Hydrochlorothiazide: Hydrochlorothiazide is not metabolized by CYP enzymes and does not induce or inhibit these enzymes. It is therefore regarded as probably not porphyrinogenic. Candesartan: Mainly eliminated in unchanged form, in minor parts metabolised by CYP 2C9. One reference and clinical observations point to non- porphyrinogenicity.

Hydrochlorothiazide: Sulfonamide congener. Candesartan: Angiotensin II receptor antagonist. Mainly eliminated in unchanged form, to a lesser extent metabolized in the liver by 2C9. Less potent inhibitor of CYP 2C9. Thunell, patient reports (n=5): tolerated. Andersson, patient report (n=1): tolerated. French list: authorized

Hydrochlorothiazide: Hydrochlorothiazide is a thiazide diuretic that inhibits reabsorption of electrolytes in the distal tubule, leading to increased excretion of water, sodium, chloride, potassium, magnesium and other electrolytes. It is administered orally.

Hydrochlorothiazide: Hydrocholorothiazide is not metabolized, but is eliminated mainly unchanged in the urine. The plasma half-life is about 9,4 – 13 hours (Beermann 1976, Drugbank, SPC).

Hydrochlorothiazide: In an in ovo study of chick embryo livers, methyclothiazide, another thiazide drug, was found to have potential for induction of ALAS, whereas hydroclorothiazide and other thiazides was found not to have these effects (Anderson 1981). The results from these types of animal studies are not directly transferable to human, and cannot be given weight in the judgement of porphyrinogeniciry of drugs (Hift 2011).

Hydrochlorothiazide: Thunell, patient report (n=1): tolerated. Andersson, patient reports (n=10): tolerated. Peters: On basis of clinical experience probably not porphyrinogenic.

Hydrochlorothiazide: Uneventful use reported in 9 patients with acute porphyria. Candesartan: Uneventful use reported in 44 patients with acute porphyria.