Amlodipine + Valsartan + Hydrochlorothiazide

Essential hypertension when blood pressure control needs three drugs: an angiotensin II receptor blocker (ARB), a dihydropyridine calcium channel blocker and a thiazide diuretic. Per ESC 2024, ESH 2023 and the Spanish SEH-LELHA 2022 guideline, the triple combination, preferably as a single pill, is the second step when a dual combination has not brought blood pressure to target. If blood pressure stays above target on full doses of all three drugs, this is resistant hypertension: adherence is checked and secondary causes are excluded first, then spironolactone is added. In Spain the fixed-dose tablet is licensed as substitution therapy (AEMPS SmPC): the patient is first stabilised on the same three components taken separately or as a dual combination plus the third drug, then switched to the equivalent dose. Strengths 5/160/12.5, 10/160/12.5, 5/160/25, 10/160/25 and 10/320/25 mg once daily; the full effect at the maximum dose is reached after 2 weeks. In the registration randomised trial (Calhoun 2009, n=2271, 8 weeks; figures from the AEMPS SmPC) the 10/320/25 mg dose lowered blood pressure by 39.7/24.7 mmHg, 6.2–8.2/3.3–5.3 mmHg more than any of the three dual combinations; 71% reached blood pressure below 140/90 mmHg versus 45–54%. Contraindications: second and third trimesters of pregnancy, severe renal impairment (eGFR <30 mL/min), anuria and dialysis, hepatic impairment and cholestasis, refractory hypokalaemia, hyponatraemia and hypercalcaemia, symptomatic hyperuricaemia (gout), aliskiren in diabetes or eGFR <60, severe hypotension and shock, high-grade aortic stenosis and obstructive hypertrophic cardiomyopathy, haemodynamically unstable heart failure after myocardial infarction. Not recommended in the first trimester; women planning pregnancy are switched to another regimen in advance, and the drug is stopped as soon as pregnancy is confirmed; not recommended during breastfeeding. Hydrochlorothiazide raises the risk of non-melanoma skin cancer with cumulative dose (EMA PRAC assessment, AEMPS note 2018): sun protection, skin checks, and review of the prescription in patients with prior skin cancer. Monitor potassium, sodium, creatinine and uric acid: the thiazide can lower blood sodium and potassium and trigger a gout attack. Interactions: lithium (toxicity), potassium supplements and potassium-sparing diuretics, NSAIDs, ACE inhibitors or aliskiren (dual RAAS blockade), CYP3A4 inhibitors and grapefruit (amlodipine), simvastatin no higher than 20 mg/day.

ICD-10: I10 · ICD-11: BA00