) 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.
    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.
    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.
    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.
    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.
    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
    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.
    Alosetron: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as isoniazid, INH, however, this interaction has not been studied.
    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%.
    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.
    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.
    Aripiprazole: (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.
    Artemether; Lumefantrine: (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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    Atazanavir; Cobicistat: (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.
    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.
    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.
    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.
    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.
    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) 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.
    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.
    Brompheniramine; Guaifenesin; Hydrocodone: (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) 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.
    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.
    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.
    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 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.
    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.
    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.
    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 isoniazid, INH could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Carbamazepine: (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.
    Carbinoxamine; Hydrocodone; Phenylephrine: (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) 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.
    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.
    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.
    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.
    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.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (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) 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) 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) 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.
    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%.
    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.
    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.
    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.
    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.
    Clopidogrel: (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: (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: (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: (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.
    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.
    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.
    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.
    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.
    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.
    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.
    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: (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.
    Darunavir: (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: (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: (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.
    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.
    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.
    Diazepam: (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.
    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.
    Diphenhydramine; Hydrocodone; Phenylephrine: (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: (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.
    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).
    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.
    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.
    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.
    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.
    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.
    Eliglustat: (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.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (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: (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.
    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.
    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.
    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.
    Esomeprazole: (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.
    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.
    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.
    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.
    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.
    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.
    Finerenone: (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: (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.
    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.
    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.
    Fosphenytoin: (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.
    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) 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) 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.
    Haloperidol: (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.
    Homatropine; Hydrocodone: (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.
    Hydrocodone: (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.
    Hydrocodone; Ibuprofen: (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.
    Hydrocodone; Phenylephrine: (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.
    Hydrocodone; Potassium Guaiacolsulfonate: (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.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (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.
    Hydrocodone; Pseudoephedrine: (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.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (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.
    Ibuprofen; 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.
    Imipramine: (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, imipramine and concurrent serotonergic agents should be discontinued.
