ANGIOTENSIN-CONVERTINGENZYME (ACE) INHIBITORS (Systemic)

Some commonly used brand names are:

In the U.S.?

• Accupril ¹⁰
• Aceon ⁹
• Altace ¹¹
• Capoten ²
• Lotensin ¹
• Mavik ¹²
• Monopril ⁶
• Prinivil ⁷
• Univasc ⁸
• Vasotec ^{4 5}
• Zestril ⁷

In Canada?

• Accupril ¹⁰
• Altace ¹¹
• Capoten ²
• Coversyl ⁹
• Inhibace ³
• Lotensin ¹
• Mavik ¹²
• Monopril ⁶
• Prinivil ⁷
• Vasotec ^{4 5}
• Zestril ⁷

Category

• Antihypertensive ?Benazepril; Captopril; Cilazapril; Enalapril; Enalaprilat; Fosinopril; Lisinopril; Moexipril; Perindopril; Quinapril; Ramipril; Trandolapril
• Vasodilator, congestive heart failure?Benazepril; Captopril; Cilazapril; Enalapril; Fosinopril; Lisinopril; Quinapril; Ramipril; Trandolapril

Description

ACE inhibitors belong to the class of medicines called highblood pressure medicines (antihypertensives). They are used to treat highblood pressure (hypertension).

High blood pressure adds to the workload of the heart and arteries. Ifit continues for a long time, the heart and arteries may not function properly.This can damage the blood vessels of the brain, heart, and kidneys, resultingin a stroke, heart failure, or kidney failure. High blood pressure may alsoincrease the risk of heart attacks. These problems may be less likely to occurif blood pressure is controlled.

Lisinopril, captopril, ramipril, and trandolapril are used in some patientsafter a heart attack. After a heart attack, some of the heart muscle is damagedand weakened. The heart muscle may continue to weaken as time goes by. Thismakes it more difficult for the heart to pump blood. Lisinopril use may bestarted within 24 hours after a heart attack to increase survival rate. Captopril,ramipril, and trandolapril help slow down the further weakening of the heart.

Captopril is also used to treat kidney problems in some diabetic patientswho use insulin to control their diabetes. Over time, these kidney problemsmay get worse. Captopril may help slow down the further worsening of kidneyproblems.

In addition, some ACE inhibitors are used to treat congestive heart failureor may be used for other conditions as determined by your doctor.

The exact way that these medicines work is not known. They block an enzymein the body that is necessary to produce a substance that causes blood vesselsto tighten. As a result, they relax blood vessels. This lowers blood pressureand increases the supply of blood and oxygen to the heart.

These medicines are available only with your doctor's prescription, inthe following dosage forms:

Oral
• Benazepril
  • Tablets (U.S. and Canada)
• Captopril
  • Tablets (U.S. and Canada)
• Cilazapril
  • Tablets (Canada)
• Enalapril
  • Tablets (U.S. and Canada)
• Fosinopril
  • Tablets (U.S. and Canada)
• Lisinopril
  • Tablets (U.S. and Canada)
• Moexipril
  • Tablets (U.S.)
• Perindopril
  • Tablets (U.S. and Canada)
• Quinapril
  • Tablets (U.S. and Canada)
• Ramipril
  • Capsules (U.S. and Canada)
• Trandolapril
  • Tablets (U.S. and Canada)

Parenteral
• Enalaprilat
  • Injection (U.S. and Canada)

Before Using This Medicine

In deciding to use a medicine, the risks of taking the medicine must beweighed against the good it will do. This is a decision you and your doctorwill make. For the angiotensin-converting enzyme (ACE) inhibitors, the followingshould be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to benazepril, captopril, cilazapril, enalapril, fosinopril,lisinopril, moexipril, perindopril, quinapril, ramipril, or trandolapril.Also tell your health care professional if you are allergic to any other substances,such as foods, preservatives, or dyes.

