Isoniazid / pyrazinamide / rifampin Side Effects

Not all side effects for isoniazid / pyrazinamide / rifampin may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to isoniazid / pyrazinamide / rifampin: oral tablet

In addition to its needed effects, some unwanted effects may be caused by isoniazid / pyrazinamide / rifampin. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking isoniazid / pyrazinamide / rifampin:

More common
  • Clumsiness or unsteadiness
  • dark urine
  • loss of appetite
  • nausea and vomiting
  • numbness, tingling, burning, or pain in the hands and feet
  • pain in large and small joints
  • unusual tiredness or weakness
  • yellow eyes or skin
Less common
  • Chills
  • difficulty with breathing
  • dizziness
  • fever
  • headache
  • itching
  • muscle and bone pain
  • redness of the skin
  • shivering
  • skin rash
Rare
  • Bloody or cloudy urine
  • blurred vision or loss of vision, with or without eye pain
  • convulsions (seizures)
  • greatly decreased frequency of urination or amount of urine
  • mental depression
  • mood or mental changes
  • sore throat
  • unusual bleeding or bruising

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

More common
  • Diarrhea
  • stomach pain
Less common
  • Sore mouth or tongue

This medicine commonly causes urine, stool, saliva, sputum, sweat, and tears to turn reddish-orange to reddish-brown. This side effect does not usually require medical attention.

Dark urine and yellowing of the eyes or skin (signs of liver problems) caused by isoniazid are more likely to occur in patients 50 years of age and older.

For Healthcare Professionals

Applies to isoniazid / pyrazinamide / rifampin: oral tablet

General

The adverse effects observed during treatment with isoniazid / pyrazinamide / rifampin were consistent with those reported with the individual components. The most common side effects reported with isoniazid were those affecting the nervous system and the liver. The primary side effect associated with pyrazinamide was a hepatic reaction.

Hepatic

Hepatic side effects have included hepatitis with jaundice (conjunctival and deep) and at least 1 serious jaundice reaction in patients taking isoniazid, pyrazinamide, and rifampin as separate tablets and capsules during clinical trials. Alterations in liver enzymes (SGOT, SGPT) have been reported in patients taking isoniazid, pyrazinamide, and rifampin as the combination tablet and as separate tablets and capsules during clinical trials. Hepatic side effects have been reported frequently with isoniazid and have included elevated serum transaminases (SGOT, SGPT), bilirubinemia, bilirubinuria, jaundice, and occasionally severe and sometimes fatal hepatitis. Hepatotoxicity has been reported with pyrazinamide use. Jaundice, transient abnormalities in liver function tests (e.g., elevations in serum bilirubin, BSP, alkaline phosphatase, serum transaminases), and, rarely, hepatitis or a shocklike syndrome (with liver involvement and abnormal liver function tests) have been reported with rifampin use.

Prodromal symptoms are often observed with isoniazid-associated liver reactions and usually include anorexia, nausea, vomiting, fatigue, malaise, and weakness. Mild and transient elevation of serum transaminase levels occurs in 10% to 20% of patients taking isoniazid. The abnormality usually occurs in the first 4 to 6 months of treatment but can occur at any time during therapy. Enzyme levels usually return to normal even with treatment continuation; however, progressive liver damage occurs in some cases. Isoniazid should be discontinued at once if signs or symptoms indicative of liver damage are detected. The frequency of progressive liver damage increases with age. It is rare in patients under 20, but occurs in up to 2.3% of patients over 50 years of age.

Hepatotoxicity associated with pyrazinamide appears to be dose related and may occur at any time during therapy.

Nervous system

Nervous system side effects have included headache, insomnia, and diffuse paresthesia of the legs in patients taking isoniazid / pyrazinamide / rifampin during clinical trials. Nervous system side effects have been reported frequently with isoniazid and have included peripheral neuropathy and paresthesias. Convulsions and toxic encephalopathy have rarely been reported with standard isoniazid doses. Headache, fever, drowsiness, fatigue, ataxia, dizziness, pains in extremities, and generalized numbness have been reported with rifampin use.

Peripheral neuropathy associated with isoniazid is dose-dependent, most often occurs in malnourished patients and in patients predisposed to neuritis (such as alcoholics and diabetics), and generally follows paresthesias of the hands and feet. The rate is higher in slow acetylators.

Dermatologic

Dermatologic side effects have included rash, erythroderma, erythema, exfoliative dermatitis, Lyell syndrome, urticaria, skin rash (localized and diffuse), pruritus, and sweating in patients taking isoniazid / pyrazinamide / rifampin during clinical trials. Rarely, acne and photosensitivity have been reported with pyrazinamide use. Mild and self-limiting cutaneous reactions associated with rifampin consist of flushing and itching (with or without rash). More serious cutaneous reactions associated with rifampin may be due to hypersensitivity and are uncommon.

Gastrointestinal

Gastrointestinal side effects have included nausea, vomiting, digestive pain, and diarrhea in patients taking isoniazid / pyrazinamide / rifampin during clinical trials. Nausea, vomiting, pancreatitis, and epigastric distress have been reported with isoniazid use. Gastrointestinal disturbances including nausea, vomiting, and anorexia have been reported with pyrazinamide use. Heartburn, epigastric distress, anorexia, nausea, vomiting, flatulence, cramps, diarrhea, pseudomembranous colitis, and a brownish-red or orange discoloration of feces, saliva, and sputum have been reported with rifampin use.

