Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.zoster vaccine recombinantMonitor Closely (1)leflunomide decreases effects of zoster vaccine recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce the effectiveness of zoster vaccine recombinant. >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; colitis, including microscopic colitis 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; pulmonary hypertension 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 Contraindications Pregnancy Hypersensitivity Severe hapatic impairment Current treatment with teriflunomide Cautions Hepatotoxicity reported (see Black Box Warnings) Vaccination with live vaccines not recommended Potential increase risk for malignancy Increase in blood pressure reported with therapy; check blood pressure before initiating therapy and periodically thereafter 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; if patient develops peripheral neuropathy, consider discontinuing and performing accelerated elimination procedure Interstitial lung disease (ILD) reported and has been associated with fatal outcomes; risk increased with prior history of ILD; if pulmonary symptoms worsen in patients with pre-exixting ILD, consider discontinuing therapy and performing accelerated drug elimination procedure Active metabolite 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 metabolite If inadvertent pregnancy occurs discontinue immediately and call (877) 311-8972; cholestyramine may reduce risk to fetus May cause immunosuppression; not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections; if a serious infection occurs, consider interrupting therapy and initiating accelerated drug elimination procedure Cases of tuberculosis reported in clinical studies; prior to initiating therapy, screen all patients for active and inactive (“latent”) tuberculosis infection as per commonly used diagnostic tests; drug not studied in patients with positive tuberculosis screen; safety in individuals with latent tuberculosis infection unknown; treat patients testing positive for tuberculosis with standard medical practice prior to therapy; monitor carefully during treatment for possible reactivation of infection Pancytopenia, agranulocytosis and thrombocytopenia reported with therapy; most frequently reported in patients who received concomitant treatment with methotrexate or other immunosuppressive agents, or who had recently discontinued these therapies; in some cases, patients had a prior history of a significant hematologic abnormality Perform white blood cell count and hemoglobin or hematocrit at baseline and monthly for six months following initiation of therapy and every 6-to 8 weeks thereafter; monitor monthly if administered concomitantly with methotrexate or other potential immunosuppressive agents; discontinue treatment if bone marrow suppression occurs in patients taking therapy and perform accelerated drug elimination procedure When decision is made to switch to another anti-rheumatic agent with potential for hematologic suppression, consider monitoring for hematologic toxicity as systemic exposure to both compounds may overlap Stevens-Johnson syndrome and toxic epidermal necrolysis reported (rare); discontinue therapy and perform accelerated drug elimination procedure 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 Accelerated elimination The active metabolite of leflunomide, teriflunomide, is eliminated slowly from plasma; use of accelerated drug elimination procedure will rapidly reduce plasma concentrations of leflunomide and active metabolite, teriflunomide Without use of accelerated drug elimination procedure, may take up to 2 years to reach plasma teriflunomide concentrations of less than 0.02 mg/L, the plasma concentration not associated with embryo-fetal toxicity in animals Consider accelerated elimination procedure at any time after discontinuation of therapy, and in particular, when patient has experienced a severe adverse reaction (eg, hepatotoxicity, serious infection, bone marrow suppression, Steven Johnson Syndrome, toxic epidermal necrolysis, peripheral neuropathy, interstitial lung disease), suspected hypersensitivity, or has become pregnant All women of childbearing potential recommended to undergo accelerated elimination procedure after stopping treatment Pregnancy A pregnancy exposure registry monitors pregnancy outcomes in women exposed to therapy during pregnancy; health care providers and patients are encouraged to report pregnancies by calling 1-877-311-8972 or visit http://www.pregnancystudies.org/participate-ina-study/ Drug is contraindicated for use in pregnant women because of potential for fetal harm; pregnancy exposure registry data are not available to inform presence or absence of drug-associated risk with use of drug during pregnancy Lowering plasma concentration of active metabolite, teriflunomide, by instituting an accelerated drug elimination procedure as soon as pregnancy is detected may decrease risk to fetus from therapy; the accelerated drug elimination