LEFRA-20
Leflunomide 20 mg
What it does
Leflunomide is a medication used to help manage certain autoimmune conditions by suppressing the immune system.
Commonly used for: rheumatoid arthritis, psoriatic arthritis
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Sourcing - Kenya onlyRegistration & product details
Source: Zambia Medicines Regulatory Authority · fetched 2026-03-12 00:01:54 · updated 2026-09-24 03:33:38
Drug Interactions
66Pharmacodynamic Warnings
Leflunomide appears in TABLE 1: Drugs that cause hepatotoxicity
Leflunomide appears in TABLE 15: Drugs that cause myelosuppression
Severe (1)
Leflunomide - increases risk of immunosuppression
Filgotinib is predicted to increase the risk of immunosuppression when given with leflunomide. Avoid.
Moderate (4)
Cladribine - increases exposure
Leflunomide is predicted to increase the exposure to cladribine. Avoid or adjust dose. Also see TABLE 15 p. 1520
Olanzapine - decreases exposure
Leflunomide is predicted to decrease the exposure to olanzapine. Monitor and adjust dose.
Rosuvastatin - increases exposure
Leflunomide is predicted to increase the exposure to statins (rosuvastatin). Adjust dose. Also see TABLE 1 p. 1517
Theophylline - decreases exposure
Leflunomide is predicted to decrease the exposure to theophylline. Adjust dose.
Unknown (61)
Adefovir - increases exposure
Leflunomideispredictedtoincreasetheexposuretoadefovir. oTheoretical
Agomelatine - decreases exposure
Leflunomideispredictedtodecreasetheexposureto agomelatine.oTheoretical
Alpelisib - increases exposure
Leflunomideispredictedtoincreasetheexposuretoalpelisib. oTheoretical
Aminophylline - decreases exposure
Leflunomide decreases the exposure to aminophylline. Adjust dose.
Anaesthetics,local - decreases exposure
Leflunomide is predicted to decrease the exposure to anaesthetics, local (ropivacaine).
Data from BNF 85 (British National Formulary). This is not a substitute for professional medical advice. Matched via: exact
About this medicine
Leflunomide is a medication used to help manage certain autoimmune conditions by suppressing the immune system.
What it treats
- rheumatoid arthritis
- psoriatic arthritis
How it works
It works by reducing the activity of the immune system to help lower inflammation and joint damage.
Who it's for
This medicine is for adults with autoimmune diseases, particularly those affecting the joints.
Cautions
- • Be careful if taking other medications that can harm the liver.
- • Avoid drugs that can lower blood cell counts.
AI-assisted summary grounded in BNF data - general information only, not medical advice. Always confirm with your pharmacist or doctor.
Clinical monograph: Leflunomide
BNF-referencedLeflunomide is a pyrimidine synthesis inhibitor primarily utilized in the management of autoimmune diseases, particularly rheumatoid arthritis (RA) and psoriatic arthritis. It acts as a prodrug, being rapidly converted to its active metabolite, A77 1726, which exerts immunomodulating effects by inhibiting the proliferation of activated lymphocytes. Leflunomide is indicated for use in adults under specialist guidance, due to its potential side effects and the need for monitoring.
Indications
- Moderate to severe active rheumatoid arthritis
- Active psoriatic arthritis
Dosage
Adults: Initially 100 mg once daily for 3 days, then reduced to 10–20 mg once daily.
Mechanism of action
Leflunomide is metabolized to A77 1726, which primarily functions by inhibiting dihydroorotate dehydrogenase, an enzyme crucial for de novo pyrimidine synthesis. This inhibition leads to decreased levels of uridine monophosphate (rUMP), ultimately resulting in reduced DNA and RNA synthesis, G1 cell cycle arrest, and inhibition of T-cell proliferation and autoantibody production by B cells. The drug's action is particularly effective against activated autoimmune lymphocytes, which heavily rely on de novo pyrimidine synthesis.
Pharmacodynamics
Leflunomide exhibits its therapeutic effects in conditions characterized by heightened T-cell activity, such as rheumatoid arthritis. The drug's inhibition of pyrimidine synthesis is particularly impactful on activated T cells, which require a significant increase in pyrimidine pools for proliferation. By targeting the de novo synthesis pathway, leflunomide preferentially disrupts the metabolism of these activated lymphocytes, leading to its immunosuppressive effects.
Pharmacokinetics
Leflunomide is well absorbed following oral administration, with peak plasma concentrations typically reached within 6 to 12 hours. The drug is extensively metabolized in the liver, primarily to its active metabolite A77 1726. Leflunomide has a long half-life, allowing for once-daily dosing after an initial loading phase. The drug's elimination is primarily through the feces, with renal excretion of unchanged drug being minimal. Plasma concentrations may be affected by liver function and other medications.
Contra-indications
- Severe hepatic impairment
- Significant blood dyscrasias
- Pregnancy
- Known hypersensitivity to leflunomide or any of its components
Adverse effects
- Abdominal pain
- Appetite decreased
- Diarrhoea
- Headache
- Mood altered
- Nausea
- Skin reactions
- Vision disorders
- Vomiting
- Leukopenia
- Thrombocytopenia
- Cardiomyopathy
- Psychiatric disorders including depression and psychosis
- Peripheral neuropathy
- Dizziness
- Photosensitivity reactions
- Severe skin adverse reactions (SCARs)
Interactions
- Filgotinib - Severe interaction (increases risk of immunosuppression)
- Olanzapine - Moderate interaction (decreases exposure)
- Cladribine - Moderate interaction (increases exposure)
- Rosuvastatin - Moderate interaction (increases exposure)
- Theophylline - Moderate interaction (decreases exposure)
- Adefovir - Unknown interaction (increases exposure)
- Agomelatine - Unknown interaction (decreases exposure)
- Alpelisib - Unknown interaction (increases exposure)
- Aminophylline - Unknown interaction (decreases exposure)
- Ropivacaine - Unknown interaction (decreases exposure)
Precautions
- Monitor liver function tests regularly
- Caution in patients with renal impairment
- Caution in patients with active infections
- Monitor for signs of severe skin reactions
- Monitor complete blood counts for hematological issues
Pregnancy
Leflunomide is contraindicated in pregnancy due to potential teratogenic effects. Women of childbearing potential should use effective contraception during treatment and for at least two years after discontinuation.
