What it's for (Indications)
- Leflunomide is indicated for the management of rheumatoid arthritis, a chronic autoimmune inflammatory joint disease, by managing pain and reducing disease progression through its antiproliferative and anti-inflammatory effects.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | The recommended dosage of leflunomide is 20 mg once daily. Treatment may be initiated with or without a loading dose, depending on the patient's risk for hepatotoxicity and myelosuppression. For patients at low risk, a loading dose of 100 mg daily for 3 days may be given to achieve steady-state concentrations more rapidly. The maximum recommended daily dosage is 20 mg once daily. If 20 mg once daily is not tolerated, the dosage may be decreased to 10 mg once daily. Before starting treatment, patients should be screened for active and latent tuberculosis, blood pressure, and undergo relevant laboratory tests. Females of reproductive potential must have a negative pregnancy test and use effective contraception during treatment and during the washout period (up to 2 years or until plasma levels are below 0.02 mg/L). Males with partners of reproductive potential also need to use effective contraception during treatment and the washout period. If pregnancy occurs, a drug elimination procedure should be considered. |
Safety & Warnings
Common Side Effects
- Common side effects include diarrhea, respiratory infection, nausea, headache, rash, abnormal liver enzymes (indicating altered liver function), dyspepsia, increased blood pressure, stomach upset, stomach pain, oral disorders, dizziness, asthenia (weakness), paraesthesia (abnormal sensation), weight loss, allergy, hair loss, and dry skin.
- Less common or serious adverse reactions include severe hepatotoxicity (liver toxicity, including fatal liver failure), leucopenia (reduced white blood cells, indicative of bone marrow suppression), tenosynovitis (inflammation around tendon), severe immunosuppression leading to serious infections, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug reactions with eosinophilia and systemic symptoms (DRESS), skin ulcers, peripheral neuropathy, and interstitial lung disease.
Serious Warnings
- Black Box Warning: WARNING: EMBRYO-FETAL TOXICITY and HEPATOTOXICITY. Leflunomide is contraindicated in pregnant women due to the potential for severe fetal harm. Pregnancy must be excluded prior to treatment initiation, and effective contraception must be used by females of reproductive potential and males with partners of reproductive potential during treatment and for a specified washout period post-treatment. Severe liver injury, including fatal liver failure, has been reported; patients with pre-existing liver disease or elevated liver enzymes (ALT >2 times ULN) should not typically be treated. Liver enzymes must be monitored regularly.
- Patients should be monitored for severe hepatotoxicity, including fatal liver failure; ALT levels must be monitored at baseline, every 2 weeks for the first 6 months, and periodically thereafter.
- A washout procedure is required if liver enzymes elevate.
- Bone marrow suppression (leucopenia, blood dyscrasias) and severe immunosuppression are risks, necessitating a differential blood count before and during treatment, and a washout if toxicity occurs.
- Serious infections, including active and latent tuberculosis, can occur; patients should be screened for TB before treatment and report any signs of infection immediately.
- Severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, DRESS, and skin ulcers have been reported.
- Blood pressure should be monitored due to potential increases.
- Peripheral neuropathy and interstitial lung disease are also potential risks.
- Patients should be screened for blood pressure and laboratory tests before initiating therapy.
How it Works (Mechanism of Action)
Leflunomide is an isoxazole immunomodulatory agent that inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme crucial for de novo pyrimidine synthesis. This inhibition leads to antiproliferative activity and an anti-inflammatory effect.