Worst Pills, Best Pills

An expert, independent second opinion on more than 1,800 prescription drugs, over-the-counter medications, and supplements

Drug Profile

Do NOT stop taking this or any drug without the advice of your physician. Some drugs can cause severe adverse effects when they are stopped suddenly.

Limited Use [what does this mean?]
Generic drug name: benazepril (ben AY ze pril)
Brand name(s): LOTENSIN
GENERIC: available FAMILY: Angiotensin Converting Enzyme (ACE) INHIBITORS
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: benazepril and hydrochlorothiazide (ben AY ze pril and hy droe klor oh THYE a zide)
Brand name(s): LOTENSIN HCT
GENERIC: available FAMILIES: Angiotensin Converting Enzyme (ACE) INHIBITORS, Thiazide Diuretics
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: captopril (KAP toe pril)
Brand name(s): CAPOZIDE
GENERIC: available FAMILY: Angiotensin Converting Enzyme (ACE) INHIBITORS
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: captopril and hydrochlorothiazide (KAP toe pril and hye droe klor oh THYE a zide)
Brand name(s):
GENERIC: available FAMILIES: Angiotensin Converting Enzyme (ACE) INHIBITORS, Thiazide Diuretics
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: enalapril (n AL ap ril)
Brand name(s): EPANED, VASOTEC
GENERIC: available FAMILY: Angiotensin Converting Enzyme (ACE) INHIBITORS
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: enalapril and hydrochlorothiazide (n AL ap ril and hye droe klor oh THYE a zide)
Brand name(s): VASERETIC
GENERIC: available FAMILIES: Angiotensin Converting Enzyme (ACE) INHIBITORS, Thiazide Diuretics
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: fosinopril (foe SIN oh pril)
Brand name(s):
GENERIC: available FAMILY: Angiotensin Converting Enzyme (ACE) INHIBITORS
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: fosinopril and hydrochlorothiazide (foe SIN oh pril and hye droe klor oh THY a zide)
Brand name(s):
GENERIC: available FAMILIES: Angiotensin Converting Enzyme (ACE) INHIBITORS, Thiazide Diuretics
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: lisinopril (liss sin o prill)
Brand name(s): PRINIVIL, QBRELIS, ZESTRIL
GENERIC: available FAMILY: Angiotensin Converting Enzyme (ACE) INHIBITORS
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: lisinopril and hydrochlorothiazide (liss SIN o pril and hye droe klor oh THYE a zide)
Brand name(s): PRINZIDE, ZESTORETIC
GENERIC: available FAMILIES: Angiotensin Converting Enzyme (ACE) INHIBITORS, Thiazide Diuretics
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: moexipril (moe EX i prill)
Brand name(s): UNIVASC
GENERIC: available FAMILY: Angiotensin Converting Enzyme (ACE) INHIBITORS
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: moexipril with hydrochlorothiazide
Brand name(s): UNIRETIC
GENERIC: available FAMILY: Angiotensin Converting Enzyme (ACE) INHIBITORS
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: perindopril (per IN doe pril)
Brand name(s): ACEON
GENERIC: available FAMILY: Angiotensin Converting Enzyme (ACE) INHIBITORS
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: perindopril and amlodipine
Brand name(s): PRESTALIA
GENERIC: available FAMILY: Other Drugs for High Blood Pressure
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: quinapril (KWIN a pril)
Brand name(s): ACCUPRIL
GENERIC: available FAMILY: Angiotensin Converting Enzyme (ACE) INHIBITORS
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: quinapril hydrochloride and hydrochlorothiazide
Brand name(s): ACCURETIC, QUINARETIC
GENERIC: available FAMILY: Other Drugs for High Blood Pressure
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: ramipril (RA mi pril)
Brand name(s): ALTACE
GENERIC: available FAMILY: Angiotensin Converting Enzyme (ACE) INHIBITORS
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: trandolapril (tran DOL ap ril)
Brand name(s): MAVIK
GENERIC: available FAMILY: Angiotensin Converting Enzyme (ACE) INHIBITORS
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: amlodipine and benazepril (am LOE di peen and ben AY ze pril)
Brand name(s): LOTREL
GENERIC: available FAMILIES: Angiotensin Converting Enzyme (ACE) INHIBITORS, Calcium Channel Blockers, long-acting
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: verapamil and trandolapril (ver AP a mil and tran DOE la pril)
Brand name(s): TARKA
GENERIC: available FAMILIES: Angiotensin Converting Enzyme (ACE) INHIBITORS, Calcium Channel Blockers, long-acting
Find the drug label by searching at DailyMed.

