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: candesartan (kan de SAR tan)
Brand name(s): ATACAND
GENERIC: available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: candesartan and hydrochlorothiazide (can de SAR tan and hye droe klor oh THYE a zide)
Brand name(s): ATACAND HCT
GENERIC: available FAMILIES: Angiotensin Receptor Blockers (ARBs), Thiazide Diuretics
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: eprosartan (ep roe SAR tan)
Brand name(s): TEVETEN
GENERIC: not available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: irbesartan (ir be SAR tan)
Brand name(s): AVAPRO
GENERIC: available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: irbesartan and hydrochlorothiazide (ir be SAR tan and hye droe klor oh THYE a zide)
Brand name(s): AVALIDE
GENERIC: available FAMILIES: Angiotensin Receptor Blockers (ARBs), Thiazide Diuretics
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: losartan (loe SAR tan)
Brand name(s): COZAAR
GENERIC: available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: losartan and hydrochlorothiazide (loe SAR tan and hye droe klor oh THYE a zide)
Brand name(s): HYZAAR
GENERIC: available FAMILIES: Angiotensin Receptor Blockers (ARBs), Thiazide Diuretics
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: telmisartan (tel mi SAR tan)
Brand name(s): MICARDIS
GENERIC: available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: telmisartan and hydrochlorothiazide (tel mi SAR tan and hye droe klor oh THYE a zide)
Brand name(s): MICARDIS HCT
GENERIC: available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: valsartan (val SAR tan)
Brand name(s): DIOVAN
GENERIC: available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: valsartan and hydrochlorothiazide (val SAR tan and hye droe klor oh THYE a zide)
Brand name(s): DIOVAN HCT
GENERIC: available FAMILIES: Angiotensin Receptor Blockers (ARBs), Thiazide Diuretics
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: olmesartan (ol me SAR tan)
Brand name(s): BENICAR
GENERIC: available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: olmesartan and hydrochlorothiazide (ol me SAR tan and hye droe klor oh THYE a zide)
Brand name(s): BENICAR HCT
GENERIC: available FAMILIES: Angiotensin Receptor Blockers (ARBs), Thiazide Diuretics
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: olmesartan with hydrochlorothiazide plus amlodipine
Brand name(s): TRIBENZOR
GENERIC: available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: telmisartan and amlodipine
Brand name(s): TWYNSTA
GENERIC: available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: valsartan with amlodipine
Brand name(s): EXFORGE
GENERIC: available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: valsartan with hydrochlorothiazide plus amlodipine
Brand name(s): EXFORGE HCT
GENERIC: available FAMILY: Angiotensin Receptor Blockers (ARBs)
Find the drug label by searching at DailyMed.

Pregnancy and Breast-feeding Warnings [top]

Pregnancy Warning

When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, angiotensin receptor blockers should be discontinued as soon as possible.

Breast-feeding Warning

These drugs are excreted in animal milk and it is likely that this occurs in humans. Because of the potential for serious adverse effects due to blocking the renin-angiotensin system in nursing infants, you should not take these drugs while nursing.

Safety Warnings For This Drug [top]

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.

Facts About This Drug [top]

 

Combination Drugs Containing Angiotensin II Receptor Blockers

If you are taking any of the angiotensin II receptor blocker–hydrochlorothiazide combination products listed at the top of this page, read the additional information pertaining to hydrochlorothiazide.

WARNING: FETAL TOXICITY

When pregnancy is detected, discontinue angiotensin II receptor blockers (ARBs) as soon as possible.  Drugs that act directly on the renin-angiotensin system can cause injury and death to...

 

Combination Drugs Containing Angiotensin II Receptor Blockers

If you are taking any of the angiotensin II receptor blocker–hydrochlorothiazide combination products listed at the top of this page, read the additional information pertaining to hydrochlorothiazide.

WARNING: FETAL TOXICITY

When pregnancy is detected, discontinue angiotensin II receptor blockers (ARBs) as soon as possible.  Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.[1]

 

These drugs are known as angiotensin II receptor blockers (ARBs). The primary use of this family of drugs is to lower high blood pressure. Public Citizen lists them all as Limited Use drugs (offering limited benefit or benefiting certain people or conditions), except for olmesartan, which has been designated as Do Not Use because it has been found to cause sprue-like enteropathy. Patients with this disorder have inflammation and damage primarily involving the inner lining of the small intestine, which plays a key role in digesting and absorbing food. It also can involve the inner lining of the stomach and colon. Affected patients typically experience severe, chronic diarrhea, malnutrition and weight loss.

