Hydrochlorothiazide: Hydrochlorothiazide is not metabolized by CYP enzymes and does not induce or inhibit these enzymes. It is therefore regarded as probably not porphyrinogenic. Olmesartan Medoxomil: Olmesartan is not metabolized by CYP, and no CYP interaction potential is observed in vitro nor anticipated.

Hydrochlorothiazide: Sulfonamide congener. Olmesartan Medoxomil: Angiotensin II receptor antagonist. In medicinal products for oral administration, it is available as the prodrug olmesartanmedoxemil.

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. Olmesartan Medoxomil: Olmesartan medoxomil is used in the treatment of essential hypertension.

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). Olmesartan Medoxomil: The prodrug olmesartan medoxomil is rapidly converted to the pharmacologically active metabolite, olmesartan, by esterases in the gut mucosa and in portal blood during absorption from the gastrointestinal tract (SPC). Olmesartan is not further metabolized, and is excreted primarily via the bile (up to 90 per cent), and the rest by renal excretion (Yang 2016). Olmesartan had no clinically relevant inhibitory effects on in vitro human CYP 1A1/2, 2A6, 2C8/9, 2C19, 2D6, 2E1 and 3A4 (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. Olmesartan Medoxomil: Uneventful use reported in 3 patients with acute porphyria.