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Rifater Side Effects

Generic Name: isoniazid / pyrazinamide / rifampin

Note: This document contains side effect information about isoniazid / pyrazinamide / rifampin. Some of the dosage forms listed on this page may not apply to the brand name Rifater.

For the Consumer

Applies to isoniazid / pyrazinamide / rifampin: oral tablet


Oral route (Tablet)

Severe and sometimes fatal hepatitis has been reported with isoniazid therapy and may occur even after many months of treatment. The risk for hepatitis increases with advancing age and alcohol use. Monthly clinical evaluation and liver function tests should be performed and therapy discontinued if symptoms of signs develop. Patients with tuberculosis should be given appropriate treatment with alternative drugs. If therapy must be reinstituted after resolution of hepatic symptoms, small and gradual dose increases should be employed and treatment should be withdrawn immediately if there is any indication of recurrent liver involvement.

Along with its needed effects, isoniazid/pyrazinamide/rifampin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking isoniazid / pyrazinamide / rifampin:

More Common

  • Clumsiness or unsteadiness
  • coughing or spitting up blood
  • dark urine
  • fast, irregular, pounding, or racing heartbeat or pulse
  • loss of appetite
  • nausea
  • numbness, tingling, burning, or pain in the hands and feet
  • pain in large and small joints
  • tightness in the chest
  • unusual tiredness or weakness
  • vomiting
  • yellow eyes or skin

Less Common

  • Chills
  • difficulty in breathing
  • dizziness
  • fever
  • headache
  • hearing loss
  • muscle and bone pain
  • ringing or buzzing or other unexplained noise in the ears
  • shivering
  • skin rash, itching, or redness


  • Black, tarry stools
  • bleeding gums
  • blistering, peeling, or loosening of the skin
  • bloody or cloudy urine
  • blurred vision or loss of vision, with or without eye pain
  • greatly decreased frequency of urination or amount of urine
  • mental depression
  • mood or mental changes
  • pinpoint red spots on the skin
  • seizures
  • sore throat
  • unusual bleeding or bruising

Some side effects of isoniazid / pyrazinamide / rifampin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More Common

Less Common

  • Sore mouth or tongue

Incidence Not Known

  • Tooth discoloration

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.[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%)

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: Hepatic enzyme increased, hyperbilirubinemia, increased serum alkaline phosphatase, increased serum transaminases, transient liver function test abnormalities[Ref]


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


Rare (0.01% to 0.1%): Eosinophilia systemic symptoms, toxic epidermal necrolysis

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


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

Frequency not reported: Erythema, pruritus, rash, urticaria


Frequency not reported: Allergic dermatitis, erythema multiforme, face edema, itching with/without rash, pemphigoid, pruritus, rash pruritic, 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

Frequency not reported: Convulsions, loss of tendon reflexes, memory impairment, paresthesia, polyneuritis, toxic encephalopathy, 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 discomfort, 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: 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%): Fever


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


Frequency not reported: 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, 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: Decreased hemoglobin, eosinophilia, hemolytic anemia[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[Ref]



Rare (0.01% to 0.1%): Interstitial nephritis


Rare (0.01% to 0.1%): Acute renal failure, acute tubular necrosis, interstitial nephritis, renal insufficiency

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, hyperuricemia, reduced urate excretion


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


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


Frequency not reported: Gynecomastia


Rare (0.01% to 0.1%): Adrenal insufficiency[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: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome


Frequency not reported: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, flu syndrome, influenza[Ref]



Frequency not reported: Optic atrophy, optic neuritis


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



Frequency not reported: Erythroid hyperplasia[Ref]


1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

2. "Product Information. Rifater (isoniazid / pyrazinamide / rifampin)." SmithKline Beecham, Philadelphia, PA.

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.

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