Breast-feeding
The manufacturer advises caution when using leflunomide during breastfeeding due to the risk of accumulation in breast milk and potential effects on the infant.
Storage
Store at room temperature, away from moisture and heat. Keep out of reach of children.
Formulations
- Oral tablets
AI-synthesized from BNF references - general information only, not a substitute for professional medical advice or the current BNF. Verify doses with a pharmacist.
Molecular reference: Leflunomide
PubChem CID 3899Molecular formula: C12H9F3N2O2
Mechanism of action
Leflunomide is a prodrug that is rapidly and almost completely metabolized following oral administration to its pharmacologically active metabolite, A77 1726. This metabolite is responsible for essentially all of the drug's activity in-vivo. The mechanism of action of leflunomide has not been fully determined, but appears to primarily involve regulation of autoimmune lymphocytes. It has been suggested that leflunomide exerts its immunomodulating effects by preventing the expansion of activated autoimmune lymphocytes via interferences with cell cycle progression. In-vitro data indicates that leflunomide interferes with cell cycle progression by inhibiting dihydroorotate dehydrogenase (a mitochondrial enzyme involved in de novo pyrimidine ribonucleotide uridine monophosphate (rUMP)synthesis) and has antiproliferative activity. Human dihydroorotate dehydrogenase consists of 2 domains: an α/β-barrel domain containing the active site and an α-helical domain that forms a tunnel leading to the active site. A77 1726 binds to the hydrophobic tunnel at a site near the flavin mononucleotide. Inhibition of dihydroorotate dehydrogenase by A77 1726 prevents production of rUMP by the de novo pathway; such inhibition leads to decreased rUMP levels, decreased DNA and RNA synthesis, inhibition of cell proliferation, and G1 cell cycle arrest. It is through this action that leflunomide inhibits autoimmune T-cell proliferation and production of autoantibodies by B cells. Since salvage pathways are expected to sustain cells arrested in the G1 phase, the activity of leflunomide is cytostatic rather than cytotoxic. Other effects that result from reduced rUMP levels include interference with adhesion of activated lymphocytes to the synovial vascular endothelial cells, and increased synthesis of immunosuppressive cytokines such as transforming growth factor-β (TGF-β). Leflunomide is also a tyrosine kinase inhibitor. Tyrosine kinases activate signalling pathways leading to DNA repair, apoptosis and cell proliferation. Inhibition of tyrosine kinases can help to treating cancer by preventing repair of tumor cells. Leflunomide exhibits anit-inflammatory activity by inhibiting cyclooxygenase-2 (COX-2). It has been suggested that leflunomide exerts its immunomodulating effects by preventing the expansion of activated autoimmune lymphocytes via interference with cell cycle progression. ... In vitro data indicate that leflunomide interferes with cell cycle progression by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase; there also is in vitro evidence that the drug inhibits protein tyrosine kinase activity in dividing cells and possesses other effect that may contribute to its immunomodulating activity. ... In this study, we examined the effect of A771726 /active metabolite of leflunomide/ on osteoclast formation and bone-resorbing activity in vitro, using cultures of bone marrow-derived osteoclast progenitors and purified functionally mature osteoclasts, and then we elucidated the molecular mechanism of action of the effect of A771726 on osteoclasts. A771726 inhibited osteoclast formation from macrophage colony-stimulating factor (M-CSF)-dependent osteoclast progenitors in the presence of receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL), without any other types of cells present, in a dose-related manner, similar to the inhibition in cultures of unfractionated bone marrow cells. In addition, A771726 suppressed bone resorption by isolated mature osteoclasts. These results indicate that A771726 directly and intrinsically inhibited the differentiation and function of osteoclast lineage cells without any mediation by other cells. The inhibition by A771726 was not restored by the simultaneous addition of uridine, and may be independent of the blockade of NF-kappaB activation and the tyrosine phosphorylation of proteins. Thus, leflunomide, through its active metabolite, has the potential to prevent bone loss by directly inhibit
Pharmacodynamics
Leflunomide is a pyrimidine synthesis inhibitor indicated in adults for the treatment of active rheumatoid arthritis (RA). RA is an auto-immune disease characterized by high T-cell activity. T cells have two pathways to synthesize pyrimidines: the salvage pathways and the de novo synthesis. At rest, T lymphocytes meet their metabolic requirements by the salvage pathway. Activated lymphocytes need to expand their pyrimidine pool 7- to 8-fold, while the purine pool is expanded only 2- to 3-fold. To meet the need for more pyrimidines, activated T cells use the de novo pathway for pyrimidine synthesis. Therefore, activated T cells, which are dependent on de novo pyrimidine synthesis, will be more affected by leflunomide's inhibition of dihydroorotate dehydrogenase than other cell types that use the salvage pathway of pyrimidine synthesis.
Source: PubChem (NCBI) · pathways from PathBank, Reactome, WikiPathways & PharmGKB.
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The same active ingredient registered across other registries we cover - including different brands.