Isoniazid / Pyrazinamide / Rifampin Side Effects

Medically reviewed by Drugs.com. Last updated on Jun 15, 2025.

Applies to isoniazid / pyrazinamide / rifampin: oral tablet.

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: skin rash, fever, swollen glands, muscle aches, severe weakness, unusual bruising, and joint pain or stiffness.

Rifater can cause severe liver symptoms, especially in people who are 35 and older. Call your doctor at once if you have any of these early signs of liver damage: nausea, vomiting, upper stomach pain, weakness, tiredness, loss of appetite, or yellowing of your skin or eyes.

Also call your doctor right away if you have:

• numbness, tingling, or burning pain in your hands or feet;

• vision problems, pain behind your eyes;

• wheezing, trouble breathing; or

• severe stomach pain, diarrhea that is watery or bloody.

Common side effects may include:

• numbness or tingling;

• red discoloration of your teeth, sweat, urine, saliva, and tears;

• nausea, vomiting, stomach pain;

• mild rash or itching; or

• joint or muscle pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

See also:

For healthcare professionals

Applies to isoniazid / pyrazinamide / rifampin: oral tablet.

General adverse events

Isoniazid: The most frequently reported side effects are those affecting the nervous system and liver.

Pyrazinamide: The most frequently reported side effects are those affecting the liver.

Rifampin: The most frequently reported side effects are thrombocytopenia and those affecting the nervous system.^[Ref]

Hepatic

• Common (1% to 10%): Hepatitis with conjunctival jaundice, hepatitis with deep jaundice
• Frequency not reported: ALT alterations, AST alterations, jaundice reaction, liver enzyme alterations

Isoniazid:

• Very common (10% or more): Mild/transient serum transaminase elevations (up to 20%)
• Common (1% to 10%): Progressive liver damage
• Uncommon (0.1% to 1%): Severe hepatitis/fatal hepatitis
• Frequency not reported: Bilirubinemia, elevated serum transaminases (ALT, AST), jaundice

Pyrazinamide:

• Common (1% to 10%): Symptomless abnormality of hepatic cell function
• Frequency not reported: Acute yellow liver atrophy/fatal acute yellow liver atrophy, clinical jaundice, hepatotoxicity, liver tenderness

Rifampin:

• Common (1% to 10%): ALT increased, AST increased, blood bilirubin increased
• Rare (0.01% to 0.1%): Abnormal liver function tests, hepatitis, shock-like syndrome with hepatic involvement
• Frequency not reported: Cholestasis, hepatic enzyme increased, hepatitis, hepatotoxicity, hyperbilirubinemia, increased GGT, increased serum alkaline phosphatase, increased serum bilirubin, increased serum transaminases, jaundice, transient liver function test abnormalities^[Ref]

Common prodromal symptoms of severe/fatal hepatitis included anorexia, fatigue, malaise, nausea, vomiting, and weakness.

Mild and transient transaminase elevations usually occurred in the first 4 to 6 months of treatment with isoniazid, and enzyme levels typically returned to normal without patients needing to discontinue treatment.

Progressive liver damage was age-related, and more commonly occurred in patients over 50 years of age.^[Ref]

Dermatologic

• Common (1% to 10%): Diffuse skin rash, erythema, erythroderma, exfoliative dermatitis, Lyell syndrome, pruritus, rash, sweating, urticaria

Isoniazid:

• Frequency not reported: Acne, exfoliative dermatitis, exfoliative skin eruptions, maculopapular skin eruptions, morbilliform skin eruptions, pemphigus, purpuric skin eruptions, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis

Pyrazinamide:

• Rare (0.01% to 0.1%): Acne, photosensitivity
• Frequency not reported: Erythema, pruritus, rash, urticaria

Rifampin:

• Frequency not reported: Acute generalized exanthematous pustulosis, allergic dermatitis, cutaneous reactions, erythema multiforme, face edema, itching with/without rash, pemphigoid/pemphigoid reaction, pruritus, rash pruritic, serious cutaneous reactions, skin reaction, Stevens-Johnson syndrome, sweat discoloration, toxic epidermal necrolysis, urticaria^[Ref]

