Granulomatosis with Polyangiitis (Wegener Granulomatosis) Medication

Updated: Nov 21, 2016
  • Author: Christopher L Tracy, MD; Chief Editor: Herbert S Diamond, MD  more...
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Medication

Medication Summary

The combination of cyclophosphamide (intravenous or oral) and corticosteroids remained the recommended therapy for induction of remission in generalized granulomatosis with polyangiitis (GPA) for years. In 2011, however, the FDA approved the use of rituximab, a monoclonal antibody that targets B cells, as an alternative to cyclophosphamide for the treatment of AAV (GPA and microscopic polyangiitis).

Prophylaxis against Pneumocystisjiroveci pneumonia should be instituted while patients are taking cyclophosphamide or rituximab and corticosteroids (particularly high-dose corticosteroids) and for at least 6 months following these medications. Typically, trimethoprim-sulfamethoxazole (TMP-SMZ) at 160/800 mg 3 times weekly is used. If the patient has a sulfa allergy, dapsone 100 mg daily can be substituted.

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Corticosteroids

Class Summary

Corticosteroids have immunosuppressant and anti-inflammatory action used to reduce activity of systemic vasculitis. High-dose methylprednisolone is used to halt pulmonary hemorrhage and reverse crescentic glomerulonephritis.

Prednisone

Prednisone is used as an immunosuppressant in the treatment of autoimmune disorders and vasculitis. By reversing increased capillary permeability and suppressing polymorphonuclear neutrophil (PMN) activity, it may decrease inflammation.

Methylprednisolone (Medrol, Solu-Medrol, Depo-Medrol)

Methylprednisolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

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Antineoplastics, Alkylating

Class Summary

These agents have improved the prognosis of GPA. Cyclophosphamide is initiated with high-dose corticosteroids but is continued for at least 3-6 months (until there is significant disease improvement and/or remission).

Cyclophosphamide

Cyclophosphamide is chemically related to nitrogen mustards. As an alkylating agent, cyclophosphamide's mechanism of action of active metabolites may involve cross-linking of deoxyribonucleic acid (DNA), which may interfere with the growth of normal and neoplastic cells. Complete blood cell (CBC) counts should be checked every 1-2 weeks while taking daily oral cyclophosphamide and at days 10 and 14 of each intravenous cyclophosphamide pulse to monitor for bone marrow suppression.

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Immunosuppressants

Class Summary

These agents are useful in patients who experience significant adverse effects with cyclophosphamide induction therapy, as induction therapy in mild to moderate disease, and, most commonly, for maintenance of remission. The immunosuppressive drug is generally started at a lower dose and gradually increased over time. The onset of effect generally takes several weeks; therefore, the use of these drugs in induction therapy for severe disease is not advised.

Azathioprine (Imuran, Azasan)

Azathioprine inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting the synthesis of DNA, ribonucleic acid (RNA), and proteins. Its effects may decrease the proliferation of immune cells and result in lower autoimmune activity.

Methotrexate (Rheumatrex, Trexall)

Methotrexate has an unknown mechanism of action in the treatment of inflammatory reactions; it may affect immune function. This agent ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust the dose gradually to attain a satisfactory response.

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Antineoplastics, Monoclonal Antibody

Class Summary

In 2011, rituximab gained FDA approval for GPA; it is a promising alternative therapy to cyclophosphamide for induction of remission.

Rituximab (Rituxan)

Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The antibody is an IgG1 kappa immunoglobulin containing murine light- and heavy-chain variable region sequences and human constant region sequences.

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Antibiotics

Class Summary

Trimethoprim-sulfamethoxazole (TMP-SMZ) is recommended for prophylaxis against Pjiroveci pneumonia, typically as a daily dose, with single-strength dosing, or a dose of 3 times weekly with double-strength dosing. It is continued for as long as the patient is on immunosuppressive therapy. Data show that TMP-SMZ may be beneficial in decreasing relapses during maintenance therapy of GPA. Twice-daily dosing should not be combined with methotrexate, if possible, due to the risk of pancytopenia.

Additionally, in adults, TMP-SMZ has been shown to prevent relapses of GPA in remission. [16] This action of TMP-SMZ may be due to anti-inflammatory action or decrease in infections, particularly respiratory tract infections.

Trimethoprim-sulfamethoxazole (Septra DS, Bactrim, Bactrim DS)

TMP-SMZ inhibits the bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, inhibiting folic acid synthesis. This results in the inhibition of bacterial growth. The antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa.

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