Blood Pressure
Atacand (Candesartan Cilexetil) Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
Hyperkalemia
- Concomitant use of ATACAND with drugs that may increase potassium levels may increase the risk of hyperkalemia [see Drug Interactions (7)]. Monitor serum potassium periodically
Agents Increasing Serum Potassium Other drugs that affect serum potassium
- Coadministration of ATACAND with potassium sparing diuretics, potassium supplements, potassium-containing salt substitutes or other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.
- Increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium
Patient Information - Who should not take Atacand? are diabetic and taking Aliskiren
Source : FDA (March 2016)
Benicar (olmesartan medoxomil) Tablets: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
Benicar (olmesartan) is an angiotensin II receptor antagonist. Olmesartan keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow. Benicar is used to treat high blood pressure (hypertension) in adults and children who are at least 6 years old. It is sometimes given together with other blood pressure medications.
DRUG INTERACTIONS
- Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists, including Benicar. Monitor serum lithium levels during concomitant use.
- Data from one controlled trial and an epidemiologic study have suggested that high-dose olmesartan may increase cardiovascular (CV) risk in diabetic patients, but the overall data are not conclusive. The randomized, placebo-controlled, double-blind ROADMAP trial (Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention trial, n=4447) examined the use of olmesartan, 40 mg daily, vs. placebo in patients with type 2 diabetes mellitus, normoalbuminuria...
- The epidemiologic study included patients 65 years and older with overall exposure of > 300,000 patient-years. In the sub-group of diabetic patients receiving high-dose olmesartan (40 mg/d) for > 6 months, there appeared to be an increased risk of death (HR 2.0, 95% CI 1.1, 3.8) compared to similar patients taking...
- Overall, these data raise a concern of a possible increased CV risk associated with the use of high-dose olmesartan in diabetic patients. There are, however, concerns with the credibility of the finding of increased CV risk, notably the observation in the large epidemiologic study for a survival...
Hyzaar (losartan potassium hydrochlorothiazide) 50-12.5 mg, 100-12.5 mg, and 100-25 mg Tablets
BOXED WARNING
Warning: fetal toxicity
- When pregnancy is detected, discontinue Hyzaar as soon as possible.
- Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS, Fetal Toxicity
Fetal Toxicity
Pregnancy Category D
- Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated ..... (section extensively revised - see PI)
- Pregnancy: Female patients of childbearing age should be told about the consequences of exposure to Hyzaar during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.
- Neonates with a history of in utero exposure to Hyzaar: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renalfunction.
What is the most important information I should know about Hyzaar?
- Hyzaar can cause harm or death to an unborn baby
- Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant.
- If you get pregnant while taking Hyzaar, tell your doctor right away.
Source : FDA (Jan 2014)
Cozaar (losartan potassium) 25 mg, 50 mg, and 100 mg Tablets
BOXED WARNING
Warning: fetal toxicity
- When pregnancy is detected, discontinue COZAAR as soon as possible.
- Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS, Fetal Toxicity
Fetal Toxicity
Pregnancy Category D
- section extensively revised - see PI
Pregnancy:
- Female patients of childbearing age should be told about the consequences of exposure to COZAAR during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.
- If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
What is the most important information I should know about COZAAR?
- COZAAR can cause harm or death to an unborn baby
- Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant.
- If you get pregnant while taking COZAAR, tell your doctor right away.
Source : FDA (Jan 2014)
Seniors Need to Be Wary When Starting BP Meds
Older hypertensive patients may be at risk for hip fracture after initiation of blood pressure-lowering therapy, researchers found.
The risk for hip fracture was a relative 43% greater in the month-and-a-half after starting on any antihypertensive compared with other time periods (incidence rate ratio 1.43, 95% CI 1.19 to 1.72), according to Debra Butt, MD, of the Scarsborough Hospital in Ontario, and colleagues.
That finding is consistent with prior observational studies evaluating the relationship between initiation of antihypertensive treatment and falling, a primary risk factor in more than 90% of hip fractures, the researchers reported online in Archives of Internal Medicine.
"In following practice guidelines for the treatment of hypertension as standardized approaches to disease management, physicians need to be aware of the effect of drug therapies on fracture risk because it may have important implications for the elderly population and the healthcare system," they wrote.
