Rifampin Side Effects
Some side effects of rifampin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
For the Consumer
Applies to rifampin: oral capsule
Get emergency medical help if you have any of these signs of an allergic reaction while taking rifampin: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have a serious side effect such as:
fever, chills, body aches, flu symptoms;
joint pain or swelling;
easy bruising or bleeding, weakness;
urinating less than usual or not at all; or
nausea, stomach pain, loss of appetite, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).
Less serious side effects of rifampin may include:
tired feeling; or
red or orange colored urine, stools, tears, sweat, or saliva.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect.
For Healthcare Professionals
Applies to rifampin: compounding powder, intravenous powder for injection, oral capsule
Gastrointestinal side effects have included nausea and dyspepsia in 2% of patients. Heartburn, anorexia, vomiting, flatulence, cramps and diarrhea have also been observed. Rare cases of pill-induced esophagitis and pseudomembranous colitis have been associated with the use of rifampin.
Hyperbilirubinemia and hepatitis have been reported in up to 3% of patients. Approximately 50% of hepatotoxicity has been observed during the first month of therapy.
If rifampin is essential in the treatment of patients with liver disease, extreme caution and strict medical supervision should be exercised. Baseline liver function tests should be obtained and monitored every two weeks during therapy.
Hepatic side effects have included cases of hepatitis and severe hepatotoxicity with fatal outcome. Fatal cases of hepatotoxicity have been observed in patients with existing liver dysfunction and in patients with normal liver function who are also taking other hepatotoxic drugs. Jaundice, hepatitis, transient abnormalities in liver function tests (e.g., elevations in serum bilirubin, BSP, alkaline phosphatase, serum transaminases), and hyperbilirubinemia have been reported. Baseline and periodic liver function testing are recommended for all patients on long-term rifampin therapy.
The 'flu-like syndrome' generally occurs with intermittent dosing of rifampin, in patients with poor adherence to daily rifampin therapy, and when daily rifampin is resumed after a drug free period.
Immunologic side effects have included flu-like syndrome presenting as fever, malaise, nausea, vomiting, petechiae and myalgias. This syndrome is probably an immune-mediated reaction. Rarely, dyspnea and shock have been associated with once-daily rifampin therapy.
There have been rare case reports of reversible acute renal failure due to glomerulonephritis and renal epithelial cell injury in patients receiving rifampin. Often in these patients other immune-mediated reactions occur, such as hemolysis and thrombocytopenia. Antibodies to rifampin have been identified in some affected patients. Generally these reactions occur after reintroduction of the drug following a lapse in therapy, although they have also been associated with continuous therapy.
Renal side effects have included elevations in BUN and serum uric acid. Hemoglobinuria, hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have been reported. These events are generally associated with an immune-mediated reaction which occurs after interruption in rifampin therapy. Standard doses may produce orange-colored urine.
Petechiae associated with thrombocytopenia may occur in 1% of patients who are receiving rifampin. Rifampin antibodies have been demonstrated in some of these patients. Thrombocytopenia is seen most frequently in patients receiving weekly therapy or after a lapse in therapy, but has also been reported during daily therapy. Decreased hemoglobin and transient leukopenia have been reported in patients who had chronic diseases and in whom other medications were given, which made it difficult to definitively determine if these adverse effects were due to rifampin.
A 76-year-old male with a diagnosis of Mycobacterium kansasii pulmonary disease experienced leukocytoclastic vasculitis, thrombocytopenia, and acute renal failure coincident with rifampin therapy. He was admitted to the hospital with a one-week history of fever, dry cough, dyspnea, oliguria, and bilateral edema in lower extremities. He was treated for the Mycobacterium kansasii pulmonary disease with a combined preparation of isoniazid 50 mg, rifampin 250 mg, rifampin 600 mg, and pyrazinamide 1500 mg (Rifater). On the patients admission, laboratory data showed acute renal failure (serum creatinine 9.6 mg/dL, urea 168 mg/dL) and thrombocytopenia (platelets 85 x 10 (3)/ microliter). Other results were WBC count 13,300/ microliter, hemoglobin 13.9 g/dL, and proteinuria, with urine protein 1.5 g/L. Pyrazinamide was discontinued and broad spectrum antimicrobials were introduced. Two weeks after pyrazinamide was discontinued, clinical and analytical parameters normalized. With the goal of treating Mycobacterium kansasii, a controlled trial of rifampin at increasing doses (80 mg the first day, 150 mg the second day, 200 mg the third day) was attempted a week later. The day following reintroduction, a palpable purpura appeared, serum creatinine increased (1.9 mg/dL), and the platelet count dropped. Rifampin was withdrawn on the fourth day; 4 days later, the serum creatinine level returned to within normal limits and skin purpura disappeared. Skin purpura biopsy demonstrated leukocytoclastic vasculitis. Two weeks later, the patient was discharged with normal renal function and platelet count.
