Can rifampin (Rifampicin) cause hemolytic anemia?

From the Guidelines

Rifampin can cause hemolytic anemia, although it is a relatively rare adverse effect. According to the study published in the American Journal of Respiratory and Critical Care Medicine 1, intermittent administration of doses of rifampin > 10 mg/kg may be associated with hemolytic anemia, among other reactions. Key points to consider include:

• The mechanism of rifampin-induced hemolytic anemia is thought to be immune-mediated, where the drug triggers antibody formation against red blood cells, leading to their premature destruction.
• This reaction is more likely to occur with intermittent therapy or when treatment is resumed after interruption.
• Patients taking rifampin should be monitored for signs of hemolytic anemia, including:
  • Fatigue
  • Pallor
  • Shortness of breath
  • Jaundice
  • Dark urine
• Laboratory findings may show:
  • Decreased hemoglobin
  • Elevated indirect bilirubin
  • Increased lactate dehydrogenase
  • A positive direct Coombs test
• If hemolytic anemia is suspected, rifampin should be discontinued immediately and alternative antimicrobial therapy considered, as noted in the study 1. The risk of this adverse effect should be weighed against the benefits of rifampin, particularly in patients with tuberculosis or other serious infections where rifampin is a key component of treatment. Patients with a history of hemolytic disorders may be at increased risk and should be monitored more closely, as suggested by the potential for rifampin to induce hemolytic anemia 1.

From the FDA Drug Label

Doses of rifampin greater than 600 mg given once or twice weekly have resulted in a higher incidence of adverse reactions, including the "flu syndrome" (fever, chills, and malaise), hematopoietic reactions (leukopenia, thrombocytopenia, or acute hemolytic anemia) Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremia syndrome, some fatal, have been reported with rifampin.

Yes, rifampin can cause hemolytic anemia 2, 2.

• Hematopoietic reactions including acute hemolytic anemia have been reported with high doses of rifampin.
• Thrombotic microangiopathy (TMA), which can include hemolytic uremia syndrome, has also been reported with rifampin.

From the Research

Rifampin and Hemolytic Anemia

• Rifampin has been associated with hemolytic anemia in several case reports, with evidence suggesting that this condition can occur even with daily therapy 3, 4.
• The mechanism of rifampin-induced immune hemolytic anemia is thought to involve the formation of drug-antibody complexes that adhere to the surface of red blood cells, leading to intravascular hemolysis 4.
• Intermittent or interrupted rifampin therapy has been linked to a higher risk of severe immunoallergic reactions, including hemolytic anemia, acute renal failure, and disseminated intravascular coagulation 5, 6.
• Clinical features of rifampin-associated hemolytic anemia may include fever, abdominal pain, and vomiting, and can be life-threatening in some cases 3, 5, 7.
• Discontinuation of rifampin therapy is often necessary to resolve the hemolysis, and may be accompanied by other treatments such as intravenous immune globulin and prednisolone 3, 7.

Key Findings

• Rifampin-induced hemolytic anemia can occur with daily or intermittent therapy 3, 4.
• The condition is often characterized by acute intravascular hemolysis, which can lead to kidney injury and other complications 7.
• A complete history of previous exposure to rifampin is recommended before initiating intermittent therapy with this medication 5.

Reported Cases

• A 58-year-old woman developed autoimmune hemolytic anemia related to rifampicin, which resolved after drug withdrawal and treatment with intravenous immune globulin and prednisolone 3.
• A patient with Mycobacterium leprae infection experienced recurrent episodes of disseminated intravascular coagulation after intermittent exposures to rifampin 5.
• A case of hemolytic anemia following rifampicin administration was complicated by acute renal failure, and subsided spontaneously after withdrawal of the drug 4.
• A tuberculosis patient developed rifampin-induced acute intravascular hemolysis leading to heme pigment-related kidney injury, which resolved after discontinuation of rifampin therapy 7.