Dosing & Uses
Dosage Forms & Strengths
100 mg PO qDay for 3 day initially, THEN 10-20 mg PO qDay
- Drug elimination process recommended to achieve nondetectable plasma levels (ie, <0.02 mg/L) after discontinuation
- Step 1: Administer cholestyramine 8 g PO TID 11 days; the 11 days do not need to be consecutive unless there is a need to lower the plasma level rapidly
- Step 2: Verify plasma levels <0.02 mg/L by 2 separate tests at least 14 days apart; if plasma levels >0.02 mg/L, consider additional cholestyramine treatment
- Without the drug elimination procedure, it may take up to 2 years to reach plasma M1 metabolite levels <0.02 mg/L due to individual variation in drug clearance
Safety and efficacy not established
Serious - Use Alternative
Significant - Monitor Closely
Respiratory infections (15%)
Abdominal pain (5%)
Abnormal LFT's (5%)
Accidental injury (5%)
Back pain (5%)
Joint disorder (4%)
Weight loss (4%)
Allergic reaction (2%)
Chest pain (2%)
Dry skin (2%)
Body as a whole: Opportunistic infections, severe infections including sepsis that may be fatal
Hematologic: Agranulocytosis, leukopenia, neutropenia, pancytopenia, thrombocytopenia
Hepatic: Hepatitis, jaundice/cholestasis, severe liver injury such as hepatic failure and acute hepatic necrosis that may be fatal
Respiratory: Interstitial lung disease, including interstitial pneumonitis and pulmonary fibrosis, which may be fatal
Nervous system: Peripheral neuropathy
Skin and appendages: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis including cutaneous necrotizing vasculitis, cutaneous lupus erythematosus, pustular psoriasis or worsening psoriasis; rare cases of drug reaction with eosinophilia and systemic symptoms (DRESS) reported
Black Box Warnings
Contraindicated in pregnancy
Do not use in pregnant women or in women of childbearing age who do not use reliable contraception
Avoid pregnancy during treatment and during the drug elimination period following treatment (ie, M1 metabolite <0.02 mcg/mL)
Severe liver injury
- 49 cases of severe liver injury identified, including 14 cases of fatal liver failure
- Do not use with pre-existing liver disease
- Do not use if elevated liver enzymes (ALT >2 X ULN)
- Coadministration with other drugs that cause liver injury increases risk
- Recommend ALT monitoring monthly for 6 months after initiating, and q6-8weeks thereafter
- If ALT rises to >3X ULN, interrupt therapy while investigating probable cause; if likely leflunomide-induced, initiate cholestyramine washout to speed elimination and conduct follow-up LFTs at least weekly until ALT value within normal range; if not leflunomide-induced ALT elevation, may consider resuming leflunomide
Pregnancy, women of childbearing potential (unless contraception used)
Liver disease, hepatitis B/C seropositive
Active serious infections
Concomitant live virus vaccines
Risk of hepatotoxicity (see Black Box Warnings)
Potential increase risk for malignancy
Rare cases of drug reaction with eosinophilia and systemic symptoms (DRESS) reported; discontinue therapy; a drug elimination procedure recommended
Co-administration of teriflunomide with leflunomide not recommended, as leflunomide is parent compound of teriflunomide
Peripheral neuropathy reported; most recover after discontinuing drug; risk factors include age >60 years, concomitant neurotoxic drugs, and diabetes
Interstitial lung disease (ILD) reported and has been associated with fatal outcomes; risk increased with prior history of ILD
Active metabolite A77 1726 has very long half-life and this should be considered when administering live vaccines or planning pregnancy; all women of childbearing potential are advised to receive cholestyramine 8 g TID x11 days to hasten elimination of A77 1726
If inadvertent pregnancy occurs discontinue immediately and call (877) 311-8972; cholestyramine may reduce risk to fetus
Stevens-Johnson syndrome and toxic epidermal necrolysis reported (rare)
Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate
Pregnancy & Lactation
Pregnancy Category: X
Lactation: not known if excreted in breast milk
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Mechanism of Action
Not fully understood
Metabolite inhibits pyrimidine nucleotide synthesis; antiproliferative for T-cells
Peak plasma time: 6-12 hr
Detectable for up to 2 years
Protein bound: >99%
Vd: 0.13 L/kg
GI mucosa, liver
Metabolites: A77 1726 (active)-undergoes hepatic recirculation
Half-life: 14-18 days
Clearance: 31 mL/hr
Renal elimination predominant during first 96 hr, thereafter fecal elimination predominates
Excretion: Feces 48%; urine: 43%
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