procedure includes verification that plasma teriflunomide concentration is less than 0.02 mg/L Advise females to notify healthcare provider immediately if pregnancy occurs or is suspected during treatment; women receiving treatment who wish to become pregnant should discontinue drug and undergo an accelerated drug elimination procedure to achieve plasma teriflunomide concentrations < 0.02 mg/L (0.02 mcg/mL) Exclude pregnancy in females of reproductive potential before starting treatment Advise females of reproductive potential to use effective contraception during treatment and while undergoing a drug elimination procedure until verification that the plasma teriflunomide concentration is < 0.02 mg/L Animal data In animal reproduction studies, oral administration of leflunomide during organogenesis at a dose of 1/10 of and equivalent to maximum recommended human dose (MRHD) based on AUC, respectively in rats and rabbits, caused teratogenicity (rats and rabbits) and embryo-lethality (rats) Lactation Clinical lactation studies not conducted to assess presence of drug in human milk, effects on breastfed child, or on milk production; because of potential for serious adverse reactions in a breastfed infant, advise a nursing woman to discontinue breastfeeding during therapyPregnancy 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. 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% BRAND FORM. UNIT PRICE PILL IMAGE Arava oral- 20 mg tabletArava oral- 10 mg tabletleflunomide oral- 10 mg tabletleflunomide oral- 20 mg tabletleflunomide oral- 10 mg tabletleflunomide oral- 10 mg tabletleflunomide oral- 20 mg tabletleflunomide oral- 10 mg tabletleflunomide oral- 20 mg tabletleflunomide oral- 20 mg tabletleflunomide oral- 20 mg tabletleflunomide oral- 10 mg tabletleflunomide oral- 20 mg tabletleflunomide oral- 10 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationleflunomide oral LEFLUNOMIDE - ORAL (leh-FLEW-no-mide) COMMON BRAND NAME(S): Arava WARNING: Leflunomide must not be used during pregnancy because it may cause serious harm (possibly death) to an unborn baby. Women of childbearing age must have a negative pregnancy test before starting this medication. They must also use reliable forms of birth control before starting leflunomide, while taking it, and after stopping it until they have finished taking another drug that helps leflunomide leave the body and confirmed through 2 blood tests that the leflunomide levels are very low (see How to Use section). If you become pregnant or think you may be pregnant, inform your doctor right away (see Precautions section).This drug may rarely cause serious (possibly fatal) liver disease. Most cases occur within 6 months of taking this drug. If you already have liver disease (such as hepatitis B or C), leflunomide should not be used. Liver function (blood) tests must be performed periodically while taking leflunomide. Tell your doctor right away if you notice nausea/vomiting that doesn't stop, dark urine, light-colored stools, stomach/abdominal pain, yellowing eyes/skin. See Drug Interactions section. USES: This medication is used to treat rheumatoid arthritis, a condition in which the body's defense system (immune system) fails to recognize the body as itself and attacks the healthy tissues around the joints. Leflunomide helps to reduce the joint damage/pain/swelling and helps you to move better. It works by weakening your immune system and decreasing swelling (inflammation). HOW TO USE: Take this medication by mouth with or without food as directed by your doctor, usually once daily. Take this medication exactly as prescribed. You may be instructed to take a higher dose for the first 3 days of treatment.The dosage is based on your medical condition and response to treatment.Take this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time each day.After treatment is stopped, a different drug (cholestyramine) may be given as directed to help remove leflunomide from your body. This procedure is used if you need a rapid removal of the drug from your system (for example, if you are a female/male planning to have children, or suffering from severe side effects). Without the procedure, the drug may stay in your body for up to 2 years. Consult your doctor or pharmacist for more details.Tell your doctor if your symptoms last or get worse. SIDE EFFECTS: Diarrhea, nausea, and dizziness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: cough, numbness/tingling of hands/feet, hair loss, chest pain, fast/pounding heartbeat, increased thirst/urination, muscle cramp/pain, mental/mood changes, vision changes, easy bruising/bleeding, unusual growths/lumps, unexplained weight loss, unusual tiredness.This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.This medication may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. Get medical help right away if you have any signs of infection (such as sore throat that doesn't go away, fever, swollen lymph nodes, chills).A very serious allergic reaction to this drug is rare. However, get