Beginning treatment with blood pressure-lowering medication can induce orthostatic hypotension accompanied by dizziness, fainting, or syncope, all of which may contribute to the risk of falling and, consequently, fracture. Most studies looking at the association between antihypertensive drug use and fracture risk, however, have looked at longer-term drug exposure.
To assess the more immediate risk of fracture, Butt and colleagues analyzed data from 301,591 community-dwelling older individuals with hypertension who started antihypertensive treatment from April 2000 to March 2009. The information was collected from healthcare administrative databases in Ontario.
The mean age of the patients was 81, and 81% were female. Only 6% had a history of hip fracture.
During the 10-year study period, there were 1,463 incident proximal femoral fractures.
The risk of sustaining such a fracture was significantly higher during the 45 days after starting antihypertensive treatment than during three 45-day control periods prior to starting treatment and three 45-day periods after the initial exposure period.
Accounting for age and use of other medications implicated in falls -- such as psychotropic drugs -- did not change the findings.
The relationship was generally consistent for all classes of antihypertensives (IRRs 1.30 to 1.58), although it reached statistical significance only for ACE inhibitors (IRR 1.53, 95% CI 1.12 to 2.10) and beta-blockers (IRR 1.58, 95% CI 1.01 to 2.48).
"The risk of first-dose hypotension has been described with the use of specific ACE inhibitors (e.g., captopril, enalapril, lisinopril, and ramipril) and is related to venodilation, which produces marked venous pooling with a consequent fall in cardiac output and profound hypotension," the authors noted.
Beta-blockers "are less effective in controlling hypertension in older patients because the number of beta-adrenergic receptors is decreased and the affinity for both agonist and antagonist is reduced," they wrote. "Adverse effects of bradycardia, decreased cardiac output, induction of peripheral vasoconstriction, and depression or confusion also have been described with beta-blockers and may result in fall injuries."
The researchers acknowledged some limitations of the study, including the possibility that some older individuals received drug samples from their physicians that would not have been captured in the drug database and the possibility that starting antihypertensive drug treatment could be associated with other behavioral changes related to a greater risk for hip fracture, including increased exercise.
Source : MedPage Today via Archives of Internal Medicine
Source reference: Butt D, et al "The risk of hip fracture after initiating antihypertensive drugs in the elderly" Arch Intern Med 2012; DOI: 10.1001/2013.jamainternmed.469.
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Lotensin (benazepril hydrochloride) tablets
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
May 2012
Summary View
BOXED WARNING
- wording modified from previous BW
WARNINGS
Anaphylactoid and Possibly Related Reactions
Head and Neck Angioedema
- Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to nonblacks
- Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases ...
- Pregnancy: Female patients of childbearing age should be told about the consequences of exposure to Lotensin during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible
- Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors (including benazepril) during therapy with lithium. Monitor serum lithium levels when used concomitantly with Lotensin.
- Other: The pharmacokinetics of benazepril are not affected by the following drugs: hydrochlorothiazide, furosemide, chlorthalidone, digoxin, propranolol, atenolol, nifedipine, amlodipine, naproxen, acetylsalicylic acid, or cimetidine. Likewise the administration of benazepril does not substantially affect the pharmacokinetics of these medications (cimetidine kinetics were not studied).
- Neonates with a history of in utero exposure to Lotensin: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Benazepril, which crosses the placenta, can theoretically be removed from the neonatal circulation by these means; there are occasional reports of benefit from these maneuvers with another ACE inhibitor, but experience is limited.
- The long-term effects of benazepril on growth and development have not been studied. Infants below the age of 1 year should not be given Lotensin because of the risk of effects on kidney development.
- Other adverse experiences reported in controlled clinical trials (in less than 1% of benazepril patients or with less than 1% difference in incidence between benazepril or placebo treatment), and rarer events seen in post-marketing experience, include the following (in some, a causal relationship to drug use is uncertain):
- Gastrointestinal: added... nausea
- Other: added... fatigue
Summary View
CONTRAINDICATIONS
- Lotensin is also contraindicated in patients with a history of angioedema with or without previous ACE inhibitor treatment.
Source : FDA
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FDA Drug Safety Communication: New Warning and Contraindication for blood pressure medicines containing aliskiren (Tekturna)
[4-20-2012] The U.S. Food and Drug Administration (FDA) is warning of possible risks when using blood pressure medicines containing aliskiren with other drugs called angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with diabetes or kidney (renal) impairment. These drug combinations should not be used (are contraindicated) in patients with diabetes. In addition, a new warning is being added to avoid use of these drug combinations in patients with kidney impairment. The labels for the aliskiren drugs are being updated based on preliminary data from a clinical trial, “Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE).”
