From the Guidelines
Rifampin can cause several side effects, including gastrointestinal upset, liver problems, and interactions with other medications, and patients should be closely monitored for these adverse effects, especially liver function, as evidenced by the most recent study 1. The most common adverse reactions to rifampin include gastrointestinal issues, such as nausea, vomiting, diarrhea, and abdominal pain, as well as liver problems, which may present as yellowing of the skin or eyes, dark urine, or unusual fatigue 1. Some patients may experience flu-like symptoms, especially when taking rifampin intermittently rather than daily, and rifampin can also cause blood disorders, skin rashes, and headaches 1. It's essential to note that rifampin significantly interacts with many medications by increasing liver enzyme activity, potentially reducing the effectiveness of oral contraceptives, anticoagulants, antidiabetics, and other drugs 1. Patients should always inform healthcare providers about all medications they're taking before starting rifampin, and if severe side effects occur, especially signs of liver problems or unusual bleeding, medical attention should be sought immediately 1. Regular monitoring of liver function is typically recommended during rifampin treatment, as supported by the guidelines for the treatment of latent tuberculosis infection 1. Key considerations for rifampin use include:
- Gastrointestinal upset
- Liver problems
- Interactions with other medications
- Flu-like symptoms
- Blood disorders
- Skin rashes
- Headaches
- Regular monitoring of liver function As the most recent and highest quality study 1 provides the best evidence for the side effects of rifampin, it is crucial to prioritize this information when making clinical decisions.
From the FDA Drug Label
ADVERSE REACTIONS The following adverse reactions associated with the use of rifampin were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure Gastrointestinal Heartburn, epigastric distress, anorexia, nausea, vomiting, jaundice, flatulence, cramps, and diarrhea have been noted in some patients. Although Clostridium difficile has been shown in vitro to be sensitive to rifampin, pseudomembranous colitis has been reported with the use of rifampin (and other broad-spectrum antibiotics) Therefore, it is important to consider this diagnosis in patients who develop diarrhea in association with antibiotic use. Tooth discoloration (which may be permanent) may occur. Hepatic Hepatotoxicity including transient abnormalities in liver function tests (e.g., elevations in serum bilirubin, alkaline phosphatase, serum transaminases, gamma-glutamyl transferase), hepatitis, a shock-like syndrome with hepatic involvement and abnormal liver function tests, and cholestasis have been reported. (see WARNINGS) Hematologic Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, have been reported (see WARNINGS ). Thrombocytopenia has occurred primarily with high dose intermittent therapy, but has also been noted after resumption of interrupted treatment. It rarely occurs during well-supervised daily therapy This effect is reversible if the drug is discontinued as soon as purpura occurs. Cerebral hemorrhage and fatalities have been reported when rifampin administration has been continued or resumed after the appearance of purpura. Rare reports of disseminated intravascular coagulation have been observed Leukopenia, hemolytic anemia, decreased hemoglobin, bleeding, and vitamin K–dependent coagulation disorders (abnormal prolongation of prothrombin time or low vitamin K–dependent coagulation factors) have been observed. Agranulocytosis has been reported very rarely Central Nervous System Headache, fever, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion, behavioral changes, muscular weakness, pains in extremities, and generalized numbness have been observed. Psychoses have been rarely reported. Rare reports of myopathy have also been observed. Ocular Visual disturbances have been observed Endocrine Menstrual disturbances have been observed. Rare reports of adrenal insufficiency in patients with compromised adrenal function have been observed. Renal Elevations in BUN and serum uric acid have been reported. Rarely, hemolysis, hemoglobinuria, hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have been noted These are generally considered to be hypersensitivity reactions. They usually occur during intermittent therapy or when treatment is resumed following intentional or accidental interruption of a daily dosage regimen, and are reversible when rifampin is discontinued and appropriate therapy instituted Dermatologic Cutaneous reactions are mild and self-limiting and do not appear to be hypersensitivity reactions. Typically, they consist of flushing and itching with or without a rash. More serious cutaneous reactions which may be due to hypersensitivity occur but are uncommon Hypersensitivity Reactions Occasionally, pruritus, urticaria, rash, pemphigoid reaction, erythema multiforme, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms syndrome (see WARNINGS), vasculitis, eosinophilia, sore mouth, sore tongue, and conjunctivitis have been observed
The side effects of rifampin include:
- Gastrointestinal: heartburn, epigastric distress, anorexia, nausea, vomiting, jaundice, flatulence, cramps, and diarrhea
- Hepatic: hepatotoxicity, hepatitis, and cholestasis
- Hematologic: thrombotic microangiopathy, thrombocytopenia, leukopenia, hemolytic anemia, and agranulocytosis
- Central Nervous System: headache, fever, drowsiness, fatigue, ataxia, dizziness, and psychoses
- Dermatologic: cutaneous reactions, flushing, itching, and rash
- Hypersensitivity Reactions: anaphylaxis, pruritus, urticaria, and Stevens-Johnson syndrome 2
From the Research
Rifampin Side Effects
- Hepatic toxicity is a major adverse effect of rifampin, which is dose-related and mainly observed in patients with underlying liver disease 3
- Immunoallergic effects of rifampin can be minor (cutaneous, gastrointestinal, or influenzalike syndrome) or major (hemolytic anemia, shock, or acute renal failure) 3
- Rifampicin can cause gastrointestinal disturbances like anorexia, nausea, vomiting, abdominal discomfort, and diarrhea 4
- Upper gastrointestinal bleeding due to hemorrhagic gastric erosions has been reported as a rare side effect of rifampicin 4
- Liver function tests can be used to predict rifampicin metabolism in cirrhosis, and patients with bilirubin concentrations exceeding 50 mumol/l may require a reduction in rifampicin dosage 5
- Combination of rifampin with other drugs can result in liver function test elevations, and concomitant administration with ritonavir-boosted protease inhibitors and lorlatinib has been associated with considerable LFT elevations 6
- The potential role of rifampin in the metabolic activation of certain drugs into metabolites with hepatic effects should be considered when conducting rifampin drug-drug interaction studies 6