    Indinavir: (Minor) Indinavir and isoniazid, INH, administered concurrently for 1 week resulted in a 13% increase in isoniazid AUC. No effects on indinavir pharmacokinetics were reported. No dosage adjustments for either agent are recommended.
    Isocarboxazid: (Major) In theory, concurrent use of isoniazid, INH with non-selective monoamine oxidase inhibitors (MAOIs), such as isocarboxazid, increase the risk of a hypertensive crisis. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity.
    Isoflurane: (Major) Anesthetic requirements may be increased for isoflurane with concomitant use of isoniazid, INH. The cytochrome P450 (CYP) 2E1 isoenzyme appears to be a predominant enzyme responsible for human oxidative isoflurane metabolism. Isoniazid, INH has been shown to induce CYP2E1. Additionally, the concurrent use of isoflurane and isoniazid may increase the risk of hepatotoxicity.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of isoniazid, INH and rifampin. 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. Rifampin can increase the metabolism of isoniazid, INH into a hepatotoxic metabolite (hydrazine). The impact of this drug interaction, however, appears minimal; combination therapy is routinely used in treating tuberculosis. Hepatotoxicity as a result of this interaction may be more significant in INH slow acetylators, patients with preexisting hepatic disease, or patients receiving anesthetics. 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 pyrazinamide, PZA 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.
    Isoniazid, INH; Rifampin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of isoniazid, INH and rifampin. 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. Rifampin can increase the metabolism of isoniazid, INH into a hepatotoxic metabolite (hydrazine). The impact of this drug interaction, however, appears minimal; combination therapy is routinely used in treating tuberculosis. Hepatotoxicity as a result of this interaction may be more significant in INH slow acetylators, patients with preexisting hepatic disease, or patients receiving anesthetics. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Itraconazole: (Major) Use of isoniazid is not recommended for 2 weeks before or during itraconazole therapy. Isoniazid may reduce itraconazole serum concentrations resulting in antifungal treatment failure.
    Ixabepilone: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with isoniazid is necessary; consider the use of an alternative agent to isoniazid that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and isoniazid is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Ketoconazole: (Major) Avoid the concomitant use of isonazid for 2 weeks before and during treatment with ketoconazole. Isoniazid may decrease the biovailability of ketoconazole resulting in antifungal treatment failure. If coadministration is necessary, monitor the antifungal activity of ketoconazole and increase the dose as necessary.
    Leflunomide: (Major) Concomitant use of isonazid with leflunomide may increase the risk for hepatotoxicity. Caution and close monitoring are advised if these drugs are used together.
    Lemborexant: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with isoniazid, INH as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; isoniazid is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
    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.
    Levoketoconazole: (Major) Avoid the concomitant use of isonazid for 2 weeks before and during treatment with ketoconazole. Isoniazid may decrease the biovailability of ketoconazole resulting in antifungal treatment failure. If coadministration is necessary, monitor the antifungal activity of ketoconazole and increase the dose as necessary.
    Levomilnacipran: (Moderate) Due to the risk of serotonin syndrome, concurrent use of levomilnacipran 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, levomilnacipran and concurrent serotonergic agents should be discontinued.
    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.
    Lidocaine; Prilocaine: (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.
    Linezolid: (Major) In theory, concurrent use of isoniazid, INH with other drugs that possess MAO-inhibiting activity, such as linezolid, may result in hypertensive crises, fever, delirium, circulatory collapse, seizures, coma, or death. Similar severe adverse events have occurred after combining other MAOIs. The manufacturer of linezolid contraindicates use of linezolid with any monoamine oxidase inhibitor (MAOI) or within two weeks of taking an MAOI. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity. Linezolid is an antibiotic that is also a non-selective MAOI.
    Lomitapide: (Major) Concomitant use of lomitapide and isoniazid, INH may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Isoniazid, INH is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
    Lonafarnib: (Major) Avoid coadministration of lonafarnib and isoniazid; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. If coadministration is unavoidable, reduce to or continue lonafarnib at a dosage of 115 mg/m2 and closely monitor patients for lonafarnib-related adverse reactions. Resume previous lonafarnib dosage 14 days after discontinuing isoniazid. Lonafarnib is a sensitive CYP3A4 substrate and isoniazid is a weak CYP3A4 inhibitor.
    Mefloquine: (Moderate) Mefloquine is metabolized by CYP3A4. Isoniazid is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
    Melatonin: (Minor) Melatonin may potentiate the antibacterial effects of isoniazid, INH against M. tuberculosis as evidenced by in vitro studies. It is unknown what effect melatonin has on isoniazid, INH activity, serum concentrations, or tuberculosis infection when the two therapies are combined in vivo. More study is needed.
    Meperidine: (Major) Isoniazid, INH has been shown to have some non-selective MAO-inhibiting properties. Because meperidine possesses serotonergic properties and the combination of serotonergic agents and MAO-inhibitors has resulted in the development of serotonin syndrome, meperidine should be used cautiously in patients receiving isoniazid, INH.
    Meperidine; Promethazine: (Major) Isoniazid, INH has been shown to have some non-selective MAO-inhibiting properties. Because meperidine possesses serotonergic properties and the combination of serotonergic agents and MAO-inhibitors has resulted in the development of serotonin syndrome, meperidine should be used cautiously in patients receiving isoniazid, INH.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (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.
    Methylene Blue: (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.
