| Azathioprine (AZA) |
Initial: 50 mg/day Dose increase: 25-50 mg/week or two weeks Aimed dose: 2-3 mg/kg/day |
Extremes of weight, old age, hepatic insufficiency and renal insufficiency give rise to higher risk of toxicity Low levels of TPMT: increased risk of myelosuppression |
Xanthine oxidase inhibitors increases toxicity (e.g. allopurinol) ACEi increases the chance of leukopenia AZA reduces warfarin effect |
CBC, Cr, AST, ALT on starting and weekly after dose changes, until stable dose is reached; and then every 12 weeks thereafter |
Can continue to be given during pregnancy but should not be started during it. Safe in breastfeeding. |
| Methotrexate (MTX) |
Initial: 7.5-15 mg/day Dose increase: 5-10 mg per 2 weeks or 4 weeks Aimed dose: 20-25 mg/day |
Supplementation of folic acid 5 mg one day after MTX administration |
Other drugs that deplete folate (e.g. sulfamethoxazole-trimethoprim) increase myelosuppression risk
|
CBC, Cr, AST, ALT on starting and weekly after dose changes, until stable dose is reached; and then every 12 weeks thereafter |
Contraindicated during pregnancy and lactation |
| Mycophenolate mofetil (MMF) |
Initial: 500 mg daily for several days Target dose: 1.5 and 3 grams divided twice daily |
Do not exceed 2 grams daily if GFR < 25 ml/min |
Proton pump inhibitors can decrease MMF absorption. Rifampin decrease MMF serum concentration and acyclovir can increase it. MMF may decrease serum concentrations of hormonal contraceptives (pills, patches and vaginal rings) |
Prior to MMF therapy: CBC, liver function tests, Cr, urinalysis, serological tests for HBV and HCV, screening for latent tuberculosis (TST or IGRA). New CBC 1-2 weeks after the start of therapy and if no evidence of bone marrow suppression, check every 6-8 weeks |
Contraindicated during pregnancy and lactation |
| Cyclosporin |
Initial dose: 2.5 mg/kg every 12 hours Adjustment of dose according to serum level, to achieve 100-150 mcg/liter |
Increased risk of lymphoproliferative disorders |
Selective serotonin reuptake inhibitors, statins, azole antifungals, non-dihydropyridine calcium channel blockers and angiotensin receptor blockers raise cyclosporin level Rifampicin, carbamazepine, phenytoin and phenobarbital decrease cyclosporin level |
Serum cyclosporin electrolytes, Cr, AST, ALT, coagulation tests, hemolysis biomarkers Annual dermatoscopic evaluation |
This should be given during pregnancy if the benefits outweigh the risks Breastfeeding is contraindicated |
| Cyclophosphamide (CYP) |
Initial: 500-750 mg/m2 every 4 weeks Dose adjustment: According to leukocyte nadir (7th-14th day of infusion). Less than 3500 leukocytes or less than 1500 neutrophils reduces the next dose by 20-25%. If leukocytes are higher than 4000, consider an increase of 20-25% at the next dose. |
Attention regarding hydration on the day of the infusion. Consider mesna in children and patients with cardiopathy or nephropathy. Higher doses increase chances of cancer (leukemia, bladder and skin cancer). Male and female infertility (risk increases with an accumulated dose higher than 10 g). Dose adjusted with GFR < 10 ml/min. |
Ondansetron, clopidogrel, paroxetine and sertraline could reduce the CYP effect. Phenytoin, carbamazepine and rifampicin could increase the toxicity. |
CBC, Cr, AST, ALT and urinalysis monthly (7th-14th day after the infusion) |
Contraindicated during pregnancy and lactation |
| Infliximab |
IV 3-7 mg/kg at 0, 2 and 6 weeks, with maintenance infusions every 4 to 8 weeks. |
In heart failure, individualize risk and benefit: NYHA Class I/II no adjustment necessary, monitor closely; NYHA Class III or IV: ≤ 5 mg/kg. No renal adjustment. If hepatotoxicity during treatment (jaundice and/or increase in liver enzymes (≥ 5 times ULN), discontinue treatment. Consider antihistamines, acetaminophen and/or corticosteroids to prevent infusion-related reactions. Caution in patients with history of seizures. |
Enhances the risk of T-cell non-Hodgkin’s lymphoma and increases serum concentration of active metabolite when used with azathioprine. |
Active and latent TB screening prior and during therapy; HBV screening prior to initiating (all) and during and for several months after therapy (HBV carriers); AST, ALT. Attention for signs and symptoms of malignancy (hepatosplenomegaly, persistent fever, weight loss) |
Live vaccines should be avoided for the first 6 months of life if the exposure occurs after the 1st trimester of pregnancy. Compatible with breastfeeding but should be discussed (potential transfer into breast milk 2-3 days after dose). |
| Adalimumab |
40 mg every other week subcutaneously |
No dosage adjustments for renal or hepatic impairment. No dose particularity for geriatric patients. No contraindications reported. |
Concurrent use with azathioprine, methotrexate and prednisone increases risk of serious infection. |
Active and latent TB screening prior to and during therapy; HBV screening prior to initiating (all) and during and for several months after therapy (HBV carriers); AST, ALT. Attention for signs and symptoms of malignancy (hepatosplenomegaly, persistent fever, weight loss) |
Live vaccines should be avoided for the first 6 months of life if the exposure occurs after the 1st trimester of pregnancy. Compatible with breastfeeding but should be discussed (potential transfer into breast milk 2-3 days after dose). |
| Rituximab |
