Isoniazid / pyrazinamide / rifampin Side Effects

Medically reviewed by Drugs.com. Last updated on Jul 26, 2023.

Applies to isoniazid / pyrazinamide / rifampin: oral tablet.

Warning

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:

Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Signs of lupus like a rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs.
Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
Signs of too much acid in the blood (acidosis) like confusion; fast breathing; fast heartbeat; a heartbeat that does not feel normal; very bad stomach pain, upset stomach, or throwing up; feeling very sleepy; shortness of breath; or feeling very tired or weak.
Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
Chest pain or pressure.
Coughing up blood.
Fever, chills, or sore throat; any unexplained bruising or bleeding; or feeling very tired or weak.
Flu-like signs.
A heartbeat that does not feel normal.
Swollen gland.
Joint pain or swelling.
Period (menstrual) changes.
Ringing in ears.
Muscle pain or weakness.
Shortness of breath.
Cough.
Sweating a lot.
Swelling in the arms or legs.
Purple spots or redness of the skin.
Dizziness or passing out.
A burning, numbness, or tingling feeling that is not normal.
Seizures.
Memory problems or loss.
Change in eyesight, eye pain, or very bad eye irritation.
Change in balance.
Feeling confused, not able to focus, or change in behavior.
Change in tooth color. These changes may be long-lasting.

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:

Change in color of body fluids to orange or red.
Feeling sleepy.
Headache.
Diarrhea.
Gas.
Upset stomach or throwing up.
Stomach pain or cramps.
Heartburn.
Trouble sleeping.
Anxiety.
Not hungry.

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 https://www.fda.gov/medwatch.

For Healthcare Professionals

Applies to isoniazid / pyrazinamide / rifampin: oral tablet.

General

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

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]

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]

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

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]

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]

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

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

Isoniazid:

Frequency not reported: Gynecomastia

Rifampin:

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