Nervous system

• Common (1% to 10%): Diabetic coma, diffuse paresthesia of the legs, headache, vertigo, vertigo with loss of equilibrium

Isoniazid:

• Common (1% to 10%): Peripheral neuropathy
• Uncommon (0.1% to 1%): Convulsions, memory impairment, neurotoxicity, toxic encephalopathy
• Frequency not reported: Loss of tendon reflexes, neuritis, paresthesia, polyneuritis, seizures, vertigo

Rifampin:

• Common (1% to 10%): Dizziness, headache
• Frequency not reported: Ataxia, cerebral hemorrhage/fatal cerebral hemorrhage, drowsiness, generalized numbness, inability to concentrate^[Ref]

Cerebral hemorrhage and fatal cerebral hemorrhage have occurred in patients who have continued or resumed treatment with rifampin after the appearance of purpura.

Polyneuritis associated with isoniazid (e.g., muscle weakness, loss of tendon reflexes, paresthesia) was unlikely to occur at the recommended daily dose of this combination drug.

High doses of isoniazid have resulted in convulsions and toxic encephalopathy.^[Ref]

Gastrointestinal

• Common (1% to 10%): Diarrhea, digestive pain, nausea, vomiting

Isoniazid:

• Frequency not reported: Constipation, dry mouth, epigastric distress, nausea, pancreatitis, vomiting

Pyrazinamide:

• Frequency not reported: Nausea, peptic ulcer aggravation, vomiting

Rifampin:

• Common (1% to 10%): Nausea, vomiting
• Uncommon (0.1% to 1%): Diarrhea
• Frequency not reported: Abdominal discomfort, cramps, epigastric distress, flatulence, gastrointestinal disorder, heartburn, pseudomembranous colitis, sore mouth, sore tongue, tooth discoloration/permanent tooth discoloration^[Ref]

Cardiovascular

• Common (1% to 10%): Angina, chest tightness, diffuse chest pain, leg edema, palpitation, phlebitis

Isoniazid:

• Frequency not reported: Vasculitis

Rifampin:

• Frequency not reported: Bleeding, blood pressure decreased, edema, edema extremities, flushing with/without rash, shock, vasculitis^[Ref]

Other

• Common (1% to 10%): Persistent fever, spiking fever, tinnitus

Isoniazid:

• Frequency not reported: Fatigue, fever, malaise, weakness

Pyrazinamide:

• Rare (0.01% to 0.1%): Death, fever
• Frequency not reported: Malaise

Rifampin:

• Common (1% to 10%): Chills, pyrexia
• Frequency not reported: Fatigue, fetal-maternal hemorrhage, fever, postpartum hemorrhage^[Ref]

Musculoskeletal

• Common (1% to 10%): Arthralgia, diffuse joint pain, long bone pain

Isoniazid:

• Frequency not reported: Muscle weakness, systemic lupus erythematosus-like syndrome

Pyrazinamide:

• Common (1% to 10%): Mild arthralgia, myalgia
• Frequency not reported: Arthralgia

Rifampin:

• Rare (0.01% to 0.1%): Myopathy
• Frequency not reported: Bone pain, extremity pain, muscle weakness^[Ref]

Respiratory

• Common (1% to 10%): Coughing, hemoptysis, total pneumothorax

Rifampin:

• Frequency not reported: Discolored sputum, dyspnea, shortness of breath, wheezing^[Ref]

Psychiatric

• Common (1% to 10%): Anxiety, insomnia

Isoniazid:

• Uncommon (0.1% to 1%): Toxic psychosis

Rifampin:

• Rare (0.01% to 0.1%): Psychoses
• Frequency not reported: Behavioral changes, mental confusion, psychotic disorder^[Ref]

Local

• Common (1% to 10%): Localized joint pain, localized skin rash^[Ref]

Hematologic

Isoniazid:

• Frequency not reported: Agranulocytosis, anemia, aplastic anemia, eosinophilia, hemolytic anemia, lymphadenopathy, sideroblastic anemia, thrombocytopenia

Pyrazinamide:

