Utility of acetazolamide for headaches in the setting of pulmonary arterial hypertension – A case report

Abstract Background Treprostinil, a prostacyclin analog, remedies pulmonary arterial hypertension through vasodilation of both pulmonary and systemic arterial vascular beds. Headache is a known side effect of treprostinil and prostacyclin analogs in general, but the mechanism by which they cause headache is unknown. Current recommendations for treatment of severe headaches from prostacyclin analogs include only one drug class, opioids. Acetazolamide is a carbonic anhydrase inhibitor that lowers intracranial pressure by reducing the production of cerebrospinal fluid. Case A 44‐year‐old female inpatient developed a continuous headache, much worse supine than standing, shortly after starting treprostinil for pulmonary artery hypertension. Imaging studies showed no explanatory anatomical process. Her comorbidities precluded the use of triptans, ergots, and non‐steroidal anti‐inflammatory drugs, but her headache resolved rapidly with acetazolamide 250 mg twice daily. Acetazolamide and furosemide were stopped due to hypokalemia and vomiting, whereupon her headaches returned. Acetazolamide but not furosemide was then restarted, again with resolution of her headaches despite cessation of oxycodone. Discussion/Conclusion This sequence suggests that treprostinil may cause headache by elevating intracranial pressure (ICP), possibly through cerebral vasodilation. We suspect that acetazolamide may have reduced her ICP enough to resolve her headache. To our knowledge, this report is the first description of both the possible underlying mechanism of action whereby prostacyclin analogs may cause headache, as well as treatment of the underlying cause of the headache rather than the symptom.