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Teriflunomide is a brand name for Teriflunomide. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE Teriflunomide tablets are indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Teriflunomide tablets are a pyrimidine synthesis inhibitor indicated…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION The recommended dose of teriflunomide tablets is 7 mg or 14 mg orally once daily. Teriflunomide tablets can be taken with or without food. Monitoring to Assess Safety: • Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide tablets therapy.
1) ] . • Obtain a complete blood cell count (CBC) within 6 months before the initiation of treatment with teriflunomide tablets. 4) ] . 4) ] . 2) ] . 9) ] . 7 mg or 14 mg orally once daily, with or without food. ( 2 )
11) ] Most common adverse reactions (≥ 10% and ≥ 2% greater than placebo): headache, diarrhea, nausea, alopecia, increase in ALT. gov/medwatch. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
A total of 2047 patients receiving teriflunomide tablets (7 mg or 14 mg once daily) constituted the safety population in the pooled analysis of placebo-controlled studies in patients with relapsing forms of multiple sclerosis; of these, 71% were female.
The average age was 37 years. Table 1 lists adverse reactions in placebo-controlled trials with rates that were at least 2% for teriflunomide tablets patients and also at least 2% above the rate in placebo patients. The most common were headache, an increase in ALT, diarrhea, alopecia, and nausea.
3% of all patients in the teriflunomide tablets 7 mg, teriflunomide tablets 14 mg, and placebo treatment arms, respectively).
Table 1:
Adverse Reactions in Pooled Placebo-Controlled Studies in Patients with Relapsing Forms of Multiple Sclerosis Teriflunomide Tablets 7 mg Teriflunomide Tablets 14 mg Placebo Adverse Reaction (N = 1045) (N = 1002) (N = 997) Headache 18% 16% 15% Increase in Alanine aminotransferase 13% 15% 9% Diarrhea 13% 14% 8% Alopecia 10% 13% 5% Nausea 8% 11% 7% Paresthesia 8% 9% 7% Arthralgia 8% 6% 5% Neutropenia 4% 6% 2% Hypertension 3% 4% 2% Cardiovascular Deaths Four cardiovascular deaths, including three sudden deaths, and one myocardial infarction in a patient with a history of hyperlipidemia and hypertension were reported among approximately 2600 patients exposed to teriflunomide tablets in the premarketing database.
5 WARNINGS AND PRECAUTIONS • Elimination of teriflunomide tablets can be accelerated by administration of cholestyramine or activated charcoal for 11 days. 3 ) • Teriflunomide tablets may decrease WBC. A recent CBC should be available before starting teriflunomide tablets.
Monitor for signs and symptoms of infection. Consider suspending treatment with teriflunomide tablets in case of serious infection. Do not start teriflunomide tablets in patients with active infections. 4 ) • Stop teriflunomide tablets if patient has anaphylaxis, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms; initiate rapid elimination.
7 ) • If patient develops symptoms consistent with peripheral neuropathy, evaluate patient and consider discontinuing teriflunomide tablets. 8 ) • Teriflunomide tablets may increase blood pressure. Measure blood pressure at treatment initiation and monitor blood pressure during treatment.
1 Hepatotoxicity Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with teriflunomide tablets in the postmarketing setting.
Patients with pre-existing liver disease and patients taking other hepatotoxic drugs may be at increased risk for developing liver injury when taking teriflunomide tablets. Clinically significant liver injury can occur at any time during treatment with teriflunomide tablets.
Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) greater than two times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with teriflunomide tablets.
Teriflunomide tablets are contraindicated in patients with severe hepatic impairment [see Contraindications (4) ] . 8%) of patients receiving placebo, during the treatment period. These elevations occurred mostly within the first year of treatment.
1) ] . • Pregnant women and females of reproductive potential not using effective contraception. 1) ] . • Patients with a history of a hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in teriflunomide tablets.
5) ]. 3) ]. 5 ) • Current leflunomide treatment ( 4 )
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These cardiovascular deaths occurred during uncontrolled extension studies, one to nine years after initiation of treatment. A relationship between teriflunomide tablets and cardiovascular death has not been established. 4%) patients in the placebo group.
These elevations were transient. Some elevations were accompanied by hyperkalemia. Teriflunomide tablets may cause acute uric acid nephropathy with transient acute renal failure because teriflunomide tablets increase renal uric acid clearance.
8% of placebo-treated patients. 3 mmol/L. 2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of teriflunomide tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
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Half of the cases returned to normal without drug discontinuation. 3) ] . Of the patients who underwent discontinuation and accelerated elimination in controlled trials, half returned to normal or near normal values within 2 months. One patient in the controlled trials in adult patients developed ALT 32 times the ULN and jaundice 5 months after initiation of teriflunomide tablets 14 mg treatment.