 

ARBs, as well as angiotensin-converting enzyme (ACE) inhibitors, have an effect on the natural substance angiotensin, which can raise blood pressure. Like ACE inhibitors, ARBs appear to be less effective than other drugs at lowering blood pressure in most African-Americans.[2] ACE inhibitors have a long-term protective benefit on the heart and kidneys, and information is becoming available on the effect of ARBs on these conditions.

In 2005, the Food and Drug Administration (FDA) approved candesartan (ATACAND) for the treatment of heart failure in patients with left ventricular systolic dysfunction (the chambers of the left side of the heart do not pump blood normally.) Specifically, it was approved to reduce cardiovascular deaths and to reduce heart failure hospitalizations.[3]

In 2007, the FDA also approved valsartan (DIOVAN) for the treatment of hypertension in patients ages 6 to 16 years.[4]

Side effects

Like ACE inhibitors, ARBs cause elevated levels of potassium in the blood. Unlike ACE inhibitors, ARBs do not cause a dry, hacking cough, as is often the case with ACE inhibitors.

Angioedema(hive-like swelling beneath the skin, especially around the eyes and lips); severe allergic reactions, including anaphylactic shock; and rare cases of rhabdomyolysis (breakdown ordisintegration of muscle) have been reported in patients taking ARBs.

Hypotension (low blood pressure) may occur during major surgery with anesthesia in patients treated with ARBs due to blockage of the renin-angiotensin system. Very rarely, hypotension may be severe enough to warrant the use of intravenous fluids, vasopressors (medications that raise blood pressure), or both.[5]

Candesartan

The product label for candesartan warns that caution should be observed when initiating therapy in patients with heart failure. Patients who have heart failure and are given candesartan commonly have hypotension. In a study called the CHARM program, hypotension was reported in 18.8 percent of patients taking candesartan versus 9.8 percent of patients taking a placebo. The incidence of hypotension leading to drug discontinuation in candesartan-treated patients was 4.1 percent, compared with 2.0 percent in placebo-treated patients. Monitoring of blood pressure is recommended while the drug dosage is being adjusted and should be checked periodically thereafter.[3]

Valsartan

There have been reports of spontaneous abortion, oligohydramnios (placenta insufficiency) and newborn kidney dysfunction when pregnant women have inadvertently (presumably not knowing they were pregnant) taken valsartan.[6]

Studies show ... 

All ARBs: Kidney toxicity and high blood potassium

A study published in March 2011 in the Canadian Medical Association Journal (CMAJ) found that people prescribed an ARB in combination with an ACE inhibitor 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 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 risks of kidney toxicity from the prescription of this combination are not reduced in the everyday practice of medicine and actually are increased.[7]

An article in the December 2012 issue of Worst Pills, Best Pills News warned readers against combining an ARB with an ACE inhibitor or with the hypertension drug aliskiren (TEKTURNA) because two large studies demonstrated that such drug combinations fail to provide additional benefits but do cause a higher rate of several life-threatening adverse effects than does therapy using only one of these medications. These adverse 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 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.[8]

In October 2014, a study in the 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.[9] (Read more in the June 2015 Worst Pills, Best Pills News.)

Losartan (COZAAR)

A study on diabetic patients with nerve damage (neuropathy) found that losartan offered protection to the nerves (neuroprotection) but no reduction in the rate of death from cardiovascular causes. About 30 percent of patients died of cardiovascular events. In another study involving similar patients, irbesartan showed evidence of neuroprotection, but the study had a 24 percent incidence of cardiovascular events.[10]In a third study, losartan was compared with the ACE inhibitor captopril to assess their effects on survival in patients with heart failure. Captopril was found to be superior to losartan in improving survival in these elderly heart failure patients.[11]

Telmisartan (MICARDIS)

Prescrire International published an article examining the use of telmisartan in high-risk cardiovascular patients. The authors found that there was not a lot of evidence showing telmisartan is effective in these patients. The authors also stated that telmisartan is “no more effective than [the ACE inhibitor] ramipril [ALTACE]” in high-risk cardiovascular patients.[12]

