TERIFLUNOMIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TERIFLUNOMIDE (TERIFLUNOMIDE).

How it works

Teriflunomide inhibits dihydroorotate dehydrogenase, a key enzyme in de novo pyrimidine synthesis, thereby reducing proliferation of activated T and B lymphocytes.

What the body does with it

Metabolism	Teriflunomide is primarily metabolized via hydrolysis to its inactive metabolite, followed by glucuronidation and biliary excretion. Minor involvement of CYP450 enzymes (CYP1A2, CYP2C19).
Excretion	Primarily biliary/fecal (approximately 60% unchanged drug and metabolites in feces, 23% in urine). Renal elimination of unchanged drug is minimal (<0.5%). Enterohepatic recycling contributes to long half-life.
Half-life	Terminal half-life approximately 18-19 days (range 10-30 days) due to enterohepatic recirculation. Clinical context: Requires prolonged elimination (up to 2 years to reach undetectable levels) due to slow clearance; accelerated elimination with cholestyramine or activated charcoal may be needed for toxicity.
Protein binding	>99% bound, primarily to albumin.
Volume of Distribution	Approximately 0.1 L/kg (low distribution, mainly in plasma), indicating minimal tissue penetration.
Bioavailability	Oral: ~100% (well absorbed).
Onset of Action	Oral: Clinical effects (immunomodulation) begin after several weeks; maximum benefit typically observed after 4-6 weeks of daily dosing.
Duration of Action	Duration continues for weeks after discontinuation due to slow elimination; immunosuppressive effects persist until drug is cleared from plasma (half-life ~18 days).

Classification & Brands

Dosing & administration

7 mg orally once daily with or without food.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not recommended for use in severe renal impairment (CrCl <30 mL/min) due to limited data.
Liver impairment	Contraindicated in patients with severe hepatic impairment (Child-Pugh class C). Use with caution in mild to moderate hepatic impairment; monitor liver enzymes.
Pediatric use	Not approved for pediatric use; safety and efficacy not established in patients <18 years.
Geriatric use	No specific dose adjustment, but caution due to potential age-related hepatic, renal, or cardiac dysfunction; monitor liver function and blood counts regularly.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TERIFLUNOMIDE (TERIFLUNOMIDE).

Breastfeeding	Excreted in human milk. M/P ratio not established. Potential for serious adverse reactions in nursing infants; discontinue breastfeeding or drug.
Teratogenic Risk	Category X: Teratogenic in animals. First trimester: Risk of major malformations (neural tube, skeletal). Second/third trimester: Risk of fetal death, growth restriction. Contraindicated in pregnancy. Initiate only after negative pregnancy test.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Warning: Hepatotoxicity. Teriflunomide may cause severe liver injury, including fatal outcomes. Assess hepatic function before and during treatment. Contraindicated in patients with severe hepatic impairment.

Side Effect Profile

Serious Effects

Absolute Contraindications

Severe hepatic impairment. Pregnancy or women of childbearing potential not using effective contraception. Known hypersensitivity to teriflunomide or leflunomide. Immunodeficiency syndromes, bone marrow dysplasia, severe uncontrolled infections.

Clinical Precautions

Precautions

Monitor liver enzymes regularly; risk of hepatotoxicity. Increased risk of infections, including tuberculosis; screen for latent infections. Hematologic effects: decreases in white blood cell count; monitor CBC. Peripheral neuropathy may occur. Risk of pancreatitis. Monitor blood pressure due to potential increase. Delay live vaccinations. Women of childbearing potential should use effective contraception due to teratogenicity.

Clinical Tips & Counseling

Drug interactions

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TERIFLUNOMIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TERIFLUNOMIDE (TERIFLUNOMIDE).

How it works

Teriflunomide inhibits dihydroorotate dehydrogenase, a key enzyme in de novo pyrimidine synthesis, thereby reducing proliferation of activated T and B lymphocytes.

What the body does with it

Metabolism	Teriflunomide is primarily metabolized via hydrolysis to its inactive metabolite, followed by glucuronidation and biliary excretion. Minor involvement of CYP450 enzymes (CYP1A2, CYP2C19).
Excretion	Primarily biliary/fecal (approximately 60% unchanged drug and metabolites in feces, 23% in urine). Renal elimination of unchanged drug is minimal (<0.5%). Enterohepatic recycling contributes to long half-life.
Half-life	Terminal half-life approximately 18-19 days (range 10-30 days) due to enterohepatic recirculation. Clinical context: Requires prolonged elimination (up to 2 years to reach undetectable levels) due to slow clearance; accelerated elimination with cholestyramine or activated charcoal may be needed for toxicity.
Protein binding	>99% bound, primarily to albumin.
Volume of Distribution	Approximately 0.1 L/kg (low distribution, mainly in plasma), indicating minimal tissue penetration.
Bioavailability	Oral: ~100% (well absorbed).
Onset of Action	Oral: Clinical effects (immunomodulation) begin after several weeks; maximum benefit typically observed after 4-6 weeks of daily dosing.
Duration of Action	Duration continues for weeks after discontinuation due to slow elimination; immunosuppressive effects persist until drug is cleared from plasma (half-life ~18 days).

Classification & Brands

Dosing & administration

7 mg orally once daily with or without food.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not recommended for use in severe renal impairment (CrCl <30 mL/min) due to limited data.
Liver impairment	Contraindicated in patients with severe hepatic impairment (Child-Pugh class C). Use with caution in mild to moderate hepatic impairment; monitor liver enzymes.
Pediatric use	Not approved for pediatric use; safety and efficacy not established in patients <18 years.
Geriatric use	No specific dose adjustment, but caution due to potential age-related hepatic, renal, or cardiac dysfunction; monitor liver function and blood counts regularly.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TERIFLUNOMIDE (TERIFLUNOMIDE).

Breastfeeding	Excreted in human milk. M/P ratio not established. Potential for serious adverse reactions in nursing infants; discontinue breastfeeding or drug.
Teratogenic Risk	Category X: Teratogenic in animals. First trimester: Risk of major malformations (neural tube, skeletal). Second/third trimester: Risk of fetal death, growth restriction. Contraindicated in pregnancy. Initiate only after negative pregnancy test.
Fetal Monitoring