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 methotrexate 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.

Methotrexate is primarily excreted unchanged through the kidneys, and there is no evidence of CYP-metabolism. It does not inhibit nor induce CYP3A4. No reports of drug interactions indicating induction or inhibition of CYP2C9.

Methotrexate is a mixture containing at least 85% 4-amino-10-methylfolic acid, calculated on the anhydrous basis, and small amounts of related compounds. Structurally, the primary constituent of methotrexate differs from folic acid in the substitution of an amino group for a hydroxyl group in the pteridine nucleus and in the addition of a methyl group on the amino nitrogen between the pteroyl and benzoyl groups.

Methotrexate, a folic acid antagonist, is an antineoplastic agent and immunosuppressant used in the management of acute lymphoblastic leukaemia, for Burkitts and other non-Hodgkins lymphomas, as well as in the treatment of choriocarcinoma and other gestational trophoblastic tumours, and for the adjuvant therapy of osteosarcoma and breast cancer. It may also be used in malignant neoplasms of the bladder and head and neck, and some other neoplasms. It is also used in the treatment of active rheumatoid arthritis and psoriasis. Methotrexate has two different ATC-codes, methotrexate in oral formulations is classified in L04AX03, while L01BA01 describes parenteral use.

Methotrexate is excreted primarily unchanged by the kidneys via glomerular filtration and active transport. 58-92% of a single dose is excreted within 24 hours following IV administration. Methotrexate does not appear to undergo significant metabolism at low doses; after high-dose therapy the 7-hydroxy metabolite has been detected. When high-dose methotrexate is administered as a short intravenous infusion (4-6 h), most of the drug is cleared by the kidneys, but with longer infusions (24 h), about 40% of the drug is metabolised in the liver (Relling, 2000). Methotrexate did not activate PXR or increase CYP3A4 or CYP2B6 activity (Luo, 2002; Faucette, 2004; Sinz, 2006). Methotrexate did not affect the metabolism of vinblastine (Zhou-Pan, 1993). Methotrexate was not found to inhibit CYP3A4 activity (Baumhakel, 2001). No reports of drug interactions indicating induction or inhibition of CYP2C9.

Used uneventfully by a 55 year old AIP woman (S. Thunell, Sweden). Uneventful use reported in one patient with AIP (C. Andersson, Sweden).

Uneventful use reported in three patients with PV (Samuels, 1984).

Uneventful use reported in 6 patients with acute porphyria, 5 patients have used parenteral methotrexate (L01BA01) and 1 patient has used oral methotrexate (L04AX03).