Pregnancy?Use of ACE inhibitors during pregnancy, especiallyin the second and third trimesters (after the first three months) can causelow blood pressure, severe kidney failure, too much potassium, or even deathin the newborn. Therefore, it is important that you checkwith your doctor immediately if you think that you may be pregnant.Be sure that you have discussed this with your doctor before taking this medicine.In addition, if you are taking:

• Benazepril?Benazepril has not beenshown to cause birth defects in animals when given in doses more than 3 timesthe highest recommended human dose.
• Captopril?Studies in rabbits andrats at doses up to 400 times the recommended human dose have shown that captoprilcauses an increase in deaths of the fetus and newborn. Also, captopril hascaused deformed skulls in the offspring of rabbits given doses 2 to 70 timesthe recommended human dose.
• Enalapril?Studies in rats at dosesmany times the recommended human dose have shown that use of enalapril causesthe fetus to be smaller than normal. Studies in rabbits have shown that enalaprilcauses an increase in fetal death. Enalapril has not been shown to cause birthdefects in rats or rabbits.
• Fosinopril?Studies in rats haveshown that fosinopril causes the fetus to be smaller than normal. Studiesin rabbits have shown that fosinopril causes fetal death, probably due toextremely low blood pressure. In rats, birth defects such as skeletal andfacial deformities were seen. However, it is not clear that the deformitieswere related to fosinopril. Birth defects were not seen in rabbits.
• Lisinopril?Studies in mice and ratsat doses many times the recommended human dose have shown that use of lisinoprilcauses a decrease in successful pregnancies, a decrease in the weight of infants,and an increase in infant deaths. It has also caused a decrease in successfulpregnancies and abnormal bone growth in rabbits. Lisinopril has not been shownto cause birth defects in mice, rats, or rabbits.
• Moexipril?Studies in rats givenup to 90 times the recommended human dose, and studies in rabbits given upto 0.7 times the recommended human dose, did not show that moexipril causesbirth defects in animals.
• Perindopril?Studies in rabbits givenup to 50 times the recommended human dose, and monkeys given up to 17 timesthe recommended human dose, did not show that perindopril causes birth defectsin animals.
• Quinapril?Studies in rats have shownthat quinapril causes lower birth weights and changes in kidney structureof the fetus. However, birth defects were not seen in rabbits given quinapril.
• Trandolapril?Studiesin rabbits, rats, and monkeys did not show that trandolapril causes any birthdefects in animals.

Breast-feeding??

• Benazepril, captopril, enalapril enalaprilat,and fosinopril?These medicines pass into breast milk.
• Cilazapril, lisinopril, moexipril, perindopril,quinapril, ramipril, and trandolapril?It is not known whetherthese medicines pass into breast milk. However, these medicines have not beenreported to cause problems in nursing babies.

Children?Children may be especially sensitive to the bloodpressure-lowering effect of ACE inhibitors. This may increase the chanceof side effects or other problems during treatment. Therefore, it is especiallyimportant that you discuss with the child's doctor the good that this medicinemay do as well as the risks of using it.

Older adults?This medicine has been tested in a limited numberof patients 65 years of age or older and has not been shown to cause differentside effects or problems in older people than it does in younger adults.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When you are takingor receiving ACE inhibitors it is especially important that your health careprofessional know if you are taking any of the following:

• Alcohol or
• Diuretics (water pills)?Effects on blood pressure may be increased.In addition, some diuretics make the increase in potassium in the blood causedby ACE inhibitors even greater

• Potassium-containing medicines or supplements or
• Salt substitutes or
• Low-salt milk?Use of these substances with ACE inhibitors mayresult in an unusually high potassium level in the blood, which can lead toheart rhythm and other problems

Other medical problems? The presence of other medicalproblems may affect the use of the ACE inhibitors. Make sure you tell yourdoctor if you have any other medical problems, especially:

