ANGIOTENSIN-CONVERTINGENZYME (ACE) INHIBITORS AND HYDROCHLOROTHIAZIDE (Systemic)?

Some commonly used brand names are:

In the U.S.?

• Accuretic ⁶
• Capozide ²
• Lotensin HCT ¹
• Prinzide ⁴
• Uniretic ⁵
• Vaseretic ³
• Zestoretic ⁴

In Canada?

• Accuretic ⁶
• Prinzide ⁴
• Vaseretic ³
• Zestoretic ⁴

? Not commercially available in Canada.

Category

• Antihypertensive?Benazepril and Hydrochlorothiazide; Captopril and Hydrochlorothiazide; Enalapriland Hydrochlorothiazide; Lisinopril andHydrochlorothiazide; Moexipril and Hydrochlorothiazide; Quinapril and Hydrochlorothiazide
• Vasodilator, congestive heart failure?Captopril and Hydrochlorothiazide; Enalapriland Hydrochlorothiazide; Lisinopril andHydrochlorothiazide

Description

This combination belongs to the class of medicinescalled high blood pressure medicines (antihypertensives). It is used to treathigh blood 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.

The exact way in which benazepril, captopril, enalapril, lisinopril, moexipril,and quinapril work is not known. They block an enzyme in the body that isnecessary to produce a substance that causes blood vessels to tighten. Asa result, they relax blood vessels. This lowers blood pressure and increasesthe supply of blood and oxygen to the heart. Hydrochlorothiazide helps reducethe amount of salt and water in the body by acting on the kidneys to increasethe flow of urine; this also helps to lower blood pressure.

This combination may also be used for other conditions as determined byyour doctor.

This medicine is available only with doctor's prescription, in the followingdosage forms:

Oral
• Benazepril and Hydrochlorothiazide
  • Tablets (U.S.)
• Captopril and Hydrochlorothiazide
  • Tablets (U.S.)
• Enalapril and Hydrochlorothiazide
  • Tablets (U.S. and Canada)
• Lisinopril and Hydrochlorothiazide
  • Tablets (U.S. and Canada)
• Moexipril and Hydrochlorothiazide
  • Tablets (U.S.)
• Quinapril and Hydrochlorothiazide
  • Tablets (U.S. and Canada)

Before Using This Medicine

In deciding to use a medicine,the risks of taking the medicine must be weighed against the good it willdo. This is a decision you and your doctor will make. For the angiotensin-convertingenzyme (ACE) inhibitors and hydrochlorothiazide, the following should be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to benazepril, enalapril, captopril, lisinopril, moexipril,quinapril, sulfonamides (sulfa drugs), bumetanide, furosemide, acetazolamide,dichlorphenamide, or methazolamide or to hydrochlorothiazide or any of theother thiazide diuretics (water pills). Also tell your health care professionalif you are allergic to any other substances, such as foods, sulfites or otherpreservatives, or dyes.

Pregnancy?Studies with this combination medicine have not beendone in pregnant women. However, use of any of the ACE inhibitors duringpregnancy, especially in the second and third trimesters (after the firstthree months), can cause low blood pressure, kidney failure, too much potassium,or even death in newborns. Therefore, it is importantthat you check with your doctor immediately if you think that you may be pregnant. Be sure that you have discussed this with your doctor before takingthis medicine. In addition, if your medicine contains:

• Benazepril?Studies in rats, miceand rabbits at doses up to 300 times the recommended human dose showed noevidence of birth defects.
• Captopril?Studies in rabbits andrats at doses up to 400 times the recommended human dose have shown that captoprilcauses an increase in death 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.
• 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 and rabbitsdid not show moexipril to cause birth defects.
• Quinapril?Studies in rats showedquinapril caused reduced body weights but did not show it to cause birth defectsin either rats or rabbits.
• Hydrochlorothiazide?Hydrochlorothiazidehas not been shown to cause birth defects or other problems in animal studies.However, when hydrochlorothiazide is used during pregnancy, it may cause sideeffects including jaundice, blood problems, and low potassium in the newbornbaby.