Cardiovascular

Cardiovascular side effects have included phlebitis, chest tightness, diffuse chest pain, angina, and palpitation in patients taking isoniazid / pyrazinamide / rifampin during clinical trials. Decrease in blood pressure has been reported with intermittent rifampin use.

Respiratory

Respiratory side effects have included coughing, hemoptysis, and total pneumothorax in patients taking isoniazid / pyrazinamide / rifampin during clinical trials. Shortness of breath and wheezing have been reported with intermittent rifampin use.

Hematologic

Thrombocytopenia has been associated with rifampin therapy. It has typically occurred with high dose intermittent treatment, but has also been observed following resumption of interrupted therapy. Thrombocytopenia rarely occurs during supervised daily therapy and is usually reversible when rifampin is discontinued as soon as purpura occurs. However, cerebral hemorrhage and fatalities have occurred when treatment was continued or resumed after the appearance of purpura.

Hematologic side effects associated with isoniazid have included agranulocytosis, anemia (hemolytic, sideroblastic, or aplastic), thrombocytopenia, and eosinophilia. Rarely, thrombocytopenia, sideroblastic anemia (with erythroid hyperplasia, vacuolation of erythrocytes, and increased serum concentration), and adverse effects on blood clotting mechanisms have been reported with pyrazinamide use. Thrombocytopenia, leukopenia, hemolytic anemia, decreased hemoglobin, disseminated intravascular coagulation (rare), and agranulocytosis (rare) have been reported with rifampin use.

Musculoskeletal

Musculoskeletal side effects have included arthralgia, long bones pain, and joint pain (localized and diffuse) in patients taking isoniazid / pyrazinamide / rifampin during clinical trials. Rheumatic syndrome has been reported with isoniazid use. Mild arthralgia and myalgia have frequently been reported with pyrazinamide use. Muscular weakness and myopathy (rare) have been reported with rifampin use.

Endocrine

Endocrine side effects have included diabetic coma in patients taking isoniazid / pyrazinamide / rifampin during clinical trials. Gynecomastia has been reported with isoniazid use. Rare reports of adrenal insufficiency in patients with compromised adrenal function have been reported with rifampin use.

Metabolic

Metabolic side effects have included alterations in serum uric acid levels in patients taking isoniazid, pyrazinamide, and rifampin as the combination tablet and as separate tablets and capsules during clinical trials. Pyridoxine deficiency, pellagra, hyperglycemia, and metabolic acidosis have been reported with isoniazid use. Hyperuricemia, gout, and porphyria (rare) have been reported with pyrazinamide use. Elevated serum uric acid has also been reported with rifampin.

Other

Other side effects have included fever (spiking and persistent), tinnitus, vertigo (including with loss of equilibrium), and leg edema in patients taking isoniazid / pyrazinamide / rifampin during clinical trials. Systemic lupus erythematosus-like syndrome has been reported with isoniazid use. Rarely, fever has been reported with pyrazinamide use. Edema (face and extremities), "flu" syndrome (fever, chills, headache, dizziness, and bone pain), shock, and a brownish-red or orange discoloration of sweat have been reported with rifampin use.

The "flu" syndrome and shock associated with rifampin have occurred with intermittent dosage regimens. The "flu" syndrome has also been reported with irregular use of rifampin or resumption of daily administration following a drug free interval.

Hypersensitivity

Hypersensitivity side effects have included generalized hypersensitivity in patients taking isoniazid / pyrazinamide / rifampin during clinical trials. General hypersensitivity reactions have been reported as serious in patients taking isoniazid, pyrazinamide, and rifampin as separate tablets and capsules during clinical trials. Hypersensitivity reactions including anaphylactic reactions, Stevens-Johnson syndrome, fever, skin eruptions (morbilliform, maculopapular, purpuric, or exfoliative), lymphadenopathy, and vasculitis have been reported with isoniazid use. Hypersensitivity reactions including rashes, urticaria, pruritus, and erythema and angioedema (rare) have been reported with pyrazinamide use. Anaphylaxis (rare) and occasionally pruritus, urticaria, rash, pemphigoid reaction, erythema multiforme including Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis, eosinophilia, sore mouth, sore tongue, and conjunctivitis have been reported with rifampin use.

Renal

Renal side effects associated with pyrazinamide have rarely included interstitial nephritis. Elevations in blood urea nitrogen and serum uric acid have been reported with rifampin use. Hemolysis, hemoglobinuria, hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have rarely been reported with rifampin and are usually considered hypersensitivity reactions.

Renal hypersensitivity reactions usually occur during intermittent treatment or in patients resuming treatment following intentional or accidental interruption of the daily regimen. These reactions are reversible when rifampin is discontinued and appropriate therapy started.

Psychiatric

Psychiatric side effects have included anxiety in patients taking isoniazid / pyrazinamide / rifampin during clinical trials. Psychiatric side effects associated with isoniazid are infrequent with standard doses and have included memory impairment and toxic psychosis. Inability to concentrate, mental confusion, psychoses, and behavioral changes have been reported with rifampin use.

Ocular

Ocular side effects associated with isoniazid are infrequent with standard doses and have included optic neuritis and atrophy. Visual disturbances and a brownish-red or orange discoloration of tears have been reported with rifampin use.

Genitourinary

Genitourinary side effects associated with pyrazinamide have rarely included dysuria. Menstrual disturbances and a brownish-red or orange discoloration of urine have been reported with rifampin use.

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