Arava: Targeted Symptom Control for Rheumatoid Arthritis
| Product dosage: 10mg | |||
|---|---|---|---|
| Package (num) | Per pill | Price | Buy |
| 30 | $1.88 | $56.25 (0%) | 🛒 Add to cart |
| 60 | $1.52 | $112.51 $91.41 (19%) | 🛒 Add to cart |
| 90 | $1.40 | $168.76 $125.57 (26%) | 🛒 Add to cart |
| 120 | $1.33 | $225.02 $159.72 (29%) | 🛒 Add to cart |
| 180 | $1.27 | $337.53 $229.04 (32%) | 🛒 Add to cart |
| 270 | $1.23
Best per pill | $506.29 $332.50 (34%) | 🛒 Add to cart |
| Product dosage: 20mg | |||
|---|---|---|---|
| Package (num) | Per pill | Price | Buy |
| 30 | $3.31 | $99.45 (0%) | 🛒 Add to cart |
| 60 | $2.70 | $198.90 $161.73 (19%) | 🛒 Add to cart |
| 90 | $2.49 | $298.35 $224.01 (25%) | 🛒 Add to cart |
| 120 | $2.39 | $397.80 $286.29 (28%) | 🛒 Add to cart |
| 180 | $2.28 | $596.70 $409.85 (31%) | 🛒 Add to cart |
| 270 | $2.21
Best per pill | $895.04 $597.70 (33%) | 🛒 Add to cart |
Synonyms | |||
Arava (leflunomide) is a disease-modifying antirheumatic drug (DMARD) specifically developed for the management of active rheumatoid arthritis in adults. This immunomodulatory agent works by selectively inhibiting pyrimidine synthesis in rapidly dividing cells, such as activated lymphocytes, which play a central role in the autoimmune inflammatory processes underlying rheumatoid arthritis. Unlike some broader immunosuppressants, Arava offers a more targeted mechanism of action, aiming to reduce disease progression while managing symptomatic flare-ups. Its efficacy in improving physical function and delaying structural joint damage has been established through extensive clinical trials, making it a cornerstone in modern rheumatologic therapeutic regimens.
Features
- Active pharmaceutical ingredient: Leflunomide
- Available in 10 mg, 20 mg, and 100 mg tablet formulations
- Selective inhibition of dihydroorotate dehydrogenase (DHODH)
- Long half-life active metabolite (teriflunomide) allowing for once-daily dosing
- Demonstrated efficacy in reducing signs and symptoms of active rheumatoid arthritis
- Slows progression of structural joint damage as evidenced by radiographic findings
- Improves physical function as measured by standardized assessment tools
Benefits
- Reduces joint pain, swelling, and morning stiffness associated with active rheumatoid arthritis
- Helps preserve joint integrity and physical function by slowing disease progression
- Provides convenient once-daily dosing regimen that supports treatment adherence
- Offers an alternative treatment option for patients who have had inadequate response to other DMARDs
- May allow for reduction in concomitant corticosteroid use when effective disease control is achieved
- Demonstrates sustained efficacy in long-term management of rheumatoid arthritis symptoms
Common use
Arava is indicated for the treatment of adults with active rheumatoid arthritis. It is typically prescribed when patients have demonstrated an inadequate response to one or more disease-modifying antirheumatic drugs, particularly methotrexate. Clinical use extends to patients with moderate to severe disease activity where both symptomatic control and modification of disease progression are treatment objectives. Rheumatologists may initiate Arava as monotherapy or in combination with other DMARDs, though combination therapy requires careful monitoring due to potential additive immunosuppressive effects. The medication is particularly valuable in cases where traditional DMARDs have been poorly tolerated or where specific contraindications exist for alternative agents.
Dosage and direction
The recommended dosing regimen for Arava involves a loading dose followed by maintenance therapy. For most patients, treatment initiation consists of 100 mg once daily for three days, followed by a maintenance dose of 20 mg once daily. For patients who cannot tolerate the 20 mg dose, the maintenance dose may be reduced to 10 mg daily. Administration should occur at approximately the same time each day, with or without food, though consistency in administration relative to meals is recommended to maintain stable pharmacokinetics.
Dosage adjustments are necessary in specific patient populations. For elderly patients, no specific dose adjustment is typically required based on age alone, but careful monitoring is advised due to potential age-related decreases in hepatic or renal function. In patients with pre-existing liver impairment or stable liver disease, the maintenance dose should be reduced to 10 mg daily after the standard loading dose. For patients with renal impairment (creatinine clearance less than 30 mL/min), use is not recommended due to insufficient safety data.