    Methylprednisolone: (Minor) Corticosteroids, such as methylprednisolone, may decrease serum concentrations of isoniazid. Isoniazid serum concentrations decreased by 25% and 40% in slow and rapid acetylators, respectively, when isoniazid (10 mg/kg) was co-administered with another corticosteroid. The exact mechanism of action of the interaction is unknown. The decrease in plasma concentrations may be caused by enhanced acetylation or renal clearance of isoniazid or by an increase in total body water.
    Midazolam: (Moderate) Isoniazid, INH may decrease the hepatic oxidative metabolism of benzodiazepines if administered concomitantly. Patients receiving midazolam should be monitored for signs of altered benzodiazepine response when isoniazid is initiated or discontinued.
    Milnacipran: (Moderate) Due to the risk of serotonin syndrome, concurrent use of milnacipran 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, milnacipran and concurrent serotonergic agents should be discontinued.
    Mirtazapine: (Major) Due to the risk of serotonin syndrome, concurrent use of mirtazapine and medications with MAO-like activity, such as isoniazid, INH, should be avoided if possible. 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. If serotonin syndrome occurs, all serotonergic agents should be discontinued, and appropriate medical treatment should be implemented. In addition, mirtazapine is a substrate for 2D6, 1A2, and 3A4. Pharmacokinetic studies with some CYP3A4 inhibitors have shown that elevations in mirtazapine concentrations are possible during coadministration. Therefore, caution is advised during concurrent use of mirtazapine and inhibitors of CYP3A4 such as isoniazid, INH.
    Nanoparticle Albumin-Bound Sirolimus: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 if coadministration with isoniazid is necessary. The dose of sirolimus may also need to be reduced with coadministration of isoniazid. Monitor sirolimus serum concentrations as appropriate and watch for sirolimus-related adverse reactions with coadministration of isoniazid. Sirolimus is a sensitive CYP3A substrate with a narrow therapeutic range; isoniazid is a weak CYP3A inhibitor.
    Naproxen; Esomeprazole: (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.
    Nisoldipine: (Major) Avoid coadministration of nisoldipine with isoniazid due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and isoniazid is a CYP3A4 inhibitor.
    Nortriptyline: (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, nortriptyline and concurrent serotonergic agents should be discontinued.
    Olanzapine; 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.
    Omeprazole; Amoxicillin; Rifabutin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifabutin 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.
    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.
    Paroxetine: (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.
    Perphenazine; 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.
    Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with isoniazid. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Phenelzine: (Major) In theory, concurrent use of isoniazid, INH with non-selective monoamine oxidase inhibitors (MAOIs), such as phenelzine, increase the risk of a hypertensive crisis. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity.
    Phenytoin: (Moderate) The metabolism of phenytoin 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 may occur following withdrawal of INH.
    Probenecid; 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.
    Procarbazine: (Major) In theory, concurrent use of isoniazid, INH with other drugs that possess MAO-inhibiting activity, such as procarbazine, may result in hypertensive crises, fever, delirium, circulatory collapse, seizures, coma, or death, and the combination should be avoided if possible. Similar severe adverse events have occurred after combining other MAOIs. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity. Procarbazine is an antineoplastic agent that is also a weak MAOI. A washout period between treatment with isoniazid and procarbazine may be necessary, but specific recommendations are not available.
    Protriptyline: (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, protriptyline and concurrent serotonergic agents should be discontinued.
    Pyrazinamide, PZA: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of pyrazinamide, PZA 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.
    Rasagiline: (Major) Concurrent use of rasagiline and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and rasagiline is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although rasagiline is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of rasagiline decreases with increasing dosages.
    Rifabutin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifabutin 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.
    Rifampin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of isoniazid, INH and rifampin. 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. Rifampin can increase the metabolism of isoniazid, INH into a hepatotoxic metabolite (hydrazine). The impact of this drug interaction, however, appears minimal; combination therapy is routinely used in treating tuberculosis. Hepatotoxicity as a result of this interaction may be more significant in INH slow acetylators, patients with preexisting hepatic disease, or patients receiving anesthetics. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Rifapentine: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifapentine 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 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.
    Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and isoniazid. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
    Safinamide: (Major) Concurrent use of safinamide and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and safinamide is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although safinamide is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of safinamide decreases with increasing dosages.
    Segesterone Acetate; Ethinyl Estradiol: (Minor) Coadministration of segesterone, a CYP3A4 substrate and a moderate CYP3A4 inhibitor, such as isoniazid may increase the serum concentration of segesterone.
    Selegiline: (Major) Concurrent use of selegiline and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and selegiline is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although selegiline is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of selegiline decreases with increasing dosages.
    Sertraline: (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. 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. If combination therapy is necessary, patients should be monitored for the emergence of serotonin syndrome.
    Sevoflurane: (Major) Anesthetic requirements may be increased for sevoflurane with concomitant use of isoniazid, INH. The cytochrome P450 (CYP) 2E1 isoenzyme appears to be a predominant enzyme responsible for human oxidative sevoflurane metabolism. Isoniazid, INH has been shown to induce CYP2E1. Additionally, the concurrent use of sevoflurane and isoniazid may increase the risk of hepatotoxicity.