• Diabetes mellitus (sugar diabetes)?Increased risk of potassiumlevels in the body becoming too high, or increased effect of insulin on controlof blood sugar

• Heart or blood vessel disease or
• Low sodium diet?Lowering blood pressure may make problems resultingfrom these conditions worse

• Kidney disease or
• Liver disease?ACE inhibitors' effects may be increased becauseof slower removal of medicine from the body

• Kidney transplant?Increased risk of kidney disease caused byACE inhibitors

• Systemic lupus erythematosus (SLE)?Increased risk of bloodproblems caused by ACE inhibitors

• Previous reaction to any ACE inhibitor or previous occurrence involvinghoarseness; swelling of face, mouth, hands, or feet; or sudden trouble inbreathing?Reaction is more likely to occur again

Proper Use of This Medicine

To help youremember to take your medicine, try to get into the habit of taking it atthe same time each day.

For patients taking captopril or moexipril :

• These medicines are best taken on an empty stomach 1 hour beforemeals, unless you are otherwise directed by your doctor.

For patients taking ramiprilcapsules: If youhave trouble swallowing capsules, you may open the ramipril capsule and mixthe medicine with applesauce, water or apple juice. Mix only one dose at atime just before taking it. You may mix a dose ahead of time and save it forno more than 24 hours at room temperature or 18 hours in the refrigerator.If you are unsure about these instructions, ask your doctor or pharmacist.

For patients taking this medicine for high blood pressure:

• In addition to the use of the medicine your doctor has prescribed,treatment for your high blood pressure may include weight control and carein the types of foods you eat, especially foods high in sodium. Your doctorwill tell you which of these are most important for you. You should checkwith your doctor before changing your diet.
• Many patients who have high blood pressure will not notice any signsof the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and thatyou keep your appointments with your doctor even if you feel well.
• Remember that this medicine will not cure your high blood pressurebut it does help control it. Therefore, you must continue to take it as directedif you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problemssuch as heart failure, blood vessel disease, stroke, or kidney disease.

Dosing?The dose of the ACE inhibitor will be differentfor different patients. Follow your doctor's orders orthe directions on the label. The following information includes onlythe average doses. If your dose is different, do notchange it unless your doctor tells you to do so.

The number of capsules or tablets that you take depends on the strengthof the medicine. Also, the number of doses you take eachday, the time allowed between doses, and the length of time you take the medicinedepend on the medical problem for which you are taking the ACE inhibitor.

For benazepril
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?10 milligrams (mg) once a day at first. Then, your doctormay increase your dose to 20 to 40 mg a day taken as a single dose or dividedinto two doses.
    • Children 6 years of age and older?Use and dose must be determinedby your doctor.
    • Children under 6 years of age?Use and dose must be determinedby your doctor.

For captopril
• For oral dosage form (tablets):
  • For congestive heart failure:
    • Adults?25 to 100 mg two or three times a day.
    • Children?Dose must be determined by your doctor.
  • For high blood pressure:
    • Adults?25 to 50 mg two or three times a day.
    • Children?Dose must be determined by your doctor.
  • For kidney problems related to diabetes:
    • Adults?25 mg three times a day.
  • For treatment after a heart attack:
    • Adults?12.5 to 50 mg three times a day.

For cilazapril
• For oral dosage form (tablets):
  • For congestive heart failure:
    • Adults?0.5 mg once a day at first. Then your doctor may increaseyour dosage up to 5 mg once a day.
    • Children?Use and dose must be determined by your doctor.
  • For high blood pressure:
    • Adults?2.5 to 10 mg once a day.
    • Children?Use and dose must be determined by your doctor.

