Ramipril (oral route)

Ramipril, which is now available in generic form, is a proven and effective ACE inhibitor prescribed to treat hypertension and conditions related to or caused by high blood pressure, including prevention of myocardial infarction, stroke and heart failure.

Overview

Ramipril, which was first marketed under the brand name Altace, won FDA approval in 1991, and was made available for the treatment of high blood pressure and other related conditions, such as heart failure, congestive heart failure, stroke and hypertension in combination with diabetes. The patent expired on this medication in 2008, and it is now available in several generic forms.

Ramipril is a member of the class of medications known as angiotensin-converting enzyme inhibitors (ACE). ACE inhibitors stabilize blood pressure by affecting substances in the blood that constrict blood vessels. An inactive prodrug, ramipril is activated when it reaches the liver or the kidneys. When it is activated, it transforms into a substance known as ramiprilat, which serves as an antagonist to the mechanism that regulates the balance of water, electrolytes and hemodynamics in the blood stream. This mechanism is known as RAAS. By inhibiting RAAS and decreasing the breakdown of a chemical called bradykinin, a known vasodilator, blood vessels are less constricted and blood pressure is effectively lowered.

This relaxation of blood vessels makes ramipril an effective agent in treating hypertension and related cardiovascular conditions. It is also used as a second line or off label treatment for slowing the progression of kidney impairment in patients with diabetes mellitus.

As a strong and effective medication, ramipril also can cause a range of side effects. Most side effects are more incidental and well tolerated than not, but some can be quite significant. The biggest risk in taking this medication is that it may cause low blood pressure, which can result in lightheadedness, dizziness and disorientation, as well as possible fainting episodes that put the patient at risk of physical injury. This risk is most prevalent when patients initially begin their course of treatment and blood pressure levels are affected for the first time. For patients taking their initial dose, it is recommended that the patient take the medication in the presence of medical supervision for roughly two hours.

Ramipril should not be taken by women who are pregnant or are planning to become pregnant. It is also not recommended for nursing mothers. Patients taking diuretics are especially at risk for a dramatic drop in blood pressure, and so they should closely monitored. Sacubitril and other neprilisyn inhibitors should not be prescribed in conjunction with ramipril. There is also some risk of increased potassium levels with ramipril, so these should be monitored. Children should not be prescribed ramipril. The medication should also be stored safely away from the reach of children as there is some danger of overdose, especially in children.

Because of the risk of hypotension, if a patient who takes ramipril as part of their regular treatment regimen should require surgery that will include general anesthesia, both patient and doctor should plan carefully for that taking dosage levels of ramipril into consideration.

Rarely, patients have experienced an anaphylactic response to ramipril. This may take the form of typical allergic response, such as swelling of the throat or face. It may also take the form of angioedema in various areas of the body. This response can be dangerous to the point of fatality. Patients experiencing anything that resembles anaphylaxis should seek immediate medical treatment.

Conditions treated

  • High blood pressure (hypertension)
  • Renal dysfunction linked to diabetes
  • Prevention of heart attack
  • Prevention of heart failure following a heart attack
  • Prevention of stroke
  • Treatment of dysfunctional left ventricle
  • Heart failure
  • Scleroderma related high blood pressure (off label use)
  • Scleroderma related kidney failure (off label use)
  • Alport syndrome (off label use)

Type of medication

  • Angiotensin-converting enzyme (ACE) inhibitor

Side effects

Ramipril, like most other medications that treat high blood pressure, carries with it the risk of side effects. Most side effects are relatively mild and may go away after a few days or weeks of starting treatment. The most common effects include:

  • Diarrhea
  • Muscle weakness, especially in the legs
  • Dizziness
  • Chronic, persistent dry cough
  • Vomiting
  • Blurry vision
  • Confusion
  • Persistent nausea
  • Syncope (fainting)
  • Unusual sweating
  • Unusual weight loss

Occasionally, patients may experience more serious or significant side effects that may require more medical treatment or a change to a different medication. These can include:

  • Low blood pressure (which may include severe dizziness or fainting)
  • Jaundice linked to liver function, which may include yellowing of the skin or eyes
  • Swelling of legs or feet
  • Jaw pain
  • Cold sweats
  • Allergic reactions like swelling of the face or eyes
  • Difficulty breathing
  • Wheezing
  • Stomach pain not linked to nausea or vomiting
  • Urine that is cloudy
  • Arm pain
  • Abnormal bruising
  • Irregular heartbeat or palpitations
  • Sore throat
  • Backache
  • Low grade fever
  • Symptoms of renal impairment including difficulty urinating and reduced urine output
  • Reduced appetite
  • Chronic fatigue
  • Lightheadedness or disorientation
  • Seizure

Dosage

Ramipril is delivered as a gelatin capsule and comes in four different strengths: 1.25mg, 2.5mg, 5mg and 10mg.

