Ramipril

What Is Ramipril and What Is It Used For?

Ramipril belongs to a class of medications called ACE inhibitors (angiotensin-converting enzyme inhibitors). These drugs work by blocking the enzyme that converts angiotensin I into angiotensin II, a powerful vasoconstrictor. By inhibiting this conversion, ramipril causes blood vessels to relax and widen, which lowers blood pressure and reduces the workload on the heart.

When you take ramipril, it is absorbed through the gastrointestinal tract and converted in the liver to its active form, ramiprilat. This active metabolite binds to ACE with high affinity and has a prolonged duration of action, allowing effective once-daily dosing in most patients. The blood pressure-lowering effect begins within 1–2 hours of taking a dose and peaks at approximately 3–6 hours, with the clinical effect lasting well beyond 24 hours.

Beyond its effects on blood pressure, ramipril has several other important pharmacological actions. It reduces aldosterone secretion, which helps the body excrete sodium and retain potassium. It also inhibits the breakdown of bradykinin, a vasodilator peptide, which contributes to its blood pressure-lowering effect but is also responsible for the characteristic dry cough that some patients experience.

Approved Indications

Ramipril is approved by international regulatory agencies including the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for several important clinical indications:

• Hypertension (high blood pressure): Ramipril is used as monotherapy or in combination with other antihypertensive agents to lower blood pressure and reduce the risk of hypertension-related complications.
• Heart failure: Ramipril is used in the management of symptomatic heart failure, usually in combination with diuretics and often with digitalis glycosides and beta-blockers.
• Post-myocardial infarction: Ramipril reduces mortality and the progression to heart failure when started within the first few days following an acute heart attack complicated by heart failure.
• Cardiovascular risk reduction: Based on the landmark HOPE trial, ramipril is indicated to reduce the risk of myocardial infarction, stroke, and cardiovascular death in patients aged 55 years and older who are at high cardiovascular risk.
• Diabetic and non-diabetic nephropathy: Ramipril slows the progression of kidney disease by reducing proteinuria and preserving glomerular filtration rate, regardless of whether the underlying cause is diabetes.

The HOPE Trial

The Heart Outcomes Prevention Evaluation (HOPE) trial, published in the New England Journal of Medicine in 2000, was a landmark study that fundamentally changed the use of ramipril in clinical practice. This large randomized controlled trial enrolled 9,297 high-risk patients aged 55 or older with evidence of vascular disease or diabetes plus one additional cardiovascular risk factor.

The study found that ramipril 10 mg daily reduced the combined primary endpoint of cardiovascular death, myocardial infarction, and stroke by 22% compared to placebo (relative risk 0.78, 95% CI 0.70–0.86, p < 0.001). These benefits were observed across all subgroups, including patients with and without hypertension, diabetes, and established coronary artery disease. The HOPE trial established ramipril as a cornerstone therapy for cardiovascular risk reduction that extends beyond mere blood pressure lowering.

What Should You Know Before Taking Ramipril?

Before starting ramipril, it is essential that you have an open conversation with your prescriber about your complete medical history, all medications you are taking, and any allergies you may have. Certain conditions and medications can make ramipril unsafe or require dose adjustments and careful monitoring.

Contraindications

You should not take ramipril if any of the following apply to you:

• Allergy to ramipril or any ACE inhibitor: If you have experienced an allergic reaction to any ACE inhibitor (such as enalapril, lisinopril, or perindopril), including symptoms such as rash, difficulty swallowing or breathing, or swelling of the face, lips, tongue, or throat.
• History of angioedema: If you have ever had angioedema (rapid swelling under the skin), whether related to ACE inhibitor use or hereditary/idiopathic. Signs include itching, hives, swelling around the eyes, lips, tongue, or throat, and difficulty breathing or swallowing.
• Pregnancy (second and third trimesters): Ramipril can cause serious harm to the developing fetus, including reduced kidney function, reduced amniotic fluid, skull deformities, and death. Ramipril is not recommended in the first trimester either.
• Concomitant use with sacubitril/valsartan: Do not take ramipril within 36 hours of taking sacubitril/valsartan (used for chronic heart failure), as this significantly increases the risk of angioedema.
• Concomitant use with aliskiren in diabetes or renal impairment: The combination of ramipril with aliskiren is contraindicated in patients with diabetes mellitus or moderate-to-severe kidney disease (GFR < 60 mL/min).
• Dialysis with certain membranes: If you are undergoing dialysis with high-flux polyacrylonitrile membranes (e.g., AN69), ramipril should not be used due to the risk of anaphylactoid reactions.
• Severe bilateral renal artery stenosis: Ramipril can cause acute kidney failure in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.