For enalapril
• For oral dosage form (tablets):
  • For congestive heart failure:
    • Adults?2.5 mg once a day or two times a day at first. Yourdoctor may increase your dose to 5 to 40 mg a day taken as a single dose ordivided into two doses.
    • Children?Use and dose must be determined by your doctor.
  • For high blood pressure:
    • Adults?5 mg once a day at first. Then, your doctor may increaseyour dose to 10 to 40 mg a day taken as a single dose or divided into twodoses.
    • Children 1 month to 16 years of age?Use and dose must be determinedby your doctor.
    • Newborns?Use and dose must be determined by your doctor.
  • For treating weakened heart muscle:
    • Adults?2.5 mg two times a day at first. Then, your doctor mayincrease your dose up to 20 mg a day taken in divided doses.
• For injection dosage form:
  • For high blood pressure:
    • Adults?1.25 mg every six hours injected into a vein.
    • Children?Use and dose must be determined by your doctor.

For fosinopril
• For oral dosage form (tablets):
  • For congestive heart failure:
    • Adults?10 mg once a day at first. Then your doctor may increaseyour dose to 20 to 40 mg once a day.
  • For high blood pressure:
    • Adults?10 to 40 mg once a day.
    • Children weighing more than 50 kg (110 lbs)?5 to 10 mg a dayat first.
    • Children weighing less than 50 kg (110 lbs)?Use and dose mustbe determined by your doctor.

For lisinopril
• For oral dosage form (tablets):
  • For congestive heart failure:
    • Adults?5 to 20 mg once a day.
    • Children?Use and dose must be determined by your doctor.
  • For high blood pressure:
    • Adults?10 to 40 mg once a day.
    • Children 6 to 16 years of age?Use and dose must be determinedby your doctor.
    • Children younger than 6 years of age?Use and dose must be determinedby your doctor.
  • For immediate treatment after a heart attack:
    • Adults?5 mg once a day at first. Your doctor may increase thedose to 10 mg once a day.
    • Children?Use and dose must be determined by your doctor.

For moexipril
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?7.5 mg once a day. Then, your doctor may increase yourdose up to 30 mg a day taken as a single dose or divided into two doses.
    • Children?Use and dose must be determined by your doctor.

For perindopril
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?4 mg once a day. Then, your doctor may increase yourdosage up to 16 mg a day taken as a single dose or divided into two doses.
    • Children?Use and dose must be determined by your doctor.

For quinapril
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?10 to 20 mg once a day at first. Then, your doctor mayincrease your dosage up to 80 mg a day taken as a single dose or divided intotwo doses.
    • Children?Use and dose must be determined by your doctor.
  • For congestive heart failure:
    • Adults?5 mg twice a day at first. Then, your doctor may increaseyour dose to 20 to 40 mg a day taken in two divided doses.

For ramipril
• For oral dosage form (capsules):
  • For high blood pressure:
    • Adults?2.5 mg once a day at first. Then, your doctor may increaseyour dosage up to 20 mg a day taken as a single dose or divided into two doses.
    • Children?Use and dose must be determined by your doctor.
  • For congestive heart failure after a heart attack:
    • Adults?2.5 to 5 mg twice a day.
  • For reducing risk of heart attack, stroke or death from cardiovascularcauses
    • Adults? 2.5 mg once a day for one week. For the next threeweeks the dose is 5 mg a day, and then increased as needed to 10 mg a day.The dose may be divided if needed.

      Note:

      For use in people aged 55 and older.

For trandolapril
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 to 2 mg once a day at first. Then, your doctor mayincrease your dose to 2 to 4 mg a day taken as a single or divided into twodoses.
    • Children?Use and dose must be determined by your doctor.
  • For treatment after a heart attack:
    • Adults?1 mg once a day at first. Then, your doctor may increaseyour dose up to 4 mg a day taken as a single or divided into two doses.

Missed dose?If you miss a dose of this medicine, take it assoon as possible. However, if it is almost time for your next dose, skip themissed dose and go back to your regular dosing schedule. Do not double doses.