    Sibutramine: (Major) Isoniazid, INH possesses weak non-selective MAO-inhibiting activity and concurrent use with sibutramine should be avoided if possible. The concomitant use of sibutramine with MAOIs is contraindicated. Sibutramine is a serotonin reuptake inhibitor. Since serotonin is deaminated by monoamine oxidase-A, concurrent administration of sibutramine with drugs that inhibit this enzyme such as MAOIs can lead to 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. There should be at least a 2-week interval between discontinuation of MAOI therapy and initiation of sibutramine therapy. Similarly, there should be at least a 2-week interval after stopping sibutramine therapy and the start of MAOI therapy.
    Sirolimus: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 if coadministration with isoniazid is necessary. The dose of sirolimus may also need to be reduced with coadministration of isoniazid. Monitor sirolimus serum concentrations as appropriate and watch for sirolimus-related adverse reactions with coadministration of isoniazid. Sirolimus is a sensitive CYP3A substrate with a narrow therapeutic range; isoniazid is a weak CYP3A inhibitor.
    Sufentanil: (Major) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if isoniazid must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression, sedation, and serotonin syndrome if concurrent use of isoniazid is necessary. If isoniazid is discontinued, consider increasing the sufentanil injection 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, sufentanil is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isoniazid can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If isoniazid is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
    Tacrolimus: (Moderate) Monitor for increased tacrolimus adverse reactions if coadministered with isoniazid. Taking these drugs together may increase tacrolimus plasma concentrations, potentially resulting in adverse events. Isoniazid is a weak CYP3A4 inhibitor; tacrolimus is a substrate of CYP3A4 with a narrow therapeutic index.
    Tedizolid: (Major) Caution is warranted with concurrent use of tedizolid and drugs that possess MAOI-like activity, such as isoniazid, INH, because of the theoretical possibility of severe hyperpyretic or hypertensive crises, convulsions, or death. Tedizolid is an antibiotic that is also a weak reversible, non-selective MAO inhibitor and most potential drug interactions with tedizolid are related to this action of the drug. 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 selective serotonin reuptake inhibitors. 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.
    Theophylline, Aminophylline: (Minor) Isoniazid, INH may reduce aminophylline clearance. Although data regarding this drug interaction are conflicting, it appears that this can be explained by the duration of isoniazid administration. Larger doses of isoniazid and longer duration of isoniazid administration are more likely to affect aminophylline pharmacokinetics. At least one patient developed aminophylline toxicity as a result of this interaction with isoniazid. (Minor) Isoniazid, INH may reduce theophylline clearance. Although data regarding this drug interaction are conflicting, it appears that this can be explained by the duration of isoniazid administration. Larger doses of isoniazid and longer duration of isoniazid administration are more likely to affect theophylline pharmacokinetics. At least one patient developed theophylline toxicity as a result of this interaction with isoniazid.
    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.
    Tramadol; 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. (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.
    Tranylcypromine: (Major) In theory, concurrent use of isoniazid, INH with non-selective monoamine oxidase inhibitors (MAOIs), such as tranylcypromine, increase the risk of a hypertensive crisis. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity.
    Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with isoniazid and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and isoniazid is a weak CYP3A inhibitor.
    Trimipramine: (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, trimipramine and concurrent serotonergic agents should be discontinued.
    Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with isoniazid. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; isoniazid is a weak CYP3A4 inhibitor.
    Valproic Acid, Divalproex Sodium: (Moderate) Concomitant use of isoniazid with valproic acid may result in increased serum concentrations of valproic acid and increase the risk for serious adverse reactions, such as hepatoxicity. Several case reports demonstrated elevated valproic acid concentrations and hepatotoxicity when isoniazid was added to previously stabilized valproic acid therapy. Monitor serum valproic acid concentrations during coadministration; appropriate dosage adjustments of vaproic acid should be made.
    Venlafaxine: (Major) Due to the risk of serotonin syndrome, concurrent use of venlafaxine 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 when combined with serotonin norepinephrine reuptake inhibitors. 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, venlafaxine and concurrent serotonergic agents should be discontinued.
    Vilazodone: (Major) Due to the risk of serotonin syndrome, concurrent use of vilazodone 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 when combined with selective serotonin reuptake inhibitors. 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.
    Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with isoniazid is necessary. Vinorelbine is a CYP3A4 substrate and isoniazid is a weak CYP3A4 inhibitor.
    Voriconazole: (Moderate) Voriconazole is a primary substrate of the CYP2C19 isoenzyme. Theoretically, isoniazide, a CYP2C19 inhibitor, may result in elevated voriconazole serum concentrations when coadministered.
    Vortioxetine: (Major) Due to the risk of serotonin syndrome, concurrent use of vortioxetine 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 when combined with vortioxetine. 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. Patients receiving isoniazid in combination with vortioxetine should be monitored for the emergence of serotonin syndrome or other adverse effects. If serotonin syndrome is suspected, vortioxetine and concurrent serotonergic agents should be discontinued.
    Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with isoniazid is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Isoniazid is a weak CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
    Zalcitabine, ddC: (Major) It is recommended that zalcitabine, ddC not be used in combination with isoniazid due to additive peripheral neuropathy seen with concomitant use.