Pregnancy and Breast-feeding Warnings [top]

Pregnancy Warning

In a published retrospective epidemiological study, infants whose mothers had taken an ACE inhibitor during their first trimester of pregnancy appeared to have an increased risk of major congenital malformations compared with infants whose mothers had not undergone first trimester exposure to ACE inhibitor drugs. The number of cases of birth defects is small and the findings of this study have not yet been repeated.[1]

Breast-feeding Warning

These drugs are known to be excreted either in animal or human milk. Because of the potential for serious adverse effects in nursing infants, you should not take these drugs while nursing.

Safety Warnings For This Drug [top]

FDA BLACK BOX PREGNANCY WARNING

When used in pregnancy, ACE inhibitors can cause injury and even death to the developing fetus.  When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible.[2],[3]

Cough Alert

A common adverse effect, after taking ACE inhibitors for a few weeks, is a dry, hacking cough, especially in women. Check with your doctor about a four-day withdrawal from your ACE inhibitor to determine if this is the cause of your cough. This trial withdrawal can prevent unnecessary and sometimes costly tests and treatments.

Warning

A fixed-combination drug should not be the first drug used to treat your high blood pressure. You may not need more than one drug. If you do need two drugs, the fixed-combination product may not contain the dose of each drug that is right for you. Your doctor has to regularly check your condition and reevaluate the effect of the drug(s) you take. This may mean adjusting doses, and even changing drugs, to ensure proper treatment. This fixed-combination drug may be the best drug for you, but it should be used only after you have tried each of its ingredients separately, in varying doses. If the doses that you need to control your high blood pressure match those in this fixed-combination product, use it if the combination drug is more convenient.

Heat Stress Alert

These drugs can affect your body’s ability to adjust to heat, putting you at risk of “heat stress.” If you live alone, ask a friend to check on you several times during the day. Early signs of heat stress are dizziness, lightheadedness, faintness, and slightly high temperature. Call your doctor if you have any of these signs. Drink more fluids (water, fruit and vegetable juices) than usual—even if you’re not thirsty—unless your doctor has told you otherwise. Do not drink alcohol.

Facts About This Drug [top]

 

Combination Drugs Containing ACE Inhibitors
If you are taking any of the ACE inhibitor–hydrochlorothiazide combination products listed above, also read the additional information pertaining to hydrochlorothiazide.

 

WARNING: FETAL TOXICITY

When pregnancy is detected, discontinue ACE inhibitors as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death in the developing fetus.

These medicines belong to a group...

 

Combination Drugs Containing ACE Inhibitors
If you are taking any of the ACE inhibitor–hydrochlorothiazide combination products listed above, also read the additional information pertaining to hydrochlorothiazide.

 

WARNING: FETAL TOXICITY

When pregnancy is detected, discontinue ACE inhibitors as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death in the developing fetus.

These medicines belong to a group of drugs used to treat high blood pressure called angiotensin-converting enzyme (ACE) inhibitors. Captopril (CAPOTEN), lisinopril (PRINIVIL, ZESTRIL) and enalapril (VASOTEC) are the preferred ACE inhibitors because they have been on the market the longest.