Storage?To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store in the bathroom, near the kitchen sink, or in otherdamp places. Heat or moisture may cause the medicine to break down.
• Do not keep outdated medicine or medicine no longer needed. Be surethat any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

It isimportant that your doctor check your progress at regular visits to make surethat this medicine is working properly and to check for unwanted effects.

For patients taking this medicine for high blood pressure:

• Do not take other medicines unless they havebeen discussed with your doctor. This especially includes over-the-counter(nonprescription) medicines for appetite control, asthma, colds, cough, hayfever, or sinus problems, since they may tend to increase your blood pressure.

Dizziness or light-headedness may occur after the first dose of this medicine,especially if you have been taking a diuretic (water pill). Make sure youknow how you react to this medicine before you drive, use machines, or doanything else that could be dangerous if you are dizzy.

Check with your doctor right away if you become sick while taking thismedicine, especially with severe or continuing nausea and vomiting or diarrhea.These conditions may cause you to lose too much water and lead to low bloodpressure.

Notify your doctor immediately if you are or become pregnant while takingthis medicine.

Check with your doctor if you have any signs of infection such as chills,fever, or sore throat, because these may be signs of neutropenia.

Check with your doctor right away if you have symptoms of jaundice (yellowskin or eyes) because these may be signs of a serious liver condition.

Dizziness, light-headedness, or fainting also may occur if you exerciseor if the weather is hot. Heavy sweating can cause loss of too much waterand low blood pressure. Use extra care during exercise or hot weather.

Avoid alcoholic beverages until you have discussedtheir use with your doctor. Alcohol may make the low blood pressureeffect worse and/or increase the possibility of dizziness or fainting.

Check with your doctor if you experience any welts or swelling around yourface, throat or tongue. Swelling in the mouth or throat area may cause breathingto become very difficult and could result in death.

Check with your doctor if you have strong stomach pain. This could be asymptom of a condition called intestinal angioedema. Your doctor may haveto use a CT scan or an ultrasound to diagnose this condition.

Before having any kind of surgery (including dental surgery) or emergencytreatment, tell the medical doctor or dentist in charge that you are takingthis medicine.

For patients taking captopril or fosinopril:

• Before you have any medical tests, tell the doctor in charge thatyou are taking this medicine. The results of some tests may be affected bythis medicine.

Side Effects of This Medicine

Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects.Although not all of these side effects may occur, if they do occur they mayneed medical attention.

Check with your doctorimmediately if any of the following side effects occur:

Rare

Fever and chills; hoarseness; swelling of face, mouth, hands, or feet; trouble in swallowing or breathing (sudden); stomachpain, itching of skin, or yellow eyes or skin

Check with your doctor assoon as possible if any of the following side effects occur:

Less common

Dizziness, light-headedness, or fainting; skin rash, with or without itching, fever, or joint pain

Rare

Abdominal pain, abdominal distention, fever, nausea, or vomiting; chest pain

Signs and symptoms of too much potassium in the body

Confusion; irregular heartbeat; nervousness; numbness or tingling inhands, feet, or lips; shortness of breath or difficultybreathing; weakness or heaviness of legs

Other side effects may occur that usually do not need medical attention.These side effects may go away during treatment as your body adjusts to themedicine. However, check with your doctor if any of the following side effectscontinue or are bothersome:

More common

Cough (dry, persistent); headache

Less common

Diarrhea; loss of taste; nausea; unusual tiredness

Other side effects not listed abovemay also occur in some patients. If you notice any other effects, check withyour doctor.

Additional Information

Once a medicine has been approvedfor marketing for a certain use, experience may show that it is also usefulfor other medical problems. Although these uses are not included in productlabeling, ACE inhibitors are used in certain patients with the following medicalconditions:

• Hypertension in scleroderma (high blood pressure in patients withhardening and thickening of the skin)
• Renal crisis in scleroderma (kidney problems in patients with hardeningand thickening of the skin)

Other than the above information, there is no additional information relatingto proper use, precautions, or side effects for these uses.