Usage
- Medical Conditions: Teriflunomide is prescribed for the treatment of relapsing forms of multiple sclerosis (MS) in adults and children 10 years of age and older. These forms include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
- Pharmacological Classification: Immunomodulatory agent, pyrimidine synthesis inhibitor.
- Mechanism of Action: Teriflunomide inhibits dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine synthesis, thereby reducing the proliferation of rapidly dividing cells, including activated lymphocytes, which play a crucial role in the pathogenesis of MS.
Alternate Names
- International Nonproprietary Name (INN): Teriflunomide
- Brand Name: Aubagio
How It Works
- Pharmacodynamics: Teriflunomide selectively and reversibly inhibits DHODH, leading to a reduction in pyrimidine synthesis. This primarily affects activated lymphocytes, reducing their proliferation and impacting the inflammatory cascade in MS. It does not affect resting lymphocytes or other cells that can utilize the salvage pathway for pyrimidine synthesis.
- Pharmacokinetics:
- Absorption: Teriflunomide is well-absorbed orally, reaching peak plasma concentrations within 1 to 2 hours when taken without food. Food intake may slightly delay the time to peak concentration but does not affect the extent of absorption.
- Metabolism: Minimally metabolized. It does not involve cytochrome P450 (CYP) enzymes.
- Elimination: Primarily via biliary excretion (approximately 60%). Around 25% is excreted unchanged in the urine. The elimination half-life is long, approximately 18-19 days, due to enterohepatic recirculation. An accelerated elimination procedure with cholestyramine or activated charcoal can be employed to reduce plasma concentrations more rapidly if needed (e.g., in cases of suspected severe adverse reactions or pregnancy).
Dosage
Standard Dosage
Adults:
Children (10 years and older):
- Body weight > 40 kg: 14 mg orally once daily.
- Body weight ≤ 40 kg: 7 mg orally once daily.
- Children reaching a stable body weight above 40 kg should switch to the 14 mg dose.
Special Cases:
- Elderly Patients (≥65 years): Use with caution due to limited data and potential for increased comorbidities and concomitant medications. Closer monitoring is recommended.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction:
- Mild to moderate impairment: No dose adjustment needed.
- Severe impairment: Contraindicated.
- Patients with Comorbid Conditions: Monitor closely, especially in patients with hypertension, infections, or pre-existing liver disease.
Clinical Use Cases
Teriflunomide is specifically indicated for relapsing forms of MS. It is not indicated for other conditions listed (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations).
Dosage Adjustments
- No dose adjustments are needed based solely on renal impairment.
- For hepatic dysfunction, follow the guidelines mentioned in the “Special Cases” section above.
- Other comorbidities or patient-specific factors may warrant closer monitoring or adjustments in clinical practice.
Side Effects
Common Side Effects
- Headache
- Nausea
- Diarrhea
- Hair thinning/loss (usually temporary)
- Elevated liver enzymes (monitor regularly)
- Paresthesia (tingling, burning, numbness)
Rare but Serious Side Effects
- Severe liver injury (including fatal liver failure)
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Interstitial lung disease
- Hypertension
- Infections (due to immunosuppression)
- Peripheral neuropathy
Long-Term Effects
- The potential long-term effects of teriflunomide are still being studied, but some effects, like peripheral neuropathy or liver injury, can be chronic. Regular monitoring is crucial.
Contraindications
- Hypersensitivity to teriflunomide or leflunomide.
- Severe hepatic impairment (Child-Pugh class C).
- Pregnancy and women of childbearing potential not using reliable contraception.
- Breastfeeding.
- Severe immunodeficiency states (e.g., AIDS).
- Severe active infection.
Drug Interactions
- Leflunomide (concomitant use is contraindicated)
- Potentially hepatotoxic drugs (increased risk of liver injury)
- Live attenuated vaccines (avoid use)
- Some medications may affect teriflunomide plasma concentrations (e.g., cholestyramine, activated charcoal accelerate elimination; rifampin may decrease teriflunomide levels). Consult drug interaction resources for a comprehensive list.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X (contraindicated). Teriflunomide is highly teratogenic.
- Fetal Risks: Significant risk of major birth defects.
- Breastfeeding: Contraindicated as it may be excreted in breast milk.
- Safer alternatives should be considered for women who are pregnant or breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibits DHODH, reducing lymphocyte proliferation.
- Side Effects: Hair loss, nausea, diarrhea, elevated liver enzymes, infections, peripheral neuropathy, serious liver injury.
- Contraindications: Pregnancy, severe liver disease, breastfeeding, severe immunodeficiency.
- Drug Interactions: Leflunomide, hepatotoxic drugs, live vaccines.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults/Children >40kg: 14 mg daily; Children ≤40kg: 7 mg daily.
- Monitoring Parameters: Liver function tests (ALT, AST, bilirubin), blood pressure, complete blood count, signs of infection.
Popular Combinations
Teriflunomide is typically used as monotherapy in MS. Combination therapy with other MS disease-modifying therapies is not routinely recommended due to the limited data on efficacy and increased potential for adverse effects.
Precautions
- Monitor liver function regularly.
- Monitor blood pressure.
- Evaluate for infections promptly.
- Ensure strict adherence to contraception in women of childbearing potential.
- Accelerated elimination procedure may be needed in cases of pregnancy or toxicity.
- Caution in elderly patients.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Teriflunomide?
A: Adults and children >40kg: 14 mg orally once daily. Children ≤40kg: 7 mg orally once daily.
Q2: How does Teriflunomide work in MS?
A: It inhibits DHODH, reducing the proliferation of activated lymphocytes involved in the inflammatory process of MS.
Q3: What are the most common side effects?
A: Hair loss, nausea, diarrhea, elevated liver enzymes, paresthesia.
Q4: Is Teriflunomide safe during pregnancy?
A: No, it is contraindicated during pregnancy due to its teratogenic effects.
Q5: What are the major contraindications for using Teriflunomide?
A: Severe liver disease, pregnancy, breastfeeding, severe immunodeficiency.
A: It is minimally metabolized and does not involve CYP enzymes. It is eliminated mainly through biliary excretion.
Q7: Can Teriflunomide be used with other MS drugs?
A: Generally used as monotherapy. Combining with other MS drugs is not routinely recommended due to limited efficacy and safety data.
Q8: What monitoring is required during Teriflunomide therapy?
A: Regular liver function tests, blood pressure monitoring, complete blood counts, and vigilance for signs of infection.
Q9: How long does Teriflunomide stay in the body after discontinuation?
A: Teriflunomide has a long half-life (18-19 days), and it can take up to two years for it to be completely eliminated. An accelerated elimination procedure with cholestyramine or activated charcoal can be used to expedite removal if needed.
Q10: What should be done if a patient on Teriflunomide becomes pregnant?
A: Discontinue Teriflunomide immediately and start an accelerated elimination procedure. Inform the patient about the potential fetal risks and provide appropriate counseling. Referral to a specialist for further management is recommended.
