Enalapril is a medicine for high blood pressure and heart failure (ACE inhibitor). It is taken orally, with or without food. It can cause a dry cough — a common effect of this class of medicines.
Also known as: Renitec
Severe hyperkalaemia. Combining an ACE inhibitor (Enalapril) with a potassium-sparing diuretic (Spironolactone) significantly increases the risk of hyperkalaemia, especially in patients with renal impairment, diabetes or potassium supplements.
Enalapril reduces aldosterone production and spironolactone blocks the aldosterone receptor in the distal tubule: the combined effect is a marked reduction in potassium excretion. Hyperkalaemia is more frequent in patients with renal impairment, diabetes, advanced age or taking potassium supplements, and may present with muscle weakness, paraesthesias and arrhythmias. The combination is valid and common in heart failure with reduced ejection fraction, where benefit is proven — what is required is surveillance: potassium and creatinine about 1 week after starting or adjusting the dose, and reassessment if renal function worsens.
ACE inhibitor + aldosterone antagonist: additive potassium retention, with risk of hyperkalaemia, especially with reduced GFR, diabetes or advanced age. Monitor potassium and creatinine about 1 week after starting or adjusting.
Enalapril lowers aldosterone (less K+ excretion), an effect amplified by Spironolactone, which directly blocks the aldosterone receptor — serum K+ rises through two pathways.
Serum K+ and creatinine in week 1, then every 4–6 weeks for the first 3 months.
Muscle weakness, paraesthesia, arrhythmias, tall T waves on ECG.
Check serum K+ one week after starting. Consider dose reduction or therapeutic alternatives. Educate the patient on hyperkalaemia symptoms.
DailyMed/FDA (NIH/NLM) — approved Enalapril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b31372f7-cda3-4ead-a481-4cde62e843fd ; approved Spironolactone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73564b3d-8ede-4008-b75c-1277153b5bb6
No clinically relevant adverse interaction. An ACE inhibitor plus a calcium-channel blocker is a first-line antihypertensive combination; additive hypotension is expected and only requires BP monitoring during titration. Not contraindicated.
Enalapril (ACE inhibitor) and amlodipine (calcium-channel blocker) are frequently combined in the treatment of hypertension and coronary disease, with complementary effects: the ACE inhibitor blocks the renin-angiotensin system and amlodipine relaxes vascular smooth muscle. There is no relevant adverse interaction; the additive hypotensive effect is the intended therapeutic mechanism and only requires blood pressure monitoring, especially at start and at dose adjustments. In patients with amlodipine-induced peripheral oedema, the ACE inhibitor may even attenuate it.
No clinically relevant adverse interaction. First-line antihypertensive combination; monitor blood pressure during titration.
Usual and recommended combination. Start at low doses and titrate gradually; monitor blood pressure in the early weeks.
DailyMed/FDA (NIH/NLM) — approved Enalapril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b31372f7-cda3-4ead-a481-4cde62e843fd ; approved Amlodipine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=58a67272-c4c7-4e2c-85a5-9d39034d12c3
Reduced antihypertensive effect and risk of renal injury. NSAIDs blunt the ACE inhibitor and increase the risk of renal impairment, especially in elderly or dehydrated patients.
NSAIDs inhibit the synthesis of renal prostaglandins, which are essential to maintain afferent arteriolar vasodilation in patients with reduced renal blood flow; ACE inhibitors block angiotensin II, which constricts the efferent arteriole. The combination can cause acute kidney injury (especially in the elderly, dehydration, heart failure or diuretic use), reduce the antihypertensive and nephroprotective effect of enalapril and cause sodium retention and possible hyperkalaemia. Monitor blood pressure, creatinine and potassium after starting or adjusting the NSAID, ensure adequate hydration and consider an analgesic alternative (paracetamol).
Enalapril + ibuprofen: the NSAID reduces the antihypertensive and nephroprotective effect of the ACE inhibitor and can worsen renal function. Monitor blood pressure, creatinine and potassium.
NSAIDs inhibit renal prostaglandins and retain sodium/water, opposing the ACE inhibitor mechanism.
BP and creatinine after 2 weeks of regular NSAID use.
Oedema, reduced urine output, rising BP.
Prefer Paracetamol as analgesic. If an NSAID is needed, use the lowest dose for the shortest time, with renal function monitoring.
DailyMed/FDA (NIH/NLM) — approved Enalapril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b31372f7-cda3-4ead-a481-4cde62e843fd ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e
ACE inhibitor + potassium: risk of hyperkalaemia (especially in renal impairment or diabetes).
Angiotensin-converting enzyme inhibitors (ACEIs) such as enalapril reduce aldosterone secretion and, with it, renal potassium excretion. Concomitant potassium supplements (potassium chloride) can lead to hyperkalaemia, especially in patients with renal impairment, diabetes, advanced age or taking other potassium-raising drugs (ARBs, potassium-sparing diuretics, NSAIDs). Potassium should be started cautiously, with monitoring of serum potassium and renal function after initiation or dose adjustment, and patients warned about hyperkalaemia symptoms (muscle weakness, fatigue, palpitations, paraesthesias).
ACE inhibitor + potassium: risk of hyperkalaemia, especially in renal impairment or diabetes. Monitor serum potassium.
ACE inhibitors reduce aldosterone and K+ excretion; potassium supplementation adds risk.
Serum potassium and renal function.
Weakness, paraesthesia, arrhythmias.
Monitor serum potassium; use potassium supplements with caution.