The loading dose regimen is designed to achieve steady-state concentrations of the active metabolite more rapidly. However, some clinicians may opt to forego the loading dose in patients who may be more susceptible to adverse effects, initiating therapy directly with the maintenance dose, though this approach will delay the achievement of therapeutic levels by several weeks.
Precautions
Several important precautions must be observed when prescribing Arava. Hepatic monitoring is essential, as elevations in liver enzymes have been observed. Baseline liver function tests (ALT, AST) should be obtained before treatment initiation, and monitoring should continue at least monthly for the first six months of therapy, then periodically thereafter. If ALT elevations greater than two times the upper limit of normal occur, dose reduction or drug discontinuation should be considered, with more frequent monitoring.
Hematological monitoring is recommended due to potential effects on blood cell counts. Complete blood counts, including platelet counts, should be performed at baseline and monitored periodically during therapy. Patients should be advised to report promptly any signs of infection, unusual bruising, or bleeding, as these may indicate bone marrow suppression.
Blood pressure monitoring is advised, as hypertension has been reported in patients taking leflunomide. Baseline blood pressure measurement and periodic monitoring during treatment are recommended, with appropriate management if hypertension develops.
Respiratory monitoring is important, as interstitial lung disease has been reported, sometimes with fatal outcomes. Patients with pre-existing interstitial lung disease may be at higher risk. Any new onset or worsening pulmonary symptoms should be promptly evaluated, with consideration of drug discontinuation and appropriate diagnostic measures.
Skin reactions ranging from rash to more severe reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported. Patients should be advised to report any skin changes or mucosal lesions immediately.
Contraindications
Arava is contraindicated in patients with known hypersensitivity to leflunomide or any component of the formulation. It must not be used in patients with severe hepatic impairment or pre-existing liver disease, including hepatitis B or C infection, unless the potential benefits clearly outweigh the risks and with appropriate monitoring. The medication is contraindicated in patients with severe immunodeficiency, bone marrow dysplasia, or severe uncontrolled infections.
Use is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception, due to the teratogenic potential and long half-life of the active metabolite. Arava is pregnancy category X, meaning it is known to cause fetal harm. Women of childbearing potential must have a negative pregnancy test before starting treatment and must use effective contraception during therapy and during the drug elimination procedure after discontinuation.
Concomitant use with other hepatotoxic drugs, particularly other DMARDs with known hepatotoxic potential, is generally contraindicated unless closely monitored. The combination with other immunosuppressive agents may increase the risk of serious infections and requires careful risk-benefit assessment.
Possible side effects
The most common adverse reactions observed with Arava treatment include gastrointestinal disturbances such as diarrhea (occurring in up to 27% of patients), nausea (approximately 13%), abdominal pain (up to 10%), and dyspepsia. These symptoms are often dose-related and may diminish with continued treatment or dose reduction.
Hepatic enzyme elevations are frequently observed, with ALT increases occurring in approximately 15% of patients. Most elevations are mild to moderate and reversible with dose adjustment or discontinuation. Serious hepatic reactions, including cases of liver failure, have been reported, though rarely.
Dermatological reactions occur in approximately 15% of patients, ranging from mild rash to more severe reactions. Alopecia (hair loss) is reported in approximately 10-17% of patients, typically reversible upon discontinuation.
Hypertension develops in approximately 10% of patients, usually within the first few months of treatment. Regular blood pressure monitoring is essential.
Other reported side effects include respiratory effects such as upper respiratory tract infections, bronchitis, and interstitial lung disease (rare); neurological effects including headache and dizziness; and hematological effects such as mild anemia, leukopenia, and thrombocytopenia.
Weight loss of approximately 2-3 pounds has been observed in clinical trials, though the clinical significance is unclear. Rare but serious adverse effects include severe infections, peripheral neuropathy, and Stevens-Johnson syndrome.
Drug interaction
Arava demonstrates several clinically significant drug interactions that require careful management. Concomitant use with other hepatotoxic drugs, including methotrexate, may increase the risk of liver toxicity. If combination therapy is necessary, enhanced monitoring of liver function is essential.
The active metabolite of leflunomide is highly protein-bound and may displace other highly protein-bound drugs from binding sites, potentially increasing their pharmacological effects. This is particularly relevant for warfarin and other oral anticoagulants, requiring close monitoring of coagulation parameters.
Drugs that induce cytochrome P450 enzymes, particularly rifampin, may increase the metabolism of leflunomide’s active metabolite, potentially reducing its efficacy. Conversely, drugs that inhibit these enzymes may increase systemic exposure.
Live vaccines should not be administered during Arava treatment due to the potential for diminished immune response and increased risk of vaccine-related complications. The interval between discontinuing Arava and administering live vaccines should follow the recommended drug elimination procedure.