A list of medicines containing aliskiren is found in the Drug Facts box. Lists of approved ACEIs and ARBs are found in Tables 2 and 3.
In ALTITUDE, the risks of kidney (renal) impairment, low blood pressure (hypotension), and high potassium blood levels (hyperkalemia) in a group of patients taking aliskiren plus an ARB or ACEI increased relative to a group of patients taking placebo plus an ARB or ACEI. The preliminary data from ALTITUDE also demonstrated a slight excess of cardiovascular events (death or stroke) in the aliskiren group [see Data Summary]; however, FDA has reached no definite conclusion regarding an actual link between these drugs and death or stroke. FDA will evaluate the final trial results as well as results from other aliskiren trials and will communicate any new information when it becomes available.
The following recommendations are being added to the drug labels for aliskiren-containing products as of 4/20/12:
- A new contraindication against the use of aliskiren with ARBs or ACEIs in patients with diabetes because of the risk of renal impairment, hypotension, and hyperkalemia.
- A warning to avoid use of aliskiren with ARBs or ACEIs in patients with moderate to severe renal impairment (i.e., where glomerular filtration rate [GFR] < 60 mL/min).
Additional Information for Patients
Do not stop taking aliskiren without talking to your healthcare professional. Stopping aliskiren suddenly can cause problems if your high blood pressure (hypertension) is not treated.
- Tell your healthcare professional if you are taking an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB). (See Tables 2 and 3)
- Tell your healthcare professional if you have been diagnosed with diabetes or kidney problems.
- Discuss any questions you have about aliskiren with your healthcare professional.
- Report any side effects you experience to the FDA MedWatch program using the information in the “Contact FDA” box at the bottom of the page.
- Concomitant use of aliskiren with ARBs or ACEIs in patients with diabetes is contraindicated because of the risk of renal impairment, hypotension, and hyperkalemia.
- Avoid use of aliskiren with ARBs or ACEIs in patients with renal impairment where GFR < 60 mL/min.
- Valturna (a combination drug containing aliskiren and valsartan) should not be used in patients with diabetes.
- Valturna will no longer be marketed after July 2012. See Novartis’s website for more information.
- Be aware of the preliminary findings from the ALTITUDE trial for death and stroke; FDA has not concluded that there is a link between these drugs and death or stroke [see Data Summary]
- Report adverse events involving aliskiren to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.
FDA has evaluated preliminary data from ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints), a clinical trial conducted post-approval. ALTITUDE was terminated early for lack of efficacy and because risks of renal impairment, hypotension, and hyperkalemia were observed to be greater in diabetic patients treated with aliskiren than in patients treated with placebo. The information below describes the ALTITUDE interim trial results.
Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)
The purpose of ALTITUDE was to determine whether aliskiren (compared to placebo), on top of conventional treatment, reduces death and disease caused by the heart, the circulatory system and the kidney. Patients with type 2 diabetes with renal disease (defined either by the presence of albuminuria or reduced GFR) were randomized to aliskiren 300 mg daily (n=4283) or placebo (n=4296). All patients were receiving concomitant therapy with an ARB or ACEI. The primary efficacy outcome was the time to the first event of the primary composite endpoint, which consisted of cardiovascular death, resuscitated sudden death, non-fatal myocardial infarction, non-fatal stroke, unplanned hospitalization for heart failure, onset of end-stage renal disease, renal death, and doubling of serum creatinine concentration from baseline sustained for at least one month.
After a median patient follow up of about 27 months, the trial was terminated early for lack of efficacy. Greater risks of renal impairment, hypotension and hyperkalemia were observed in aliskiren- compared to placebo-treated patients as shown in the Table 1 below.
Table 1. Incidence of Selected Adverse Reactions in ALTITUDE1
Aliskiren N=4283 Placebo N=4296
Serious Adverse Event* (%) Adverse Event (%) Serious Adverse Event* (%) Adverse Event (%)
Renal 4.7 12.4† 3.3 10.4†
Hypotension 2.0 18.6†† 1.7 14.8††
Hyperkalemia 1.1 36.9 0.3 27.1
1 as reported by the investigator
†renal failure, renal failure acute, renal failure chronic, renal impairment
††dizziness, dizziness postural, hypotension, orthostatic hypotension, presyncope, syncope
*A Serious Adverse Event (SAE) is defined as an event that: is fatal or life-threatening, results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; requires inpatient hospitalization or prolongation of existing hospitalization; or is medically significant (i.e., an event that jeopardizes the patient or may require medical or surgical intervention to prevent one of the outcomes previously listed).
