Teriflunomide (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- AUBAGIO
- TERIFLUNOMIDE
Boxed Warning
• Hepatotoxicity Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with teriflunomide in the postmarketing setting [see Warnings and Precautions (5.1)]. Concomitant use of teriflunomide with other hepatotoxic drugs may increase the risk of severe liver injury. Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide tablets therapy. Monitor ALT levels at least monthly for six months after starting teriflunomide tablets [see Warnings and Precautions (5.1)]. If drug induced liver injury is suspected, discontinue teriflunomide tablets and start an accelerated elimination procedure with cholestyramine or charcoal [see Warnings and Precautions (5.3)]. Teriflunomide tablets are contraindicated in patients with severe hepatic impairment [see Contraindications (4)]. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking teriflunomide tablets. • Embryofetal Toxicity Teriflunomide tablets are contraindicated for use in pregnant women and in females of reproductive potential who are not using effective contraception because of the potential for fetal harm. Teratogenicity and embryolethality occurred in animals at plasma teriflunomide exposures lower than that in humans. Exclude pregnancy before the start of treatment with teriflunomide tablets in females of reproductive potential. Advise females of reproductive potential to use effective contraception during teriflunomide tablets treatment and during an accelerated drug elimination procedure after teriflunomide tablets treatment. Stop teriflunomide tablets and use an accelerated drug elimination procedure if the patient becomes pregnant [see Contraindications (4), Warnings and Precautions (5.2, 5.3), Use in Specific Populations (8.1, 8.3), and Clinical Pharmacology (12.3)].
Indications and Usage
Teriflunomide tablets are indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
Dosage and Administration
The recommended dose of teriflunomide tablet is 7 mg or 14 mg orally once daily. Teriflunomide tablets can be taken with or without food. Monitoring to Assess Safety Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide tablets therapy. Monitor ALT levels at least monthly for six months after starting teriflunomide tablets [see Warnings and Precautions (5.1)]. Obtain a complete blood cell count (CBC) within 6 months before the initiation of treatment with teriflunomide tablets. Further monitoring should be based on signs and symptoms of infection [see Warnings and Precautions (5.4)]. Prior to initiating teriflunomide tablets, screen patients for latent tuberculosis infection with a tuberculin skin test or blood test for mycobacterium tuberculosis infection [see Warnings and Precautions (5.4)]. Exclude pregnancy prior to initiation of treatment with teriflunomide tablets in females of reproductive potential [see Warnings and Precautions (5.2)]. Check blood pressure before start of teriflunomide tablets treatment and periodically thereafter [see Warnings and Precautions (5.10)].
Contraindications
Teriflunomide tablet is contraindicated in/with: ● Patients with severe hepatic impairment [see Warnings and Precautions (5.1)]. ● Pregnant women and females of reproductive potential not using effective contraception. Teriflunomide tablet may cause fetal harm [see Warnings and Precautions (5.2, 5.3) and Use in Specific Populations (8.1)]. ● Patients with a history of a hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in teriflunomide tablet. Reactions have included anaphylaxis, angioedema, and serious skin reactions [see Warnings and Precautions (5.5)]. ● Coadministration with leflunomide [see Clinical Pharmacology (12.3)].
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the prescribing information: • Hepatotoxicity [see Contraindications (4) and Warnings and Precautions (5.1)] • Bone Marrow Effects/Immunosuppression Potential/Infections [see Warnings and Precautions (5.4)] • Hypersensitivity Reactions [see Contraindications (4) and Warnings and Precautions (5.5)] • Serious Skin Reactions [see Warnings and Precautions (5.6)] • Drug Reaction with Eosinophilia and Systemic Symptoms [see Warnings and Precautions (5.7)] • Cutaneous or Mucocutaneous Ulcers and Impaired Wound Healing [see Warnings and Precautions (5.8)] • Peripheral Neuropathy [see Warnings and Precautions (5.9)] • Increased Blood Pressure [see Warnings and Precautions (5.10)] • Respiratory Effects [see Warnings and Precautions (5.11)] • Pancreatitis in Pediatric Patients [see Warnings and Precautions (5.12)]
Drug Interactions
Effect of Teriflunomide Tablets on CYP2C8 Substrates Teriflunomide is an inhibitor of CYP2C8 in vivo. In patients taking teriflunomide tablets, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3)]. Effect of Teriflunomide Tablets on Warfarin Coadministration of teriflunomide tablets with warfarin requires close monitoring of the international normalized ratio (INR) because teriflunomide tablets may decrease peak INR by approximately 25%. Effect of Teriflunomide Tablets on Oral Contraceptives Teriflunomide tablets may increase the systemic exposures of ethinylestradiol and levonorgestrel. Consideration should be given to the type or dose of contraceptives used in combination with teriflunomide tablets [see Clinical Pharmacology (12.3)]. Effect of Teriflunomide Tablets on CYP1A2 Substrates Teriflunomide may be a weak inducer of CYP1A2 in vivo. In patients taking teriflunomide tablets, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3)]. Effect of Teriflunomide Tablets on Organic Anion Transporter 3 (OAT3) Substrates Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking teriflunomide tablets, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3)]. Effect of Teriflunomide Tablets on BCRP and Organic Anion Transporting Polypeptide B1 and B3 (OATP1B1/1B3) Substrates Teriflunomide inhibits the activity of
Mechanism of Action
Teriflunomide, an immunomodulatory agent with anti-inflammatory properties, inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme involved in de novo pyrimidine synthesis. The exact mechanism by which teriflunomide exerts its therapeutic effect in multiple sclerosis is unknown but may involve a reduction in the number of activated lymphocytes in CNS.
Overdosage
There is no experience regarding teriflunomide overdose or intoxication in humans. Teriflunomide 70 mg daily up to 14 days was well tolerated by healthy subjects. In the event of clinically significant overdose or toxicity, cholestyramine or activated charcoal is recommended to accelerate elimination [see Warnings and Precautions (5.3)].