Teriflunomide is an active pharmaceutical ingredient in the Dihydroorotate Dehydrogenase (Dhodh) Inhibitors group (L04AK). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised February 20, 2026[1]
1 for important information on the population for which efficacy has been established).
How to take
GB
CACanada· Health Canada
8 products
Uses
CAOfficial regulatory label· revised March 22, 2025[2]
NAT-TERIFLUNOMIDE (teriflunomide) is indicated for: • monotherapy for the treatment of patients with relapsing remitting multiple sclerosis (RRMS) to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.
NAT-TERIFLUNOMIDE should only be prescribed by clinicians who are experienced in the diagnosis and management of multiple sclerosis. 1 Pediatrics Pediatrics (< 18 years of age): The safety and efficacy of teriflunomide tablets have not been established in pediatric patients and NAT-TERIFLUNOMIDE is not recommended in this patient population.
2 Geriatrics Clinical studies of teriflunomide did not include patients over 65 years old. NAT-TERIFLUNOMIDE should be used with caution in patients aged 65 years and over. 4 Geriatrics).
EUEuropean Union· EMA
3 products
Uses
EUOfficial regulatory label· revised May 29, 2026[3]
1 for important information on the population for which efficacy has been established).
How to take
EUOfficial regulatory label
USUnited States· FDA
1 product
Uses
USOfficial regulatory label· revised August 24, 2022[4]
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 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.
( 1 )
How to take
Drug interactions
Known interactions involving Teriflunomide. Select one for details. This list is informational and not a complete interaction checker.
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[1]MHRA (UK) · PLGB494450180 · revised February 20, 2026
[2]Health Canada (DPD) · 02500310 · revised March 22, 2025
[3]European Medicines Agency · EMEA/H/C/005962 · revised May 29, 2026
[4]FDA DailyMed · 1824aae5-58af-43… · revised August 24, 2022 [PDF]
[5]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
The treatment should be initiated and supervised by a physician experienced in the management of multiple sclerosis. Posology Adults In adults, the recommended dose of teriflunomide is 14 mg once daily. Paediatric population (10 years and older) In paediatric patients (10 years of age and above), the recommended dose is dependent on body weight: - Paediatric patients with body weight >40 kg: 14 mg once daily.
- Paediatric patients with body weight ≤40 kg: 7 mg once daily. Paediatric patients who reach a stable body weight above 40 kg should be switched to 14 mg once daily. Film-coated tablets can be taken with or without food. Special populations Elderly population Teriflunomide should be used with caution in patients aged 65 years and over due to insufficient data on safety and efficacy.
Renal impairment No dose adjustment is necessary for patients with mild, moderate or severe renal impairment not undergoing dialysis. Patients with severe renal impairment undergoing dialysis were not evaluated. 3). Hepatic impairment No dose adjustment is necessary for patients with mild and moderate hepatic impairment.
3). Paediatric population (less than 10 years of age) The safety and efficacy of teriflunomide in children aged below 10 years have not been established. No data are available. Method of administration The film-coated tablets are for oral use.
The tablets should be swallowed whole with some water.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised February 20, 2026[1]
5%). In general, headache, diarrhoea, nausea and alopecia, were mild to moderate, transient and infrequently led to treatment discontinuation. Teriflunomide is the main metabolite of leflunomide. The safety profile of leflunomide in patients suffering from rheumatoid arthritis or psoriatic arthritis may be pertinent when prescribing teriflunomide in MS patients.
Tabulated list of adverse reactions Teriflunomide was evaluated in a total of 2,267 patients exposed to teriflunomide (1,155 on teriflunomide 7 mg and 1,112 on teriflunomide 14 mg) once daily for a median duration of about 672 days in four placebo- controlled studies (1,045 and 1,002 patients for teriflunomide 7 mg and 14 mg, respectively) and one active comparator study (110 patients in each of the teriflunomide treatment groups) in adult patients with relapsing forms of MS (Relapsing Multiple Sclerosis, RMS).
Listed below are the adverse reactions reported with teriflunomide in placebo- controlled studies in adult patients, reported for teriflunomide 7 mg or 14 mg from clinical studies in adult patients. Frequencies were defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness. 1% in patients treated with placebo. 1%) patients treated with teriflunomide 14 mg. 1% in the placebo group. 3%) Mild increases in transaminase, ALT below or equal to 3-fold ULN were more frequently seen in teriflunomide-treated groups as compared to placebo.