Breast-feeding?

• Benazepril?Passes into breast milk.However, this medicine has not been reported to cause problems in nursingbabies.
• Captopril?Passes into breast milk.However, this medicine has not been reported to cause problems in nursingbabies.
• Enalapril?Passes into breast milk.However, this medicine has not been reported to cause problems in nursingbabies.
• Lisinopril?It is not known whether lisinopril passes into breast milk. However, this medicine has not been reportedto cause problems in nursing babies.
• Moexipril?It is not known whethermoexipril passes into breast milk. However, this medicine has not been reportedto cause problems in nursing babies.
• Quinapril?Passes into breast milk.However, this medicine has not been reported to cause problems in nursingbabies.
• Hydrochlorothiazide?Passes intobreast milk. However, this medicine has not been reported to cause problemsin 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. Extra caution may be necessarywhen using hydrochlorothiazide in infants with jaundice because it can makethis condition worse. Therefore, it is especially important that you discusswith the child's doctor the good that this medicine may do as well as therisks of using it.

Older adults?Dizziness or lightheadedness and symptoms of toomuch potassium loss may be more likely to occur in the elderly, who may bemore sensitive to the effects of this medicine.

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 taking ACE inhibitorsand hydrochlorothiazide it is especially important that your health care professionalknow if you are taking any of the following:

• Cholestyramine or
• Colestipol?Use with thiazide diuretics may prevent the diureticfrom working properly; the diuretic should be taken at least 1 hour beforeor 4 hours after cholestyramine or colestipol

• Diabetes medication (insulin or tablets)?Blood sugar levelsmay change; extra care in self monitoring is necessary

• Digitalis glycosides (heart medicine)?If potassium levels inthe body are decreased, symptoms of digitalis toxicity may occur

• Diuretics (water pills)?Effects on blood pressure may be increased

• Lithium (e.g., Lithane)?Risk of lithium overdose, even at lowdoses, may be increased

• 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

• Tetracycline?Use with quinapril will decrease the effects oftetracycline

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

• Gout (or history of)?Hydrochlorothiazide may increase the amountof uric acid in the body, which can lead to gout

• Heart or blood vessel disease or
• Heart attack or stroke (recent)?Lowering blood pressure maymake problems resulting from these conditions worse

• Kidney disease or
• Liver disease?Effects may be increased because of slower removalfrom the body

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

• Pancreatitis (inflammation of the pancreas)?Hydrochlorothiazidecan make this condition worse

• Systemic lupus erythematosus (SLE) (or history of)?Hydrochlorothiazidemay worsen the condition, and there is an increased risk of blood problemscaused by ACE inhibitors

• Previous reaction to benazepril, captopril, enalapril, lisinopril,moexipril, or quinapril involving hoarseness; swelling of face, mouth, hands,or feet; or sudden trouble in breathing?Reaction is more likely to occuragain

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 and hydrochlorothiazide or moexipril and hydrochlorothiazide:

• This medicine is best taken on an empty stomach 1 hour before meals,unless you are otherwise directed by your doctor.

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.

This medicine may cause you to have an unusual feeling of tiredness whenyou begin to take it. You may also notice an increase in the amount of urineor in your frequency of urination. After you have taken the medicine for awhile, these effects should lessen. In general, to keep the increase in urinefrom affecting your sleep:

• If you are to take a single dose a day, take it in the morning afterbreakfast.
• If you are to take more than one dose a day, take the last dose nolater than 6 p.m., unless otherwise directed by your doctor.

However, it is best to plan your dose or doses according to a schedulethat will least affect your personal activities and sleep. Ask your healthcare professional to help you plan the best time to take this medicine.

