Leflunomide

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Generic Name of Leflunomide - Learn More

Leflunomide

Leflunomide Precaution - What You Need to Know

Leflunomide is an immunosuppressive agent primarily used to treat autoimmune conditions such as rheumatoid arthritis (RA) and psoriatic arthritis. It is important to exercise caution when using leflunomide in certain populations and individuals with pre-existing conditions. In pregnancy, leflunomide is contraindicated due to its potential teratogenic effects, including birth defects. If a woman becomes pregnant while taking leflunomide, the drug should be discontinued immediately, and the patient should undergo a process of eliminating the drug from the system, typically involving cholestyramine or activated charcoal to accelerate the elimination process. Breastfeeding is also contraindicated, as leflunomide is excreted in breast milk, and its potential effects on a nursing infant are unknown.

In patients with pre-existing liver conditions, such as hepatitis or cirrhosis, leflunomide should be used with caution, as it may cause hepatotoxicity, including liver failure. Liver function should be closely monitored before starting treatment, during treatment, and after discontinuation. Regular liver enzyme monitoring is essential to detect early signs of liver damage.

Leflunomide should also be used cautiously in patients with a history of bone marrow suppression, as it can lead to hematologic toxicity, such as thrombocytopenia, leukopenia, or anemia. Monitoring of blood cell counts is necessary to detect any significant abnormalities. In patients with chronic infections, particularly tuberculosis or hepatitis B, leflunomide may worsen the condition, and appropriate screening should be done before treatment initiation.

Leflunomide Indication - Uses and Benefits

Leflunomide is approved for the treatment of rheumatoid arthritis (RA) in adults, either as a monotherapy or in combination with other disease-modifying antirheumatic drugs (DMARDs). It helps to reduce inflammation and prevent joint damage in patients with moderate to severe RA. Leflunomide is also used to treat psoriatic arthritis, where it reduces joint pain, swelling, and stiffness associated with the condition.

Off-label, leflunomide has been used in the treatment of other autoimmune diseases, such as systemic lupus erythematosus (SLE), vasculitis, and Crohn’s disease, although its effectiveness in these conditions requires careful consideration. The drug’s mechanism of action, inhibition of pyrimidine synthesis, leads to immunosuppression, which is beneficial in managing these chronic inflammatory conditions. Despite some off-label uses, it is primarily indicated for RA and psoriatic arthritis and is recommended for patients who have failed or are intolerant to methotrexate, another common DMARD.

Leflunomide Contraindications - Important Warnings

Leflunomide is contraindicated in several patient populations, particularly due to its teratogenic effects. It should not be used during pregnancy, as it has been shown to cause birth defects in animal studies. In women of childbearing potential, leflunomide should only be prescribed if alternative treatments are not suitable. Effective contraception should be used during treatment, and patients should undergo a washout procedure (e.g., cholestyramine treatment) before attempting pregnancy.

The drug is also contraindicated in patients with severe liver impairment or active liver disease, as it can exacerbate liver damage and may lead to life-threatening hepatotoxicity. Those with a history of significant bone marrow suppression, including severe anemia, leukopenia, or thrombocytopenia, should avoid leflunomide due to the risk of hematologic toxicity.

In addition, leflunomide should not be given to patients with active or uncontrolled infections, as its immunosuppressive action may exacerbate these conditions. Patients with hypersensitivity to the drug or its components should also avoid its use.

Leflunomide Side Effects - What to Expect

Common side effects of leflunomide include gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal pain, which may subside with time or dose adjustment. Other common side effects include headaches, rash, and hair thinning.

Serious side effects include liver toxicity, which can be life-threatening. Patients should have liver function tests (LFTs) performed regularly before, during, and after treatment. Signs of liver damage include jaundice, dark urine, and abdominal pain, and should prompt immediate discontinuation of the drug.

Hematologic toxicity is another serious concern, with potential effects including low white blood cell counts (leukopenia), low red blood cell counts (anemia), and low platelet counts (thrombocytopenia). Regular blood counts should be monitored to detect any significant changes.

Less common but severe side effects include peripheral neuropathy, lung disease (including pneumonitis), and severe skin reactions. In rare cases, leflunomide may trigger an allergic reaction, leading to symptoms such as rash, swelling, or difficulty breathing. Patients should be educated to seek immediate medical help if they experience signs of an allergic reaction or other serious side effects.

