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ESRU

Enalapril + Hydrochlorothiazide

Fixed-dose combination: ACE inhibitor plus thiazide diuretic

ATC code: C09BA02(Enalapril and diuretics)

Updated · Methodology

Indications

A

Hypertension

Second line

Essential hypertension uncontrolled on enalapril monotherapy. Per ESH/ 2023 and SEH-LELHA 2023, ACE inhibitor + thiazide is a well-proven second-line pair with long-term outcome data (HOPE, PROGRESS). Dose: 10/25, 20/12.5, 20/25 mg once daily. Full effect at 2–4 weeks. In Black patients, ACE inhibitor efficacy is lower than CCBs or thiazides in monotherapy, but the thiazide component of the combination compensates.

Sources

  1. AEMPS: Ficha técnica de Enalapril (2024)
  2. ESC: 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. (2024)

ICD-10: I10 · ICD-11: BA00

How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Enalapril inhibits ACE – angiotensin I is not converted to active angiotensin II, aldosterone falls, vessels dilate, and BP drops. Hydrochlorothiazide excretes sodium, chloride, and water via distal tubules. Enalapril offsets thiazide-induced potassium loss and RAAS activation.

Safety

Contraindications

  • Hypersensitivity
  • History of angioedema (including hereditary)
  • Pregnancy (2nd-3rd trimester)
  • Severe hepatic and renal impairment
  • Bilateral renal artery stenosis
  • Concomitant aliskiren in diabetes or CrCl <60
  • Concomitant sacubitril/valsartan

Serious adverse effects

  • Angioedema
  • Acute kidney injury
  • Severe hyperkalemia
  • Cholestatic jaundice

Common adverse effects

  • Dry cough (10–15%)
  • Dizziness
  • Hypotension
  • Hyperkalemia
  • Hyponatremia
  • Hyperuricemia
  • Increased creatinine

Pregnancy: can you take Enalapril + Hydrochlorothiazide?

Contraindicated from the 2nd trimester (ACE inhibitor fetopathy: oligohydramnios, fetal renal failure, skull hypoplasia). Switch to methyldopa, labetalol, or slow-release nifedipine in advance.

Breastfeeding: can you take Enalapril + Hydrochlorothiazide?

Enalapril is compatible (RID 0.2%, Hale L2). High-dose thiazide may reduce milk supply in the first postpartum weeks; at standard 12.5 mg no effect is typical. After 6–8 weeks of breastfeeding the combination is well tolerated.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Monitoring

Creatinine and K+ at 1–2 weeks after start or up-titration and yearly thereafter. Dry cough in 10–15% – switch to ARB + thiazide if bothersome.

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Frequently asked

What is Enalapril + Hydrochlorothiazide used for?

Enalapril + Hydrochlorothiazide is evaluated for the following indications with varying evidence strength: Hypertension (evidence tier A). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Enalapril + Hydrochlorothiazide?

Common side effects of Enalapril + Hydrochlorothiazide (≥ 1 in 100): Dry cough (10–15%), Dizziness, Hypotension, Hyperkalemia, Hyponatremia, Hyperuricemia. See the Safety section for uncommon and serious reactions.

Is Enalapril + Hydrochlorothiazide safe during pregnancy?

Contraindicated from the 2nd trimester (ACE inhibitor fetopathy: oligohydramnios, fetal renal failure, skull hypoplasia). Switch to methyldopa, labetalol, or slow-release nifedipine in advance.

Is Enalapril + Hydrochlorothiazide compatible with breastfeeding?

Enalapril is compatible (RID 0.2%, Hale L2). High-dose thiazide may reduce milk supply in the first postpartum weeks; at standard 12.5 mg no effect is typical. After 6–8 weeks of breastfeeding the combination is well tolerated.

Who should not take Enalapril + Hydrochlorothiazide?

Enalapril + Hydrochlorothiazide is contraindicated in: Hypersensitivity; History of angioedema (including hereditary); Pregnancy (2nd-3rd trimester); Severe hepatic and renal impairment; Bilateral renal artery stenosis. Full list in the Safety section.

Other drugs in this group

Irbesartan, Irbesartan + Hydrochlorothiazide, Lisinopril, Losartan, Losartan + Hydrochlorothiazide, Sacubitril + Valsartan, Amlodipine + Olmesartan, Azilsartan medoxomil + chlorthalidone