teriflunomide

(redirected from Aubagio)

teriflunomide

(ter-i-floo-noe-mide) ,

Aubagio

(trade name)

Classification

Therapeutic: anti multiple sclerosis agents
Pharmacologic: immune response modifiers
Pregnancy Category: X

Indications

Management of relapsing forms of multiple sclerosis (MS).

Action

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

Therapeutic effects

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

Pharmacokinetics

Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: >99%.
Metabolism and 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.

Time/action profile (decrease in disability progression)

ROUTEONSETPEAKDURATION
PO3–6 mounknownunknown

Contraindications/Precautions

Contraindicated in: Severe hepatic impairment;Concurrent leflunomide treatment;Live virus vaccinations;Active acute or chronic infection;Severe immunodeficiency, bone marrow disease or severe uncontrolled infection; Lactation: Discontinue teriflunomide or discontinue breast feeding; Obstetric: Pregnancy or woman with childbearing potential using unreliable contraception (may cause fetal harm).
Use Cautiously in: Pre-existing liver disease;Severe immunodeficiency, bone marrow disease or severe uncontrolled infection;Hypertension (treat appropriately prior); Geriatric: Age >60 yr, concurrent neurotoxic medications or diabetes mellitus (↑ risk of peripheral neuropathy); Obstetric: Women with child-bearing potential; Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Cardiovascular

  • hypertension

Respiratory

  • interstitial lung disease (rare) (life-threatening)

Gastrointestinal

  • hepatotoxicity (life-threatening)
  • diarrhea (most frequent)
  • ↑ transaminases (most frequent)
  • nausea (most frequent)

Genitourinary

  • acute renal failure (urate nephropathy)

Dermatologic

  • severe skin reactions including stevens-johnson syndrome and toxic epidermal necrolysis
  • alopecia (most frequent)

Fluid and Electrolyte

  • hyperkalemia
  • hypophosphatemia

Hematologic

  • leukopenia
  • neutropenia
  • thrombocytopenia

Neurologic

  • paresthesia (most frequent)
  • peripheral neuropathy

Miscellaneous

  • atypical infections, including Latent tuberculosis (life-threatening)
  • influenza (most frequent)

Interactions

Drug-Drug interaction

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 ethinylestradiol 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 tolive virus vaccines.

Route/Dosage

Oral (Adults) 7 or 14 mg once daily.

Availability

Film-coated tablets: 7 mg, 14 mg

Nursing implications

Nursing assessment

  • Assess BP before starting and periodically during therapy. Treat hypertension as needed.
  • Lab Test Considerations: Monitor liver function tests (transaminases, bilirubin) within 6 months 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.
    • Obtain a pregnancy test from female patients prior to beginning therapy.
    • Monitor CBC with platelet count within 6 months prior to starting and periodically during therapy based on signs and symptoms of infection. Mean decrease in WBC occurs during first 6 wks and remains low during therapy.
    • Monitor INR closely in patients taking warfarin, a decrease in warfarin peak may occur.

Potential Nursing Diagnoses

Impaired physical mobility (Indications)

Implementation

  • Administer a tuberculin skin test prior to administration of teriflunomide. Patients with active latent TB should be treated for TB prior to therapy.
  • Oral: Administer once daily without regard to food.
  • Drug Elimination Procedure: 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.

Patient/Family Teaching

  • 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.
  • Advise patient that teriflunomide is teratogenic. 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, accelerated eliminated procedure may be used to decrease blood levels more rapidly. Male patients with female partner 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 years. Females of childbearing potential are recommended to undergo accelerated elimination procedure upon discontinuation of teriflunomide. 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.