The risks of stroke (2.7% aliskiren vs. 2.0% placebo) and death (6.9% aliskiren vs. 6.4% placebo) were numerically higher in aliskiren-treated patients. At this time, however, the significance of these findings is unknown; FDA has reached no conclusion regarding a link between aliskiren treatment and these cardiovascular-related events.
In an FDA analysis of data from U.S. outpatient retail pharmacies in 2011, it was found that approximately 22% of patients on aliskiren products (Tekturna, Tekturna HCT, Tekamlo, and Amturnide) had concurrent use with ACEIs/ARBS and diabetic medications and approximately 30.5% of Valturna patients received concurrent therapy with diabetic medications.2
FDA will review the final study data (including follow-up information on patients who discontinued aliskiren in ALTITUDE) and data from other ongoing trials with aliskiren when they become available.
Table 2. Approved Angiotensin Converting Enzyme Inhibitors
Brand name Generic name
Aceon perindopril erbumine
Accupril quinapril hydrochloride
Accuretic quinapril hydrochloride and hydrochlorothiazide
Altace ramipril
Capoten captopril
Capozide captopril and hydrochlorothiazide
Lotensin benazepril hydrochloride
Lotensin HCT benazepril hydrochloride and hydrochlorothiazide
Lotrel benazepril hydrochloride and amlodipine besylate
Mavik trandolapril
Prinivil lisinopril
Prinzide lisinopril and hydrochlorothiazide
Tarka trandolapril and verapamil hydrochloride
Univasc moexipril hydrochloride
Uniretic moexipril hydrochloride and hydrochlorothiazide
Zestril lisinopril
Zestoretic lisinopril and hydrochlorothiazide
Table 3. Approved Angiotensin Receptor Blockers
Brand name Generic name
Atacand candesartan cilexetil
Atacand HCT candesartan cilexetil and hydrochlorothiazide
Avalide irbesartan and hydrochlorothiazide
Avapro irbesartan
Benicar olmesartan medoxomil
Benicar HCT olmesartan medoxomil and hydrochlorothiazide
Cozaar losartan potassium
Diovan valsartan
Diovan HCT valsartan and hydrochlorothiazide
Edarbi azilsartan kamedoxomil
Hyzaar losartan potassium and hydrochlorothiazide
Micardis telmisartan
Micardis HCT telmisartan and hydrochlorothiazide
Teveten eprosartan mesylate
Teveten HCT eprosartan mesylate and hydrochlorothiazide
Twynsta telmisartan and amlodipine besylate
Facts about aliskiren-containing products
Aliskiren is a renin inhibitor used to treat high blood pressure (hypertension) by lowering blood pressure.
- Aliskiren is found in the following medications:
- Amturnide (aliskiren hemifumarate, amlodipine besylate, and hydrochlorothiazide)
- Tekturna (aliskiren hemifumarate)
- Tekturna HCT (aliskiren hemifumarate and hydrochlorothiazide)
- Tekamlo (aliskiren hemifumarate and amlodipine besylate)
- Valturna (aliskiren hemifumarate and valsartan)*
- In 2011, a total of approximately 2.4 million prescriptions for aliskiren-containing products were dispensed to 451,000 patients from U.S. outpatient retail pharmacies.1
Novartis to revamp Rasilez label with safety risks
The data on Rasilez's safety risks is coming home to roost. The Novartis ($NVS) blood-pressure drug will get a new warning in Europe at regulators' request, after a recent trial flagged links to stroke and kidney problems.
The Swiss drugmaker will revise the drug's European label to say that Rasilez should not be used in patients with diabetes or kidney problems who are also using ACE inhibitors or angiotensin receptor blockers. Like Rasilez, ACE inhibitors and ARBs are used to treat high blood pressure.
"In addition, the agency recommended the inclusion of a warning that the combination of aliskiren and ACE inhibitor or ARB is not recommended in all other patients because adverse outcomes cannot be excluded," the EMA's Committee for Medicinal Products for Human Use said (as quoted by Reuters).
