Medication Summary

The agents used in treatment of paroxysmal nocturnal hemoglobinuria (PNH) include the following:

Complement inhibitors (eg, pegcetacoplan, eculizumab, ravulizumab), to stop hemolysis
Recombinant erythropoietin or androgens, to stimulate erythropoiesis
Anticoagulants, to treat thrombotic complications
Immunosuppressive agents, to stimulate hematopoiesis in the aplastic phase

Class Summary

Pegcetacoplan binds to complement protein C3 and its activation fragment C3b, thereby regulating C3 cleavage and generation of downstream effector of complement activation.

Two other monoclonal antibodies (ravulizumab and eculizumab) bind downstream in the complement cascade to C5 with high affinity inhibit cleavage to C5a (proinflammatory anaphylatoxin) and C5b (initiating subunit of the terminal complement complex [C5b-9]). The prevents generation of the terminal complement complex C5b9. This action inhibits terminal complement-mediated intravascular hemolysis in patients with PNH.

All three of these agents carry Black Box warnings regarding increased risk of meningococcal infection. Because of that risk, they are available only through a restricted program, under a Risk Evaluation and Mitigation Strategy, which providers must enroll in.

Pegcetacoplan (Empaveli)

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Indicated for adults with paroxysmal nocturnal hemoglobinuria (PNH). Administered as a twice weekly SC infusion. After proper training in SC infusion, the patient/care-giver may administer, if the healthcare provider deems appropriate.

Ravulizumab (Ultomiris)

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Indicated for paroxysmal nocturnal hemoglobinuria (PNH) in adults, adolescents, and children as young as 1 month. Long-acting IV product that allows for every 8 week dosing starting 2 weeks after a single loading dose in patients weighing at least 20 kg. Every 4 week dosing is needed if weight less than 20 kg.

Eculizumab (Soliris)

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Indicated for adults with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. After weekly IV loading doses over 5 weeks, maintenance doses are administered every 2 weeks.

Class Summary

Androgens are used to stimulate erythropoiesis by increasing endogenous levels of erythropoietin and by enhancing the response of precursor cells to the growth factor.

Attenuated androgens, such as danazol, are recommended for use in women, as the attenuated androgen has fewer adverse virilizing and masculinizing effects.

Oxymetholone (Anadrol-50)

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Anabolic and androgenic derivative of testosterone in an oral formulation.

Used to stimulate erythropoiesis by increasing endogenous levels of erythropoietin and by enhancing the response of precursor cells to the growth factor.

Danazol (Danocrine)

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Synthetic steroid analogue, derived from ethisterone, with strong antigonadotropic activity (inhibits LH and FSH) and weak androgenic action without adverse virilizing and masculinizing effects. Increases levels of C4 component of the complement. May push the resting hematopoietic stem cells into cycle, making them more responsive to differentiation by hematopoietic growth factors. May also stimulate endogenous secretion of erythropoietin.

May impair clearance of immunoglobulin-coated platelets and decreases autoantibody production.

Class Summary

Antithymocyte globulin is an antiserum to human T cells.^[35]The mechanism of action of polyclonal antilymphocyte preparations to suppress immune responses is not fully understood.

Antithymocyte globulin rabbit (ATG rabbit, Thymoglobulin)

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Off-label use for PNH. Purified preparation of pasteurized polyclonal IgG obtained from rabbits immunized against human thymocytes (T cells) for IV use. This preparation has replaced the equine preparation (Atgam) on the market and is considered an equivalent.

Questions

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Media Gallery

This series of containers holds urine of a patient with paroxysmal nocturnal hemoglobinuria, showing the episodic nature of the dark urine (hemoglobinuria) during intravascular hemolysis, usually occurring at night. Early morning urine is cola-colored. This may occur at different times of the day and vary from patient to patient. Permission to use this image has been granted by the American Society of Hematology Slide Bank, 3rd edition.
The Ham test (acidified serum lysis) establishes the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), demonstrating a characteristic abnormality of PNH red blood cells by acidified fresh normal serum. Here is a PNH patient's (Pt) red blood cells lysed by normal serum at room temperature (RT) and at 37°C compared with normal red cells (no hemolysis) (control [C]). Heated serum at 56°C inactivates complement and prevents hemolysis in PNH cells. Permission to use this image has been granted by the American Society of Hematology Slide Bank, 3rd edition.
In paroxysmal nocturnal hemoglobinuria (PNH), the absence of anchor proteins that bind complement-regulating proteins (eg, CD55, CD59) to the surface of red blood cells (RBCs) leaves these RBCs susceptible to destruction by the complement membrane attack complex (MAC). Image courtesy of Haematologica. 2010 April;95(4).

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Sections Paroxysmal Nocturnal Hemoglobinuria
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Presentation
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Medication
Questions & Answers
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References

Paroxysmal Nocturnal Hemoglobinuria Medication

Medication Summary

Complement Inhibitors