teriflunomide

Absorption: Well absorbed following oral administration.

Distribution: Well distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Metabolized via hydrolysis to inactive metabolites. 38% excreted in feces; 23% excreted in urine.

Half-Life: 18–19 days.

Time/Action Profile ⬆ ⬇

(↓ in disability progression)

ROUTE	ONSET	PEAK	DURATION
PO	3–6 mo	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to teriflunomide or leflunomide;
Severe hepatic impairment
;
Concurrent use of leflunomide;
Live-virus vaccinations;
Active acute or chronic infection;
Rep:
Women of reproductive potential not using effective contraception
;
OB:
Pregnancy
;
Lactation: Lactation.

Use Cautiously in:

Mild or moderate hepatic impairment
;
Severe immunodeficiency, bone marrow disease, or severe uncontrolled infection;
Concurrent use of neurotoxic medications or diabetes mellitus (↑ risk of peripheral neuropathy);
Hypertension (control before therapy is initiated);
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.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension

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

F and E: hyperkalemia, hypophosphatemia

GI: ↑liver enzymes, diarrhea, nausea, HEPATOTOXICITY

GU: acute renal failure (urate nephropathy)

Hemat: leukopenia, neutropenia, thrombocytopenia

Neuro: paresthesia, peripheral neuropathy

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

Interactions ⬆ ⬇

Drug-drug:

May ↑ levels and risk of toxicity of CYP2C8 substrates, including paclitaxel, pioglitazone, and repaglinide.
May ↓ levels and effectiveness of CYP1A2 substrates, including alosetron, duloxetine, theophylline, 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 risk of toxicity 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.
Breast cancer resistant protein inhibitors, including cyclosporine, eltrombopag, and gefitinib, may ↑ levels and risk of toxicity.

Route/Dosage ⬆ ⬇

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

Availability ⬆ ⬇

(Generic available)

Film-coated tablets: 7 mg; 14 mg

Assessment ⬆ ⬇

Assess BP before starting and periodically during therapy. Treat hypertension as needed.
Assess for rash periodically during therapy. May cause SJS or TEN. Discontinue teriflunomide if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, 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.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Monitor liver function tests (transaminases, bilirubin) within 6 mo before starting therapy and monthly thereafter for at least the 1st 6 mo. Do not administer if ALT >2 times upper limit of normal (ULN). Consider discontinuing therapy if serum transaminases ↑ >3 times ULN. Monitor serum transaminases 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 within 6 mo before starting and periodically during therapy based on signs and symptoms of infection. Mean ↓ in WBC occurs during 1st 6 wk and remains low during therapy.
- Monitor INR closely in patients taking warfarin.

Implementation ⬆ ⬇

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: Women of reproductive potential who either wish to become pregnant or become pregnant during therapy and men who want to father a child must discontinue 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 every 8 hr for 11 days. If cholestyramine 8 g regimen is not well tolerated, cholestyramine 4 g every 8 hr can be used; or (2) Administer 50 g of 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 two separate tests ≥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 provider promptly if symptoms of severe allergic reactions, liver problems (nausea, vomiting, stomach pain, ↓ appetite, tiredness, yellowing of skin or whites of eyes, 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 provider 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 provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
Instruct patient to avoid vaccinations with live vaccines during and following therapy without consulting health care provider.
Discuss the possibility of hair loss with patient. Explore methods of coping.
Rep:
May cause fetal harm. Advise women of reproductive potential and male patients with female partners of reproductive potential to use effective birth control during therapy and until levels of teriflunomide <0.02 mg/L. If pregnancy is planned or suspected or if breastfeeding, notify health care provider immediately; an accelerated elimination procedure may be used to ↓ levels more rapidly. Women of reproductive potential are also recommended to undergo accelerated elimination procedure on discontinuation of therapy. Inform patient of pregnancy safety surveillance program that monitors pregnancy outcomes in women exposed to teriflunomide. Encourage to report pregnancy by calling 1-800-745-4447, option 2. Advise patient to avoid breastfeeding during therapy.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