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Rifater Side Effects

Generic name: isoniazid / pyrazinamide / rifampin

Medically reviewed by Last updated on Mar 11, 2021.

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 associated with isoniazid, a component of rifampin, isoniazid and pyrazinamide, therapy may occur and may develop even after many months of treatment. The risk of developing hepatitis is age related. Approximate case rates by age are: 0 per 1000 for persons under 20 years of age, 3 per 1000 for persons in the 20 to 34 year age group, 12 per 1000 for persons in the 35 to 49 year age group, 23 per 1000 for persons in the 50 to 64 year age group, and 8 per 1000 for persons over 65 years of age. The risk of hepatitis is increased with daily consumption of alcohol. Precise data to provide a fatality rate for isoniazid-related hepatitis is not available; however, in a US Public Health Service Surveillance Study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis.Therefore, patients given rifampin, isoniazid and pyrazinamide, which contains isoniazid, should be carefully monitored and interviewed at monthly intervals. Serum transaminase concentration becomes elevated in about 10% to 20% of patients, usually during the first few months of therapy, but it can occur at any time. Usually enzyme levels return to normal despite continuance of drug, but in some cases progressive liver dysfunction occurs. Patients should be instructed to report immediately any of the prodromal symptoms of hepatitis, such as fatigue, weakness, malaise, anorexia, nausea, or vomiting. If these symptoms appear or if signs suggestive of hepatic damage are detected, rifampin, isoniazid and pyrazinamide should be discontinued promptly since continued use of the drug in these cases has been reported to cause a more severe form of liver damage.Patients with tuberculosis should be given appropriate treatment with alternative drugs. If isoniazid, a component of rifampin, isoniazid and pyrazinamide, must be reinstituted, it should be reinstituted only after symptoms and laboratory abnormalities have cleared. Rifampin, isoniazid and pyrazinamide should not be restarted, instead, isoniazid ,should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent liver involvement. Treatment should be deferred in persons with acute hepatic diseases.

Side effects requiring immediate medical attention

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 the 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


  • Agitation
  • black, tarry stools
  • bleeding gums
  • blistering, peeling, or loosening of the skin
  • blood in the urine or stools
  • blurred vision or loss of vision, with or without eye pain
  • bruising
  • cloudy urine
  • confusion
  • cough
  • darkening of the skin
  • difficulty in swallowing
  • fainting
  • feeling that others are watching you or controlling your behavior
  • feeling that others can hear your thoughts
  • feeling, seeing, or hearing things that are not there
  • fever with or without chills
  • general feeling of tiredness or weakness
  • greatly decreased frequency of urination or amount of urine
  • hives
  • hoarseness
  • hostility
  • increased blood pressure
  • increased thirst
  • irritability
  • light-colored stools
  • lower back or side pain
  • mental depression
  • muscle tenderness, wasting, or weakness
  • painful or difficult urination
  • persistent bleeding or oozing from puncture sites, mouth, or nose
  • pinpoint red spots on the skin
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • seizures
  • severe mood or mental changes
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • swelling of the face, ankles, fingers, hands, or lower legs
  • unusual behavior
  • unusual bleeding or bruising
  • unusual drowsiness, dullness, or feeling of sluggishness
  • weight gain

Incidence not known

  • Ankle, knee, or great toe pain
  • back pain
  • being forgetful
  • bleeding under the skin
  • bloating
  • bloody, severe, or watery diarrhea
  • blue-yellow color blindness
  • bone pain
  • chest pain
  • cold, clammy skin
  • constipation
  • difficulty with speaking
  • double vision
  • dry mouth
  • fast, weak pulse
  • flushed, dry skin
  • fruit-like breath odor
  • hair loss
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • increased hunger
  • increased menstrual flow or vaginal bleeding
  • increased urination
  • indigestion
  • joint pain, stiffness, or swelling
  • lightheadedness
  • muscle tremors
  • nosebleeds
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • pale skin
  • paralysis
  • prolonged bleeding from cuts
  • rapid, deep breathing
  • red or dark brown urine
  • red skin lesions, often with a purple center
  • red, irritated eyes
  • restlessness
  • slow speech
  • sores, welts, blisters
  • stiff neck
  • stomach cramps or pain
  • sweating
  • swollen glands
  • unpleasant breath odor
  • unusual weight loss

Get emergency help immediately if any of the following symptoms of overdose occur while taking isoniazid / pyrazinamide / rifampin:

Symptoms of overdose

  • Blurred vision
  • confusion
  • decreased awareness or responsiveness
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • fainting
  • fast, pounding, or irregular heartbeat or pulse
  • feeling of fullness in the upper abdomen or stomach
  • loss of consciousness
  • low blood pressure or slow pulse
  • pain in the upper abdomen or stomach
  • reddish-orange to reddish-brown color of the urine, stool, saliva, sputum, sweat, and tears
  • seeing, hearing, or feeling things that are not there
  • seizures
  • severe sleepiness
  • slurring of speech
  • swelling around the eyes and face
  • unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
  • yellow eyes or skin

Side effects not requiring immediate medical attention

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:

Less common

  • Sore mouth or tongue

Incidence not known

  • Belching
  • bloated or full feeling
  • excess air or gas in the stomach or bowels
  • not able to concentrate
  • pain or discomfort in the chest, upper stomach, or throat
  • swelling of the breasts or breast soreness in both females and males
  • 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 (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 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%): 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

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]

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%): 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]


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]


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]



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]


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]



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]

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]



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


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



Frequency not reported: Erythroid hyperplasia[Ref]

More about Rifater (isoniazid / pyrazinamide / rifampin)

Consumer resources

Professional resources

Related treatment guides


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.