When prescribed ramipril to treat hypertension, the usual recommended dosage is 2.5mg taken once daily to start treatment. This medication is taken orally. The dosage can then be elevated up to a limit of 20mg, taken once or twice daily. If use of this medication alone does not reduce and regulate blood pressure levels in the patient, a diuretic medication may be added to the treatment plan.

When ramipril is prescribed to address congestive heart failure, the initial recommended dose is 2.5mg taken twice a day. If that is effective, the maintenance prescription is 5mg daily, taken twice a day. If this dosage causes the development of hypotension, dosage may need to be reduced to 1.25mg a day until the hypotension has been stabilized. This may require decreasing or eliminating the use of a diuretic in conjunction with ramipril.

If ramipril is prescribed to prevent heart failure or reduce the risk of another myocardial infarction, the standard recommended prescription is, to begin with, 2.5mg daily for the first week. After initial treatment, the daily dose moves to 5mg daily, for up to three weeks. After that period of treatment, dosage may go up to 10mg per day or be reduced as needed. The higher dosage levels may be split up and taken twice a day for a more stabilized effect.

For patients with swallowing issues, the contents of the capsule can be added to water, apple sauce or apple juice. Patients must consume all of it and the solution may be stored up to 24 hours before being consumed (48 hours if stored in the refrigerator).

For patients with renal dysfunction, recommended dosage may be reduced by up to 25%. For patients who have been on ramipril for an extended period, regular monitoring of potassium levels and renal function are recommended.

Ramipril is not recommended for pediatric patients in any dosage.

Patients should take ramipril at the same time every day. The medication may be taken with food or without.

Interactions

Ramipril interacts with many medications. It has major interaction with over 80 medications. These include:

  • Aliskiren
  • Valsarten
  • Azilsarten
  • Hydrochlorothiazide
  • Amlodipine
  • Phenobarbital
  • Potassium iodide
  • Allopurinol
  • Ephedrine
  • Bisacodyl
  • Sodium phosphate
  • Potassium chloride
  • Polyethylene glycol 3350
  • Candesartan
  • Citric acid
  • Chlorpheniramine
  • Codeine
  • Potassium citrate
  • Eprosartan
  • Gold
  • Losartan
  • Triamterene
  • Methylene blue
  • Phenyl salicylate
  • Hyoscyamine
  • Iodine
  • Iron dextran
  • Leflunomide
  • Lomitapide
  • Lidocaine
  • Lithium
  • Mipomersan
  • Nebivolol
  • Olmesartan
  • Potassium acetate
  • Parenteral solution with added electrolytes
  • Potassium acid phosphate
  • Ragweed pollen extract
  • Potassium gluconate
  • Sacubitril
  • Tizanidine
  • Spironolactone
  • Trimethoprim
  • Teriflunomide

In total, ramipril has some level of interactivity with 670 different medications.

It also interacts with potassium absorbed in the body nutritionally, so patients taking ramipril should avoid ingesting too much potassium from food, as it can raise potassium in the blood to unsafe levels. Patients should also avoid salt substitutes, as these items often contain potassium salts, which have a similar effect on the body.

Warnings

Ramipril should not be taken by pregnant women or any woman who may become pregnant. It has been proven to be toxic to unborn children, and is categorized as a Pregnancy Class D medication. It is also not recommended for women who are nursing, as some residual medication may accumulate in breast milk.

There is an increased risk of hypotension and dangerously low blood pressure during surgery for patients taking ramipril, as its effects can be exacerbated by some of the medication in anesthesia.

Ramipril is often used to slow the progression of renal impairment and kidney disease. However, for patients with significant renal dysfunction, the dosage level should be reduced to as low as 25% of the usual dose. Even at that level, ramipril has been found to be efficacious in treating high blood pressure and damage to kidneys.

The lowest strength capsule (1.25mg) contains a small amount of a yellow dye that has been known to cause allergic reaction in some patients, particularly those with sensitivity to aspirin. Some patients have also had allergic reactions and an anaphylactic response to ramipril. This may include typical allergic reactions, such as rash, hives or swelling of the throat, mouth or face.

Other allergic reactions may include angioedema, which can occur in the head or neck region of the body or the intestinal area. Patients who are also undergoing dialysis may be more likely to experience angioedema. This is also true for patients taking mTOR inhibitors, such as temsirolinus, or neprilysin inhibitors, like sacubitril.

Another rare danger of long term use of ramipril is the risk of reduced liver function. It has been linked to the development of cholestatic jaundice, which can progress to necrosis of the liver. Left unchecked, this may prove fatal for the patient. Patients who are already suffering from some level of hepatic impairment should be monitored very closely and liver function checked often. If jaundice appears, patients should discontinue their use of ramipril.

While ramipril is often used to treat renal impairment, if the patient has a condition called renal stenosis, ramipril may actually worsen kidney function. These patients should also be checked often for increased levels of blood urea nitrogen and creatine in the urine, as well as decreased urine output.

Very infrequently, ramipril has been linked to a lowering of hemoglobin levels and overall red blood cell count, although this is usually mild. In even rarer cases, it has also suppressed bone marrow production and led to the development of conditions like agranulocytosis or pancytopenia. White blood cell counts can also be reduced, which can lead to increased risk of infection.

