Table 1.
Summary and treatment recommendations for myasthenia gravis
| Therapy | Starting Dose | Maintenance Dose | Onset of Action |
Adverse Events | Monitoring | Comment |
|---|---|---|---|---|---|---|
| First-line therapies | ||||||
| Pyridostigmine | 60 mg every 6 h while awake | 60–120 mg every 3–8 h while awake | 15–30 min | Loose stools, n/v, diarrhea | None | Patients can learn over time to adjust dosage; with current dosing, cholinergic crisis is rare |
| Prednisone | Rapid induction regimen: 60–100 mg/d for 2–4 wk; slow titration regimen: 10 mg/d, increase by 10 mg every 5–7 d up to 60–100 mg | 60–100 mg/d, followed by a slow alternate day taper | 2–4 wk | HTN, hyperglycemia, fluid retention, weight gain, bone density loss, neuropsychiatric | Weight, BP, glucose, potassium, bone density monitoring | With high doses, watch for early worsening. Seen in as many as half of patients; single morning dose; minimize long-term exposure |
| Thymectomy | — | — | 6–12 mo | — | — | See text |
| Second-line therapies | ||||||
| Azathioprine | 50 mg, single morning dose | Increase by 50 mg every 2–4 wk; goal dose 2–3 mg/kg/d | 12–18 mo | Flu-like illness, n/v, hepatotoxicity; leukopenia | CBC, LFTs monthly. Weekly only for first month | Major drug interaction with allopurinol; uncertain degree of fetal risk in pregnancy |
| Cyclosporine | 100 mg twice daily | Goal dose 3–6 mg/kg/d, divided in 2 daily doses | 1–3 mo | Nephrotoxicity, HTN, infection, hepatotoxicity, hirsutism, tremor, gum hyperplasia, neoplasia | BP, monthly cyclosporine trough level <300 ng/mL, BUN/Cr, LFTs, CBC | Different preparations/brands are not bioequivalent and should not be mixed; trough level goal 100–150 ng/mL; watch for medication interactions |
| Intravenous Immunoglobulin | 2 g/kg divided over 2–5 d | 0.4–1 g/kg every 4 wk; try to decrease frequency over time | 1–2 wk | Headache, urticaria, nephrotoxic, thrombotic events | BUN/Cr | Avoid in patients with recent thrombotic event; can pretreat with APAP 1000 mg PO for headache prophylaxis; with diphenhydramine 25 mg PO for urticaria prophylaxis |
| Third-line therapies | ||||||
| Methotrexate | 10 mg/wk | Increase by 2.5 mg every 2 wk, up to 20 mg/wk | — | Hepatotoxicity, pulmonary fibrosis, infection, neoplasia | Monthly LFT, CBC | Consider liver biopsy at 2 g cumulative dose |
| Mycophenolate mofetil | 500 mg twice daily | 1000–1500 mg twice daily | 2–12 mo | Diarrhea, nausea, emesis, leukopenia | Monthly CBC, twice for first month | Risk of fetal harm including teratogenicity |
| Plasmapheresis | One plasma volume exchanged per procedure; 5 procedures every other day | — | 1–2 exchanges | Hypotension, hypocalcemia, fever, urticaria, infection, pneumothorax, PE | Blood pressure, calcium | Venous access preferable when available; Not infrequent but mild complications; In centers with significant experience discontinuation rates low |
| Fourth–line therapies | ||||||
| Rituximab | 375 mg/mm2 given weekly for 4 wk; 750 mg/mm2 given twice and 2 wk apart | Cycle may be repeated at 6 mo as needed | 1–3 mo | Infusion-related headache, nausea, chills, hypotension; anemia, leukopenia, thrombocytopenia | Frequent CBC in first month; then monthly | Can pretreat with APAP 1000 mg PO for headache prophylaxis; with diphenhydramine 25 mg PO for pruritus prophylaxis |
| Fifth-line therapies | ||||||
| Eculizumab | 900 mg/wk for 4 wk; 1200 mg for the fifth week; and 1200 mg every 2 wk thereafter | 1200 mg every 2 wk | 2–4 wk | Mild infusion-related adverse events; life-threatening and fatal meningococcal infections have occurred | Likely CBC and complete metabolic profile | Must administer meningococcal vaccination before starting therapy. May pretreat with APAP 1000 mg PO and diphenhydramine 25 mg PO for headache and pruritus prophylaxis |
| Cyclophosphamide | 0.5–1 g/m2 IV induction dose | 0.5–1 g/m2 IV monthly maintenance dose for 6 mo; adjust dose based on trough neutrophil count | 6–12 mo | Bone marrow suppression, infertility, hemorrhagic cystitis, alopecia, infections, neoplasia, teratogenicity, nausea | Daily to weekly CBC with attention to trough absolute neutrophil count; urinalysis | Must hydrate IV; must administer antiemetics and consider bladder prophylaxis for hemorrhagic cystitis |
Abbreviations: APAP, acetaminophen; BP, blood pressure; BUN, blood urea nitrogen; CBC, complete blood count; Cr, creatinine; HTN, hypertension; IV, intravenous; LFT, liver function tests; n/v, nausea, vomiting; PE, pulmonary embolus.