arava
Pharmaranks rates Arava 3.5/5 for recall safety — an independent score from its FDA recall history and its manufacturer's record. Arava (Leflunomide) is an antirheumatic agent used to treat Rheumatoid Arthritis.
Leflunomide · by Sanofi Aventis US
Based on 1 source · Recall-safety score from FDA recall history — this product's own recalls and its manufacturer's record. Not an efficacy or quality rating. methodology →
Key facts
- Active ingredient
- Leflunomide
- Drug class
- Antirheumatic Agent
- Form
- Tablet
- Strength
- Leflunomide 100MG · Leflunomide 10MG · Leflunomide 20MG
- Type
- Prescription (Rx)
- Brand or generic
- Brand-name
- May treat
- rheumatoid arthritis
- Manufacturer
- Sanofi Aventis US
- What the pharmacy pays
- ~$9.44 for 30 — not your price
- FDA application
- NDA020905
- FDA boxed warning
- Yes — see the boxed warning
What is Arava?
From the FDA label:ARAVA (leflunomide) is a pyrimidine synthesis inhibitor. The chemical name for leflunomide is N-(4´-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide. It has an empirical formula C 12 H 9 F 3 N 2 O 2 , a molecular weight of 270.2 and the following structural formula: ARAVA is available for oral administration as tablets containing 10, 20, or 100 mg of active drug. Combined with leflunomide are the following inactive ingredients: colloidal silicon dioxide, crospovidone, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, povidone, starch, talc, titanium dioxide, and yellow ferric oxide (20 mg tablet only). Chemical Structure
How to use
Loading dosage for patients at low risk for ARAVA-associated hepatotoxicity and ARAVA-associated myelosuppression: 100 mg daily for 3 days. ( 2.1 ) Maintenance dosage: 20 mg daily. ( 2.1 ) Maximum recommended daily dosage: 20 mg once daily. ( 2.1 ) If 20 mg once daily is not tolerated, may decrease dosage to 10 mg once daily. ( 2.1 ) Screen patients for active and latent tuberculosis, pregnancy test (females), blood pressure, and laboratory tests before starting ARAVA. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of ARAVA is 20 mg once daily. Treatment may be initiated with or without a loading dose, depending upon the patient's risk of ARAVA-associated hepatotoxicity and ARAVA-associated myelosuppression. The loading dose provides steady-state concentrations more rapidly. For patients who are at low risk for ARAVA-associated hepatotoxicity and ARAVA-associated myelosuppression, the recommended ARAVA loading dose is 100 mg once daily for 3 days. Subsequently administer 20 mg once daily. For patients at high risk for ARAVA-associated hepatotoxicity (e.g., those taking concomitant methotrexate) or ARAVA-associated myelosuppression (e.g., patients taking concomitant immunosuppressants), the recommended ARAVA dosage is 20 mg once daily without a loading dose [see Warnings and Precautions (5.2 , 5.4) ] . The maximum recommended daily dose is 20 mg once per day. Consider…
Side effects
The following serious adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions (5.2) ] Immunosuppression [see Warnings and Precautions (5.4) ] Bone marrow suppression [see Warnings and Precautions (5.4) ] Serious infections [see Warnings and Precautions (5.4) ] Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reactions with eosinophilia and systemic symptoms [see Warnings and Precautions (5.5) ] Skin ulcers [see Warnings and Precautions (5.6) ] Peripheral neuropathy [see Warnings and Precautions (5.8) ] Interstitial lung disease [see Warnings and Precautions (5.9) ] The most commonly reported adverse reactions (≥10%) regardless of relation to ARAVA treatment were diarrhea, respiratory infection, nausea, headache, rash, abnormal liver enzymes, and dyspepsia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis U.S. LLC at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. In clinical studies (Trials 1, 2, and 3), 1,865 patients were treated with ARAVA administered as either monotherapy or in…
FDA Boxed Warning (the FDA’s most serious warning)
Boxed (black-box) warning — from the FDA label