    PREGNANCY AND LACTATION

    Pregnancy

    Use isoniazid during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies of isoniazid 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.

    Isoniazid is excreted into breast milk. Encourage breast-feeding for women who are noninfectious and taking first-line tuberculosis agents, such as isoniazid, 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.[42734] [61094]

    MECHANISM OF ACTION

    Molecular Pharmacology: Isoniazid, INH inhibits a variety of enzymes. In mycobacterial cells, isoniazid appears to interfere with mycolic acid synthesis, disrupting the synthesis of the bacterial cell wall. The exact antimycobacterial action, however, is uncertain. Isoniazid inhibits plasma monoamine oxidase, but, unlike the chemically related iproniazid, does not inhibit mitochondrial MAO. It also inhibits mycobacterial MAO and diamine oxidase and mammalian diamine oxidase. Inhibition of these oxidases interferes with the metabolism of both tyramine and histamine. The mechanism by which isoniazid causes toxicity in humans has also been identified. In vitro studies show that isoniazid induces cytotoxicity via apoptosis in both hepatoma and lymphoma cells. Apoptosis was accompanied by a breakdown in mitochondrial membrane potential and the presence of DNA strand breaks. This resulted in a significant disruption of the cell cycle in mammalian cells.
     
    Clinical Pharmacology: INH is bactericidal or bacteriostatic, depending on the drug concentration within an infected site and the susceptibility of the organism. INH is bactericidal against rapidly dividing intracellular and extracellular organisms such as those found in extracellular cavitary lesions but is bacteriostatic against organisms found within closed caseous lesions and macrophages that divide slowly and intermittently. Rifampin and pyrazinamide may be more effective against these slowly dividing organisms than INH. Since mycolic acids are unique to mycobacteria, this explains isoniazid's remarkable selectivity for mycobacteria. Cross-resistance between INH and other antitubercular agents has not been demonstrated except for ethionamide, which is structurally related to INH.  Resistance in tuberculosis infections develops rapidly with monotherapy. Resistance to INH occurs due to mutations in the KatG, inhA, kasA, and ahpC genes.
     
    Although isoniazid does not appear to inhibit mitochondrial monoamine oxidase, some patients taking isoniazid have experienced flushing, headache, and palpitations after ingesting tyramine-containing foods. This reaction suggests it may inhibit plasma monoamine oxidase. INH is not known to possess clinically-significant antidepressant activity, however.

    PHARMACOKINETICS

    Isoniazid is most often administered orally but can also be administered intramuscularly. It is distributed into all body tissues and fluids, penetrates inflamed meninges and achieves therapeutic levels in the CSF. Isoniazid crosses the placenta and is distributed into breast milk. It is not significantly bound to plasma proteins. Metabolism occurs in the liver to inactive metabolites, primarily via acetylation. The half-life is 1—4 hours, depending on the patient's acetylation rate; however, the effectiveness of the drug does not appear to be altered if dosed only once daily. Approximately 75% of the drug and its metabolites are excreted in the urine. The remainder is excreted in the feces, saliva, and sputum.
     
    Affected cytochrome P450 isoenzymes: CYP2C19, CYP3A4, CYP2A6, CYP2C9, CYP2D6, CYP2E1
    Isoniazid has been associated with many clinically significant interactions involving reduced drug metabolism. It is a potent inhibitor of CYP2C19 and an inhibitor of CYP3A4 in vitro. It only weakly inhibits CYP2A6, CYP2C9, and CYP2D6. Results are conflicting for CYP1A2, but it appears that only negligible inhibition occurs. Also, isoniazid has demonstrated both inhibitory and inducing actions on the hepatic isoenzyme CYP2E1. This dual affect is theorized to result from isoniazid competitively blocking the active site on the CYP2E1 isoenzyme resulting in decreased metabolism of the substrate as well as preserving CYP2E1. Upon disassociation from the active site, more CYP2E1 isoenzyme is available resulting in a temporary increased enzymatic activity.

    Oral Route

    Following oral administration, isoniazid is absorbed rapidly from the GI tract. Peak serum levels are attained within 1—2 hours after an oral dose. Food decreases the rate and extent of absorption.