DailyMed (FDA) — approved Enalapril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f103b9f9-e081-419d-a2d8-b86acda834dd ; approved Potassium chloride label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eb56a807-ea94-4edb-9811-a04b19568468 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining Lithium with Enalapril increases serum Lithium concentrations, with a risk of toxicity.
Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs that cause sodium elimination, including ACE inhibitors; the enalapril label describes cases of lithium toxicity in patients on enalapril and lithium, reversible after discontinuation of both, and recommends monitoring serum lithium levels frequently if enalapril is given with lithium. The mechanism involves reduced renal lithium elimination associated with sodium depletion. Monitor lithium levels at the start and during the combination and watch for signs of toxicity (tremor, confusion, ataxia, diarrhoea).
Enalapril + lithium: lithium toxicity reported with ACE inhibitors. Monitor lithium levels frequently during the combination.
Angiotensin-converting enzyme inhibitors such as Enalapril reduce the renal clearance of Lithium, raising its levels.
Watch for signs of Lithium toxicity after starting Enalapril.
Signs of Lithium toxicity after starting Enalapril require level testing and evaluation.
Monitor Lithium levels and renal function if the combination is needed.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 ; approved Enalapril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b31372f7-cda3-4ead-a481-4cde62e843fd — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Enhanced hypotensive effect. The combination may cause symptomatic hypotension in the first weeks, especially with prior volume depletion.
The combination of an ACE inhibitor with a thiazide is a well-established fixed combination for hypertension, with an approximately additive antihypertensive effect (the enalapril label states the blood pressure effects are "approximately additive" with thiazide diuretics) and a benefit in reducing thiazide-induced hypokalaemia. The risks to watch: (1) first-dose hypotension — in patients with volume/sodium depletion from the diuretic, the enalapril label recommends correcting the depletion or reducing the initial dose; (2) renal function — hypovolaemia can raise creatinine; (3) electrolytes — the balance between thiazide hypokalaemia and the ACE inhibitor hyperkalaemic tendency (the thiazide label states it may be used in patients in whom hyperkalaemia cannot be risked, including patients taking ACE inhibitors). Monitor BP, creatinine and potassium after initiation/adjustment; start with low doses in the elderly and in volume-depleted patients.
Enalapril + hydrochlorothiazide: additive antihypertensive effect (common fixed combination). Watch for first-dose hypotension, renal function and potassium.
The thiazide lowers circulating volume and the ACE inhibitor lowers peripheral resistance — the synergistic effect lowers BP more sharply.
BP in week 1; creatinine and electrolytes (K+, Na+) at 2 weeks.
Dizziness, syncope, cramps, intense thirst — possible signs of hypotension or hyponatraemia.
Start at low doses. Monitor BP and renal function in the first 2 weeks.
DailyMed/FDA (NIH/NLM) — approved Enalapril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b31372f7-cda3-4ead-a481-4cde62e843fd ; approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565
High potassium intake or salt substitutes may increase the risk of hyperkalaemia in patients treated with enalapril.
Avoid potassium-containing salt substitutes; monitor potassium in at-risk patients.
EMC-UK (MHRA) — approved Enalapril SmPC: https://www.medicines.org.uk/emc/product/15458/smpc
Enalapril is contraindicated in previous ACE-inhibitor-associated angioedema or hereditary/idiopathic angioedema.
Do not use in patients with a history of angioedema.
EMC-UK (MHRA) — approved Enalapril SmPC: https://www.medicines.org.uk/emc/product/15458/smpc
Enalapril is contraindicated in pregnancy: ACE inhibitors may cause fetal renal injury, oligohydramnios and skull hypoplasia, especially in the 2nd and 3rd trimesters.
Do not start in pregnancy; if pregnancy is detected, stop enalapril immediately.
Not recommended during breastfeeding; prefer an alternative with an established safety profile.
Women of childbearing age must use effective contraception during treatment.
EMC-UK (MHRA) — approved Enalapril SmPC: https://www.medicines.org.uk/emc/product/15458/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Angiotensin-converting enzyme inhibitor (ACEI); prodrug hydrolysed to enalaprilat, the active inhibitor. Reduces angiotensin II formation and increases bradykinin, lowering peripheral vascular resistance and blood pressure, with reduced preload and afterload in heart failure. In hypertension, onset of antihypertensive activity occurs ~1 hour after the dose, with peak at 4–6 hours.
Enalaprilat blocks the conversion of angiotensin I to angiotensin II (potent vasoconstrictor) and reduces bradykinin degradation. The blood pressure effect is similar standing and supine; symptomatic orthostatic hypotension is infrequent, except in volume-depleted patients.
Peak serum enalapril concentrations occur ~1 hour after an oral dose; absorption is ~60% (by urinary recovery) and is not influenced by food. Enalaprilat peaks occur 3–4 hours after the dose. Approximately 94% of the dose is recovered in urine and faeces as enalaprilat or enalapril.
Enalapril is hydrolysed to enalaprilat (more potent inhibitor; poorly absorbed orally). The serum profile of enalaprilat shows a prolonged terminal phase, apparently representing a small fraction bound to ACE — the amount bound does not increase with dose (saturable site). There is no evidence of other metabolites.
The effective half-life of enalaprilat accumulation after multiple doses of enalapril is ~11 hours. With GFR ≤30 mL/min, enalaprilat peaks and troughs increase, time to peak increases and the effective half-life is prolonged; enalaprilat is dialysable (62 mL/min).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