EMBRYO-FETAL TOXICITY and HEPATOTOXICITY WARNING: EMBRYO-FETAL TOXICITY and HEPATOTOXICITY See full prescribing information for complete boxed warning. Embryo-Fetal Toxicity Teratogenicity and embryo-lethality occurred in animals administered leflunomide. ( 5.1 , 8.1 ) Exclude pregnancy prior to initiating ARAVA therapy. ( 5.1 , 8.3 ) Advise use of effective contraception in females of reproductive potential during treatment and during a drug elimination procedure. ( 5.1 , 5.3 , 8.3 ) Stop ARAVA and use an accelerated drug elimination procedure if the patient becomes pregnant. ( 5.1 , 5.3 , 8.1 ) Hepatotoxicity Severe liver injury and fatal liver failure have been reported. ( 5.2 ) Avoid ARAVA use in patients with pre-existing liver disease, or those with serum alanine aminotransferase (ALT) >2 × ULN. ( 5.2 , 8.6 ) Use caution when ARAVA is given with other potentially hepatotoxic drugs. ( 5.2 ) Monitor ALT levels. Interrupt ARAVA treatment if ALT elevation >3-fold ULN. If likely leflunomide-induced, start accelerated drug elimination procedure and monitor liver tests weekly until normalized. ( 5.2 , 5.3 ) Embryo-Fetal Toxicity ARAVA is contraindicated for use in pregnant women because of the potential for fetal harm. Teratogenicity and embryo-lethality occurred in animals administered leflunomide at doses lower than the human exposure level. Exclude pregnancy before the start of treatment with ARAVA in females of reproductive potential. Advise females of reproductive potential to use effective contraception during ARAVA treatment and during an accelerated drug elimination procedure after ARAVA treatment. Stop ARAVA and use an accelerated drug elimination procedure if the patient becomes pregnant [see Contraindications (4) , Warnings and Precautions (5.1 , 5.3) , Use in Specific Populations (8.1 , 8.3) ], and Clinical Pharmacology (12.3) ] . Hepatotoxicity Severe liver injury, including fatal liver failure, has been reported in patients treated with ARAVA. ARAVA is contraindicated in patients with severe hepatic impairment. Concomitant use of ARAVA with other potentially hepatotoxic drugs may increase the risk of liver injury. Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) >2 × ULN before initiating treatment, are at increased risk and should not be treated with ARAVA. Monitor ALT levels at least monthly for six months after starting ARAVA, and thereafter every 6 to 8 weeks. If leflunomide-induced liver injury is suspected, stop ARAVA treatment, start an accelerated drug elimination procedure, and monitor liver tests weekly until normalized [see Contraindications (4) , Warnings and Precautions (5.2 , 5.3) , Use in Specific Populations (8.6) ] .
Warnings
Important safety information
After stopping ARAVA, it is recommended that an accelerated drug elimination procedure be used to reduce the plasma concentrations of the active metabolite, teriflunomide. ( 5.3 ) Severe infections (including sepsis), pancytopenia, agranulocytosis, and thrombocytopenia: Stop ARAVA and use accelerated elimination procedure. Do not start ARAVA in patients with active infection. Monitor CBCs during treatment with ARAVA. ( 5.4 ) Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS): Stop ARAVA and use accelerated elimination procedure. ( 5.5 ) Skin ulcers: If skin ulcer is suspected, discontinue leflunomide treatment and consider an accelerated drug elimination procedure. ( 5.6 ) Peripheral neuropathy: If patient develops symptoms consistent with peripheral neuropathy, evaluate patient and consider discontinuing ARAVA. ( 5.8 ) Interstitial lung disease: May be fatal. New onset or worsening symptoms may necessitate discontinuation of ARAVA and initiation of accelerated elimination procedure. ( 5.9 ) Increased blood pressure: Monitor and treat. ( 5.11 ) 5.1 Embryo-Fetal Toxicity ARAVA may cause fetal harm when administered to a pregnant woman. Teratogenicity and embryo-lethality occurred in animal reproduction studies with leflunomide at doses lower than the human exposure level [see Use in Specific Populations (8.1) ] . ARAVA is contraindicated for use in pregnant women [see Contraindications (4) ] . Exclude pregnancy before starting treatment with ARAVA in females of reproductive potential [see Dosage and Administration (2.2) ] . Advise females of reproductive potential to use effective contraception during ARAVA treatment and during an accelerated drug elimination procedure after ARAVA treatment [see Use in Specific Populations (8.3) ] . If a woman becomes pregnant while taking ARAVA, stop treatment with ARAVA, apprise the patient of the potential risk to a fetus, and perform an accelerated drug elimination procedure to achieve nondetectable plasma concentrations of teriflunomide, the active metabolite of leflunomide [see Warnings and Precautions (5.3) ] . Upon discontinuing ARAVA, it is recommended that all females of reproductive potential undergo an accelerated drug elimination procedure. Women receiving ARAVA treatment who wish to become pregnant must discontinue ARAVA and undergo an accelerated drug elimination procedure, which includes verification that plasma concentrations of the active metabolite of leflunomide, teriflunomide, are less than 0.02 mg/L (0.02 mcg/mL). Based on animal data, human plasma concentrations of teriflunomide of less than 0.02 mg/L (0.02 mcg/mL) are expected to have minimal embryo-fetal risk [see Contraindications (4) , Warnings and Precautions (5.3) , and Use in Specific Populations (8.1) ] . 