Leflunomide Pregnancy Category ID - Safety Information

5

Leflunomide Mode of Action - How It Works

Leflunomide works by inhibiting the enzyme dihydroorotate dehydrogenase (DHODH), which is involved in the de novo synthesis of pyrimidine bases. Pyrimidines are essential building blocks for DNA and RNA, and their inhibition leads to a reduction in the proliferation of activated T and B lymphocytes. This suppression of lymphocyte proliferation is the primary mechanism by which leflunomide exerts its immunosuppressive effects, making it beneficial in the treatment of autoimmune diseases like rheumatoid arthritis and psoriatic arthritis.

Pharmacodynamically, leflunomide reduces the number of circulating immune cells, particularly T-cells, which play a significant role in the inflammatory response. By limiting T-cell activation and proliferation, leflunomide helps to reduce the chronic inflammation and tissue damage associated with autoimmune diseases.

Pharmacokinetically, leflunomide is well absorbed after oral administration, and its active metabolite, A77 1726, reaches peak plasma concentrations within a few hours. The drug has a half-life of up to 19 days, which is prolonged due to enterohepatic circulation. This long half-life requires special attention to drug washout in cases of side effects or discontinuation of treatment.

Leflunomide Drug Interactions - What to Avoid

Leflunomide has several notable drug-drug interactions due to its mechanism of action and its effect on the immune system. Key interactions include:

- Methotrexate: Co-administration with methotrexate, another DMARD, may increase the risk of liver toxicity. Both drugs can have hepatotoxic effects, so combined use should be avoided unless closely monitored by a healthcare provider.
- Cyclosporine: Leflunomide may increase the serum levels of cyclosporine, potentially leading to toxicity. Patients using both drugs together should be carefully monitored for adverse effects such as nephrotoxicity.
- Warfarin: Leflunomide can interact with warfarin, potentially altering the anticoagulant effect. Close monitoring of INR levels is recommended for patients receiving both drugs.
- Rifampin: Rifampin, an antibiotic used for tuberculosis, can decrease the effectiveness of leflunomide by inducing the liver enzymes that metabolize leflunomide. This could lower leflunomide's efficacy in treating autoimmune conditions, requiring dose adjustments.

There are no significant food interactions with leflunomide, but alcohol consumption should be minimized due to the increased risk of liver toxicity. Lifestyle factors such as smoking may exacerbate the immune suppression effects of leflunomide, so patients should be advised to quit smoking if possible.

Leflunomide Adult Dose - Recommended Dosage

For adults with rheumatoid arthritis, the typical starting dose of leflunomide is 100 mg daily for the first 3 days, followed by a maintenance dose of 20 mg daily. In some cases, the dose may be adjusted based on the patient’s response to treatment or tolerability. For psoriatic arthritis, the same initial and maintenance doses are typically used.

If treatment needs to be stopped due to side effects, a washout regimen is often recommended, which typically involves using cholestyramine or activated charcoal to hasten the elimination of the drug from the body. It is important for patients to follow their healthcare provider’s instructions regarding dosing adjustments and to report any signs of side effects immediately.

Leflunomide Child Dose - Dosage for Children

Leflunomide is not approved for use in pediatric patients under the age of 18. There is limited safety and efficacy data in children, and its use in this population is generally avoided unless the benefits clearly outweigh the risks. If leflunomide is considered for pediatric use in rare circumstances, close monitoring of liver function, hematologic parameters, and overall health status is essential. Alternative treatments should be considered first for children with autoimmune conditions.

Leflunomide Renal Dose - Dosage for Kidney Conditions

Leflunomide does not require specific dose adjustments in patients with mild to moderate renal impairment. However, in patients with severe renal impairment (creatinine clearance <30 mL/min), leflunomide should be used with caution, and careful monitoring is recommended. The drug is primarily metabolized in the liver, and the risk of accumulation is lower in patients with renal impairment.

In patients on hemodialysis, leflunomide may be removed by dialysis, and its dosage may need adjustment based on clinical monitoring. As with all patients, regular liver function tests should be performed.