The frequency of elevations above 3-fold ULN and higher was balanced across treatment groups. These elevations in transaminase occurred mostly within the first 6 months of treatment and were reversible after treatment cessation. The recovery time varied between months and years.
6% receiving placebo. 2%). 2% of each group. Severe […]
GBOfficial regulatory label· Warnings and precautions· revised February 20, 2026[1]
Monitoring Before treatment Before starting treatment with teriflunomide the following should be assessed: • Blood pressure • Alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) • Complete blood cell count including differential white blood cell and platelet count.
During treatment During treatment with teriflunomide the following should be monitored: • Blood pressure Check periodically • Alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) Liver enzymes should be assessed at least every four weeks during the first 6 months of treatment and regularly thereafter.
Consider additional monitoring when teriflunomide is given in patients with pre-existing liver disorders, given with other potentially hepatotoxic drugs or as indicated by clinical signs and symptoms such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine.
Liver enzymes should be assessed every two weeks during the first 6 months of treatment, and at least every 8 weeks thereafter for at least 2 years from initiation of treatment. For ALT (SGPT) elevations between 2- and 3-fold the upper limit of normal, monitoring must be performed weekly.
g. infections) during treatment. Accelerated elimination procedure Teriflunomide is eliminated slowly from the plasma. 02 mg/l, although due to individual variation in substance clearance it may take up to 2 years. 2 for procedural details).
8). These elevations occurred mostly within the first 6 months of treatment. Cases of drug-induced liver injury (DILI) have been observed during treatment with teriflunomide, sometimes life-threatening. Most cases of DILI occurred with time to onset of several weeks or several months after treatment initiation of teriflunomide, but DILI can also occur with prolonged use.
The risk for liver enzyme increases and DILI with teriflunomide might be higher in patients with pre-existing liver disorder, concomitant treatment with other hepatotoxic drugs, and/or consumption of substantial quantities of alcohol.
Patients should therefore be closely monitored for signs and symptoms of liver injury. Teriflunomide therapy should be discontinued and accelerated elimination procedure considered if liver injury is suspected. If elevated liver enzymes (greater than 3-fold ULN) are confirmed, teriflunomide therapy should be discontinued In case of treatment discontinuation, liver tests should be pursued until normalisation of transaminase levels.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised February 20, 2026[1]
1. Patients with severe hepatic impairment (Child-Pugh class C). 6). 6). 6). g. acquired immunodeficiency syndrome (AIDS). Patients with significantly impaired bone marrow function or significant anaemia, leukopenia, neutropenia or thrombocytopenia.
4). Patients with severe renal impairment undergoing dialysis, because insufficient clinical experience is available in this patient group. g. in nephrotic syndrome.
This is not medical advice. Consult a qualified healthcare professional.
How to take
CAOfficial regulatory label· revised March 22, 2025[2]
1 Dosing Considerations Monitoring recommended prior to initiating and during treatment: Obtain transaminase and bilirubin levels within 6 months before initiation of NAT-TERIFLUNOMIDE therapy. Monitor ALT levels at least monthly for at least six months after starting NAT-TERIFLUNOMIDE (see 7 WARNINGS AND PRECAUTIONS, Hepatic/ Biliary/Pancreatic).
Obtain a complete blood cell count (CBC) within 6 months before the initiation of treatment with NAT- TERIFLUNOMIDE and periodically during treatment. Further monitoring should be based on signs and symptoms of infection (see 7 WARNINGS AND PRECAUTIONS, Hematologic).
Prior to initiating NAT-TERIFLUNOMIDE, screen patients for latent tuberculosis infection (see 7 WARNINGS AND PRECAUTIONS, Immune - Infections). Check blood pressure before start of NAT-TERIFLUNOMIDE treatment and periodically throughout treatment (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular).
1 Pregnant Women). 2 Recommended Dose and Dosage Adjustment The recommended dose of NAT-TERIFLUNOMIDE is 14 mg orally once daily which can be taken with or NAT-TERIFLUNOMIDE (Teriflunomide Tablets) Page 6 of 43 without food. Pediatric patients The safety and efficacy of teriflunomide have not been established in pediatric patients and NAT- TERIFLUNOMIDE is not recommended in this patient population.
