From the Guidelines
Rifampicin can cause several side effects, with the most common being orange-red discoloration of body fluids including urine, tears, sweat, and saliva, as well as gastrointestinal effects such as nausea, vomiting, abdominal pain, and diarrhea, as noted in 1 and 1.
Common Side Effects
- Orange-red discoloration of body fluids
- Gastrointestinal effects: nausea, vomiting, abdominal pain, and diarrhea
- Liver problems: mild enzyme elevations to severe hepatitis, particularly in patients with pre-existing liver disease or when combined with other hepatotoxic medications
- Flu-like symptoms: fever, chills, and muscle aches, especially with intermittent dosing
Less Common Side Effects
- Blood disorders
- Skin rashes
- Hypersensitivity reactions
Important Considerations
- Rifampicin is known for significant drug interactions as it induces liver enzymes, reducing the effectiveness of many medications including oral contraceptives, anticoagulants, and some antiretrovirals, as highlighted in 1 and 1.
- Patients should be monitored with regular liver function tests during treatment, and they should inform healthcare providers about rifampicin use before starting any new medications due to potential interactions.
- The most recent and highest quality study, 1, provides a comprehensive overview of the common side effects and toxicities of rifampicin, which is essential for guiding clinical practice and ensuring patient safety.
From the FDA Drug Label
WARNINGS Hepatotoxicity of hepatocellular, cholestatic, and mixed patterns has been reported in patients treated with rifampin. Systemic hypersensitivity reactions were reported with Rifampin for Injection administration Signs and symptoms of hypersensitivity reactions may include fever, rash, urticaria, angioedema, hypotension, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia, elevated liver transaminases or flu-like syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, chills, aches, itching, sweats, dizziness, shortness of breath, chest pain, cough, syncope, palpitations) Cases of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome have been reported with rifampin 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 Hematologic Thrombocytopenia has occurred primarily with high dose intermittent therapy, but has also been noted after resumption of interrupted treatment. 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 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, vasculitis, eosinophilia, sore mouth, sore tongue, and conjunctivitis have been observed Anaphylaxis has been reported rarely.
Side effects of rifampicin include:
- Hepatotoxicity
- Systemic hypersensitivity reactions
- Severe cutaneous adverse reactions
- Hematologic reactions (thrombocytopenia, leukopenia, hemolytic anemia)
- Central nervous system reactions (headache, fever, drowsiness)
- Ocular reactions (visual disturbances)
- Endocrine reactions (menstrual disturbances, adrenal insufficiency)
- Renal reactions (elevations in BUN and serum uric acid, hemolysis)
- Dermatologic reactions (cutaneous reactions, hypersensitivity reactions)
- Anaphylaxis 2, 2
From the Research
Side Effects of Rifampicin
The side effects of rifampicin can be categorized into several types, including:
- Hepatotoxicity: Rifampicin can cause liver damage, and risk factors include high age, malnutrition, and high alcohol consumption 3.
- Gastric reactions: Gastrointestinal disturbances like anorexia, nausea, vomiting, abdominal discomfort, and diarrhea are known adverse effects of rifampicin 3, 4.
- Allergic reactions: Rifampicin can cause allergic reactions, including fever, rash, and anaphylactic reactions 5, 6.
- Hematologic effects: Rifampicin can cause thrombocytopenia, hemolytic anemia, and renal failure 5, 6.
- Ocular toxicity: Although not directly associated with rifampicin, ocular toxicity can occur with other anti-tuberculosis drugs like ethambutol 3.
Specific Cases of Rifampicin-Induced Side Effects
- A case of upper gastrointestinal bleeding due to hemorrhagic gastric erosions was reported after ingestion of rifampicin 4.
- A 39-year-old man suffered from an immediate hypersensitivity reaction with anaphylactic manifestations after receiving a low dose of rifampicin 6.
- A 76-year-old male patient experienced a type II hypersensitivity reaction in the form of thrombopenia after receiving rifampicin 6.
- A case of immune complex hypersensitivity reaction was reported, resulting in hepato-renal failure after rifampicin treatment 6.
Mechanisms of Rifampicin-Induced Liver Injury
- Rifampicin can induce severe liver injury, and the underlying mechanism involves the farnesoid X receptor (Fxr)-multidrug resistance-associated proteins (Mrps) signaling pathway 7.
- Changes in serum bile acid levels, including increased cholic acid and decreased secondary bile acids, can lead to liver injury in mice 7.
- Potential biomarkers for early detection of rifampicin-induced liver injury include cholic acid, deoxycholic acid, lithocholic acid, taurodeoxycholic acid, and tauroursodeoxycholic acid 7.