II. Indications
-
Rheumatoid Arthritis
- First line DMARD instead of Methotrexate
- Has been used in combination with Methotrexate (but increased hepatotoxicity risk)
- Psoriatic Arthritis (off-label use)
III. Contraindications
- Hepatotoxicity risk factors including severe hepatic insufficiency
- Renal Insufficiency
- Severe Immunodeficiency
- Myelosuppression
- Serious infections
- Pregnancy
IV. Mechanism
- Pyrimidine inhibitor
- T-Cell Activation and proliferation inhibitor
- Similar to Methotrexate in effects
- Onset of action in 1-2 months
V. Dosing
- Start 20 mg orally once daily
- Loading dose: 100 mg orally daily for 3 days
- Loading dose is avoided in most cases (rarely used)
- Loading dose increases adverse effects (e.g. hepatotoxicity)
- Most prescribers start with maintenance dosing
- Maintenance: 10 mg orally daily (or 20 mg orally every other day)
- Higher Dose (if inadequate relief at lower dose): 20 mg orally daily
VI. Pharmacokinetics
- Half-Life: 18 days
VII. Adverse Effects
- Nausea (may limit use)
- Diarrhea
- Headache
- Alopecia
- Hepatotoxicity
- Liver injury occurs in 1 in 200 patients
- Increased Liver transaminases (e.g. AST, SGOT)
- Increased hepatotoxicity risk when combined with Methotrexate or Immunosuppressants
-
Interstitial Lung Disease
- Lung injury (observe for new onset cough)
- Other rare, serious adverse effects
-
Overdose or pregnancy detected
- See other references or contact poison control for protocol
- Administer Activated Charcoal 50 grams orally or by Nasogastric Tube every 6 hours for 24 hours
- Administer Cholestyramine 8 grams orally three times daily for up to 11 days
- May follow Teriflunomide levels
- May direct repeat charcoal and Cholestyramine courses if levels >0.02 mg/L
VIII. Safety
- Avoid in Lactation
- Pregnancy Category X
- Avoid in pregnancy (Teratogenic)
- Screen for pregnancy before use and use reliable Contraception
IX. Drug Interactions
-
Warfarin
- Increases INR
- Drugs that increase Leflunomide levels
- Drugs that decrease Leflunomide levels
X. Monitoring
- Labs
- Aspartate Transaminase (SGOT, AST)
- Complete Blood Count with Platelet Count
- History
- Ask about new onset cough
- Timing
- Check baseline and then monthly for 6 months
- Check every 6-8 weeks afterward
XI. Efficacy
- Comparable to Methotrexate
- Used with Methotrexate for maximal effect
XII. Resources
XIII. References
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- Sharp (2000) Arthritis Rheum 43:495-505 [PubMed]
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Related Studies
leflunomide (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
LEFLUNOMIDE 10 MG TABLET | Generic | $0.44 each |
LEFLUNOMIDE 20 MG TABLET | Generic | $0.50 each |
Ontology: leflunomide (C0063041)
Definition (NCI) | A derivative of isoxazole used for its immunosuppressive and anti-inflammatory properties. As a prodrug, leflunomide is converted to an active metabolite, A77 1726, which blocks dihydroorotate dehydrogenase, a key enzyme of de novo pyrimidine synthesis, thereby preventing the expansion of activated T lymphocytes. This agent also inhibits various protein tyrosine kinases, such as protein kinase C (PKC), thereby inhibiting cell proliferation. (NCI04) |
Definition (NCI_NCI-GLOSS) | An anticancer drug that works by inhibiting a cancer cell growth factor. |
Definition (PDQ) | A derivative of isoxazole used for its immunosuppressive and anti-inflammatory properties. As a prodrug, leflunomide is converted to an active metabolite, A77 1726, which blocks dihydroorotate dehydrogenase, a key enzyme of de novo pyrimidine synthesis, thereby preventing the expansion of activated T lymphocytes. This agent also inhibits various protein tyrosine kinases, such as protein kinase C (PKC), thereby inhibiting cell proliferation. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42253&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42253&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1128" NCI Thesaurus) |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C045463 |
SnomedCT | 109143003, 386981009 |
LNC | LP34970-1, MTHU017708 |
English | 4-Isoxazolecarboxamide, 5-methyl-N-(4-(trifluoromethyl)phenyl)-, leflunomide, N-(4-trifluoromethyphenyl)-5-methylisoxazole-4-carboxamide, 4-Isoxazolecarboxamide, 5-Methyl-N-(4-(trifluoromethyl)phenyl)-, leflunomide (medication), LEFLUNOMIDE, leflunomide [Chemical/Ingredient], Leflunomide (product), Leflunomide (substance), Leflunomide |
Spanish | leflunomida (producto), leflunomida (sustancia), leflunomida |
Ontology: Arava (C0718644)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C045463 |
English | arava, Hoechst Brand of Leflunomide, Aventis Behring Brand of Leflunomide, Aventis Brand of Leflunomide, Aventis Pharma Brand of Leflunomide, Arava |