Dosing and uses of Aubagio (teriflunomide)
Adult dosage forms and strengths
tablet
- 7mg
- 14mg
Multiple Sclerosis
Indicated for treatment of relapsing forms of multiple sclerosis
7 mg or 14 mg PO qDay
Dosing Considerations
Gender: Drug clearance decreased by 23% in females compared with males
Requires regular monitoring to assess safety (see Cautions)
Administration
May be taken with or without food
Pediatric dosage forms and strengths
Safety and efficacy not established
Aubagio (teriflunomide) adverse (side) effects
>10%
Headache (19-22%)
Diarrhea (15-18%)
Increased ALT (12-14%)
Alopecia (10-13%)
Influenza (9-12%)
Nausea (9-14%)
Paresthesia (9-10%)
Phosphatemia (5-18%)
1-10%
URTI (9%)
Bronchitis (5-8%)
Upper abdominal pain (5-6%)
Sinusitis (4-6%)
Musculoskeletal pain (4-5%)
Hypertension (4%)
Toothache (4%)
Increased GGT (3-5%)
Anxiety (3-4%)
Myalgia (3-4%)
Pruritus (3-4%)
Blurred vision (3%)
Cystitis (2-4%)
Viral gastroenteritis (2-4%)
Oral herpes (2-4%)
Neutropenia (2-4%)
Increased AST (2-3%)
Seasonal allergy (2-3%)
Burning sensation (2-3%)
Palpitations (2-3%)
Decreased weight (2-3%)
Decreased neutrophil count (2-3%)
Sciatica (1-3%)
Conjunctivitis (1-3%)
Increased WBC (1-3%)
Acne (1-3%)
Carpal tunnel syndrome (1-3%)
Leukopenia (1-2%)
Abdominal distention (1-2%)
<1%
Cardiovascular death (0.25%)
Postmarketing Reports
Hypersensitivity reactions
Severe skin reactions (including toxic epidermal necrolysis and Stevens-Johnson syndrome)
Thrombocytopenia
Interstitial lung disease
Pancreatitis
Warnings
Black box warnings
Hepatotoxicity: severe liver injury including fatal liver failure has been reported with other drugs in class; monitor liver enzymes monthly for 6 months and discontinue if liver injury is suspected
Risk of teratogenicity: animal data shows major birth defects if used during pregnancy; contraindicated in women of child bearing potential who are not using reliable contraception
Contraindications
Hypersensitivity
Severe hepatic impairment
Pregnancy
Current leflunomide treatment
Cautions
Severe liver injury including fatal liver failure and dysfunction have been reported in patients treated with leflunomide; similar risk to be expected
Use with caution in patients with pre-existing liver dysfunction; monitor liver enzymes routinely
May take an average of 8 months to clear drug from plasma; consider accelerated elimination with cholestyramine or activated charcoaL
Decreases in white blood cell count and platelet count have been observed
Not recommended for patients with serious immunodeficiency; do not initiate treatment in patients with active acute or chronic infections
Peripheral neuropathy, including polyneuropathy and mononeuropathy have been reported; evaluate patient and consider discontinuing therapy
May cause an increases in renal uric acid clearance and decreases in serum uric acid
Use caution in hyperkalemia
Anaphylaxis and severe allergic reactions reported; signs and symptoms have included dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue.
Cases of serious skin reactions, including cases of Stevens-Johnson syndrome (SJS) and a fatal case of toxic epidermal necrolysis (TEN), reported
Very rare cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) reported In patients treated with leflunomide, the parent compound
May increase blood pressure; measure blood pressure at treatment initiation and monitor blood pressure during treatment
Interstitial lung disease, including acute interstitial pneumonitis, reported; use with caution in patients with pre-existing respiratory conditions; monitor for new or worsening respiratory symptoms
May decrease WBC; a recent CBC should be available before starting teriflunomide; monitor for signs and symptoms of infection; consider suspending treatment with teriflunomide in case of serious infection; do not start teriflunomide in patients with active infections
Pregnancy and lactation
Pregnancy category: X
Teratogenic; may cause major birth defects
Lactation: detected in rat milk after single dose administration; may cause growth abnormalities; avoid use
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Aubagio (teriflunomide)
Mechanism of action
Tetrapeptide epoxyketone proteasome inhibitor that irreversibly binds to the N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome; has antiproliferative and proapoptotic activities in vitro in solid and hematologic tumor cells
Absorption
Peak plasma time: 1-4 hr
Distribution
Protein Bound: 99%
Vd: 11 L
Metabolism
Primary biotransformation to minor (inactive) metabolites by hydrolysis
Secondary pathways: oxidation, N-acetylation, sulfate conjugation
CYP2C8 inihibitor; CYP1A2 inducer
Elimination
Total body clearance: 30 mL/hr