Patients should not take ramipril in conjunction with aliskiren or telmisartan.

Less than 15% of patients on ramipril therapy develop hyperkalimia, which is an increase in serum potassium levels. Patients with renal conditions are at greater risk of increased potassium issues.

Many patients using ramipril or any other ACE inhibitor develop a dry persistent cough. This cough is usually not serious or dangerous, but can be irritating and inconvenient. Its presence should also be factored in when diagnosing other respiratory ailments. One of the biggest risks of this cough is that its presence may mask other conditions that require treatment.

In clinical studies of over 4000 patients, some risk of certain conditions and symptoms emerged as warning for this product.

  • 3% of patients developed angina pectoris
  • 1% of patients experienced diarrhea
  • 4% of patients experienced noticeable dizziness
  • 2% of patients experienced nausea and vomiting
  • 2% of patients experienced syncope and vertigo
  • 1% of patients developed abnormal kidney function
  • 8% of patients developed persistent cough
  • 11% of patients experienced some level of hypotension

Some patients also developed some dermatologic conditions, including rash, sensitivity to sunlight, Stevens-Johnson syndrome and purpura.

Some patients also developed anxiety, depression and increased insomnia. Other neurologic conditions, such as neuralgia, tremor, tinnitus and neuropathy have also been reported.

There have also been reported incidences of eosinophilic pneumonitis. Arthritis and myalgia have been reported as well. Rarely, patients have reported experiencing increased sweating, malaise and weight gain. There have also been report of patients taking insulin developing hypoglycemia when taking ramipril concomitantly.

Ramipril has not been tested with pediatric patients. There is no data to measure its risks or efficacy. It is not recommended for use in children.

It is possible to overdose on ramipril. There is not a recommended treatment protocol for overdose, but the risk is dangerously low blood pressure and can be fatal. Patients should seek immediate medical treatment if overdose is suspected. Extremely low blood pressure is also a risk for patients on ramipril undergoing surgery. Physicians and surgeons need to be aware of the patient's dosage levels of ramipril and factor that into the surgical plan for the patient.

Storage

Ramipril capsules should be kept in the original container with the accurate dosage level label on the bottle. The medication should be kept tightly sealed with the safety lock on the cap engaged. It should also kept in a cool, dry environment away from the reach of children and animals.

This medication should be disposed of safely, not placed in a trash receptacle or flushed down the toilet. Unused ramipril should not end up in a landfill or in the water supply. Patients can consult the FDA website on safe disposal of medications or ask their pharmacist about drug take-back programs or other disposal options.

If ramipril is taken accidentally, especially by a child, contact poison control immediately and seek medical treatment.

Summary

The medication ramipril is part of a family of drugs known as angiotensin-converting enyzyme (ACE) inhibitors. These drugs are prescribed primarily to treat hypertension. It is also effective in the treatment of a range of cardiovascular conditions, including prevention of heart attack, prevention of stroke and treatment after a heart attack. A relatively new application of ramipril is in the treatment of renal impairment, particularly when associated with diabetes. Ramipril has proven effective in slowing the progression of kidney disease in these patients.

Like any medication, ramipril carries the risk of side effects for those that take it. Some of these side effects are mild and can be tolerated by the patient in most cases. These side effects include some dizziness, a persistent cough, headache, upset stomach or diarrhea. If the patient experiences one or more of these side effects, they will often resolve themselves after a few weeks of taking ramipril. Another common side effect is hypotension, or low blood pressure. This can cause the patient to have real fatigue, dizziness or vertigo-like symptoms and fainting. This will often regulate as the patient's body grows accustomed to the medication. If it does not improve, the dosage level of ramipril should be adjusted.

Ramipril can also cause very serious side effects that may contraindicate continued use of the medication. Use of ramipril has been linked to the development of hepatic impairment and decreased liver function. It may cause decreased red blood cell or white blood cell counts, which can lead to the development of other more serious problems. In cases of renal stenosis, ramipril may actually worsen kidney function. This medication can also cause anaphylaxis and acute allergic reactions, which can prove fatal in very rare cases.

This medication must not be taken by pregnant women as it has known fetal toxicity. Women on ramipril who become pregnant should discontinue its use immediately and inform their doctor. Ramipril is also not appropriate for pediatric patients, having never been tested in children. It should also be kept away from children and stored safely.

Ramipril and other ACE inhibitors interact with many other medications. Patients should inform their doctor of all medications they take to avoid dangerous combinations of medication. Patients taking ramipril and their physicians should proceed with caution when a patient requires any sort of surgery, as ramipril may interact with medications in the anesthesia.

Ramipril was originally marketed under the brand name Altace, but since 2008, it has been available in several generic forms. It continues to be used as a primary treatment for hypertension and heart health care.

 

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Last Reviewed:
January 30, 2018
Last Updated:
January 27, 2018
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