Hematologic side effects have included thrombocytopenia, leukopenia, hemolytic anemia, and decreased hemoglobin, in less than 1% of patients. Thrombocytopenia has occurred primarily with high dose intermittent therapy, and after resumption of interrupted therapy. Red cell aplasia, agranulocytosis, methemoglobinemia, and disseminated intravascular coagulation have been reported very rarely. Hemolysis has been described as part of an immune-mediated reaction which generally occurs after interruptions in therapy. At least one case of rifampin-related leukocytoclastic vasculitis, thrombocytopenia, and acute renal failure has been reported.
Dermatologic side effects have included cutaneous reactions that are mild and self-limiting and usually not associated with a hypersensitivity to rifampin. These reactions generally manifest as itching and flushing with or without rash. Serious dermatologic reactions that resulted from hypersensitivity have been reported rarely.
Nervous system side effects have included headache, paresthesias, and weakness. Other central nervous system side effects reported have included drowsiness, fatigue, ataxia, dizziness, decreased concentration, mental confusion, behavioral changes, muscular weakness, pain, and numbness.
Drug level monitoring may be necessary in patients who remain acid-fast bacilli smear positive after 3 months of directly observed therapy. Dosage may be titrated upwards to keep the rifampin level in the therapeutic range.
Metabolic side effects have included increases in hepatic metabolism of thyroxine (T4) and triiodothyronine (T3). A fall in plasma concentration time curve of rifampin and an increase in renal clearance due to a decrease in protein-bound drug has been reported in pulmonary tuberculosis patients who are often malnourished.
Cardiovascular side effects have been reported rarely. These have included decreased blood pressure when rifampin dosages were administered intermittently.
A 35-year-old male who was diagnosed with pulmonary tuberculosis experienced multiple hypersensitivity reactions coincident with rifampin therapy. After being admitted to the hospital with multiple symptoms of tuberculosis, the patient was prescribed rifampin, isoniazid, pyrazinamide, and ethambutol. Two hours after taking the first pill of rifampin (600 mg), the patient developed anaphylactic shock, liver injury, hemolytic anemia, acute renal failure, and disseminated intravascular coagulation. Direct and indirect antiglobulin (Coombs) tests were positive. RFP-dependent IgG and IgM antibodies with complement fixing capability were observed in the serum. The patient was transferred to the intensive care unit and underwent hemodialysis. Clinical recovery and return of laboratory data to normal levels occurred over a 5-week period. The patient was subsequently given isoniazid, pyrazinamide, ethambutol, ciprofloxacin, and recovered from tuberculosis.
Hypersensitivity side effects have included urticaria, rash, pruritus, pemphigoid reaction, erythema multiforme including Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis, eosinophilia, sore mouth, sore tongue, and conjunctivitis. Rarely, anaphylaxis has been reported. At least one case of multiple hypersensitivity reactions including anaphylactic shock, liver injury, hemolytic anemia, acute renal failure, and disseminated intravascular coagulation have also been reported.
Endocrine side effects have included menstrual disturbances and rare reports of adrenal insufficiency in patients with impaired adrenal function.
Musculoskeletal side effects have included myopathy and muscular weakness.
Ocular side effects have included visual disturbances. Ocular side effects are generally limited to patients who wear contact lenses. Rifampin can cause a red-brown or orange discoloration of tears which can stain contact lenses.
Psychiatric side effects have rarely included psychoses.
Respiratory side effects have included shortness of breath and wheezing with the use of intermittent dosage regimens. A 'flu syndrome' may appear if rifampin is taken irregularly or if daily administration is resumed after a drug free interval.
Other side effects have rarely included edema of the face and extremities.
Fatal acute overdoses have been reported with doses ranging from 14 to 60 grams of rifampin. Alcohol or a history of alcohol abuse was involved in some of the fatal and nonfatal cases. The minimum acute lethal or toxic dose is not well established.
More rifampin resources
- rifampin Concise Consumer Information (Cerner Multum)
- rifampin Intravenous Advanced Consumer (Micromedex) - Includes Dosage Information
- rifampin MedFacts Consumer Leaflet (Wolters Kluwer)
- Rifampin Professional Patient Advice (Wolters Kluwer)
- Rifampin Monograph (AHFS DI)
- Rifadin Prescribing Information (FDA)
- Rifadin MedFacts Consumer Leaflet (Wolters Kluwer)
- Rifadin Advanced Consumer (Micromedex) - Includes Dosage Information
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