Public Citizen's Health Research Group has designated all of these drugs as Limited Use.

ACE inhibitors are effective drugs for the treatment of high blood pressure (hypertension) and congestive heart failure in older adults. After a heart attack, treatment with some ACE inhibitors prevents subsequent heart failure and reduces morbidity and mortality (the rate of disease-related sickness and death).[4] The American Heart Association-modified secondary-prevention guidelines recommend that ACE inhibitors be "considered for all patients with vascular disease."[5]

In general, patients older than 60 should take less than the usual adult dose of these drugs.

Since enalapril stays in the body longer than captopril, its adverse effects may last longer. At times, when using ACE inhibitors, the blood pressure goes too low, especially with the first dose. Older people are more likely to be sensitive to low blood pressure.

ACE inhibitors and kidney disease and kidney toxicity

In people with high blood pressure and kidney disease, ACE inhibitors, along with water pills (diuretics), can slow progressive kidney failure.[6],[7],[8] ACE inhibitors also may be the preferred class of drugs for controlling blood pressure in people with kidney damage caused by diabetes.[9],[7],[10]

However, ACE inhibitors can cause dangerous side effects such as bone marrow depression and, ironically, kidney disease itself, and therefore should be taken in lower doses by older adults. This may amount to less than one-third of the typical dose.

In general, patients are more likely to suffer harmful effects from ACE inhibitors if they have decreased kidney function or dehydration. Because older adults generally have some decrease in kidney function, these drugs may be especially dangerous for them. In older adults, therefore, use of an ACE inhibitor requires a careful balancing of the risks and benefits by the patient and physician.

A study published in March 2011 in the Canadian Medical Association Journal (CMAJ) found that people prescribed an ACE inhibitor in combination with an angiotensin II receptor blocker (ARB) had greater risks of kidney toxicity and higher blood levels of potassium than did those using one of these two families of drugs alone.

Previous randomized, controlled trials had shown that the combination of an ACE inhibitor with an ARB increased the risk of kidney problems. The 2011 CMAJ study was conducted to test a belief held by some doctors that the combination would not cause problems in everyday clinical practice, because doctors would individualize the dosing of both drugs and thereby cut the risk of kidney problems.

The results of the CMAJ study show that the risk of kidney toxicity from the prescription of this combination are not reduced in the everyday practice of medicine and actually are increased.[11]

An article in the December 2012 issue of Worst Pills, Best Pills News warned readers against combining an ACE inhibitor with an ARB or with the hypertension drug aliskiren (TEKTURNA) because two large studies demonstrated that such drug combinations fail to provide additional benefit but do cause a higher rate of several life-threatening side effects than does therapy using only one of these medications. These side effects include low blood pressure, kidney failure and dangerously high blood potassium levels.

The April 2013 issue of Worst Pills, Best Pills News discussed another recent BMJ study. This study suggested that an increased risk of acute kidney injury (AKI) is associated with combining nonsteroidal anti-inflammatory drugs (NSAIDs) with two antihypertensive drugs: a diuretic plus either an ACE inhibitor or an ARB.

The BMJ study found that patients currently using a triple-therapy combination — a diuretic, an ACE inhibitor or an ARB, and an NSAID — have a 31 percent greater risk of developing AKI than do current users of a diuretic plus an ACE inhibitor or an ARB without an NSAID.[12]

In April 2016, the New England Journal of Medicine published a study showing that in patients with chronic heart failure, taking the ACE inhibitor enalapril with aliskiren increases the risk of low blood pressure, high blood potassium levels, and kidney impairment, while adding no benefit over taking either drug alone.[13]

ACE inhibitors and potassium levels

Patients taking a diuretic should be watched carefully or, at their physician’s discretion, be taken off that medication when an ACE inhibitor is started. ACE inhibitor decrease the potassium loss caused by thiazide-type diuretics.

