Acute Porphyria Drug Database

L04AK01 - Leflunomide
Propably not porphyrinogenic
PNP

Important Information
Patients on immunosuppressive therapy have an increased risk of infections. Since infections have a potential to trigger acute porphyric attacks vigilance is motivated regarding signs or symptoms of infection and/or possible symptoms of a porphyric attack. Side effects like nausea and vomiting may potentially be porphyrinogenic through reduction in carbohydrate intake.
Side effects
Infections are common in patients using immunosuppressants and since infections might trigger an acute porphyric attack, vigilance regarding signs and symptoms of an infection and/ or a porphyric attack is recommended. Common adverse reactions of leflunomide that can be confused with an acute porphyric attack are nausea and vomiting. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
Essentially non-CYP metabolism, probably low CYP-affinity. No observations of capacity for Cyp-induction or inhibition in clinical use. No pharmacokinetic porphyrinogenic effects are suspected.
Chemical description
Leflunomide is an isoxazole derivative, and contains an aromatic ring with a trifluoromethyl group, an isoxazole ring, and a carboxamide moiety. Leflunomide is considered a prodrug since it is rapidly and almost completely metabolized in vivo to a pharmacologically active metabolite (A77 1726, teriflunomide). Teriflunomide, a malononitrilamide, is an open-ring cyanoacetic acid metabolite.
Therapeutic characteristics
Leflunomide has immunosuppressant and antiproliferative properties and is used as a disease-modifying antirheumatic drug in the treatment of active rheumatoid arthritis. It is also used in the treatment of active psoriatic arthritis and has been investigated in the management of various solid neoplasms. It is administered orally.
Metabolism and pharmacokinetics
Leflunomide is rapidly converted to the active metabolite, Teriflunomide, by first-pass metabolism (ring opening) in gut wall and liver. The metabolic biotransformation of leflunomide to teriflunomide and subsequent metabolism is not controlled by a single enzyme and has been shown to occur in microsomal and cytosolic cellular fractions. In vitro studies indicate that teriflunomide inhibits CYP2C9 activity. In clinical trials no safety problems were observed when leflunomide and NSAIDs metabolised by CYP2C9 were co-administered.

References

  1. Drug reference publications
  2. McEvoy GK, editor. Leflunamide. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (30.08.10). #2269
  3. Sweetman SC, editor. Martindale: The complete drug reference. Leflunamide. Pharmaceutical Press 2009. #2270
  4. Summary of Product Characteristics
  5. The electronic Medicines Compendium (eMC). Arava. Summary of Product Characteristics (SPC). #2271

Similar drugs
Explore alternative drugs in similar therapeutic classes L04A / L04AK or go back.

 
© NAPOS 2024
An unhandled error has occurred. Reload 🗙