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Drug Reference

ramipril

ACE inhibitor· Brands: Altace, Tritace, RamiprilPO

Mechanism of action
Ramipril is a prodrug that is hydrolyzed in the liver to the active metabolite ramiprilat, which inhibits angiotensin-converting enzyme (ACE). This reduces the conversion of angiotensin I to angiotensin II, leading to decreased vasoconstriction, reduced aldosterone secretion, and lower blood pressure.
Pharmacokinetics
Ramipril is well absorbed orally, with a bioavailability of about 60%. It is metabolized to ramiprilat, which reaches peak plasma concentrations in 2 to 4 hours. The effective half-life of ramiprilat is approximately 13 to 17 hours, allowing once-daily dosing. Ramiprilat is primarily excreted via the kidneys, and dose adjustment is needed in renal impairment.
Indications & dosing

Hypertension

Start low and titrate according to response. Doses above 10 mg daily are not recommended.

  • adult · PO: 1.25–10 mg once daily · Start low and titrate according to response. Doses above 10 mg daily are not recommended.

Heart failure

Initiate under specialist supervision and titrate slowly, e.g. starting at 1.25 mg once daily, doubling at 2-week intervals.

  • adult · PO: 1.25–10 mg once daily · Initiate under specialist supervision and titrate slowly, e.g. starting at 1.25 mg once daily, doubling at 2-week intervals.

Post-myocardial infarction

Start at 2.5 mg twice daily, then increase to 5 mg twice daily after 5 days if tolerated.

  • adult · PO: 2.5–5 mg twice daily · Start at 2.5 mg twice daily, then increase to 5 mg twice daily after 5 days if tolerated.

Diabetic nephropathy

Initiate at 1.25 mg daily, titrate according to blood pressure and renal function. Maximum recommended dose is 5 mg daily.

  • adult · PO: 1.25–5 mg once daily · Initiate at 1.25 mg daily, titrate according to blood pressure and renal function. Maximum recommended dose is 5 mg daily.
Contraindications & precautions
  • History of angioedema · Previous angioedema with ACE inhibitors or hereditary/idiopathic angioedema.
  • Pregnancy · Ramipril may cause fetal toxicity, especially in the second and third trimester; stop if pregnancy is suspected.
  • Bilateral renal artery stenosis · Risk of acute renal failure; also unilateral stenosis in a solitary functioning kidney.
  • Concomitant use with sacubitril/valsartan · Avoid within 36 hours of switching between ramipril and sacubitril/valsartan.
  • Severe renal impairment · eGFR < 30 ml/min/1.73 m²; use with caution, reduce dose and monitor renal function.
  • Monitor blood pressure, serum creatinine and potassium before starting and periodically during therapy.
  • Use with caution in patients with renal impairment; reduce the starting dose and adjust according to renal function.
  • Avoid use with potassium-sparing diuretics or potassium supplements unless hypokalaemia is confirmed; monitor potassium closely.
  • First-dose hypotension may occur, especially in volume-depleted patients or those on diuretics; consider reducing the diuretic dose or giving a lower initial dose.
  • If angioedema occurs, stop ramipril immediately and treat appropriately; airway management may be required.
  • Avoid in pregnancy; advise effective contraception in women of childbearing potential.
Adverse effects
  • Cough
  • Dizziness
  • Headache
  • Hypotension
  • Angioedemaserious
  • Hyperkalaemiaserious
  • Acute kidney injuryserious
  • Pancreatitisserious
Interactions
  • losartanmajorAvoid the combination unless there is a compelling indication and specialist input. If used, initiate with close monitoring of serum potassium, creatinine, and blood pressure at baseline, then within 1 to 2 weeks of starting or dose adjustment, and periodically thereafter. Discontinue one agent if hyperkalaemia, significant hypotension, or worsening renal function occurs. Due to the lack of clear benefit for most indications, this combination is not recommended routinely.
  • spironolactonemajorPrescribers may use this combination in selected patients (e.g., heart failure) with close monitoring. Measure serum potassium and creatinine before starting, then within 1 week, and regularly thereafter, especially after dose changes. Avoid in patients with significant renal impairment, baseline hyperkalaemia, or high risk of worsening renal function. Consider alternatives such as eplerenone or loop diuretics if risk is high.
  • diclofenacmajorAvoid co-prescription where possible, especially in patients at high risk (elderly, dehydration, diuretic use, pre-existing renal disease, heart failure). If combined use is unavoidable, use the lowest effective dose of diclofenac for the shortest duration, ensure adequate hydration, and monitor blood pressure and renal function (serum creatinine, potassium) at baseline and within 1 to 2 weeks after starting or changing therapy. Consider alternative analgesia such as paracetamol.
  • potassium chloridemajorAvoid routine co-prescription unless there is clear hypokalaemia and careful monitoring is possible. If used together, monitor serum potassium at baseline, within 5 to 7 days after starting or changing doses, and regularly thereafter, especially during intercurrent illness. Adjust the potassium chloride dose or discontinue if hyperkalaemia occurs. Check renal function periodically.
  • ibuprofenmajorAvoid co-prescription in patients at high risk of renal impairment or hypovolaemia. If necessary, use the lowest effective dose of ibuprofen for the shortest duration, monitor renal function and blood pressure at initiation and regularly thereafter, and ensure adequate hydration. Consider alternative analgesics such as paracetamol.
  • gliclazidemoderateMonitor blood glucose more frequently when ramipril is started or its dose is changed. Advise the patient on recognising and managing hypoglycaemia. If hypoglycaemia occurs, consider reducing the gliclazide dose. This combination is not contraindicated, but close monitoring is recommended.
Renal & hepatic adjustment
  • eGFR 30–59: Initial dose 1.25 mg once daily; maximum dose 5 mg daily.
  • eGFR 0–30: Initial dose 1.25 mg once daily; maximum dose 2.5 mg daily.
  • Hepatic impairment (moderate): Use with caution; consider initial dose of 1.25 mg once daily and titrate slowly.
  • Hepatic impairment (severe): Use with caution; initial dose of 1.25 mg once daily and monitor closely.
Monitoring, pregnancy & toxicity
  • Blood pressure · Before and after dose titration
  • Serum creatinine and eGFR · Within 1-2 weeks of starting or after dose increase, then periodically
  • Serum potassium · Within 1-2 weeks of starting or after dose increase, then periodically
  • Blood urea · With renal function tests
  • Pregnancy: Contraindicated in pregnancy. Discontinue immediately if pregnancy is confirmed. ACE inhibitors can cause fetal renal damage, oligohydramnios, and neonatal hypotension.
  • Toxicity: Hypotension · Place patient supine; give IV fluids; use vasopressors if severe.
  • Toxicity: Hyperkalemia · Stop ramipril; monitor ECG and potassium; treat with calcium gluconate, sodium bicarbonate, glucose/insulin, or dialysis if severe.
  • Toxicity: Renal impairment · Monitor renal function; stop ramipril if deterioration is significant; consider specialist advice.
  • Toxicity: Angioedema · Discontinue immediately; give epinephrine (adrenaline), oxygen, and airway support.
Clinical notes
Ramipril is used for hypertension, heart failure, and following myocardial infarction. It also reduces the risk of cardiovascular events in high-risk patients. Monitor blood pressure, renal function, and serum potassium. Common adverse effects include dry cough, dizziness, hyperkalemia, and angioedema. Contraindicated in pregnancy and a history of angioedema.

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BNF; local formulary