Table 5.
Recommendations/considerations for treatment-emergent situations during teriflunomide therapy
| Treatment-emergent situations | Recommendations | Rationale |
|---|---|---|
| Hepatic | Leflunomide/teriflunomide clinical trials | |
| Contraindications | ||
| Patients with severe hepatic impairment (Child–Pugh class C) | ||
| Warnings and precautions | ||
| Mild to moderate hepatic impairment | No dosage adjustment necessary | |
| Liver injury is suspected | Discontinue teriflunomide | |
| Elevated liver enzymes (>3 × ULN) are confirmed | Consider discontinuing teriflunomide | |
| Clinical signs and symptoms, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia or jaundice, and/or dark urine occur | Assess liver enzymes | |
| Blood pressure | Leflunomide/teriflunomide clinical trials | |
| Warnings and precautions | ||
| Blood pressure increases | Manage elevations appropriately | |
| Infections | Leflunomide/teriflunomide immunomodulation | |
| Contraindications | ||
| Patients with severe, active infection until resolution | ||
| Warnings and precautions | ||
| Serious infection develops | Consider suspending treatment; consider accelerated elimination; re-assess benefits and risks prior to re-initiation of therapy | |
| Respiratory | Leflunomide | |
| Warnings and precautions | ||
| Pulmonary symptoms, such as persistent cough and dyspnea, develop | Consider discontinuing teriflunomide; investigate further as appropriate | |
| Hematologic | Leflunomide/teriflunomide immunomodulation | |
| Contraindications | ||
| Patients with significantly impaired bone marrow function or significant anemia, leucopenia, neutropenia, or thrombocytopenia | ||
| Patients with severe immunodeficiency states (e.g., AIDS) | ||
| Warnings and precautions | ||
| Clinical signs and symptoms (e.g. infection) warrant further investigation | Perform complete blood cell count as indicated | |
| Severe hematological reactions, including pancytopenia, occur | Discontinue teriflunomide and any concomitant myelosuppressive treatment | |
| Anemia, leucopenia, thrombocytopenia, impaired bone marrow function or bone marrow suppression occur | Consider accelerated elimination | |
| Hypersensitivities | Leflunomide | |
| Contraindications | ||
| Patients with severe hypersensitivity to the active substance or to any of the excipients | ||
| Warnings and precautions | ||
| Skin and/or mucosal reactions that raise suspicions of severe generalized major skin reactions (Stevens-Johnson syndrome or toxic epidermal necrolysis—Lyell’s syndrome) occur | Discontinue teriflunomide and perform accelerated elimination; do not re-expose patient to teriflunomide | |
| Ulcerative stomatitis occurs | Discontinue teriflunomide | |
| Peripheral neuropathy | Leflunomide/teriflunomide clinical trials | |
| Warnings and precautions | ||
| Peripheral neuropathy is confirmed | Consider discontinuing teriflunomide and performing accelerated elimination | |
| Renal | Teriflunomide clinical trials | |
| Contraindications | ||
| Patients with severe renal impairment undergoing dialysis | ||
| Patients with severe hypoproteinemia (e.g. nephrotic syndrome) | ||
| Warnings and precautions | ||
| Mild, moderate or severe renal impairment not undergoing dialysis | No dosage adjustment necessary | |
| Vaccination | Immunomodulatory action of teriflunomide | |
| Warnings and precautions | ||
| Live attenuated vaccines may carry risk of infections | Avoid use of live attenuated vaccines | |
| Fertility, pregnancy and lactation | Leflunomide/teriflunomide pre-clinical toxicology | |
| Contraindications | ||
| Pregnant women or women of childbearing potential who are not using reliable contraception during treatment with teriflunomide and thereafter as long as its plasma levels are above 0.02 mg/l Breast-feeding women |
||
| Warnings and precautions | ||
| A woman has plans to stop or change contraception | Discuss risks and contraception options | |
| Pregnancy is suspected | Conduct pregnancy testing | |
| Pregnancy test is positive | Discuss risk to pregnancy; rapidly lowering blood level of teriflunomide by accelerated elimination may decrease risk to the fetus | |
| A woman wishes to become pregnant | Recommend accelerated elimination | |
| Overdose | Safety precautions | |
| Warnings and precautions | ||
| Overdose of teriflunomide | Accelerated elimination | |
| Other | Leflunomide | |
| Warnings and precautions | ||
| Patient experiences adverse reaction, such as dizziness | Advise to refrain from driving cars and using machines |
AIDS acquired immunodeficiency syndrome, ULN upper limit of normal