5.2 Hepatotoxicity Severe liver injury, including fatal liver failure, has been reported in some patients treated with ARAVA. Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) of greater than twice the upper limits of normal (>2 × ULN) before initiating treatment, should not be treated with ARAVA. Use caution when ARAVA is given with other potentially hepatotoxic drugs. Monitoring of ALT levels is recommended at least monthly for six months after starting ARAVA, and thereafter every 6 to 8 weeks. If ALT elevation >3-fold ULN occurs, interrupt ARAVA therapy and investigate the cause. If likely ARAVA-induced, perform the accelerated drug elimination procedure and monitor liver tests weekly until normalized [see Warnings and Precautions (5.3) ] . If ARAVA-induced liver injury is unlikely because some other cause has been found, resumption of ARAVA therapy may be considered. If ARAVA and methotrexate are given concomitantly, follow the American College of Rheumatology (ACR) guidelines for monitoring methotrexate liver toxicity with ALT, AST, and serum albumin testing. 5.3 Procedure for Accelerated Elimination of ARAVA and its Active Metabolite The active metabolite of leflunomide, teriflunomide, is eliminated slowly from the plasma [see Clinical Pharmacology (12.3) ] . Use of an accelerated drug elimination procedure will rapidly reduce plasma concentrations of leflunomide and its active metabolite, teriflunomide. Therefore, an accelerated elimination procedure should be considered at any time after discontinuation of ARAVA, and in particular, when a patient has experienced a severe adverse reaction (e.g., hepatotoxicity, serious infection, bone marrow suppression, Stevens-Johnson Syndrome, toxic epidermal necrolysis, peripheral neuropathy, interstitial lung disease), suspected hypersensitivity, or has become pregnant. It is recommended that all women of childbearing potential undergo an accelerated elimination procedure after stopping ARAVA treatment. Without use of an accelerated drug elimination procedure, it 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. Elimination can be accelerated by the following procedures: Administer cholestyramine 8 grams orally 3 times daily for 11 days. Alternatively, administer 50 grams of activated charcoal powder (made into a suspension) orally every 12 hours for 11 days. Verify plasma teriflunomide concentrations of less than 0.02 mg/L (0.02 µg/mL) by two separate tests at least 14 days apart. If plasma teriflunomide concentrations are higher than 0.02 mg/L, repeat cholestyramine and/or activated charcoal treatment. The duration of accelerated drug elimination treatment may be modified based on the clinical status and tolerability of the elimination procedure. The procedure may be repeated as needed, based on teriflunomide concentrations and clinical status. Use of the accelerated drug elimination procedure may potentially result in return of disease activity if the patient had been responding to ARAVA treatment. 5.4 Immunosuppression, Bone Marrow Suppression, and Risk of Serious Infections ARAVA is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections. If a serious infection occurs, consider interrupting ARAVA therapy and initiating the accelerated drug elimination procedure [see Warnings and Precautions (5.3) ] . Medications like ARAVA that have immunosuppression potential may cause patients to be more susceptible to infections, including opportunistic infections, especially Pneumocystis jirovecii pneumonia, tuberculosis (including extra-pulmonary tuberculosis), and aspergillosis. Severe infections including sepsis, which may be fatal, have been reported in patients receiving ARAVA, especially Pneumocystis jirovecii pneumonia and aspergillosis. Most of the reports were confounded by concomitant immunosuppressant therapy and/or comorbid illness which, in addition to rheumatoid arthritis, may predispose patients to infection. Cases of tuberculosis were observed in clinical studies with teriflunomide, the metabolite of ARAVA. Prior to initiating ARAVA, all patients should be screened for active and inactive ("latent") tuberculosis infection as per commonly used diagnostic tests. ARAVA has not been studied in patients with a positive tuberculosis screen, and the safety of ARAVA in individuals with latent tuberculosis infection is unknown. Patients testing positive in tuberculosis screening should be treated by standard medical practice prior to therapy with ARAVA and monitored carefully during ARAVA treatment for possible reactivation of the infection. Pancytopenia, agranulocytosis, and thrombocytopenia have been reported in patients receiving ARAVA alone. These events have been reported most frequently 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…
