Table 1.
US Food and Drug Administration contraindications, warnings and precautions for representative DMTs for MSa.
| DMT | Contraindications | Warnings and precautions |
|---|---|---|
| Modest efficacy | ||
| Interferons interferon beta-1a (41) interferon beta-1b (42) |
History of hypersensitivity to natural or recombinant interferon beta, albumin or any other component of the formulation | Both agents: anaphylaxis and other allergic reactions; congestive heart failure, hepatic injury, seizures, thrombotic microangiopathy, monitoring for laboratory abnormalities interferon beta-1a only: depression, suicide, and psychotic disorders; decreased peripheral blood counts, autoimmune disorders interferon beta-1b only: depression and suicide, leukopenia, drug-induced lupus erythematosus, flu-like symptom complex, injection site necrosis and reactions |
| Glatiramer acetate (43) | Known hypersensitivity to glatiramer acetate or mannitol | Post-injection reaction, chest pain, lipoatrophy and skin necrosis, potential effects on immune response |
| Teriflunomide (44) | Severe hepatic impairment | Hepatotoxicity, embryofetal toxicity, bone marrow effects/immunosuppression potential/infections, hypersensitivity and serious skin reactions, peripheral neuropathy, increased blood pressure, respiratory effects, concomitant use with immunosuppressive or immunomodulating therapies |
| Monomethyl fumarate (45) Dimethyl fumarate (46) Diroximel fumarate (47) |
Known hypersensitivity to monomethyl-, dimethyl-, or diroximel fumarate or any of the excipients; co-administration of any of these agents | All agents: lymphopenia, flushing anaphylaxis and angioedema, PML, liver injury Monomethyl fumarate only: herpes zoster and other serious opportunistic infections |
| High efficacy | ||
| Natalizumab (48) | History of PML or a hypersensitivity reaction to natalizumab | PML, herpes infections, hypersensitivity/antibody formation, hepatotoxicity, immunosuppression/infections, laboratory test abnormalities, immunizations |
| Sphingosine-1-phosphate receptor modulators Fingolimod (49) Ponesimod (50) Ozanimod (51) Siponimod (52) |
All agents: In the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure; Presence of Mobitz type II second-degree or third degree atrioventricular block, sick sinus syndrome, (or sino-atrial block for ozanimod), unless the patient has a functioning pacemaker; Fingolimod only: baseline QTc interval ≥ 500 msec, cardiac arrhythmias requiring anti-arrhythmic treatment with Class Ia or Class III anti-arrhythmic drugs, hypersensitivity to fingolimod or its excipients; Siponimod only: CYP2C9*3/*3 genotype; Ozanimod only: severe untreated sleep apnea; concomitant use of a monoamine oxidase inhibitor. |
All agents: bradyarrhythmia and atrioventricular blocks/conduction delays, infections, macular edema, posterior reversible encephalopathy syndrome, respiratory effects, liver injury, fetal risk, severe increase in disability after discontinuation, increased blood pressure Fingolimod, ozanimod, siponimod: immune system effects after discontinuation Ozanimod, ponesimod, siponimod: unintended additive immunosuppressive effects from prior treatment with immunosuppressive or immune-modulating therapies Fingolimod and ponesimod: malignancies Fingolimod only: hypersensitivity reactions, PML |
| Alemtuzumab (53) | Infection with Human Immunodeficiency Virus. | Autoimmunity, infusion reactions, malignancies, immune thrombocytopenia, glomerular nephropathies, thyroid disorders, other autoimmune cytopenias, infections, acute acalculous cholecystitis, pneumonitis |
| Anti-CD20 B-cell depleting agents Ocrelizumab (54) Ofatumumab (55) |
Both agents: active hepatitis B virus infection; Ocrelizumab only: history of life-threatening infusion reaction to ocrelizumab |
Both agents: infusion reactions, infections, reduction in immunoglobulins, malignancies Ofatumumab only: fetal risk |
| Cladribine (56) | Current malignancy, pregnancy, breastfeeding, Human Immunodeficiency Virus infection, active chronic infections, hypersensitivity to cladribine. | Malignancies, risk of teratogenicity, lymphopenia, infections, hematologic toxicity, graft-vs.-host-disease with blood transfusion, liver injury, hypersensitivity, cardiac failure |
| Mitoxantrone (57) | Contraindicated in patients who have demonstrated prior hypersensitivity to it. | Cardiotoxicity, myelosuppression, secondary leukemia, potential human teratogen |
a
Refer to updated local prescribing information for each agent for complete information.
PML, progressive multifocal leukoencephalopathy.