Evaluation/Desired Outcomes

  • Decrease in the number of MS flares (relapses) and slowing of physical problems caused by MS.
References in periodicals archive ?
Even as Sanofi / Genzyme's Aubagio nears a potential launch later this summer, physician awareness and interest in Biogen Idec's BG-12 remains higher than most other DMAs in development, including Aubagio.
A separate Phase II trial focused exclusively on cognition utilizing Trimesta with a variety of currently marketed MS drugs, including Copaxone, Avonex, Betaseron, Extavia, Rebif, Gilenya, Aubagio and Tecfidera, is currently enrolling patients at four sites in the United States.
Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that, for the treatment of multiple sclerosis, more than 85 percent of surveyed neurologists in the EU5 (France, Germany, Italy, Spain and the United Kingdom) expect to prescribe three late-stage emerging disease-modifying therapies (DMTs)--Biogen Idec's BG-12, Sanofi/Genzyme's Aubagio and Sanofi/Genyzme/Bayer HealthCare's Lemtrada--assuming that all three drugs successfully launch.
CHAPTER 6 SMALL MOLECULE MS DRUGS 64 MARKET OVERVIEW 64 TABLE 17 GLOBAL MARKET FOR SMALL MOLECULE MS DISEASE-MODIFYING DRUGS BY INDIVIDUAL DRUG, THROUGH 2018 ($ MILLIONS) 64 SMALL MOLECULE MS DISEASE-MODIFYING DRUGS 65 COPAXONE (GLATIRAMER ACETATE, COPOLYMER 1) 65 TABLE 18 COPAXONE PIVOTAL STUDY RESULTS 66 NOVANTRONE (MITOXANTRONE) 67 GILENYA (FINGOLIMOD, FTY720) 68 TABLE 19 GILENYA PIVOTAL PHASE III STUDY RESULTS 69 AUBAGIO (TERIFLUNOMIDE) 70 TABLE 20 AUBAGIO PHASE III STUDY RESULTS FROM TEMSO AND TEMPO 70 TECFIDERA (DIMETHYL FUMARATE) 70 TABLE 21 TECFIDERA GLOBAL PHASE III CLINICAL PROGRAM 71 FIRATEGRAST (SB683699, T-0047) 72 SIPONIMOD (BAF312) 73 ONO-4641 73 ACT-128800 73 MASITINIB 74 TRIMESTA (ESTRIOL) 74 MN-166 75
Aubagio (teriflunamide), Dimethyl Fumarate (BG-12), Daclizumab, RG1594 (ocrelizumab) and Lamtrada (alemtuzumab) are the novel late stage pipeline products likely to enter the market through to 2019.
Current Neurologist-Reported Patient Share for Tecfidera Exceeds that of Genzyme's Aubagio and Novartis's Gilenya Combined, According to Findings from Decision Resources Group
Gilenya, Aubagio and Tecfidera, is focused exclusively on cognition and is currently enrolling patients at 4 sites in the United States.
Gilenya, the first novel drug in five years, is to be joined by three new products; BG-12 from Biogen Idec, Sanofi's Aubagio and Genzyme's Lemtrada.
Approximately one-quarter of neurologists believe that BG-12, Sanofi / Genzyme's Aubagio, or Teva's laquinimod, if successfully launched, would be most likely to replace Gilenya.
Sanofi manufactures medications like Auvi Q for emergency treatment of allergic reactions, Aubagio for multiple sclerosis, Plavix for atherothrombosis, Clexane for thrombosis, Kynamro for homozygous familial hypercholesterolemia and approved for hypertension.
Information from Copaxone prescribing information (Teva Neuroscience, 2009), Avonex prescribing information (Biogen Idec, 2008), Rebif prescribing information (EMD Serono, 2009), Betaseron prescribing information (Bayer HealthCare Pharmaceuticals, 2010), Extavia prescribing information (Novartis Pharmaceuticals Corporation, 2012), Tecfidera prescribing information (Biogen Idec, 2013), Gilenya prescribing information (Novartis Pharmaceuticals Corporation, 2011), Tysabri prescribing information (Biogen Idec, 2011), Novantrone prescribing information (EMD Serono, 2012), and Aubagio prescribing information (Genzyme Corp.