Anticholinesterase Agents

Drug	Dosage	Remarks
Distigmine bromide	Initial dose: 5 mg PO 24 hourly before breakfast May increase to 7.5 mg PO 24 hourly on the second week then to 10 mg PO 24 hourly on the third week depending on the severity and patient’s response Max dose: 20 mg/day	Adverse Reactions Most commonly caused by over stimulation of cholinergic pathways: Increased salivation, nausea/vomiting, diarrhea, abdominal cramps Overdosage can lead to cholinergic crisis: Excessive sweating, increased peristalsis, lacrimation, involuntary defecation, urination, bradycardia, hypotension, and muscle cramps Special Instructions Major symptom of cholinergic crisis is increased muscular weakness which must be differentiated from myasthenia gravis crisis Contraindicated in patients with mechanical intestinal or urinary tract obstruction or peritonitis May affect ability to drive or operate machinery Use with caution in patients with cardiovascular disorders, asthma, gastrointestinal disease, hyperthyroidism, history of seizure disorder
Neostigmine	(Bromide salt) Oral: 75-375 mg/day PO divided by 15-40 mg/dose 2-4 hourly throughout the day and at night if required Adjust dose based on patient’s response; may give larger portion of dose at times of greater fatigue Max tolerated dose: Usually 180 mg/day Patients unable to take oral medications: (Methylsulfate salt) SC/IM: 0.5-2.5 mg given at intervals Usual daily dose range: 5-20 mg/day SC/IM
Pyridostigmine bromide	Dose range: 300-1,200 mg/day PO divided by by 60-180 mg/dose 6-12 hourly throughout the day and at night if required Adjust dose based on patient response; may give larger portion of dose at times of greater fatigue Dose >450 mg/day may cause downregulation of AChR

Corticosteroid

Drug

Dosage

Remarks

Prednisolone
(Prednisone)

Initial dose: 15-60 mg/day PO on alternate days
Increase dose slowly (usually 5-10 mg/dose to 60-80 mg on alternate days) as tolerated, until clinical improvement
Usual max dose: 6 mg/day PO
Maintain high dose regimen for 1-4 months then gradually reduce dose to lowest effective dose, preferably given every other day (usually 10-40 mg PO every other day)

Adverse Reactions

Adrenocortical insufficiency, osteoporosis, muscle wasting, pain or weakness, increased susceptibility to infection, impaired wound healing, electrolyte imbalances, glucose intolerance, diabetes mellitus, hyperglycemia, cataracts, glaucoma, Cushing’s syndrome, edema
About 10% of patients experience transient but serious worsening of myasthenia gravis symptoms in the 1st few weeks of therapy

Special Instructions

Contraindicated in patients with acute superficial herpes simplex, keratitis, systemic fungal infection, varicella
Improvement may be delayed and gradual
Avoid too early, too rapid or excessive tapering of dosage
Monitor patient closely for side effects

