ter-i-FLOO-noe-mide

• Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

• Inhibits an enzyme required for pyrimidine synthesis; has antiproliferative and anti-inflammatory effects.

• ↓incidence and severity of relapses in MS, with a decrease in disability progression.

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Eliminated via biliary excretion of unchanged drug with renal excretion of metabolites (37.5 in feces and 22.6% in urine), some metabolism occurs.

Half-life: 18–19 days.

Contraindicated in:

• Hypersensitivity to teriflunomide or leflunomide
• Severe hepatic impairment
• Concurrent leflunomide treatment
• Live virus vaccinations
• Active acute or chronic infection
• Severe immunodeficiency, bone marrow disease or severe uncontrolled infection
• Rep: Women of reproductive potential not using effective contraception.
• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• Pre-existing liver disease
• Severe immunodeficiency, bone marrow disease or severe uncontrolled infection
• Concurrent use of neurotoxic medications or diabetes mellitus (↑ risk of peripheral neuropathy)
• Hypertension (treat appropriately prior)
• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children
• Geri: ↑risk of peripheral neuropathy in older adults.

CV: hypertension.

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), alopecia.

F and E: hyperkalemia, hypophosphatemia.

GI: HEPATOTOXICITY, diarrhea, ↑transaminases, nausea.

GU: acute renal failure (urate nephropathy).

Hemat: leukopenia, neutropenia, thrombocytopenia.

Neuro: paresthesia, peripheral neuropathy.

Resp: INTERSTITIAL LUNG DISEASE (RARE).

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS, ANGIOEDEMA, AND URTICARIA), INFECTION (INCLUDING LATENT TB AND VIRAL INFECTIONS).

Drug-Drug:

• May ↑ levels and effects of drugs metabolized by the CYP2C8 enzyme system including paclitaxel, pioglitazone, repaglinide, and rosiglitazone.
• May ↓ levels and effectiveness of drugs metabolized by the CYP1A2 enzyme system including alosetron, duloxetine, thoephylline, and tizanidine.
• May ↓ response to and ↑ risk of adverse reactions from live vaccines (avoid live vaccinations and consider long half-life of teriflunomide before administering).
• May ↑ levels and effects of ethinyl estradiol and levonorgestrel.
• May ↑ risk of bleeding with warfarin.
• ↑risk of additive immunosuppression with other immunosuppressants or antineoplastics (consider long half-life of teriflunomide).
• Levels and effects may be ↑ by breast cancer resistant protein (BCRP) inhibitors including cyclosporine, eltrombopag, and gefitinib.
• May alter response to warfarin.
• May ↑ risk of adverse reactions and ↓ antibody response to live virus vaccines.

• PO (Adults): 7 mg once daily or 14 mg once daily.

• Administer a tuberculin skin test prior to administration of teriflunomide. Patients with active latent TB should be treated for TB prior to therapy.
• PO: Administer once daily without regard to food.
• Drug Elimination Procedure: Females of reproductive potential who wish to become pregnant, females who become pregnant during therapy and males who want to father a child must continue teriflunomide and go through one of the drug elimination procedures. Either of the following procedures is recommended to achieve nondetectable plasma levels <0.02 mg/L after stopping treatment with teriflunomide. 1) Administer cholestyramine 8 g 3 times daily (every 8 hrs) for 11 days. If cholestyramine 8 g is not well tolerated, cholestyramine 4 g 3 times/day can be used. or 2) Administration of 50 g oral activated charcoal powder every 12 hr for 11 days. (Days do not need to be consecutive unless rapid lowering of levels is desired.) Verify plasma levels <0.02 mg/L by 2 separate tests at least 14 days apart. Plasma levels may take up to 2 yr to reach nondetectable levels without drug elimination procedure.

Aubagio

Therapeutic Classification: anti-multiple sclerosis agents

Pharmacologic Classification: immune response modifiers, pyrimidine synthesis inhibitors

(Generic available)

• Film-coated tablets: 7 mg; 14 mg;

(decrease in disability progression)

• Assess BP before starting and periodically during therapy. Treat hypertension as needed.
• Assess for rash periodically during therapy. May cause SJS or TEN. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
• Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy and/or facial swelling, eosinophilia, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection). Discontinue teriflunomide if DRESS is confirmed.

• Verify negative pregnancy test before starting therapy.Monitor liver function tests (transaminases, bilirubin) within 6 mo of starting therapy and monthly after teriflunomide therapy begins. Do not administer if ALT >2 × upper limit of normal. Consider discontinuing therapy if serum transaminase ↑ >3 × upper limit of normal is confirmed. Monitor serum transaminase and bilirubin in patients with symptoms of liver dysfunction. If liver injury is suspected, discontinue teriflunomide, begin accelerated elimination procedure, and monitor liver function tests weekly until normal.
  • Monitor CBC with platelet count within 6 mo prior to starting and periodically during therapy based on signs and symptoms of infection. Mean decrease in WBC occurs during first 6 wk and remains low during therapy.
  • Monitor INR closely in patients taking warfarin, a decrease in warfarin peak may occur.