Dosing?The dose of these medicines will be differentfor different patients. Follow your doctor's orders orthe directions on the label. The following information includes onlythe average doses of these medicines. If your dose isdifferent, do not change it unless your doctor tells you to do so.

The number of tablets that you take depends on the strength of the medicine.

For benazepril and hydrochlorothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 tablet once a day.
    • Children?Use and dose must be determined by your doctor.

For captopril and hydrochlorothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 tablet two or three times a day.
    • Children?Dose is based on body weight and must be determinedby your doctor.

For enalapril and hydrochlorothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 tablet once or twice a day.
    • Children?Dose is based on body weight and must be determinedby your doctor.

For lisinopril and hydrochlorothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 or 2 tablets once a day.
    • Children?Dose must be determined by your doctor.

For moexipril and hydrochlorothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 or 2 tablets once a day.
    • Children?Use and dose must be determined by your doctor.

For quinapril and hydrochlorothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 tablet once or twice a day.
    • Children?Use and dose must be determined by your doctor.

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.

Dizziness or lightheadedness may occur, especially after the first doseof this medicine. Make sure you know how you react to the medicine beforeyou drive, use machines, or do anything else that could be dangerous if youare 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.

Check with your doctor if you have signs of infection, such as sore throat,fever, and/or chills. Infections may be a sign of low white blood cell count(neutropenia).

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.

Dizziness, lightheadedness, or fainting may also 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.

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 and hydrochlorothiazide:

• 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.

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.

For diabetic patients:

• Hydrochlorothiazide (contained in this combination medicine) mayraise blood sugar levels. While you are taking this medicine, be especiallycareful in testing for sugar in your urine.

Hydrochlorothiazide (contained in this combination medicine) may causeyour skin to be more sensitive to sunlight than it is normally. Exposure tosunlight, even for brief periods of time, may cause a skin rash, itching,redness or other discoloration of the skin, or a severe sunburn. When youfirst begin taking this medicine:

• Stay out of direct sunlight, especially between the hours of 10:00a.m. and 3:00 p.m., if possible.
• Wear protective clothing, including a hat. Also, wear sunglasses.
• Apply a sun block product that has a skin protection factor (SPF)of at least 15. Some patients may require a product with a higher SPF number,especially if they have a fair complexion. If you have any questions aboutthis, check with your health care professional.
• Apply a sun block lipstick that has an SPF of at least 15 to protectyour lips.
• Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor.

Before you have any medical tests, tell the doctor in charge that you aretaking this medicine. The results of some tests may be affected by this medicine.

Side Effects of This Medicine

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

Seek medical attentionimmediately or call your doctor if any of the following side effectsoccur:

Rare

Swelling of face, mouth, hands, or feet; trouble in swallowing or breathing (sudden); hoarseness; fever and chills

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

Less common

Dizziness, lightheadedness, or fainting; skin rash, with or without itching, fever, or joint pain

Rare

Chest pain; joint pain; lower back or side pain; stomach pain(severe) with nausea and vomiting; unusual bleedingor bruising; yellow eyes or skin

Signs and symptoms of too much or too little potassium in the body

Dryness of mouth; increased thirst; irregular heartbeat; mood or mentalchanges; muscle cramps or pain; numbness or tingling in hands, feet, or lips; weaknessor heaviness of legs; weak pulse

Other side effects may occurthat usually do not need medical attention. These side effects may go awayduring treatment as your body adjusts to the medicine. However, check withyour doctor if any of the following side effects continue or are bothersome:

More common

Cough (dry, persistent)

Less common

Diarrhea; headache; increased sensitivity of skin to sunlight (skin rash, itching, redness orother discoloration of skin or severe sunburn after exposure to sunlight); loss of appetite; lossof taste; stomach upset; unusual tiredness

Otherside effects not listed above may also occur in some patients. If you noticeany other effects, check with your 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 this use is not included in product labeling,ACE inhibitors and hydrochlorothiazide are used in certain patients with thefollowing medical condition:

• Congestive heart failure

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