Generic Name

Aubagio

Mechanism

• Aubagio functions as a selective, non‑competitive inhibitor of dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine synthesis.
• By limiting pyrimidine production, it preferentially suppresses the proliferation of activated T and B lymphocytes while sparing resting immune cells, thereby mitigating the inflammatory cascade that drives RRMS.
• The drug’s active metabolite has a long terminal half‑life (~18–23 days), ensuring sustained immunomodulatory effects.

Pharmacokinetics

• Absorption: Rapid and dose‑dependent; peak plasma concentration (Cmax) reached in ≈2 h after a 14‑mg dose.
• Bioavailability: Not affected by food; absorption is ~50–70 %.
• Distribution: Highly protein‑bound (>95 %); penetrates the central nervous system, facilitating action on CNS‑infiltrating lymphocytes.
• Metabolism: Primarily hepatic via CYP2C19; metabolites are inactive.
• Elimination: Renal excretion of unchanged drug (~55 %) and metabolites (~35 %).
• Half‑life: ~18–23 days; steady state reached ~15 weeks.

Indications

• RRMS: Reduces relapse rate and MRI activity; improves disability progression.

Contraindications

• Pregnancy: Teriflunomide is teratogenic; contraindicated in pregnancy and requires pre‑pregnancy contraception for at least 6 months after cessation.
• Liver disease: Severe hepatic impairment (Child‑Pugh C) is contraindicated.
• Hypersensitivity: Known allergy to teriflunomide.
• Serious infections: Avoid in patients with active uncontrolled infections.

*Warnings*:
• Hepatotoxicity (↑ALT/AST, cholestasis).
• Severe leukopenia, pancytopenia.
• Pulmonary toxicity (rare, interstitial lung disease).

Dosing

1. Initial dose: 14 mg once daily (Day 1).
2. Maintenance: 7 mg once daily (Day 2 onward).
3. Administration: Oral, preferably with food to enhance absorption.
4. Per‑manence: No dose adjustment for age, weight, or renal/hepatic function (within limits).

> Clinical Tip: Store unused doses at ≤30 °C; avoid repeated dose changes to maintain steady DHODH inhibition.

Adverse Effects

• Common
• Headache
• Diarrhea
• Nausea
• Urticaria
• Serious
• Elevated liver enzymes (≥3× ULN) → discontinue.
• Severe leukopenia (/pancytopenia) → temporary hold.
• Interstitial lung disease (dyspnea, cough) → urgent evaluation.
• Hypersensitivity reactions (angioedema, anaphylaxis).

Monitoring

• Baseline: CBC, CMP, pregnancy test (female of childbearing potential), hepatitis B/C serology.
• Routine:
• CBC and CMP every 3 months for first year, then every 6 months.
• LFTs monthly for first 6 months, then every 3 months.
• Pulmonary auscultation annually; flag respiratory symptoms promptly.
• Pregnancy: Negative pregnancy test before each dose; counsel on emergency contraception.

Clinical Pearls

• Drug Removal: In pregnancy or emergency, use the accelerated elimination protocol (10 mg/kg IV cholestyramine + 20 mg/kg oral cholestyramine) to reduce serum teriflunomide to <0.2 µg/L in <10 days.
• Severe Infection Management: If a patient develops severe infection, hold dosing until recovery; consider prophylactic granulocyte‑colony stimulating factor if ANC < 0.5 × 10⁹/L.
• Cross‑disciplinary Use: While primarily indicated for RRMS, use in neuromyelitis optica spectrum disorders (NMOSD) is off‑label; current evidence limited.
• Patient Education: Emphasize importance of monthly LFT checks and prompt reporting of flu‑like symptoms or cough.
• Lab Tracking: Use labeled “Aubagio‑dose” cards to avoid confusion with other 7‑mg oral drugs.

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