• Instruct patient to take teriflunomide as directed. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
• Advise patient to notify health care professional promptly if symptoms of liver problems (nausea, vomiting, stomach pain, loss of appetite, tiredness, skin or whites of eyes yellowing, dark urine), serious skin problems (redness or peeling), infection (fever, tiredness, body aches, chills, nausea, vomiting), or interstitial lung disease (cough, dyspnea, with or without fever) occur.
• Instruct patient to notify health care professional if symptoms of peripheral neuropathy (numbness and tingling in hands and feet different from symptoms of MS), kidney problems (flank pain), high potassium level (nausea or racing heartbeat), or high BP occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Instruct patient to avoid vaccinations with live vaccines during and following therapy without consulting health care professional.
• Discuss the possibility of hair loss with patient. Explore methods of coping.
• Rep: May cause fetal harm. Effective birth control should be used during therapy and until blood levels of teriflunomide are low enough. If pregnancy is planned or suspected, or if breast feeding notify health care professional immediately, an accelerated eliminated procedure may be used to decrease blood levels more rapidly. Male patients with female partner of reproductive potential who plans to become pregnant may also use this method. If female partner does not plan to become pregnant, use effective birth control until blood levels are low enough; may require 2 yr. Females of reproductive potential are recommended to undergo accelerated elimination procedure upon discontinuation of teriflunomide. Inform patient of pregnancy exposure registry that monitors pregnancy outcomes in women exposed to teriflunomide during pregnancy. Patients who become pregnant should be encouraged to enroll in the Aubagio Pregnancy Registry at 1-800-745-4447 to collect information about mother and baby's health. Advise patient to avoid breastfeeding during therapy.

• Decrease in the number of MS flares (relapses) and slowing of physical problems caused by MS.

NDC Code^*

• 58468- Genzyme Corporation
  • 58468-0210- Aubagio
    • 58468-0210-1- 1 BLISTER PACK in 1 CARTON (58468-0210-1) > 5 TABLET, FILM COATED in 1 BLISTER PACK

• 58468- Genzyme Corporation
  • 58468-0210- Aubagio
    • 58468-0210-2- 2 BLISTER PACK in 1 CARTON (58468-0210-2) > 14 TABLET, FILM COATED in 1 BLISTER PACK

• 58468- Genzyme Corporation
  • 58468-0210- Aubagio
    • 58468-0210-3- 1 BLISTER PACK in 1 CARTON (58468-0210-3) > 5 TABLET, FILM COATED in 1 BLISTER PACK

• 58468- Genzyme Corporation
  • 58468-0210- Aubagio
    • 58468-0210-4- 1 BOTTLE in 1 CARTON (58468-0210-4) > 30 TABLET, FILM COATED in 1 BOTTLE

• 58468- Genzyme Corporation
  • 58468-0211- Aubagio
    • 58468-0211-1- 2 BLISTER PACK in 1 CARTON (58468-0211-1) > 14 TABLET, FILM COATED in 1 BLISTER PACK

• 58468- Genzyme Corporation
  • 58468-0211- Aubagio
    • 58468-0211-2- 1 BLISTER PACK in 1 CARTON (58468-0211-2) > 5 TABLET, FILM COATED in 1 BLISTER PACK

• 58468- Genzyme Corporation
  • 58468-0211- Aubagio
    • 58468-0211-3- 1 BLISTER PACK in 1 CARTON (58468-0211-3) > 5 TABLET, FILM COATED in 1 BLISTER PACK

• 58468- Genzyme Corporation
  • 58468-0211- Aubagio
    • 58468-0211-4- 1 BOTTLE in 1 CARTON (58468-0211-4) > 30 TABLET, FILM COATED in 1 BOTTLE

• 69238- Amneal Pharmaceuticals NY LLC
  • 69238-1303- Teriflunomide
    • 69238-1303-2- 2 BLISTER PACK in 1 CARTON (69238-1303-2) > 14 TABLET, FILM COATED in 1 BLISTER PACK

• 69238- Amneal Pharmaceuticals NY LLC
  • 69238-1303- Teriflunomide
    • 69238-1303-6- 28 TABLET, FILM COATED in 1 BOTTLE (69238-1303-6)

• 69238- Amneal Pharmaceuticals NY LLC
  • 69238-1304- Teriflunomide
    • 69238-1304-2- 2 BLISTER PACK in 1 CARTON (69238-1304-2) > 14 TABLET, FILM COATED in 1 BLISTER PACK

• 69238- Amneal Pharmaceuticals NY LLC
  • 69238-1304- Teriflunomide
    • 69238-1304-6- 28 TABLET, FILM COATED in 1 BOTTLE (69238-1304-6)

• 69539- MSN LABORATORIES PRIVATE LIMITED
  • 69539-032- Teriflunomide
    • 69539-032-41- 2 BLISTER PACK in 1 CARTON (69539-032-41) > 14 TABLET, FILM COATED in 1 BLISTER PACK

• 69539- MSN LABORATORIES PRIVATE LIMITED
  • 69539-033- Teriflunomide
    • 69539-033-41- 2 BLISTER PACK in 1 CARTON (69539-033-41) > 14 TABLET, FILM COATED in 1 BLISTER PACK