Warnings and Precautions

Tell your doctor before starting ramipril if you have any of the following conditions, as special precautions, dose adjustments, or additional monitoring may be required:

• Heart disease: Patients with aortic stenosis, hypertrophic cardiomyopathy, or other conditions causing outflow tract obstruction should use ramipril with caution.
• Kidney disease: Kidney function and potassium levels should be monitored regularly. Dose reduction may be necessary in patients with impaired kidney function.
• Liver disease: Ramipril is a prodrug that requires hepatic activation. Liver disease may affect the conversion to the active metabolite and alter drug metabolism.
• Volume or salt depletion: If you are dehydrated, on a strict low-salt diet, or taking diuretics, you are at increased risk of symptomatic hypotension when starting ramipril. Your doctor may temporarily reduce or stop your diuretic before initiating ramipril.
• Connective tissue disease: Patients with scleroderma, systemic lupus erythematosus (SLE), or other connective tissue diseases are at increased risk of blood disorders such as agranulocytosis and neutropenia.
• Diabetes: Ramipril can enhance the blood sugar-lowering effect of insulin and oral antidiabetics. Blood glucose monitoring may need to be more frequent.
• High potassium: Ramipril can increase potassium levels. This risk is higher if you have kidney disease, diabetes, or are taking potassium supplements or potassium-sparing diuretics.
• Planned surgery: Tell your surgeon and anesthetist that you are taking ramipril, as it may need to be temporarily discontinued before procedures involving general anesthesia.
• Desensitization therapy: If you are undergoing hyposensitization treatment for insect venom allergy, ramipril may increase the risk of serious allergic reactions.

Pregnancy and Breastfeeding

Ramipril is classified as pregnancy category D by the FDA, meaning there is positive evidence of human fetal risk. ACE inhibitors, including ramipril, can cause serious harm to the developing fetus when used during the second and third trimesters of pregnancy. Reported effects include hypotension, renal failure, hyperkalemia, skull hypoplasia, anuria, reversible or irreversible renal failure, and death in the newborn.

If you discover you are pregnant while taking ramipril, stop the medication immediately and contact your healthcare provider. A switch to a pregnancy-safe alternative (such as methyldopa, labetalol, or nifedipine) should be made as soon as possible, ideally before conception in women planning pregnancy.

Ramipril and its active metabolite ramiprilat are excreted in breast milk in animal studies, and use during breastfeeding is not recommended. If you need ACE inhibitor therapy while breastfeeding, discuss the risks and benefits with your doctor.

Children and Adolescents

Ramipril is not recommended for use in children and adolescents under 18 years of age, as sufficient data on safety and efficacy in this population are not yet available. In pediatric patients requiring ACE inhibitor therapy, alternative agents with established pediatric dosing should be considered.

Driving and Operating Machinery

Ramipril may cause dizziness or fatigue, especially when starting treatment or after a dose increase. If you experience these symptoms, do not drive or operate heavy machinery until you know how ramipril affects you. The risk of dizziness is greatest during the first few days of treatment and can be minimized by starting with a low dose and increasing gradually.

How Does Ramipril Interact with Other Drugs?

Drug interactions with ramipril can reduce its effectiveness, increase the risk of side effects, or cause potentially dangerous reactions. It is essential that your healthcare provider has a complete list of all prescription medications, over-the-counter drugs, and dietary supplements you are taking. The most important drug interactions with ramipril are outlined below.

Major Interactions

Moderate Interactions

Alcohol

Alcohol can enhance the blood pressure-lowering effect of ramipril, potentially causing excessive dizziness, lightheadedness, or fainting. If you drink alcohol while taking ramipril, do so in moderation and be aware that the effects may be more pronounced than usual. Stand up slowly from sitting or lying positions to minimize the risk of orthostatic hypotension.

Food Interactions

Ramipril can be taken with or without food. However, you should avoid excessive consumption of potassium-rich foods (such as bananas, oranges, spinach, and potatoes) and potassium-containing salt substitutes, as ramipril already tends to increase potassium levels. Your doctor may advise regular monitoring of serum potassium, particularly if you have kidney disease or diabetes.

What Is the Correct Dosage of Ramipril?

The dose of ramipril is individualized based on the indication, the patient's response, and any coexisting conditions such as kidney or liver disease. Treatment is typically started at a low dose to minimize the risk of first-dose hypotension, and the dose is gradually increased (titrated) over several weeks until the target dose or the maximum tolerated dose is reached.

Swallow the tablets whole with a glass of water. Do not crush, chew, or break the tablets unless your doctor has specifically instructed you to do so (some formulations have a score line for splitting). Take ramipril at approximately the same time each day for consistent blood levels.

Adults

For most adult patients, treatment begins with a low dose that is doubled at intervals of 2–4 weeks, depending on the clinical response and tolerability. In hypertension, the starting dose is typically 1.25 mg or 2.5 mg once daily. If you are already taking diuretics, your doctor may advise stopping or reducing the diuretic dose 2–3 days before starting ramipril to reduce the risk of symptomatic hypotension.

For cardiovascular risk reduction (as demonstrated in the HOPE trial), the target dose is 10 mg once daily, reached gradually from an initial dose of 2.5 mg. This dose has the strongest evidence for reducing heart attack, stroke, and cardiovascular mortality.