Geriatric patients Clinical studies of teriflunomide did not include patients over 65 years old. 3 Pharmacokinetics, Special Populations and Conditions). Hepatic impairment No dosage adjustment is necessary for patients with mild and moderate hepatic impairment.
Teriflunomide is contraindicated in patients with severe hepatic impairment (see 2 CONTRAINDICATIONS, 7 WARNINGS AND PRECAUTIONS, Hepatic/ Biliary/Pancreatic and). Renal impairment No dosage adjustment is necessary for patients with severe renal impairment (see 7 WARNINGS AND PRECAUTIONS, Renal).
Patients with severe renal impairment undergoing dialysis were not evaluated. Teriflunomide is not recommended in this population. 5 Missed Dose If a dose is missed, treatment should be continued with the next dose as planned.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[2]
). The majority of patients recovered from decreased neutrophils and/or lymphocyte cell counts in less than 8 weeks, whether continuing on teriflunomide or after discontinuation. Rare cases of pancytopenia, agranulocytosis and thrombocytopenia have been reported in the postmarketing setting with leflunomide.
A similar risk is expected for teriflunomide. Obtain a complete blood cell count (CBC) within 6 months before initiating treatment with NAT- TERIFLUNOMIDE and periodically during treatment. Further monitoring should be based on signs and symptoms suggestive of infection.
In any situation in which the decision is made to switch to or from teriflunomide, from or to another agent with a known potential for hematologic suppression, monitoring for hematologic toxicity is recommended, because there will be overlap of systemic exposure to both compounds, due to the slow elimination from plasma of teriflunomide and some of the other therapies (eg, natalizumab, fingolimod).
3 Pharmacokinetics; 7 WARNINGS AND PRECAUTIONS, Accelerated Elimination Procedure). In patients with pre-existing anemia, leucopenia, and/or thrombocytopenia as well as in patients with impaired bone marrow function or those at risk of bone marrow suppression, the risk of hematological disorders is increased.
If such effects occur, the accelerated elimination procedure should be considered. NAT-TERIFLUNOMIDE (Teriflunomide Tablets) Page 9 of 43 Hepatic/ Biliary/Pancreatic Hepatic: Liver function abnormalities have been reported in some patients treated with teriflunomide in clinical trials.
Severe liver injury including fatal liver failure occurred rarely in the post marketing setting. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking teriflunomide.
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.
NAT- TERIFLUNOMIDE is contraindicated in patients with severe hepatic impairment (see 2 CONTRAINDICATIONS). Elevations of liver enzymes have been observed in patients receiving teriflunomide. 7%) of patients on placebo, during the treatment period of up to 2 years.
These elevations occurred mostly within the first 6 months of treatment. Half of the cases returned to normal without drug discontinuation. In clinical trials, teriflunomide was discontinued if the ALT elevation exceeded 3 times the ULN on two consecutive tests.
Of the patients who underwent discontinuation of teriflunomide and accelerated elimination in controlled trials, serum transaminase levels returned to normal within approximately 2 months. In controlled clinical trials, one serious case of “toxic hepatitis” was reported in a 35-year-old female patient.
The patient developed ALT 32 times the ULN and jaundice 5 months after initiation of teriflunomide 14 mg treatment. The patient was hospitalized for 5 weeks and recovered after plasmapheresis and cholestyramine accelerated elimination procedure.
Although the etiology of the hepatic event remained unclear, a causal role of teriflunomide in this case is possible. 5 Post-Market Adverse Reactions). The time to onset of DILI ranged from days to years after initiating treatment with teriflunomide.
Drug-induced liver injury events were reported in patients with and without relevant risk factors, such as a history of drug- induced hepatotoxicity or concomitant use of other hepatotoxic drugs, including some drugs used for managing multiple sclerosis.
Due to the potential for severe liver injury, exercise caution and closely monitor patients if other known or potentially hepatotoxic drugs are used in combination with teriflunomide or if there is a history of drug-induced hepatotoxicity (see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX, Hepatotoxicity and Risk of Teratogenicity).