The patient was hospitalized for 5 weeks and recovered after plasmapheresis and cholestyramine accelerated elimination procedure. Teriflunomide tablets-induced liver injury in this patient could not be ruled out. Obtain serum transaminase and bilirubin levels within 6 months before initiation of teriflunomide tablets therapy.
Monitor ALT levels at least monthly for six months after starting teriflunomide tablets. Consider additional monitoring when teriflunomide tablets are given with other potentially hepatotoxic drugs. Consider discontinuing teriflunomide tablets if serum transaminase increase (greater than three times the ULN) is confirmed.
Monitor serum transaminase and bilirubin on teriflunomide tablets therapy, particularly in patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine.
3) ] and monitor liver tests weekly until normalized. If teriflunomide tablets-induced liver injury is unlikely because some other probable cause has been found, resumption of teriflunomide tablets therapy may be considered. 2 Embryofetal Toxicity Teriflunomide tablets may cause fetal harm when administered to a pregnant woman.
1) ] . Teriflunomide tablets are contraindicated for use in pregnant women and in females of reproductive potential not using effective contraception [see Contraindications (4) ] . Exclude pregnancy before starting treatment with teriflunomide tablets in females of reproductive potential [see Dosage and Administration (2) ] .
3) ] . 3) ] . Upon discontinuing teriflunomide tablets, it is recommended that all females of reproductive potential undergo an accelerated drug elimination procedure. 02 mcg/mL). 3) ]. 1) ] . 3) ] . 02 mg/L, although because of individual variations in drug clearance it may take as long as 2 years.
An accelerated elimination procedure could be used at any time after discontinuation of teriflunomide tablets. Elimination can be accelerated by either of the following procedures: • Administration of cholestyramine 8 g every 8 hours for 11 days.
If cholestyramine 8 g three times a day is not well tolerated, cholestyramine 4 g three times a day can be used. • Administration of 50 g oral activated charcoal powder every 12 hours for 11 days. If either elimination procedure is poorly tolerated, treatment days do not need to be consecutive unless there is a need to lower teriflunomide plasma concentration rapidly.
At the end of 11 days, both regimens successfully accelerated teriflunomide elimination, leading to more than 98% decrease in teriflunomide plasma concentrations. Use of the accelerated elimination procedure may potentially result in return of disease activity if the patient had been responding to teriflunomide tablets treatment.
4 Bone Marrow Effects/Immunosuppression Potential/Infections Bone Marrow Effects A mean decrease compared to baseline in white blood cell (WBC) count of approximately 15% (mainly neutrophils and lymphocytes) and in platelet count of approximately 10% was observed in placebo-controlled trials in adult patients with 7 mg and 14 mg of teriflunomide tablets.
The decrease in mean WBC count occurred during the first 6 weeks and WBC count remained low during treatment. 8 x 109/L was observed in 10% and 12% of patients receiving teriflunomide tablets 7 mg and 14 mg, respectively, compared with 6% of patients receiving placebo.
No cases of serious pancytopenia were reported in premarketing clinical trials of teriflunomide tablets but rare cases of pancytopenia and agranulocytosis have been reported in the postmarketing setting with leflunomide. 3) ] . Cases of thrombocytopenia with teriflunomide tablets, including rare cases with platelet counts less than 50,000/mm 3 , have been reported in the postmarketing setting.
Obtain a complete blood cell count (CBC) within 6 months before the initiation of treatment with teriflunomide tablets. Further monitoring should be based on signs and symptoms suggestive of bone marrow suppression. Risk of Infection/Tuberculosis Screening Patients with active acute or chronic infections should not start treatment until the infection(s) is resolved.
If a patient develops a serious infection consider suspending treatment with teriflunomide tablets and using an accelerated elimination procedure. Reassess the benefits and risks prior to resumption of therapy. Instruct patients receiving teriflunomide tablets to report symptoms of infections to a physician.
Teriflunomide tablets are not recommended for patients with severe immunodeficiency, bone marrow disease, or severe, uncontrolled infections. Medications like teriflunomide tablets that have immunosuppression potential may cause patients to be more susceptible to infections, including opportunistic infections.
2%). 7 years. Fatal infections have been reported in the postmarketing setting in patients receiving leflunomide, especially Pneumocystis jirovecii pneumonia and aspergillosis. Most of the reports were confounded by concomitant immunosuppressant therapy and/or comorbid illness which, in addition to rheumatoid disease, may predispose patients to infection.
