Teriflunomide

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• medications that stop an enzyme called BCRP such as cyclosporine (Gengraf, Neoral, Sandimmune), eltrombopag (Promacta), gefitinib (Iressa)
• ethinylestradiol and levonorgestrel (such as Climara, Daysee, Seasonique, Quartette, Seasonale)
• medications that use an enzyme CYP2C8 such as amiodarone (Cordarone), cabazitaxel (Jevtana), carbamazepine (Tegretol), chloroquine (Aralen), diclofenac (Voltaren), ibuprofen (Advil), paclitaxel (Taxol), rosiglitazone (Avandia), repaglinide (Prandin), treprostinil (Tyvaso)
• medications that use the enzyme CYP1A2 such as alosetron (Lotronex), caffeine, clozapine (Clozaril), flutamide (Eulexin), frovatriptan (Frova), melatonin, mexiletine (Mexitil),  mirtazapine (Remeron), olanzapine (Zyprexa), ramelteon (Rozerem), rasagiline (Azilect), ropinirole (Requip), tacrine (Cognex), theophylline, tizanidine (Zanaflex), triamterene (Dyrenium), zolmitriptan (Zomig)
• warfarin (Jantoven, Coumadin)

This is not a complete list of teriflunomide drug interactions. Ask your doctor or pharmacist for more information.

Take teriflunomide exactly as your doctor tells you to take it.

The usual dosage for teriflunomide is 7 mg or 14 mg by mouth once daily, with or without food.

• Store teriflunomide at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep teriflunomide and all medicines out of reach of children.

Hepatotoxicity

Severe liver injury including fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. Concomitant use of teriflunomide with other potentially hepatotoxic drugs may increase the risk of severe liver injury. Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide therapy. Monitor ALT levels at least monthly for six months after starting teriflunomide. If drug induced liver injury is suspected, discontinue teriflunomide and start an accelerated elimination procedure with cholestyramine or charcoal. Teriflunomide is contraindicated in patients with severe hepatic impairment. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking teriflunomide.

Risk of Teratogenicity

Based on animal data, teriflunomide may cause major birth defects if used during pregnancy. Pregnancy must be excluded before starting teriflunomide. teriflunomide is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Pregnancy must be avoided during teriflunomide treatment or prior to the completion of an accelerated elimination procedure after teriflunomide treatment

Avoid being near people who have colds, the flu, or other contagious illnesses. Contact your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using teriflunomide, and for at least 6 months after you stop taking it. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using teriflunomide and call your doctor at once if you have:

• fever, chills, swollen glands, easy bruising or bleeding, muscle weakness, nausea, vomiting, tired feeling;

• skin redness or peeling;

• numbness, tingling, or burning pain in your hands or feet;

• chest pain, new or worsening cough with fever, trouble breathing;

• high blood pressure--severe headache, blurred vision, pounding in your neck or ears, nosebleed, anxiety, irregular heartbeats;

• liver problems--upper stomach pain, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes); or

• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

• nausea, diarrhea;

• thinning hair; or

• abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Multiple Sclerosis:

7 mg or 14 mg orally once a day

Use: Treatment of patients with relapsing forms of multiple sclerosis.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• cholestyramine;

• methotrexate;

• rifampin;

• warfarin (Coumadin, Jantoven);

• birth control pills or hormone replacement therapy;

• cancer medicine;

• medicine to treat an autoimmune disorder such as rheumatoid arthritis, lupus, or psoriasis;

• medicines to prevent organ transplant rejection;

• cholesterol-lowering medication--atorvastatin, lovastatin, simvastatin, Crestor, Lipitor, Vytorin, Zocor, and others; or

• steroid medicine--dexamethasone, prednisone, and others.

This list is not complete. Other drugs may interact with teriflunomide, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Pyrimidine synthesis inhibitor with immunomodulatory and disease-modifying activity in multiple sclerosis.1 4 7

Not metabolized by CYP-450 or flavin monoamine oxidase enzymes.1

Inhibits CYP2C8 and weakly induces CYP1A2.1

Substrate of the efflux transporter breast cancer resistant protein (BCRP).1 Inhibitor of BCRP, organic anion transport protein (OATP) 1B1, and organic anion transporter 3 (OAT3).1

Drug interactions may continue to occur after patient no longer is receiving teriflunomide.1 17 18 May reduce risk by using an accelerated elimination procedure after discontinuance of therapy.1 (See Accelerated Elimination Procedures under Dosage and Administration.)

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

CYP2C8 substrates: Possible increased AUC and peak plasma concentrations of substrate; monitor patients during concurrent therapy.1

CYP1A2 substrates: Possible reduced AUC and peak plasma concentrations of substrate resulting in reduced efficacy; monitor patients during concurrent therapy.1

Hepatotoxic Agents

Possible increased risk of serious hepatotoxicity during concurrent use.1 Consider additional monitoring of liver function (see Hepatotoxicity under the Boxed Warning and also under Cautions).1

Neurotoxic Agents

Possible increased risk of peripheral neuropathy.1 (See Peripheral Neuropathy under Cautions.)

Specific Drugs

Storage

Oral

20–25°C (may be exposed to 15–30°C).1

Teriflunomide is used to treat the relapsing forms of multiple sclerosis (MS). teriflunomide will not cure MS, but it may slow some disabling effects and decrease the number of relapses of the disease.

teriflunomide is available only with your doctor's prescription.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time teriflunomide is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take teriflunomide or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to teriflunomide. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

ALT elevations >3 times ULN: Discontinue teriflunomide and initiate cholestyramine or activated charcoal to enhance elimination

Drug elimination procedure: To achieve nondetectable serum concentrations (<0.02 mg/L) of teriflunomide administer either of the following:

Cholestyramine: 8 g every 8 hours for 11 days. If not tolerated, may decrease to 4 g every 8 hours for 11 days. The 11 days do not need to be consecutive unless plasma concentrations need to be lowered rapidly.

or

Activated charcoal: 50 g every 12 hours for 11 days. The 11 days do not need to be consecutive unless plasma concentrations need to be lowered rapidly.

Note: Both treatments have successfully lead to >98% decrease in teriflunomide concentrations.

Severe liver injury, including fatal liver failure, has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. Concomitant use of teriflunomide with other potentially hepatotoxic drugs may increase the risk of severe liver injury. Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide therapy. Monitor ALT levels at least monthly for 6 months after starting teriflunomide. If drug-induced liver injury is suspected, discontinue teriflunomide and start an accelerated elimination procedure with cholestyramine or charcoal. Teriflunomide is contraindicated in patients with severe hepatic impairment. Patients with preexisting liver disease may be at an increased risk of developing elevated serum transaminases when taking teriflunomide.

Teriflunomide is contraindicated for use in pregnant women and in women 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 in females of reproductive potential. Advise females of reproductive potential to use effective contraception during teriflunomide treatment and during an accelerated drug elimination procedure after teriflunomide treatment. Stop teriflunomide and use an accelerated drug elimination procedure if the patient becomes pregnant.

CBC within 6 months of initiation and periodically thereafter based on signs/symptoms of infection; serum creatinine; serum transaminase and bilirubin within 6 months of initiation of therapy and monthly during the initial 6 months of treatment. In addition, monitor for signs/symptoms of severe infection, abnormalities in hepatic function tests, symptoms of hepatotoxicity, and blood pressure (baseline and periodically thereafter). Monitor hepatic function tests weekly until normalized in patients with suspected teriflunomide-induced hepatotoxicity. Screen for tuberculosis and pregnancy prior to therapy.

-Mild and moderate hepatic impairment: No adjustment recommended
-Severe hepatic impairment: Contraindicated