For all patients, obtain serum transaminase and bilirubin levels within 6 months before initiating treatment with teriflunomide. Monitor ALT levels at least monthly for at least six months after starting NAT-TERIFLUNOMIDE. Additional monitoring is recommended if NAT-TERIFLUNOMIDE is used with other potentially hepatotoxic drugs or if there is a history of drug-induced hepatotoxicity.
Consider discontinuing NAT-TERIFLUNOMIDE if serum transaminase increase (greater than three times the ULN) is confirmed. Monitor serum transaminase and bilirubin on NAT-TERIFLUNOMIDE 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.
Patients should be advised to immediately report signs or symptoms of hepatotoxicity. If liver injury is suspected to be teriflunomide-induced, discontinue NAT-TERIFLUNOMIDE and start an accelerated elimination procedure (see 7 WARNINGS AND PRECAUTIONS, General, Accelerated Elimination Procedure) and monitor liver tests weekly until normalized.
If teriflunomide-induced liver injury is unlikely because NAT-TERIFLUNOMIDE (Teriflunomide Tablets) Page 10 of 43 some other probable cause has been found, resumption of teriflunomide therapy may be considered. Due to a potential for additive hepatotoxic effects, alcohol consumption should be avoided during treatment with NAT-TERIFLUNOMIDE.
Hypoproteinemia […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[2]
3 Pediatrics 10/2023 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES .........................................................................................................
2 TABLE OF CONTENTS ........................................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION ..................................................................................
6 7 WARNINGS AND PRECAUTIONS .............................................................................................. 1 Special Populations ...........................................................................................................
1 Pregnant Women ....................................................................................................... 2 Breast-feeding ............................................................................................................
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[2]
NAT-TERIFLUNOMIDE (teriflunomide) is contraindicated in patients: • with known hypersensitivity to teriflunomide, leflunomide (the parent compound) or to any of the nonmedicinal ingredients in the formulation. • who are currently treated with leflunomide.
• Co-administration of teriflunomide with leflunomide is contraindicated. • with severe hepatic impairment (see 7 WARNINGS AND PRECAUTIONS, Hepatic/ Biliary/Pancreatic). • who are pregnant or women of childbearing potential not using reliable contraception (see 7 WARNINGS AND PRECAUTIONS, Reproductive Health: Female and Male Potential).
NAT- TERIFLUNOMIDE may cause fetal harm when administered to a pregnant woman. Pregnancy must be excluded before start of treatment. g. AIDS). • with impaired bone marrow function or significant anemias, leucopenia, neutropenia or thrombocytopenia.
• with serious active infections. NAT-TERIFLUNOMIDE (Teriflunomide Tablets) Page 5 of 43
This is not medical advice. Consult a qualified healthcare professional.
The treatment should be initiated and supervised by a physician experienced in the management of multiple sclerosis. Posology Adults In adults, the recommended dose of teriflunomide is 14 mg once daily. Paediatric population (10 years and older) In paediatric patients (10 years of age and above), the recommended dose is dependent on body weight: - Paediatric patients with body weight > 40 kg: 14 mg once daily.
- Paediatric patients with body weight ≤ 40 kg: 7 mg once daily. Paediatric patients who reach a stable body weight above 40 kg should be switched to 14 mg once daily. Teriflunomide Viatris is only available as 14 mg film-coated tablets.
Thus, it is not possible to administer Teriflunomide Viatris to patients that require less than a full 14 mg dose. If an alternate dose is required, other teriflunomide products offering such an option should be used. Special populations 3 Elderly population Teriflunomide should be used with caution in patients aged 65 years and over due to insufficient data on safety and efficacy.
Renal impairment No dose adjustment is necessary for patients with mild, moderate or severe renal impairment not undergoing dialysis. Patients with severe renal impairment undergoing dialysis were not evaluated. 3). Hepatic impairment No dose adjustment is necessary for patients with mild and moderate hepatic impairment.
3). Paediatric population (less than 10 years of age) The safety and efficacy of teriflunomide in children aged below 10 years have not been established. No data are available. Method of administration The film-coated tablets are for oral use.
The tablets should be swallowed whole with some water. They can be taken with or without food.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised May 29, 2026[3]
5%). In general, headache, diarrhoea, nausea and alopecia, were mild to moderate, transient and infrequently led to treatment discontinuation. Teriflunomide is the main metabolite of leflunomide. The safety profile of leflunomide in patients suffering from rheumatoid arthritis or psoriatic arthritis may be pertinent when prescribing teriflunomide in MS patients.
