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Isoniazid / pyrazinamide / rifampin Side Effects

Medically reviewed by Last updated on Feb 27, 2024.

Applies to isoniazid / pyrazinamide / rifampin: oral tablet.


  • This drug may cause very bad and sometimes deadly liver problems like hepatitis. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • The chance of liver problems is higher the older you are. The chance may also be raised by drinking alcohol every day, long-term liver problems, or injection drug use. The chance of liver problems may also be raised in women, mainly women who are black or Hispanic or who have just had a baby. Most of the time, liver problems caused by this drug happen within the first 3 months of care, but they can happen at any time. Most of the time, liver function has gone back to normal but sometimes it has not. Blood work will need to be done before starting this drug and while taking it. If you have questions, talk with the doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • If you have active liver disease, talk with your doctor. This drug may not be right for you.

Serious side effects

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

Other side effects

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at

For Healthcare Professionals

Applies to isoniazid / pyrazinamide / rifampin: oral tablet.


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]


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]

Common (1% to 10%): Hepatitis with conjunctival jaundice, hepatitis with deep jaundice

Frequency not reported: ALT alterations, AST alterations, jaundice reaction, liver enzyme alterations


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


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


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


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


Rare (0.01% to 0.1%): Acne, photosensitivity

Frequency not reported: Erythema, pruritus, rash, urticaria


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

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]

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


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


Common (1% to 10%): Dizziness, headache

Frequency not reported: Ataxia, cerebral hemorrhage/fatal cerebral hemorrhage, drowsiness, generalized numbness, inability to concentrate[Ref]


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


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


Frequency not reported: Nausea, peptic ulcer aggravation, vomiting


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]


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


Frequency not reported: Vasculitis


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


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


Frequency not reported: Fatigue, fever, malaise, weakness


Rare (0.01% to 0.1%): Death, fever

Frequency not reported: Malaise


Common (1% to 10%): Chills, pyrexia

Frequency not reported: Fatigue, fetal-maternal hemorrhage, fever, postpartum hemorrhage[Ref]


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


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


Common (1% to 10%): Mild arthralgia, myalgia

Frequency not reported: Arthralgia


Rare (0.01% to 0.1%): Myopathy

Frequency not reported: Bone pain, extremity pain, muscle weakness[Ref]


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


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


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


Uncommon (0.1% to 1%): Toxic psychosis


Rare (0.01% to 0.1%): Psychoses

Frequency not reported: Behavioral changes, mental confusion, psychotic disorder[Ref]


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


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


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


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]


Common (1% to 10%): Generalized hypersensitivity


Frequency not reported: Anaphylactic reactions, hypersensitivity reactions


Rare (0.01% to 0.1%): Angioedema

Frequency not reported: Hypersensitivity reactions


Rare (0.01% to 0.1%): Anaphylaxis

Frequency not reported: Anaphylactic reaction, hypersensitivity reactions[Ref]



Rare (0.01% to 0.1%): Interstitial nephritis


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]



Frequency not reported: Bilirubinuria


Rare (0.01% to 0.1%): Dysuria


Rare (0.01% to 0.1%): Hematuria, hemoglobinuria

Frequency not reported: Chromaturia, menstrual disorder[Ref]


Frequency not reported: Serum uric acid level alterations


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


Rare (0.01% to 0.1%): Porphyria

Frequency not reported: Active gout, anorexia, gout, hyperuricemia, reduced urate excretion


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



Frequency not reported: Gynecomastia


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

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


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


Frequency not reported: DRESS syndrome


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



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


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



Frequency not reported: Erythroid hyperplasia[Ref]


1. (2001) "Product Information. Rifater (isoniazid / pyrazinamide / rifampin)." SmithKline Beecham

2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

Further information

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

Some side effects may not be reported. You may report them to the FDA.