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leflunomide (Rx)Brand and Other Names:Arava

 
 
 

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 10mg
  • 20mg
  • 100mg
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Rheumatoid Arthritis

100 mg PO qDay for 3 day initially, THEN 10-20 mg PO qDay

Discontinuing leflunomide

  • 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

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Interactions

Interaction Checker

leflunomide and

No Results

     
     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Diarrhea (17%)

            Respiratory infections (15%)

            1-10% (selected)

            Alopecia (10%)

            Hypertension (10%)

            Rash (10%)

            Nausea (9%)

            Bronchitis (7%)

            Headache (7%)

            Abdominal pain (5%)

            Abnormal LFT's (5%)

            Accidental injury (5%)

            Back pain (5%)

            Dyspepsia (5%)

            UTI (5%)

            Dizziness (4%)

            Infection (4%)

            Joint disorder (4%)

            Pruritus (4%)

            Weight loss (4%)

            Anorexia (3%)

            Cough (3%)

            Gastroenteritis (3%)

            Pharyngitis (3%)

            Stomatitis (3%)

            Tenosynovitis (3%)

            Vomiting (3%)

            Weakness (3%)

            Allergic reaction (2%)

            Chest pain (2%)

            Dry skin (2%)

            Eczema (2%)

            Pain (2%)

            Paresthesia (2%)

            Pneumonia (2%)

            Rhinitis (2%)

            Sinusitis (2%)

            Synovitis (2%)

            Postmarketing Reports

            Body as a whole: Opportunistic infections, severe infections including sepsis that may be fatal

            Gastrointestinal: Pancreatitis

            Hematologic: Agranulocytosis, leukopenia, neutropenia, pancytopenia, thrombocytopenia

            Hypersensitivity: Angioedema

            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

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            Warnings

            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

            Contraindications

            Pregnancy, women of childbearing potential (unless contraception used)

            Liver disease, hepatitis B/C seropositive

            Active serious infections

            Hypersensitivity

            Concomitant live virus vaccines

            Cautions

            Risk of hepatotoxicity (see Black Box Warnings)

            Embryotoxic

            Myelosuppressive

            Potential increase risk for malignancy

            Renal/hepatic impairment

            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

            Severe immunodeficiency

            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

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            Pregnancy & Lactation

            Pregnancy Category: X

            Lactation: not known if excreted in breast milk

            Pregnancy Categories

            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.

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            Pharmacology

            Mechanism of Action

            Not fully understood

            Metabolite inhibits pyrimidine nucleotide synthesis; antiproliferative for T-cells

            Absorption

            Bioavailability: 80%

            Peak plasma time: 6-12 hr

            Detectable for up to 2 years

            Distribution

            Protein bound: >99%

            Vd: 0.13 L/kg

            Metabolism

            GI mucosa, liver

            Metabolites: A77 1726 (active)-undergoes hepatic recirculation

            Elimination

            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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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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