Tabulated list of adverse reactions Teriflunomide was evaluated in a total of 2,267 patients exposed to teriflunomide (1,155 on teriflunomide 7 mg and 1,112 on teriflunomide 14 mg) once daily for a median duration of about 672 days in four placebo-controlled studies (1,045 and 1,002 patients for teriflunomide 7 mg and 14 mg, respectively) and one active comparator study (110 patients in each of the teriflunomide treatment groups) in adult patients with relapsing forms of MS (Relapsing Multiple Sclerosis, RMS).
Listed below are the adverse reactions reported with teriflunomide in placebo-controlled studies, reported for teriflunomide 7 mg or 14 mg from clinical studies in adult patients. Frequencies were defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness. 1% in patients treated with 13 placebo. 1%) patients treated with teriflunomide 14 mg. 1% in the placebo group. 3%) Mild increases in transaminase, ALT below or equal to 3-fold ULN were more frequently seen in teriflunomide-treated groups as compared to placebo.
The frequency of elevations above 3-fold ULN and higher was balanced across treatment groups. These elevations in transaminase occurred mostly within the first 6 months of treatment and were reversible after treatment cessation. The recovery time varied between months and years.
6% receiving placebo. Infections In placebo-controlled studies in adult patients, no increase in serious infections was observed with […]
EUOfficial regulatory label· Warnings and precautions· revised May 29, 2026[3]
Monitoring Before treatment Before starting treatment with teriflunomide the following should be assessed: • Blood pressure • Alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) 4 • Complete blood cell count including differential white blood cell and platelet count.
During treatment During treatment with teriflunomide the following should be monitored: • Blood pressure o Check periodically • Alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) o Liver enzymes should be assessed at least every four weeks during the first 6 months of treatment, and regularly thereafter.
o Consider additional monitoring when Teriflunomide Viatris is given in patients with pre- existing liver disorders, given with other potentially hepatotoxic drugs or as indicated by clinical signs and symptoms such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine.
Liver enzymes should be assessed every two weeks during the first 6 months of treatment, and at least every 8 weeks thereafter for at least 2 years from initiation of treatment. o For ALT (SGPT) elevations between 2- and 3-fold the upper limit of normal, monitoring must be performed weekly.
g. infections) during treatment. Accelerated elimination procedure Teriflunomide is eliminated slowly from the plasma. 02 mg/l, although due to individual variation in substance clearance it may take up to 2 years. 2 for procedural details).
8). These elevations occurred mostly within the first 6 months of treatment. Cases of drug-induced liver injury (DILI) have been observed during treatment with teriflunomide, sometimes life-threatening. Most cases of DILI occurred with time to onset of several weeks or several months after treatment initiation of teriflunomide, but DILI can also occur with prolonged use.
The risk for liver enzyme increases and DILI with teriflunomide might be higher in patients with pre- existing liver disorder, concomitant treatment with other hepatotoxic drugs, and/or consumption of substantial quantities of alcohol.
Patients should therefore be closely monitored for signs and symptoms of liver injury. Teriflunomide therapy should be discontinued and accelerated elimination procedure considered if liver injury is suspected. If elevated liver enzymes (greater than 3-fold ULN) are confirmed, teriflunomide therapy should be discontinued.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised May 29, 2026[3]
1. Patients with severe hepatic impairment (Child-Pugh class C). 6). 6). 6). g. acquired immunodeficiency syndrome (AIDS). Patients with significantly impaired bone marrow function or significant anaemia, leucopenia, neutropenia or thrombocytopenia.
4). Patients with severe renal impairment undergoing dialysis, because insufficient clinical experience is available in this patient group. g. in nephrotic syndrome.
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised August 24, 2022[4]
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 )
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 479 reports total. [5]
Multiple Sclerosis Relapse 45
Drug Ineffective 28
Diarrhoea 27
Condition Aggravated 26
Fall 17
Gait Disturbance 17
Fatigue 16
Asthenia 15
Multiple Sclerosis 14
Alopecia 13
Rash 13
Death 11
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised August 24, 2022[4]
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.
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.
7) ]; psoriasis or worsening of psoriasis (including pustular psoriasis and nail psoriasis); nail disorders
USOfficial regulatory label· Warnings and precautions· revised August 24, 2022[4]
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.