Patients using potassium-sparing drugs (see "Before You Use These Drugs" section below) should not use ACE inhibitors. Potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium may lead to significant increases in serum potassium, which can be fatal in extreme cases.

In October 2014, a study in The British Medical Journal (BMJ) showed that ACE inhibitors and ARBs, when used in combination with the antibiotic trimethoprim-sulfamethoxazole, can increase blood potassium levels and can increase the risk of sudden death, most likely due to abnormal heart rhythms.[14] (Read more in the June 2015 Worst Pills, Best Pills News.)

ACE inhibitors and birth defects

The possibility of birth defects when ACE inhibitors are used in the second and third trimesters of pregnancy is well known. All marketed ACE inhibitors carry a black-box warning reflecting this in their product labels, but a public advisory issued by the Food and Drug Administration (FDA) in 2006 was the first time concerns had been raised about use of the drugs during the first trimester.[15]

ACE inhibitors and swelling

Angioedema — a sudden swelling of the face, lips and particularly the tongue — is a rare but potentially life-threatening reaction to ACE inhibitors.[16],[17] Although this reaction usually occurs with the first dose, it may occur years later. Once angioedema occurs, treatment with the ACE inhibitor should be stopped and all other ACE inhibitors avoided.[17]

Intestinal angioedema also has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain with or without nausea and vomiting. In some cases, there was no prior history of facial angioedema.

ACE inhibitors and impaired liver function

The drug product information for ramipril (ALTACE) states that if a patient develops jaundice or marked elevations in liver enzymes while taking ramipril, the drug should be discontinued.[18]

First-line treatment for high blood pressure 

If you have high blood pressure, the best way to reduce or eliminate your need for medication is by improving your diet, losing weight, exercising and decreasing your salt and alcohol intake. Mild hypertension can be controlled with proper nutrition and exercise. If these measures do not lower your blood pressure enough and you need medication, hydrochlorothiazide (MICROZIDE), a water pill, is the drug of choice, starting with a low dose of 12.5 milligrams daily. Hydrochlorothiazide also costs less than other blood-pressure drugs.

If your high blood pressure is severe and hydrochlorothiazide alone does not control it, another family of high blood pressure-lowering drugs may be added to your treatment. In this case, your doctor should prescribe hydrochlorothiazide and the second drug separately, with the dose of each drug adjusted to meet your needs (rather than using a product that combines the drugs in a fixed combination).

Once your blood pressure has been normal for a year or more, a cautious decrease in drug dose and renewed attention to nondrug treatment may be worth trying, according to The Medical Letter on Drugs and Therapeutics.[19]

An editorial in the BMJ stated the following:

Treatment of hypertension is part of preventive medicine, and like all preventive strategies, its progress should be regularly reviewed by whoever initiates it. Many problems could be avoided by not starting antihypertensive treatment until after prolonged observation. ... Patients should no longer be told that treatment is necessarily for life: the possibility of reducing or stopping treatment should be mentioned at the outset.[20]

The May 2012 issue of Worst Pills, Best Pills News highlighted a BMJ study that indicated patients taking several types of commonly used antihypertensive medications are at increased risk of developing gout, a type of arthritis.

The BMJ study also showed that a small number of other antihypertensive drugs appear to have the opposite effect, decreasing the risk of gout.

All patients should be aware of the risk of gout with use of diuretics, beta-blockers, ACE inhibitors and non-losartan ARB when starting these medications or whenever their dose is increased.[21]

Regulatory actions surrounding ACE inhibitors

2006: The FDA issued a public health advisory concerning the increased possibility of birth defects in children born to mothers who took ACE inhibitors during the first trimester of pregnancy.

