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.

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.

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.

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.

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.

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.