375 m2/week for 4 consecutive weeks 1000 mg on day 1 and day 15 Premedication with 100 mg of methylprednisolone is recommended before every infusion |
Consider Ig reposition if the patient presents with recurrent infections and IgG levels lower than 6 g/L. |
Anti-neoplastic, immunomodulatory and immunosuppressive drugs. |
CBC, CD19+ assays (4-6 weeks), IgG, IgA and IgG levels (at beginning and if recurrent infections occur) Active and latent TB screening prior and during therapy; HBV screening prior to initiating; Malignancy screening. |
Contraindicated during pregnancy. Compatible with breastfeeding but should be discussed (potential transfer into breast milk 2-3 days after dose). |
| Ocrelizumab |
300 mg, IV, on days 1 and 15. 600 mg, IV, every 6 months at the following doses. Premedication with 100 mg of methylprednisolone is recommended before every infusion. |
High incidence of herpes virus infections. |
Anti-neoplastic, immunomodulatory and immunosuppressive drugs. |
CBC, CD19+ assays, IgG, IgA and IgG levels (if recurrent infections) Malignancy screening. |
Contraindicated during pregnancy and lactation |
| Ofatumumab |
20 mg, SC, on days 1, 7 and 14, and every 4 weeks after loading doses. |
Injection-site reactions |
Anti-neoplastic, immunomodulatory and immunosuppressive drugs. |
CBC, CD19+ assays, IgG, IgA and IgG levels (if recurrent infections) Malignancy screening. |
Contraindicated during pregnancy and lactation |
| Alemtuzumab |
12 mg, IV, 5 days in year 1. 12 mg IV, 3 days in years 2, 3 and 4. The infusion has to be done for 4 hours to prevent infusion-associated reactions, combined with antipyretics, antihistamines and corticosteroids prior to the infusion. |
Herpes zoster prophylaxis. Baseline thyroid hormones, platelets, creatinine levels and urine analysis. |
Anti-neoplastic, immunomodulatory and immunosuppressive drugs. |
CBC, TSH, T4, Cr, urinalysis. Every 3 months and 48 months after the last dose, testing for autoantibodies (anti-GBM, anti-thyroperoxidase, thyrotropin receptor antibodies) must be done. |
Contraindicated during pregnancy and lactation |
| Natalizumab |
300 mg, IV, every 4 weeks for 24 weeks, or longer periods in extended interval doses. |
PML in JCV-positive patients. |
Anti-neoplastic, immunomodulatory and immunosuppressive drugs. |
CBC. JCV every 6 months |
This should be given during pregnancy if the benefits outweigh the risks Breastfeeding is contraindicated |
| Cladribine |
3.5 mg/kg, orally, via 10 mg tablets, four to five days in weeks 1 and 5 for two subsequent years. Maximal dose: 100 mg. |
Total blood count, herpes zoster serology, tuberculosis screening. Vaccines should be updated. |
Anti-neoplastic, immunomodulatory and immunosuppressive drugs. |
CBC every 6 months |
Contraindicated during pregnancy and lactation |
| Dimethyl fumarate |
120 mg orally, twice a day, after 7 days start a maintenance dose of 240 mg orally twice a day. |
Administered with food for TGI effects. Aspirin should be taken if flushing. |
Anti-neoplastic, immunomodulatory and immunosuppressive drugs. |
CBC, AST, ALT, bilirubin levels, urine analysis. |
Contraindicated during pregnancy and lactation |
| Fingolimod |
0.5 mg, orally, daily |
The first dose must be taken in a hospital facility due to cardiological risk. |
Anti-neoplastic, immunomodulatory and immunosuppressive drugs. |
CBC, AST, ALT Annual dermatological and ophthalmological evaluation |
Contraindicated during pregnancy and lactation |
| Teriflunomide |
14 mg, orally, daily. |
Hair thinning |
Anti-neoplastic, immunomodulatory and immunosuppressive drugs. |
CBC, ALT, AST |
Contraindicated during pregnancy and lactation |
| Interferon β |
Interferon β 1a, 22 and 44 mcg, SC, 3 times a week |
Association with depression. |
No interactions |
CBC, AST, ALT |
No contraindications |
| Interferon β 1a, 30 mcg, IM, weekly |
| Interferon β 1b, 300 mcg, SC, every other day |
| Pegylated Interferon β 1a, 125 mcg, SC, every 14 days |
| Glatiramer acetate |
20 mg, SC, daily or 40 mg, SC, 3 times a week. |
Short-term infusion reaction (palpitation, flushing and chest tightness) |
No interactions |
CBC |
No contraindications |
| PLEX |
3-7 sessions, every other day |
Hypocalcemia risk during sessions |
No interactions |
Blood pressure, calcium, coagulation tests. |
No contraindications |
| Intravenous immunoglobulin (IVIg) |
Initial dose: Up to 2 g/kg per cycle (most cases 0.4 g/kg per day for 5 days Infusion: starting at 0.01 mL/kg/min; in situation of clinical stability, increase it every 15-30 minutes up to 0.08 mL/kg/min *Mean of at least 1 hour per flask (5 g/flask) is recommended in the presentation widely available from SUS |
IgA level dosage is recommended before start Attention to increased risk of thromboembolic events |
No interactions |
No need for routine examinations |
Can be used safely during pregnancy and breastfeeding if the benefits surpass the risks. |
| Subcutaneous immunoglobulin |
Dosage: Convert current monthly intravenous immunoglobulin dosage to weekly subcutaneous infusions of 1-2 mL/kg per week (total dosage is the same for the period: total in grams multiplied by 5 = volume in mL); infusion rate: 15-20 mL/hour/infusion site (high infusion rates during further treatment stages: up to 25-50 mL/hour/infusion site). |
IgA level assay is recommended before start Attention to increased risk of thromboembolic events |
No interactions |
No need for routine examinations |
Not assigned by FDA yet |