Who should not take Arava
ARAVA is contraindicated in: Pregnant women. ARAVA may cause fetal harm. If a woman becomes pregnant while taking this drug, stop ARAVA, apprise the patient of the potential hazard to the fetus, and begin a drug elimination procedure [see Warnings and Precautions (5.1 , 5.3) and Use in Specific Populations (8.1) ] . Patients with severe hepatic impairment [see Warnings and Precautions (5.2) ] . Patients with known hypersensitivity to leflunomide or any of the other components of ARAVA. Known reactions include anaphylaxis [see Adverse Reactions (6.1) ] . Patients being treated with teriflunomide [see Drug Interactions (7) ] . Pregnancy. ( 4 , 5.1 , 8.1 ) Severe hepatic impairment. ( 4 , 5.2 ) Hypersensitivity to ARAVA or any of its inactive components. ( 4 ) Current teriflunomide treatment. ( 4 )
Overdose — what happens if you take too much
There have been reports of chronic overdose in patients taking ARAVA at daily dose up to five times the recommended daily dose and reports of acute overdose in adults and children. Adverse events were consistent with the safety profile for ARAVA [see Adverse Reactions (6) ] . The most frequent adverse events observed were diarrhea, abdominal pain, leukopenia, anemia, and elevated liver function tests. In the event of a significant overdose or toxicity, perform an accelerated drug elimination procedure to accelerate elimination [see Warnings and Precautions (5.3) ] . Studies with both hemodialysis and CAPD (chronic ambulatory peritoneal dialysis) indicate that teriflunomide, the primary metabolite of leflunomide, is not dialyzable [see Clinical Pharmacology (12.3) ] .
U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.
Interactions
Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Drug interaction studies have been conducted with both ARAVA (leflunomide) and with its active metabolite, teriflunomide, where the metabolite was directly administered to the test subjects. Drugs metabolized by CYP2C8 and OAT3 transporters: Monitor patients because teriflunomide may increase exposure of these drugs. ( 7 ) Teriflunomide may increase exposure of ethinylestradiol and levonorgestrel. Choose an appropriate oral contraceptive. ( 7 ) Drugs metabolized by CYP1A2: Monitor patients because teriflunomide may decrease exposure of these drugs. ( 7 ) Warfarin: Monitor INR as teriflunomide may decrease INR. ( 7 ) Drugs metabolized by BCRP and OATP1B1/B3 transporters: Monitor patients because teriflunomide may increase exposure of these drugs. ( 7 ) Rosuvastatin: The dose of rosuvastatin should not exceed 10 mg once daily in patients taking ARAVA. ( 7 ) Effect of Potent CYP and Transporter Inducers Leflunomide is metabolized by CYP450 metabolizing enzymes. Concomitant use of ARAVA and rifampin, a potent inducer of CYP and transporters, increased the plasma concentration of teriflunomide by 40%. However, when coadministered with the metabolite, teriflunomide, rifampin did not affect its pharmacokinetics. No dosage adjustment is recommended for ARAVA when coadministered with rifampin. Because of the potential for ARAVA concentrations to continue to increase with multiple dosing, caution should be used if patients are to be receiving both ARAVA and rifampin [see Clinical Pharmacology (12.3) ] . Effect on CYP2C8 Substrates Teriflunomide is an inhibitor of CYP2C8 in vivo . In patients taking ARAVA, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3) ] . Effect on Warfarin Coadministration of ARAVA with warfarin requires close monitoring of the international normalized ratio (INR) because teriflunomide, the active metabolite of ARAVA, may decrease peak INR by approximately 25%. Effect on Oral Contraceptives Teriflunomide may increase the systemic exposures of ethinylestradiol and levonorgestrel. Consideration should be given to the type or dose of contraceptives used in combination with ARAVA [see Clinical Pharmacology (12.3) ] . Effect on CYP1A2 Substrates Teriflunomide, the active metabolite of ARAVA, may be a weak inducer of CYP1A2 in vivo . In patients taking ARAVA, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3) ] . Effect on Organic Anion Transporter 3 (OAT3) Substrates Teriflunomide inhibits the activity of OAT3 in vivo . In patients taking ARAVA, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3) ] . Effect on BCRP and Organic Anion Transporting Polypeptide B1 and B3 (OATP1B1/1B3) Substrates Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo . For a patient taking ARAVA, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking ARAVA [see Clinical Pharmacology (12.3) ] .