Valsartan

A study comparing the addition of the older ARB valsartan or a placebo with standard treatment in patients with heart failure found that death was more common among those taking valsartan than those taking the placebo, though the difference was not statistically significant. Disturbingly, of the patients taking an ACE inhibitor plus a beta-blocker, such as atenolol (TENORMIN), those who were given valsartan were significantly more likely to do worse or die than were those taking the placebo.[13]

Valsartan also was compared with amlodipine (NORVASC), a calcium channel blocker, and patients taking both drugs were found to have similar overall rates of mortality and similar rates of cardiovascular mortality and illness from cardiovascular causes. However, the valsartan group had a higher incidence of fatal and nonfatal heart attacks (myocardial infarction) and chest pains caused by the heart receiving too little blood and oxygen (a condition known as angina pectoris). The amlodipine group had a significantly lower incidence of myocardial infarction (but did have a higher rate of new-onset diabetes), and amlodipine was more effective in reducing blood pressure in this study, especially during the first two years of treatment.[14]

 

First-line treatment for high blood pressure

The best way to reduce or eliminate the need for medication to lower high blood pressure is to improve your diet, lose weight, exercise, and decrease salt and alcohol intake. Mild hypertension often can be controlled by proper nutrition and exercise. If these measures do not sufficiently lower your blood pressure and medication is required, hydrochlorothiazide (MICROZIDE), a water pill, should be used first, starting with a low dose. This drug is safer and also costs much less than other blood pressure drugs.

There is growing evidence that thiazide diuretics, such as hydrochlorothiazide, significantly decrease the rate of bone mineral loss in both men and women because they reduce the amount of calcium lost in the urine.[15] Research now suggests that thiazide diuretics may protect against hip fracture.[16]

Patients with more severe high blood pressure that is not controlled by hydrochlorothiazide alone can add a drug from another family of high blood pressure-lowering drugs to their treatment. In this case, the prescribing doctor would optimally prescribe the hydrochlorothiazide and the second drug separately, with the dose of each drug adjusted to meet the patient's needs, rather than using a product that contains the drugs in a fixed combination.

Regardless of which drugs are used to treat high blood pressure, once a patient's blood pressure has been normal for a year or more, a cautious decrease in dose and renewed attention to nondrug treatment may be worth trying, according to The Medical Letter on Drugs and Therapeutics.[17]

According to an editorial in the BMJ:

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.[18]

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, including ARBs other than losartan, are at increased risk of developing gout, a type of arthritis.19

Regulatory actions surrounding ARBs

2010: In June, the FDA informed the public that it was conducting an ongoing safety review in type 2 diabetes patients taking olmesartan (BENICAR). These patients were found to have a higher rate of death from cardiovascular causes than patients taking a placebo.[19]

(In June 2014, the FDA issued an advisory that it had completed its safety review of type 2 diabetes patients taking olmesartan and had found no clear evidence of an increased cardiovascular risk associated with use of the drug.[20]) In July, the FDA issued a safety alert based on a study published in the June 2010 Lancet Oncology medical journal. The alert stated that ARBs may be associated with a small increase in the risk of cancer. The FDA stated that it had not made a conclusion that ARBs increase the risk of cancer and that it was continuing to review additional information.[21](See “2011” entry below.)

2011: In June, the FDA stated that it reviewed data from a meta-analysis of 31 randomized, controlled trials comparing ARBs with other treatments. The FDA stated that it did not find any evidence of an increased risk of new cancer, cancer-related death, breast cancer, lung cancer or prostate cancer in patients receiving ARBs. Based on the data that was evaluated, a statistically significant difference in cancer deaths was not noted, and the FDA found that the benefits of ARBs continued to outweigh their potential risks.[22]

2012: In February, the FDA updated the drug product information for olmesartan to include data on pediatric use. The advisory stated that olmesartan has not been shown to be effective for hypertension in children younger than six years of age. The advisory also stated that olmesartan should not be used for hypertension in children younger than one year because it can have adverse effects on the development of immature kidneys.[23]

In April, the FDA added a black-box warning concerning fetal toxicity to the drug product information for ARBs. The warning stated that when ARBs were used during the second and third trimesters of pregnancy, reduced fetal renal function and increased fetal and neonatal morbidity and death occurred.[24]

