Advances in the Treatment of Paroxysmal Nocturnal Hemoglobinuria and the Role of Specialty and Infusion Pharmacists

Updates in paroxysmal nocturnal hemoglobinuria (PNH) management were provided by Jamile Shammo, MD, FASCP, FACP, at the 2020 National Association of Specialty Pharmacy Annual Meeting. PNH is a rare x-linked hematopoietic stem cell disorder responsible for the development of red blood cells vulnerable to complement-mediated lysis. Blood cell destruction can cause end-organ damage and thrombotic events, which may be fatal.

Dr Shammo noted, “The novel C5 inhibitor agents eculizumab and ravulizumab address the chronic complement-mediated hemolysis and can modify the PNH disease course and improve the quality of life for patients affected.”

Integrated in the presentation were videos to assist specialty and infusion pharmacists who play an active role in ensuring the appropriate dosing, administration, and safe use of these therapies. Both are indicated for the treatment of PNH and are available in a 300-mg/30-mL single-dose vial for IV infusion. Adults with PNH on eculizumab receive 600 mg weekly for the first 4 weeks, then 900 mg as a fifth dose 1 week later, followed by 900 mg every 2 weeks thereafter.

In December 2018, ravulizumabcwvz was approved and extends the maintenance dosing schedule from 2 to 8 weeks to reduce the administration burden on patients and their families. Dosing is based on the patient’s weight, and prescribing information should be consulted. In general, adults weighing 40 kg or more receive a loading dose and then 2 weeks later, a maintenance dose once every 8 weeks. When transitioning patients from eculizumab to ravulizumab, a loading dose of ravulizumab is administered 2 weeks after the last dose of eculizumab. A phase 3 noninferiority trial is underway, evaluating the subcutaneous administration of ravulizumab compared with IV. The observed safety profile was consistent with IV, and a new drug application is expected in the third quarter of 2021.

Presently, both agents are just available through a REMS program and have boxed warnings for serious meningococcal infections. Patients should be immunized with MenACWY and MenB per ACIP guidelines at least 2 weeks before administering the first dose of a C5 inhibitor. Antibacterial prophylaxis for 2 weeks should be initiated in patients who must start C5 inhibitor therapy immediately. Vaccination does not eliminate the risk of meningococcal disease; therefore, patients need to be closely monitored and counseled on early signs of infection and the importance of immediate evaluation when one is suspected. Patients must also carry a patient safety card from the manufacturer.

Dr Shammo also elaborated on the integral role pharmacists have in the management of PNH. Pharmacists not only assist their colleagues in drug preparation, but they also ensure that patients understand treatment expectations, manage adverse effects, and provide monitoring and follow-up to improve quality of life and patient outcomes. Patients should be monitored for a minimum of 1-hour postinfusion for signs and symptoms of an infusion reaction.

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