Drug class
May treat (source: NIH RxClass)
See how Arava ranks — best-rated antirheumatic agent for:
Dosage forms
Tablet
The forms currently marketed in the U.S., per the FDA National Drug Code Directory.
Ways to save
Ask for the generic
Same active ingredient, far cheaper. Is there a generic? →
Request a 90-day supply
Bulk fills usually lower the per-dose price vs monthly refills.
Use copay cards
Manufacturer copay cards & patient-assistance programs — especially for brand drugs.
Compare alternatives
A same-class option may cost less. See alternatives →
Frequently asked questions
- What does Arava treat?
- Arava (Leflunomide) may be used to treat rheumatoid arthritis, based on NIH RxClass drug-classification data (conditions a drug may treat — not a verbatim copy of the FDA-approved label). This is general reference, not medical advice.
- How is Arava rated?
- pharmaranks gives Arava a composite score of 3.5 out of 5, currently based on 1 weighted source (FDA regulatory recall-safety data weighted highest). See our methodology at /how-we-rate.
- How much does Arava cost?
- Nobody can tell you what you will pay — your price is set by your insurer's formulary, your deductible and the pharmacy's markup, and none of those are published. What IS published is what the pharmacy paid to acquire it: about $9.44 for 30, per the CMS NADAC survey. Treat that as the floor, not the quote — ask the pharmacist for the cash price as well as your copay, because for cheap generics the cash price often wins.
- Is there a coupon or discount for Arava?
- pharmaranks is an independent ratings site, not a pharmacy — we don't issue coupons or sell Arava. To pay less, ask your prescriber or pharmacist whether a generic equivalent exists, check the manufacturer's copay/savings card and patient-assistance program, and compare a pharmacy discount card against your insurance copay. Prices vary by pharmacy, insurance, and location, so always confirm at the counter. This is general reference, not medical or financial advice.
- Who makes Arava?
- Arava is marketed by Sanofi Aventis US. You can see Sanofi Aventis US's full profile, rating, and other products on pharmaranks.
- Is Arava a brand-name or generic drug?
- Arava is a brand-name product with the active ingredient Leflunomide.
- Is Arava available over the counter?
- No. Arava is a prescription (Rx) medication in the US — you need a prescription from a licensed clinician (in person or via telehealth); it isn't sold over the counter. For some conditions there are OTC alternatives — ask your pharmacist.
- What forms does Arava come in?
- Arava is currently marketed as tablet, per the FDA's National Drug Code Directory.
- What class of drug is Arava?
- Arava is classified as antirheumatic agent, per the FDA's Established Pharmacologic Class.
- Is Arava FDA-registered?
- Arava is on record with the U.S. FDA under application number NDA020905. You can verify this on its official FDA label.
- Has Arava been recalled by the FDA?
- Arava has no FDA recalls recorded under its own application in the openFDA enforcement database. Its recall-safety score reflects its manufacturer's overall recall record. This is general reference, not medical advice — check the FDA recall database for the latest alerts.
- Is Arava safe?
- There's no single safe-or-not verdict. pharmaranks gives Arava a recall-safety score of 70/100, based on its FDA recall history (no recalls under its own FDA application) — not an efficacy or side-effect rating. Review its FDA-label side effects and warnings before use, and always consult a licensed professional.
- What are the side effects of Arava?
- Arava's side effects are taken directly from its FDA label. From the label: The following serious adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions (5.2) ] Immunosuppression [see Warnings and Precautions (5.4) ] Bone marrow suppression [see Warnings and Precautions (5.4) ] Serious infections [see Warnings and Precautions… Both common and serious reactions are documented in full on this page. This is general reference from the FDA, not medical advice — always consult a professional.
Clinical content sourced from the FDA label via openFDA (U.S. FDA). View the FDA label on DailyMed → Provided for general reference only — not medical advice. Always consult a licensed professional and the current prescribing information.
Reviews
No reviews yet. Be the first to write one.
People also viewed
Compare Arava head-to-head
Browse medications A–Z
Research products from A to Z, compare independent ratings, and find alternatives.
arava
70/100