In clinical studies with teriflunomide tablets, cytomegalovirus hepatitis reactivation has been observed. In clinical studies with teriflunomide tablets in adult patients, cases of tuberculosis have been observed. Prior to initiating teriflunomide tablets, screen patients for latent tuberculosis infection with a tuberculin skin test or with a blood test for mycobacterium tuberculosis infection.
Teriflunomide tablets have not been studied in patients with a positive tuberculosis screen, and the safety of teriflunomide tablets in individuals with latent tuberculosis infection is unknown. For patients testing positive in tuberculosis screening, treat by standard medical practice prior to therapy with teriflunomide tablets.
Vaccination:
No clinical data are available on the efficacy and safety of live vaccinations in patients taking teriflunomide tablets. Vaccination with live vaccines is not recommended. The long half-life of teriflunomide tablets should be considered when contemplating administration of a live vaccine after stopping teriflunomide tablets.
Malignancy The risk of malignancy, particularly lymphoproliferative disorders, is increased with the use of some immunosuppressive medications. There is a potential for immunosuppression with teriflunomide tablets. No apparent increase in the incidence of malignancies and lymphoproliferative disorders was reported in the teriflunomide tablets clinical trials, but larger and longer-term studies would be needed to determine whether there is an increased risk of malignancy or lymphoproliferative disorders with teriflunomide tablets.
5 Hypersensitivity Reactions Teriflunomide tablets can cause anaphylaxis and severe allergic reactions [see Contraindications (4) ]. Signs and symptoms have included dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue.
Inform patients of the signs and symptoms of anaphylaxis and angioedema. 7) ] , have been reported with teriflunomide tablets. Fatal outcomes were reported in one case of TEN and one case of DRESS. Inform patients of the signs and symptoms that may signal a serious skin reaction.
Instruct patients to discontinue teriflunomide tablets and seek immediate medical care should these signs and symptoms occur. 3) ] . In such cases, patients should not be re-exposed to teriflunomide [see Contraindications (4) ] . 7 Drug Reaction with Eosinophilia and Systemic Symptoms Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, has occurred with teriflunomide tablets.
One fatal case of DRESS that occurred in close temporal association (34 days) with the initiation of teriflunomide tablets treatment has been reported in the postmarketing setting. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection.
Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. , fever, lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately.
3) ] . In such cases, patients should not be re-exposed to teriflunomide [see Contraindications (4) ] . , carpal tunnel syndrome), occurred more frequently in patients taking teriflunomide tablets than in patients taking placebo. 4% receiving placebo (4 patients).
7% (8 patients) with confirmed peripheral neuropathy (3 patients receiving teriflunomide tablets 7 mg and 5 patients receiving teriflunomide tablets 14 mg). Five of them recovered following treatment discontinuation. Not all cases of peripheral neuropathy resolved with continued treatment.
Peripheral neuropathy also occurred in patients receiving leflunomide. Age older than 60 years, concomitant neurotoxic medications, and diabetes may increase the risk for peripheral neuropathy . 3) ] . 6 mmHg for placebo. 3 mmHg for placebo.
8% for placebo. Check blood pressure before start of teriflunomide tablets treatment and periodically thereafter. Elevated blood pressure should be appropriately managed during treatment with teriflunomide tablets. 10 Respiratory Effects Interstitial lung disease, including acute interstitial pneumonitis, has been reported with teriflunomide tablets in the postmarketing setting.
Interstitial lung disease and worsening of pre-existing interstitial lung disease have been reported during treatment with leflunomide. Interstitial lung disease may be fatal and may occur acutely at any time during therapy with a variable clinical presentation.
New onset or worsening pulmonary symptoms, such as cough and dyspnea, with or without associated fever, may be a reason for discontinuation of therapy and for further investigation as appropriate. 3) ] . 11 Pancreatitis in Pediatric Patients Teriflunomide tablets are not approved for use in pediatric patients.
4) ] . 3) ] . 12 Concomitant Use with Immunosuppressive or Immunomodulating Therapies Coadministration with antineoplastic or immunosuppressive therapies used for treatment of multiple sclerosis has not been evaluated. Safety studies in which teriflunomide tablets were concomitantly administered with other immune modulating therapies for up to one year (interferon beta, glatiramer acetate) did not reveal any specific safety concerns.
The long term safety of these combinations in the treatment of multiple sclerosis has not been established. In any situation in which the decision is made to switch from teriflunomide tablets to another agent with a known potential for hematologic suppression, it would be prudent to monitor for hematologic toxicity, because there will be overlap of systemic exposure to both compounds.
3) ] .