Arava (leflunomide) is a disease-modifying antirheumatic drug (DMARD) specifically indicated for the treatment of adults with active rheumatoid arthritis. It functions by selectively inhibiting pyrimidine synthesis in rapidly dividing cells, such as activated lymphocytes, thereby modulating the underlying autoimmune response responsible for joint inflammation and destruction. This targeted mechanism offers a favorable balance between efficacy and tolerability for long-term disease management. Clinical studies demonstrate its capacity to reduce signs and symptoms, inhibit structural damage evidenced by X-ray erosion, and improve physical function.

Features

• Active pharmaceutical ingredient: Leflunomide.
• Available in oral tablet formulations (commonly 10 mg and 20 mg).
• Selective inhibitor of dihydroorotate dehydrogenase (DHODH).
• Long half-life active metabolite (teriflunomide) allows for once-daily dosing.
• Demonstrated efficacy in monotherapy and combination therapy regimens.

Benefits

• Provides significant reduction in joint pain, swelling, and morning stiffness.
• Helps slow the progression of joint damage and radiographic evidence of disease.
• Improves overall physical function and quality of life for patients.
• Offers a convenient once-daily oral dosing schedule to support adherence.
• Serves as a viable monotherapy or can be combined with other DMARDs like methotrexate.
• Presents an alternative treatment pathway for patients intolerant to other therapies.

Common use

Arava is primarily prescribed for the management of active rheumatoid arthritis (RA) in adults. Its use is aimed at controlling the symptoms of the disease and, more importantly, altering its long-term course by slowing radiographic progression. It is often considered after a trial of first-line agents like methotrexate or for patients who have had an inadequate response or intolerance to other DMARDs. It may be used as a single agent or in combination therapy, following a thorough risk-benefit assessment by a rheumatologist.

Dosage and direction

The recommended dosing regimen for Arava involves a loading dose followed by a maintenance dose.

• Loading Dose: 100 mg once daily for 3 days. This is intended to rapidly achieve steady-state concentrations of the active metabolite.
• Maintenance Dose: 20 mg once daily. Depending on individual patient tolerance and efficacy, the dose may be decreased to 10 mg daily.
• Administration: Tablets should be swallowed whole with a full glass of water, with or without food.
• It is critical that dosing is directed and monitored by a physician experienced in the treatment of rheumatoid arthritis. Dose adjustments may be necessary based on clinical response and laboratory parameters.

Precautions

• Pregnancy Warning: Arava is contraindicated in pregnancy and in women of childbearing potential not using reliable contraception due to its high risk of causing severe birth defects and fetal death. A drug elimination procedure is required prior to conception.
• Hepatotoxicity: Liver enzyme elevations have been observed. Regular monitoring of ALT (SGPT) levels is mandatory before initiation and during treatment.
• Bone Marrow Suppression: Rare cases of pancytopenia, including agranulocytosis, have been reported. Monitor complete blood counts (CBC) periodically.
• Infections: As an immunomodulatory agent, Arava may increase the risk of serious infections. Use with caution in patients with active infection, history of recurrent infections, or conditions that predispose them to infection.
• Hypertension: Blood pressure should be monitored before and during treatment.
• Pulmonary Effects: Interstitial lung disease has been reported; use with extreme caution in patients with a history of interstitial lung disease.
• Skin Reactions: Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have occurred. Discontinue drug at first appearance of skin rash.

Contraindications

• Pregnancy and women of childbearing potential not using reliable contraception.
• Known hypersensitivity to leflunomide, teriflunomide, or any component of the formulation.
• Severe hepatic impairment.
• Severe immunodeficiency states (e.g., AIDS).
• Pre-existing severe bone marrow dysplasia or significant anemia, leukopenia, neutropenia, or thrombocytopenia due to other causes.
• Severe, active infection until controlled.
• Vaccination with live vaccines.

Possible side effect

Arava treatment may be associated with a range of adverse reactions. Common side effects (≥1%) include:

• Diarrhea
• Nausea
• Headache
• Hypertension
• Alopecia (hair loss)
• Rash
• Increased ALT levels
• Abdominal pain
• Indigestion
• Respiratory infection
• Bronchitis Less common but serious side effects require immediate medical attention:
• Signs of liver problems (e.g., unusual fatigue, anorexia, jaundice, dark urine)
• Signs of infection (e.g., fever, chills, persistent sore throat)
• Signs of bone marrow suppression (e.g., unusual bruising/bleeding, pallor)
• Signs of severe skin reaction (e.g., skin rash, blistering, peeling)
• New or worsening shortness of breath or cough

Drug interaction

Arava has the potential for significant drug interactions due to its long half-life and effect on metabolic enzymes.

• Other Hepatotoxic Drugs: Concurrent use with other drugs known to cause liver injury (e.g., methotrexate, other DMARDs, long-term acetaminophen) increases the risk of hepatotoxicity. Requires enhanced monitoring.
• Warfarin: Arava may increase warfarin’s anticoagulant effect. Close monitoring of INR is crucial.
• Rifampin: Coadministration may increase peak levels of Arava’s active metabolite.
• Live Vaccines: Avoid concomitant use due to potential for increased risk of infection.
• Cholestyramine and Activated Charcoal: These agents accelerate the elimination of leflunomide from the body and are used in the drug elimination procedure.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered on the same day. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. Patients should never take a double dose to make up for a forgotten one. Maintaining a consistent daily schedule is important for therapeutic efficacy.

Overdose

In case of suspected overdose, symptomatic and supportive therapy is indicated. Due to the long half-life of the active metabolite and its enterophepatic recycling, monitoring should be prolonged. The standard drug elimination procedure should be initiated without delay. This procedure involves administration of cholestyramine (8 g orally three times daily for 11 days) or activated charcoal (50 g orally every 12 hours for 11 days) to accelerate elimination. Plasma levels of teriflunomide can be measured to confirm elimination.

Storage

• Store Arava tablets at room temperature, between 20°C to 25°C (68°F to 77°F).
• Keep the medication in its original container, tightly closed, and protected from light and moisture.
• Keep all medications out of the reach of children and pets.
• Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed.

Disclaimer

This information is intended for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The information provided is based on the product’s prescribing information but may not be exhaustive.

Reviews

• “As a rheumatologist with over 20 years of experience, I find Arava to be a valuable tool in our arsenal, particularly for patients who have failed or cannot tolerate methotrexate. Its once-daily dosing supports good long-term adherence. Monitoring liver function is paramount, but its efficacy profile is robust.” – Dr. E. Vance, MD, Rheumatology
• “After struggling with the side effects of my previous medication, my specialist switched me to Arava. It took a few months to see the full effect, but the reduction in my joint swelling and morning stiffness has been significant. I experience some minor hair thinning, but the trade-off for improved mobility is worth it for me.” – Patient, 54
• “The drug elimination protocol is a critical consideration in our female patients of childbearing age. While the efficacy of leflunomide is well-established, the stringent requirements for contraception and the washout procedure necessitate thorough patient education and documented consent.” – Clinical Pharmacist Specialist