Rifampin and Headache
Yes, rifampin can cause headache, though it is not among the most common adverse effects. Headache is specifically listed as a recognized central nervous system adverse effect in the FDA drug label, and patients should be instructed to notify their physician if they experience headache along with other concerning symptoms 1.
Frequency and Clinical Context
Headache is classified as a central nervous system adverse effect of rifampin, appearing alongside other CNS symptoms including fever, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion, behavioral changes, muscular weakness, pains in extremities, and generalized numbness 1.
The most common adverse reaction to rifampin is gastrointestinal upset, not headache. Other more frequent reactions include skin eruptions, hepatitis, and rarely thrombocytopenia, with the overall frequency of these reactions being low 2.
When Headache Becomes Concerning
Headache may be part of the "flu syndrome" that occurs with intermittent dosing regimens (doses >600 mg once or twice weekly), which includes episodes of fever, chills, headache, dizziness, and bone pain 1.
Patients should immediately notify their physician if headache occurs with fever, fatigue, myalgias, or other systemic symptoms, as this may indicate a more serious adverse reaction requiring medical evaluation 1.
In rare cases, headache preceded serious complications: One case report documented a patient who presented with headache and decreased responsiveness, ultimately found to have acute subdural hemorrhage due to rifampin-induced thrombocytopenia 3.
Clinical Management Considerations
Daily rifampin dosing (600 mg once daily) is better tolerated than intermittent high-dose regimens, with fewer adverse reactions including CNS effects 1.
Patients should be cautioned against intentional or accidental interruption of the daily dosage regimen, as resuming therapy after interruption increases the risk of hypersensitivity reactions and the flu syndrome (which includes headache) 1.
If headache develops, evaluate for other concerning symptoms including fever, unusual fatigue, bleeding manifestations, or signs of hepatotoxicity before attributing it solely to benign drug effect 1.