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Isoniazid / pyrazinamide / rifampin Side Effects

For the Consumer

Applies to isoniazid / pyrazinamide / rifampin: oral tablet

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

Rare

  • 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

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 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

Isoniazid:

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

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

Dermatologic

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

Isoniazid:

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

Pyrazinamide:

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

Frequency not reported: Erythema, pruritus, rash, urticaria

Rifampin:

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

Isoniazid:

Common (1% to 10%): Peripheral neuropathy

Frequency not reported: Convulsions, loss of tendon reflexes, memory impairment, paresthesia, polyneuritis, toxic encephalopathy, vertigo

Rifampin:

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

Frequency not reported: Ataxia, cerebral hemorrhage/fatal cerebral hemorrhage, drowsiness, generalized numbness, inability to concentrate[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 discomfort, 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: 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%): Fever

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:

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

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, 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

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]

Isoniazid:

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

Pyrazinamide:

Frequency not reported: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome

Rifampin:

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

Ocular

Isoniazid:

Frequency not reported: Optic atrophy, optic neuritis

Rifampin:

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

Oncologic

Pyrazinamide:

Frequency not reported: Erythroid hyperplasia[Ref]

References

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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