Immunosuppressants

Drug	Dosage	Remarks
Azathioprine	Initial dose: 50 mg/day PO Increase dose every 1-2 weeks Maintenance dose: 2-3 mg/kg/day PO Max dose: 250 mg/day	Adverse Reactions CNS effects (fever, malaise); GI effects (nausea/vomiting, diarrhea); Hematologic effects (leukopenia, thrombocytopenia); Other effects (increased LFT, myalgia, rarely pancreatitis, rash, alopecia, arthralgia) Increased risk of neoplasia with chronic use Special Instructions Recommended total dose during treatment should be <600 g to reduce carcinogenic risks Use with caution in patients with hepatic or renal impairment, with Thiopurine S-methyltransferase (TPMT) deficiency There have been reports of increased risk of hepatosplenic T-cell lymphoma (HSTCL) development, particularly in adolescents and young adults Monitor for signs and symptoms or malignancy (eg splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss) Monitor CBC and platelets, LFT, total bilirubin, TPMT genotyping or phenotyping
Ciclosporin (Cyclosporin)	Initial dose: 5 mg/kg/day divided 12 hourly Increase slowly as needed according to response and serum concentration	Adverse Reactions GI effects (abdominal pain, diarrhea, nausea, dyspepsia); CNS effects (tremors, headache); CV effects (hypertension, edema); Hematologic effects (leukopenia, anemia, thrombocytopenia); Other effects (gingival hyperplasia, hirsutism, hypertrichosis, renal dysfunction, nephropathy, elevated creatinine, increased triglycerides, infection, hyperkalemia, hypomagnesemia) Special Instructions Use with caution in patients with hepatic or renal impairment, with TPMT deficiency Avoid prolonged sun exposure, tanning booths and sunlamps Avoid in patients with renal dysfunction, uncontrolled hypertension, uncontrolled infections, persistently raised creatinine, malignancy, porphyria Measure trough serum Ciclosporin level Therapeutic range (by radioimmunoassay): 150-200 ng/L Monitor renal and hepatic function, BP, serum electrolytes and lipids regularly Vaccination with live-virus vaccines are not recommended Commercially available oral products differ in their bioavailability; use caution when switching from one product to another
Eculizumab	Initial dose: 900 mg IV infusion weekly for 4 doses every 7 days for the first 4 weeks Maintenance dose: 1,200 mg IV infusion at week 5 then 1,200 mg IV infusion every 2 weeks thereafter	Adverse Reactions CV effects (hypertension, hypotension, tachycardia, peripheral edema); CNS effects (headache, insomnia, fatigue, asthenia, arthralgia); Dermatologic effects (skin rash, pruritus); Metabolic effect (hypokalemia); GI effects (abdominal pain, constipation, diarrhea, nausea/vomiting); Hematologic effects (anemia, leukopenia); Other effects (nasopharyngitis, back pain) Special Instructions It is advised that patients should be immunized with meningococcal vaccines at least 2 weeks prior to initiation of therapy Use with caution in patients with active infection
Efgartigimod (Efgartigimod alfa)	10 mg/kg IV infusion weekly for 4 weeks Subsequent treatment cycles may be given based on clinical evaluation and no sooner than 50 days from the start of the previous treatment cycle Max dose: 1.2 g per IV infusion	Adverse Reactions Hematologic effects (neutropenia, leukopenia, lymphocytopenia); Immunologic effect (development of neutralizing antibodies); CNS effects (headache, paresthesia); Respiratory effect (respiratory tract infection); Other effects (urinary tract infection, myalgia, hypersensitivity) Special Instructions Patients should have up to date immunizations prior to initiation of therapy Avoid administration of live vaccines in patients undergoing Efgartigimod treatment Contraindicated in patients with history of serious hypersensitivity to Efgartigimod alfa Use with caution in patients with active infection Delay treatment in patients with active infection until infection resolves
Mycophenolate (Mycophenolic acid; Mycophenolate mofetil)	Initial dose: 500 mg PO 12 hourly May increase based on response and tolerability Maintenance dose: 1,000-1,500 mg PO 12 hourly	Adverse Reactions CV effects (hypertension, hypotension, peripheral edema, chest pain, tachycardia); CNS effects (pain, headache, insomnia, fever, dizziness, tremor, asthenia); GI effects (abdominal pain, constipation, dyspepsia, diarrhea, GI hemorrhage); Hematologic effects (leukopenia, anemia); Other effects (cellulitis, rash, arthralgia, back pain, increased risk of infection) Special Instructions Increased risk of development of lymphoma and skin malignancy Use with caution in patients with active peptic ulcer disease, renal impairment, hypoxanthine-guanine phosphoribosyl transferase (HGPRT) deficiency

Intravenous Immunoglobulin (IVIg)

Drug

Dosage

Remarks

Intravenous immunoglobulin
(IVIg, Immune globulin IV)

400 mg/kg/day IV for 4-5 days
or
1000 mg/kg/day IV for 2 days
Usual cumulative dose:
1000-2000 mg/kg IV
If well tolerated, subsequent infusion can be given over 2-3 days