Elderly Patients

Older adults may be more sensitive to the blood pressure-lowering effects of ramipril and are at higher risk of first-dose hypotension. Treatment should begin at the lowest available dose (1.25 mg once daily), and dose titration should be slower than in younger adults. Kidney function and electrolytes should be monitored regularly, as age-related decline in renal function is common.

Patients with Kidney Impairment

In patients with impaired renal function (creatinine clearance < 60 mL/min), the starting dose should be reduced and titration should be performed cautiously. The maximum daily dose in patients with severe renal impairment may be lower than 10 mg. Serum creatinine, potassium, and estimated GFR should be checked before starting treatment and monitored regularly thereafter.

Children

Ramipril is not recommended for children and adolescents under 18 years of age due to insufficient data on safety and efficacy. For pediatric hypertension or other indications requiring ACE inhibition, alternative agents with established pediatric dosing (such as enalapril) should be considered under specialist supervision.

Missed Dose

If you forget to take a dose of ramipril, take it as soon as you remember, unless it is almost time for your next scheduled dose. In that case, skip the missed dose and take your next dose at the usual time. Do not take a double dose to make up for a missed one. If you frequently forget doses, consider setting a daily alarm or using a pill organizer.

Overdose

What Are the Side Effects of Ramipril?

Like all medicines, ramipril can cause side effects, although not everybody gets them. Most side effects are mild and tend to diminish over time as your body adjusts to the medication. However, some side effects can be serious and require immediate medical attention. Understanding the potential side effects helps you recognize them early and respond appropriately.

Other Reported Side Effects

The following side effects have been reported with an unknown frequency:

• Difficulty concentrating
• Swelling of the mouth
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH), causing concentrated urine, nausea, muscle cramps, and confusion
• Raynaud's phenomenon (fingers and toes turning white/blue in cold, then red and painful when warmed)
• Gynecomastia (breast enlargement in men)
• Slowed reactions
• Burning sensation
• Changes in sense of smell
• Hair loss

The Dry Cough

A persistent dry cough is the most characteristic side effect of ACE inhibitors, affecting approximately 5–10% of patients taking ramipril. The cough is caused by the accumulation of bradykinin in the lungs and typically presents as a persistent, dry, tickling cough that is often worse at night. It usually develops within the first few months of treatment but can occur at any time.

If the cough is intolerable, your doctor may consider switching you to an angiotensin II receptor blocker (ARB), such as losartan, valsartan, or candesartan, which provide similar cardiovascular benefits without the bradykinin-mediated cough. Do not stop ramipril on your own without consulting your doctor.

How Should You Store Ramipril?

Proper storage of ramipril is essential to maintain its effectiveness and safety throughout its shelf life. Follow these storage guidelines:

• Temperature: Store at or below 25°C (77°F). Do not refrigerate or freeze.
• Light protection: Ramipril is sensitive to light. Keep the tablets in their original blister packaging or container until you are ready to take a dose.
• Moisture protection: Ramipril is sensitive to moisture. Keep the container tightly closed. If your tablets come in a bottle with a desiccant cap, do not remove the desiccant.
• Out of reach: Keep all medications out of the sight and reach of children.
• Expiry date: Do not use ramipril after the expiry date printed on the blister or carton. The expiry date refers to the last day of the stated month.
• Disposal: Do not dispose of unused tablets by flushing or in household waste. Return unused medications to your pharmacy for safe disposal to protect the environment.

What Does Ramipril Contain?

Active Ingredient

The active ingredient is ramipril, available in four tablet strengths:

• Ramipril 1.25 mg tablets
• Ramipril 2.5 mg tablets
• Ramipril 5 mg tablets
• Ramipril 10 mg tablets

Inactive Ingredients (Excipients)

The inactive ingredients (excipients) that make up the tablet formulation include:

• Hypromellose (hydroxypropyl methylcellulose)
• Microcrystalline cellulose
• Pregelatinized starch
• Sodium hydrogen carbonate
• Sodium stearyl fumarate

Each tablet contains less than 1 mmol (23 mg) of sodium, making it essentially sodium-free. This is relevant for patients on a controlled sodium diet.

Tablet Description

Ramipril tablets are white, oblong, flat, beveled-edge tablets with a score line on both sides. The tablets are marked with "R" followed by the strength (e.g., "R 1.25", "R 2.5", "R 5", "R 10"). The 2.5 mg, 5 mg, and 10 mg tablets can be divided into two equal halves along the score line. The 1.25 mg tablets have a score line to facilitate swallowing only, not for dose division.

The tablets are packed in aluminum/aluminum blisters or HDPE (high-density polyethylene) bottles with desiccant in the cap. Various pack sizes are available, including 14, 20, 28, 30, 50, 98, and 100 tablets, though not all pack sizes may be marketed in every country.

References & Sources

This article is based on international medical guidelines, regulatory documents, and peer-reviewed research. All medical claims have evidence level 1A (systematic reviews and randomized controlled trials) unless otherwise noted.

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Editorial Team

This article was written and medically reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians in clinical pharmacology, cardiology, and nephrology with documented academic backgrounds and clinical experience.