Aubagio Teriflunomide Tablets

1. Indications and Usage
Relapsing Forms of Multiple Sclerosis (MS):
Indicated for the treatment of adult and pediatric patients 10 years of age and older with relapsing forms of MS.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY. Can be taken with or without food.
Recommended Dosage:
Standard Dose: 7 mg or 14 mg once daily.
Note: The 14 mg dose provides no additional efficacy over the 7 mg dose in some populations but may increase the risk of adverse reactions.
Dose Adjustments:
Renal Impairment: No dosage adjustment is recommended for mild or moderate impairment. Use with caution in severe impairment.
Hepatic Impairment: Contraindicated in patients with severe hepatic impairment (Child-Pugh Class C).
Accelerated Elimination Procedure:
If serious toxicity occurs (e.g., severe infection, hepatotoxicity) or pregnancy is desired, an accelerated elimination procedure (using cholestyramine or activated charcoal) should be performed to rapidly reduce plasma concentrations.
3. Mechanism of Action
DHODH Inhibition:
Teriflunomide is a reversible inhibitor of dihydroorotate dehydrogenase (DHODH), a mitochondrial enzyme involved in the de novo synthesis of pyrimidines.
Selective Immunosuppression:
Rapidly proliferating T and B lymphocytes are dependent on de novo pyrimidine synthesis. By inhibiting DHODH, teriflunomide arrests the cell cycle at the G1 phase, thereby inhibiting the proliferation of these activated immune cells while largely sparing resting lymphocytes and their protective immune responses.
4. Safety and Warnings
Hepatotoxicity:
Teriflunomide can cause severe liver injury, including fatal liver failure. Liver function tests (ALT) must be monitored monthly for the first 6 months of treatment.
Teratogenicity and Embryo-Fetal Toxicity:
Boxed Warning: Teriflunomide can cause fetal harm. It is contraindicated in pregnancy. Female patients of reproductive potential and male patients with female partners of reproductive potential must use reliable contraception.
Peripheral Neuropathy:
Peripheral neuropathy (e.g., numbness, tingling) has been reported. If symptoms occur, discontinue treatment and consider accelerated elimination.
Serious Skin Reactions:
Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported.
Infections:
Increased risk of infections; screen for tuberculosis (TB) and hepatitis B (HBV) prior to initiation.
5. Adverse Reactions
Most Common (Incidence ≥5% and greater than placebo):
Nasopharyngitis, diarrhea, nausea, hair thinning (alopecia), influenza, back pain, and pain in extremities.
6. Drug Interactions
CYP2C8 Substrates:
Teriflunomide is an inhibitor of CYP2C8 and may increase exposure to drugs like repaglinide or paclitaxel.
CYP1A2 Substrates:
May decrease exposure to drugs like theophylline or caffeine.
Oral Contraceptives:
May increase ethinyl estradiol levels; monitor for side effects.
Warfarin:
May increase INR; monitor coagulation parameters closely.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Teriflunomide.
Available Strength: 7 mg and 14 mg tablets.
Appearance: 7 mg (Yellow, round) and 14 mg (Yellow, oval) film-coated tablets.
Storage: Store at 20°C to 25°C (68°F to 77°F).