2012: In April, the FDA also issued a safety communication concerning the severe adverse reactions involving the use of aliskiren with ACE inhibitors or ARBs. This warning was based on a large clinical trial (the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints, or ALTITUDE). The trial was stopped early when it became clear that combining aliskiren with either an ACE inhibitor or an ARB harmed patients and did not confer any additional benefit. The combination of aliskiren with either class also caused side effects (kidney disease, low blood pressure and high potassium levels) identical to those seen when ACE inhibitors and ARBs were given together, further confirming the risks of combination therapy.[22]

In October 2012, Public Citizen filed a petition urging the FDA to place a black-box warning on ACE inhibitors, ARBs and aliskiren.

The black-box warning requested by Public Citizen would be placed on the labels of all 18 ACE inhibitor and ARB medications, as well as aliskiren, to alert doctors and patients to the increased risk of life-threatening side effects — with no added benefit — when the drugs are used in combination with one another. Public Citizen also is petitioned the agency to require that an FDA-approved Medication Guide be distributed to all patients prescribed these drugs, as well as a “Dear Doctor” letter to physicians warning of the dangers of combination therapy.[22]

In April 2015, the FDA denied our petition.

In September 2012, the FDA issued an advisory to not co-administer aliskiren with ACE inhibitors and ARBs in patients with diabetes and to avoid using aliskiren with ACE inhibitors and ARBs in patients with renal impairment.[23]

Before You Use This Drug [top]

Do not use if you have or have had:

  • angioedema[17]
  • severe kidney disease
  • high blood potassium levels
  • liver disease
  • a potassium-sparing drug such as spironolactone (ALDACTONE), triamterene (DYRENIUM—a Do Not Use drug) or triamterene and hydrochlorothiazide (DYAZIDE/MAXZIDE)
  • pregnancy or are breast-feeding

Tell your doctor if you have or have had:

  • allergies to drugs
  • an autoimmune disease such as lupus or scleroderma
  • renal artery stenosis or generalized arteriosclerosis[24]
  • asthma or other lung problems
  • bone marrow depression
  • cerebrovascular accident
  • diabetes
  • salt-restricted diet
  • heart, kidney, or liver problems

Tell your doctor about any other drugs you take, including aspirin, herbs, vitamins, alcohol, and other nonprescription products.

When You Use This Drug [top]

  • If you take a diuretic, your doctor may taper you off of it, or lower your dose, a few days prior to starting one of these drugs. Take the first dose of any of these drugs under medical supervision. For hypertension, treatment supervision should last at least two hours and then an additional hour after your blood pressure has stabilized. Usually, this will be at a doctor’s office. Have a companion stay with you until at least six hours has elapsed from your first dose.
  • When taken for congestive heart failure, supervision should continue at least six hours. Many doctors prefer to start these drugs in a hospital. You should be watched closely for two weeks.
  • You should also be closely supervised whenever your dose of any of these drugs or diuretics is changed.
  • You may feel dizzy when rising from a lying or sitting position. If you are lying down, hang your legs over the side of the bed for a few minutes, then get up slowly. When getting up from a chair, stay by the chair until you are sure that you are not dizzy. 
  • Drink plenty of fluids to avoid dehydration, especially when exercising, during spells of hot weather, or if you have nausea, vomiting, or diarrhea. Call your doctor if any of these conditions continue or become severe.
  • Do not take other drugs without talking to your doctor first—especially nonprescription drugs for appetite control, asthma, colds, coughs, hay fever, or sinus problems.
  • Be careful not to overexert yourself, even though your chest pain may feel better. Talk to your doctor about a safe exercise program.
  • Until you know how you react to these drugs, do not drive or perform other activities requiring alertness. Do not drive after taking the first dose, or any time your dose changes.
  • Maintain some sodium (salt) in your diet, but avoid excess salt. Do not use low-salt milk, or salt substitutes containing potassium. Check with your doctor before going on any kind of diet.[25] Do not drink alcohol.
  • Take your blood pressure periodically. Having your blood pressure checked away from the doctor’s office is good practice. If possible, have your own automatic blood pressure measuring device, but be sure to have both your blood pressure and the device checked by your doctor.
  • If you plan to have any surgery, including dental, tell your doctor that you take one of these drugs.
  • Do not stop taking this drug suddenly. Your doctor must give you a schedule to lower your dose gradually.
  • Tell your doctor immediately if you suspect you are pregnant.
  • Tell your doctor if you have chills, fever, or sore throat.