Cholestyramine and activated charcoal significantly accelerate the elimination of leflunomide’s active metabolite through enhanced biliary excretion. This interaction is utilized therapeutically in the drug elimination procedure but may inadvertently reduce efficacy if these agents are used concomitantly for other indications.
Missed dose
If a dose of Arava is missed, patients should take it as soon as they remember, unless it is almost time for the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule resumed. Patients should never take a double dose to make up for a missed dose. The long half-life of the active metabolite (approximately two weeks) means that occasional missed doses are unlikely to significantly affect therapeutic efficacy, though consistency in dosing is important for maintaining stable drug levels.
For patients who miss several consecutive doses, consultation with their healthcare provider is recommended to determine if any adjustment to the treatment regimen is necessary. In cases of prolonged unintentional discontinuation, reinitiation of therapy may require consideration of another loading dose regimen, particularly if more than two weeks have passed since the last dose.
Overdose
There is limited experience with Arava overdose in humans. Based on the pharmacological profile, symptoms of overdose would likely include enhanced adverse effects, particularly gastrointestinal disturbances (severe diarrhea, nausea), hepatic enzyme elevations, and potentially hematological effects. There is no specific antidote for leflunomide overdose.
In cases of suspected overdose, the drug elimination procedure should be initiated promptly. This involves administration of cholestyramine 8 grams three times daily for 11 days, or activated charcoal 50 grams every 12 hours for 11 days. These regimens have been shown to accelerate elimination of the active metabolite, reducing plasma concentrations by approximately 40% after 24 hours and over 95% after 11 days.
Supportive care should be provided based on presenting symptoms. Gastrointestinal symptoms may require antiemetics and fluid replacement. Hepatic and hematological parameters should be monitored closely. In severe cases, particularly with significant hematological toxicity, administration of colony-stimulating factors may be considered.
Given the long half-life of the active metabolite, monitoring and supportive care may need to continue for several weeks. Hemodialysis is not effective for removing leflunomide or its active metabolite due to high protein binding.
Storage
Arava tablets should be stored at controlled room temperature, between 20°C and 25°C (68°F and 77°F), with excursions permitted between 15°C and 30°C (59°F and 86°F). The medication should be kept in its original container with the lid tightly closed to protect from moisture and light. Tablets should not be stored in bathroom cabinets or other areas subject to high humidity or temperature fluctuations.
Keep out of reach of children and pets. Do not use tablets that are discolored, damaged, or beyond the expiration date printed on the packaging. Proper disposal of unused medication is important, particularly given the teratogenic potential. Unused tablets should not be flushed down the toilet or thrown in household trash unless specific safe disposal instructions are followed.
Disclaimer
This information is provided for educational purposes only and does not constitute medical advice. The content presented here is not intended to be 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 medication.
Dosage information, indications, and safety profiles may vary based on individual patient factors, regional prescribing information, and updated clinical evidence. Healthcare professionals should consult the full prescribing information and current clinical guidelines before initiating therapy. Patients should not make changes to their medication regimen without consulting their healthcare provider.
The information presented is based on the current understanding of leflunomide pharmacology and clinical experience, but knowledge in this area continues to evolve. New safety information may emerge that could alter the risk-benefit assessment for individual patients.
Reviews
Clinical studies and post-marketing experience have demonstrated Arava’s efficacy in rheumatoid arthritis management. In randomized controlled trials, approximately 50-60% of patients achieved ACR20 response (20% improvement in arthritis symptoms) at 6 months, with significant improvements in physical function and quality of life measures. Radiographic studies have shown significantly less progression of joint damage compared to placebo.
Many rheumatologists report positive experiences with Arava, particularly in patients who have had inadequate response to methotrexate or who cannot tolerate methotrexate. The once-daily dosing is frequently cited as advantageous for patient adherence compared to some other DMARDs.
Patient reviews often highlight the gradual but significant improvement in joint pain and stiffness, typically noticeable within 4-8 weeks of initiation. Some patients report gastrointestinal side effects as challenging initially, though these often improve with continued treatment. The potential for hair thinning is mentioned by some patients as a concern, though this is usually reversible.
The need for regular monitoring is acknowledged as a drawback by some patients and providers, though most consider this a necessary aspect of DMARD therapy. The long elimination period requiring specific procedures when discontinuing treatment is noted as an important consideration, particularly for women of childbearing potential.
Overall, Arava is generally regarded as an effective option in the rheumatologist’s armamentarium, with a favorable risk-benefit profile when used appropriately in suitable patients with appropriate monitoring.