• Rare (0.01% to 0.1%): Adverse effects on blood clotting mechanisms, erythrocyte vacuolation, increased concentration of erythrocytes
• Frequency not reported: Sideroblastic anemia, sideroblastic anemia with erythroid hyperplasia, thrombocytopenia with/without purpura

Rifampin:

• Common (1% to 10%): Thrombocytopenia with/without purpura
• Uncommon (0.1% to 1%): Leukopenia
• Rare (0.01% to 0.1%): Agranulocytosis, disseminated intravascular coagulation, hemolysis
• Frequency not reported: Abnormally prolonged prothrombin time, decreased hemoglobin, eosinophilia, hemolytic anemia, low vitamin K-dependent coagulation factors, vitamin K-dependent coagulation disorders^[Ref]

Thrombocytopenia with/without purpura usually occurred with intermittent rifampin treatment or upon resumption of interrupted treatment, but was typically reversible if the drug was discontinued as soon as purpura occurred.^[Ref]

Hypersensitivity

• Common (1% to 10%): Generalized hypersensitivity

Isoniazid:

• Frequency not reported: Anaphylactic reactions, hypersensitivity reactions

Pyrazinamide:

• Rare (0.01% to 0.1%): Angioedema
• Frequency not reported: Hypersensitivity reactions

Rifampin:

• Rare (0.01% to 0.1%): Anaphylaxis
• Frequency not reported: Anaphylactic reaction, hypersensitivity reactions^[Ref]

Renal

Pyrazinamide:

• Rare (0.01% to 0.1%): Interstitial nephritis

Rifampin:

• Rare (0.01% to 0.1%): Acute renal failure, acute tubular necrosis, interstitial nephritis, renal dysfunction
• Frequency not reported: Acute kidney injury, blood creatinine increased, blood urea nitrogen elevated, renal tubular necrosis, tubulointerstitial nephritis^[Ref]

Acute renal failure, acute tubular necrosis, hematuria, hemoglobinuria, hemolysis, interstitial nephritis, and renal insufficiency are considered hypersensitivity reactions to rifampin, and usually occurred during intermittent treatment or upon resumption of treatment following intentional/accidental interruption of a daily regimen; these reactions were reversible when this drug was discontinued and appropriate therapy was given.^[Ref]

Genitourinary

Isoniazid:

• Frequency not reported: Bilirubinuria

Pyrazinamide:

• Rare (0.01% to 0.1%): Dysuria

Rifampin:

• Rare (0.01% to 0.1%): Hematuria, hemoglobinuria
• Frequency not reported: Chromaturia, menstrual disorder^[Ref]

Metabolic

• Frequency not reported: Serum uric acid level alterations

Isoniazid:

• Frequency not reported: Anorexia, hyperglycemia, metabolic acidosis, pellagra, pyridoxine deficiency

Pyrazinamide:

• Rare (0.01% to 0.1%): Porphyria
• Frequency not reported: Active gout, anorexia, gout, hyperuricemia, reduced urate excretion

Rifampin:

• Frequency not reported: Anorexia, decreased appetite, porphyria, serum uric acid elevated^[Ref]

Endocrine

Isoniazid:

• Frequency not reported: Gynecomastia

Rifampin:

• Rare (0.01% to 0.1%): Adrenal insufficiency^[Ref]

Adrenal insufficiency occurred in patients with compromised adrenal function receiving rifampin.^[Ref]

Immunologic

Isoniazid:

• Frequency not reported: Antinuclear antibodies present, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, rheumatic syndrome

Pyrazinamide:

• Frequency not reported: DRESS syndrome

Rifampin:

• Frequency not reported: DRESS syndrome, flu syndrome, influenza^[Ref]

Flu syndrome usually occurred in patients taking intermittent rifampin regimens; however, this side effect has also occurred in patients taking rifampin irregularly and in those resuming treatment after a drug-free interval.^[Ref]

Ocular

Isoniazid:

• Uncommon (0.1% to 1%): Optic atrophy, optic neuritis

Rifampin:

• Frequency not reported: Conjunctivitis, tear discoloration, visual disturbances^[Ref]

Oncologic

Pyrazinamide:

• Frequency not reported: Erythroid hyperplasia^[Ref]

Further information

Isoniazid/pyrazinamide/rifampin side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

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