In April 2012, 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 adverse 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.[25]

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 adverse effects — with no added benefit — when the drugs are used in combination with one another. Public Citizen also 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.[25]

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.[26]

2013: In July, the FDA issued a warning that olmesartan can cause a severe intestinal disorder known as sprue-like enteropathy, which causes severe, chronic diarrhea with significant weight loss. The FDA states that in the 23 cases reported to the agency, discontinuing olmesartan resulted in clinical improvement of sprue-like enteropathy symptoms. The agency has approved revised labels of all olmesartan-containing products to include warnings about this adverse effect.[27]

2017: Public Citizen petitioned the FDA to immediately require the removal from the market of all medications containing olmesartan because of increasing evidence that the drug causes sprue-like enteropathy; other ARBs have not been linked to this serious adverse event. FDA action on our petition is pending.

Before You Use This Drug [top]

Tell your doctor if you have or have had:

  • allergy to these drugs
  • diabetes
  • heart, kidney, or liver problems
  • sodium deficiency
  • dehydration due to excessive perspiration, vomiting, diarrhea, dialysis, dietary salt restriction
  • pregnancy or are breast-feeding

 

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

When You Use This Drug [top]

  • Continue to follow your diet, exercise regularly, and avoid undue stress. Do not use salt substitutes or salt-free milk.
  • Use caution when exercising or in hot weather due to risk of dehydration.
  • Drink fluids to prevent dehydration, especially when exercising during hot weather, or if you develop nausea, vomiting, or diarrhea.
  • Do not drink alcohol, which can cause dehydration.
  • The first time you take this drug, have a friend stay with you until you know how you react.
  • You may feel dizzy when rising from a lying or sitting position. When getting out of bed, hang your legs over the side of the bed for a few minutes, then get up slowly. When getting up from a chair, stay beside the chair until you are sure that you are not dizzy 
  • Until you know how you react to this drug, do not drive or perform other activities that require alertness.
  • Monitor your blood pressure periodically.
  • Do not take any other drugs without first talking to your doctor especially nonprescription drugs for appetite control, asthma, colds, coughs, hay fever, or sinus problems.
  • Notify your doctor immediately if pregnancy is suspected.
  • Check with your doctor if severe nausea, vomiting, or diarrhea continues.

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 the drug at the same time(s) each day.
  • Take with or without food. Do not break, chew, or crush this drug.
  • Do not suddenly stop taking without checking with your doctor to find out if you need to taper off these drugs.
  • 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:

ALDACTONE, amiloride, DYRENIUM, ESKALITH, INDOCIN, indomethacin, KLOTRIX, lithium, MIDAMOR, NORVIR, potassium supplements, RIFADIN, rifampin, ritonavir, spironolactone, triamterene.

Adverse Effects [top]

Call your doctor immediately if you experience:

  • cough
  • bronchitis
  • dizziness, lightheadedness, or fainting
  • fever
  • chills
  • confusion
  • headache
  • hoarseness
  • cold
  • joint, lower back, or side pain
  • sore throat
  • nosebleeds
  • bleeding gums
  • skin rash
  • swelling of lips, eyes, face, tongue, hands, or feet
  • sudden trouble swallowing or breathing
  • painful, burning, or bloody urination or changes in frequency
  • unusual tiredness or weakness
  • changes in vision
  • fast or irregular heartbeat
  • large hives
  • numbness or tingling in hands, feet, or lips
  • itching
  • loss of appetite
  • heartburn
  • pain in legs (rhabdomyolysis as action in olmesartan label)
  • stomach pain or bloating
  • loss of voice
  • yellow eyes or skin

 

Call your doctor if these symptoms continue:

  • back pain
  • cold symptoms
  • abdominal pain or heartburn (telmisartan)
  • flatulence, bloating, or gas (telmisartan)
  • coughing
  • ear congestion or pain
  • diarrhea
  • nausea (telmisartan)
  • fatigue, weakness
  • headache
  • indigestion
  • leg pain
  • muscle cramps or pain
  • nasal or sinus congestion
  • sleep disturbance
  • anxiety or nervousness

Periodic Tests[top]

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

  • blood pressure
  • digoxin levels (with telmisartan)
  • renal function determinations
  • liver function tests
  • potassium levels
  • blood counts

last reviewed March 31, 2021