How to Use This Drug [top]

  • If you miss a dose, take it as soon as you remember but skip it if it is almost time for the next dose. Do not take double doses.
  • Do not share your medication with others.
  • Take at the same time(s) each day, with the last dose at bedtime to control blood pressure overnight and decrease daytime drowsiness.
  • Take with or without food except for captopril and moexipril, which are to be taken on an empty stomach at least one hour before meals.
  • Swallow tablets whole or break in half as prescribed.
  • Continue to take, even if you feel well.
  • Store at room temperature with lid on tightly. Do not store in the bathroom. Do not expose to heat, moisture, or strong light. Keep out of reach of children.

Interactions with Other Drugs [top]

The following drugs, biologics (e.g., vaccines, therapeutic antibodies), or foods are listed in Evaluations of Drug Interactions 2003 as causing “highly clinically significant” or “clinically significant” interactions when used together with any of the drugs in this section. In some sections with multiple drugs, the interaction may have been reported for one but not all drugs in this section, but we include the interaction because the drugs in this section are similar to one another. We have also included potentially serious interactions listed in the drug’s FDA-approved professional package insert or in published medical journal articles. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. Make sure to tell your doctor and pharmacist the drugs you are taking and tell them if you are taking any of these interacting drugs:

The blood-pressure-lowering effects of the ACE inhibitors are enhanced when used with other blood-pressure-lowering drugs such as the hydrochlorothiazide (ESIDRIX, HYDRODIURIL, MICROZIDE).

Fosinopril may interact with antacids such as Maalox.

Quinapril may interact with tetracycline (ACHROMYCIN, SUMYCIN).

Ramipril may interact with the oral drugs used for type-2 diabetes or insulin.

ACE inhibitors may interact with nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (MOTRIN). Other interacting drugs are:

ADVIL, alcohol, ALDACTONE, amiloride, aspirin, chlorpromazine, digoxin, DYRENIUM, ECOTRIN, furosemide, GENUINE BAYER ASPIRIN, ibuprofen, INDOCIN, indomethacin, KATO, K-LOR, LANOXICAPS, LANOXIN, LASIX, lithium, LITHOBID, LITHONATE, MIDAMOR, MOTRIN, potassium chloride, salt substitutes, rofecoxib, SLOW-K, spironolactone, triamterene, THORAZINE, VIOXX.

Adverse Effects [top]

Seek emergency help if you experience:

  • difficulty breathing
  • sudden swelling of eyes, face, lips, throat, tongue

Call your doctor immediately if you experience:

  • chest pain or angina
  • confusion
  • dizziness, lightheadedness
  • fainting
  • fever or chills
  • irregular heartbeat
  • hoarseness
  • joint pain
  • a feeling of heaviness or weakness in your legs, awkwardness when walking
  • nervousness
  • numbness or tingling in hands, feet, lips
  • skin rash with or without itching
  • difficulty swallowing
  • swelling of hands, face, mouth, ankles, feet
  • stomach pain, nausea, vomiting
  • itchiness
  • yellow eyes or skin

Call your doctor if these symptoms continue:

  • diarrhea<
  • cough or dry, tickling sensation in throat
  • fatigue, unusual tiredness
  • headache
  • nausea, vomiting
  • altered or lost sense of taste, loss of appetite
  • urinary pain, or change in frequency or quantity of urine

Periodic Tests[top]

Ask your doctor which of these tests should be done periodically while you are taking this drug:

  • blood pressure
  • kidney function tests
  • liver function tests
  • urinary protein
  • white blood cell count
  • potassium levels

last reviewed September 30, 2021