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.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised August 24, 2022[4]
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.
This is not medical advice. Consult a qualified healthcare professional.
g. in nephrotic syndrome. Teriflunomide should not be used in patients with conditions of severe hypoproteinaemia. 8). Blood pressure must be checked before the start of teriflunomide treatment and periodically thereafter. Blood pressure elevation should be appropriately managed before and during treatment with teriflunomide.
Infections Initiation of treatment with teriflunomide should be delayed in patients with severe active infection until resolution. 8). 8), with some of them being serious, including herpetic meningoencephalitis and herpes dissemination.
They may occur at any time during treatment. Based on the immunomodulatory effect of teriflunomide, if a patient develops any serious infection, suspending treatment with teriflunomide should be considered and the benefits and risks should be reassessed prior to re-initiation of therapy.
Due to the prolonged half-life, accelerated elimination with cholestyramine or charcoal may be considered. Patients receiving teriflunomide should be instructed to report symptoms of infections to a physician. Patients with active acute or chronic infections should not start treatment with teriflunomide until the infection(s) is resolved.
The safety of teriflunomide in individuals with latent tuberculosis infection is unknown, as tuberculosis screening was not systematically performed in clinical studies. Patients tested positive in tuberculosis screening should be treated by standard medical practice prior to therapy.
Respiratory reactions Interstitial lung disease (ILD) as well as cases of pulmonary hypertension have been reported with teriflunomide in the postmarketing setting. The risk might be increased in patients with a history of ILD. ILD may occur acutely at any time during therapy with a variable clinical presentation.
ILD may be fatal. New onset or worsening pulmonary symptoms, such as persistent cough and dyspnoea, may be a reason for discontinuation of the therapy and for further investigation, as appropriate. If discontinuation of the medicinal product is necessary, initiation of an accelerated elimination procedure should be considered.
8). As a precaution, a recent complete blood cell count, including differential white blood cell count and platelets, should be available before the initiation of treatment and the complete blood cell count should be […]
19 9 DRUG INTERACTIONS............................................................................................................ 2 Drug Interactions Overview ..............................................................................................
25 11 STORAGE, STABILITY AND DISPOSAL ..................................................................................... 27 PART II: SCIENTIFIC INFORMATION ...................................................................................................
In case of treatment discontinuation, liver tests should be pursued until normalisation of transaminase levels. g. in nephrotic syndrome. Teriflunomide should not be used in patients with conditions of severe hypoproteinaemia. 8). Blood pressure must be checked before the start of teriflunomide treatment and periodically thereafter.
Blood pressure elevation should be appropriately managed before and during treatment with teriflunomide. Infections Initiation of treatment with teriflunomide should be delayed in patients with severe active infection until resolution.
8). 8), with some of them being serious, including herpetic meningoencephalitis and herpes dissemination. They may occur at any time during treatment. Based on the immunomodulatory effect of teriflunomide, if a patient develops any serious infection, suspending treatment with teriflunomide should be considered and the benefits and risks should be reassessed prior to re-initiation of therapy.
Due to the prolonged half-life, accelerated elimination with cholestyramine or charcoal may be considered. Patients receiving teriflunomide should be instructed to report symptoms of infections to a physician. Patients with active acute or chronic infections should not start treatment with teriflunomide until the infection(s) is resolved.
The safety of teriflunomide in individuals with latent tuberculosis infection is unknown, as tuberculosis screening was not systematically performed in clinical studies. Patients who tested positive in tuberculosis screening should be treated by standard medical practice prior to therapy.
Respiratory reactions Interstitial lung disease (ILD) as well as cases of pulmonary hypertension have been reported with teriflunomide in the post-marketing setting. The risk might be increased in patients with a history of ILD. ILD may occur acutely at any time during therapy with a variable clinical presentation.
ILD may be fatal. New onset or worsening pulmonary symptoms, such as persistent cough and dyspnoea, may be a reason for discontinuation of the therapy and for further investigation, as appropriate. If discontinuation of the medicinal product is necessary, initiation of an accelerated elimination procedure should be considered.
8). As a precaution, a recent complete blood cell count, including differential white blood cell count and platelets, should be available before the initiation of treatment and the complete […]
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.