Novartis also said it has written doctors around the world recommending against using Rasilez--which is sold in the U.S. as Tekturna--in patients with Type 2 diabetes if they're also receiving an ACE inhibitor or ARB. The company is also working with the FDA on guidelines for use of the drug.
Novartis stopped a Rasilez/Tekturna trial in December after data suggested it might boost the risk of stroke and kidney problems. Since then, the company has downgraded its long-term expectations for the drug and taken a $900 million charge related to that lower forecast, Bloomberg notes. Novartis now says 2012 sales will be less than half of the $557 million posted last year. The company had been hoping the products would help fill the gap left when its older blood-pressure remedy Diovan goes off patent later this year.
Source : Fierce Pharma
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Bristol-Myers recalls 65 more Avalide (generic irbesartan + hydrochlorothiazide) lots
64 million tablets recalled in U.S., Puerto Rico
* Second recall of drug in less than four months*
Recall over potential for reduced efficacy
Bristol-Myers Squibb Co (BMY.N) said it has recalled 64 million tablets of the blood pressure medicine Avalide in the United States and Puerto Rico due to the potential for reduced effectiveness.
The move, which Bristol-Myers said was undertaken as a precautionary measure, marked the second major recall in less than four months of the medicine co-marketed with French drugmaker Sanofi-Aventis (SASY.PA).
In September, Bristol-Myers recalled 62 lots, or 60 million tablets, of the drug manufactured in Puerto Rico. The new recall involved 65 lots of Avalide manufactured in plants in Humacal, Puerto Rico and Evansville, Indiana, the company said.
Avalide is a combination pill comprised of the drugs irbesartan, which is sold under the brand name Avapro, and hydrochlorothiazide, a generic diuretic.
The recall was not announced publicly but communicated via letters to wholesalers and healthcare professionals, Bristol-Myers said.
Reuters first learned of the recall from a doctor.
The problem detected was the same that led to the previous recall, a potential variability in levels of the less-soluble form of the active ingredient irbesartan.
As with the September recall, the problem suggests the possibility of reduced efficacy, although the company has not turned up evidence of reduced effectiveness, nor have there been any reports of safety problems or patient harm, Bristol-Myers spokeswoman Christina Trank said.
The affected Avalide doses were 150/12.5 milligrams, 300/12.5 mg, 300/25 mg and blister sample packs of 300/25 mg. The first number represents the irbesartan dose.
The recall did not involve stand-alone Avapro, the company said.
For the first nine months of 2010, Bristol-Myers reported combined worldwide sales of Avalide and Avapro of $924 million.
Since the September recall, Trank said the company had developed more sensitive testing methods to detect a less soluble form of the active ingredient and the new testing revealed the need for a further recall.
Patients who have purchased Avalide from the recalled lots can contact their prescribing doctor, pharmacy or Bristol-Myers customer relations, Trank said.
Bristol-Myers shares closed down 5 cents at $25.90 on the New York Stock Exchange.
Source : Reuters
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FDA Drug Safety Communication: Ongoing safety review of the angiotensin receptor blockers and cancer
The U.S. Food and Drug Administration (FDA) is conducting a review of the class of medications known as angiotensin receptor blockers (ARBs) after a recently published study suggested they may be associated with a small increased risk of cancer.
ARBs are used in patients with high blood pressure and other conditions. Brand names include Atacand, Avapro, Benicar, Cozaar, Diovan, Micardis, and Teveten. ARBs are also sold in combination with other medications (see Approved Angiotensin Receptor Blockers below).
The Agency plans to review the available data on these medications, and evaluate additional ways to better assess a possible link between use of ARBs and cancer. FDA will update the public when this review is complete.
The published study was a meta-analysis combining cancer-related findings from several clinical trials. The study found a small increased risk of reported new cancers in patients taking an ARB compared to those not taking an ARB.1 No statistically significant difference in the number of cancer deaths was observed (see Data Summary below).
These clinical trials were not designed to study the effects of ARBs on cancer risk. The findings need close examination for more detailed information about the patients who were reported to have cancer so that it can be determined whether this cancer was in fact new. ARBs have been shown to provide significant benefit in many patients with certain heart-related conditions such as high-blood pressure and heart failure.
Additional Information for Patients
- FDA has not concluded that angiotensin receptor blockers (ARBs) increase the risk of cancer. FDA is evaluating this safety concern and will update the public when additional information is available.
- FDA believes the benefits of ARBs in patients with high blood pressure and certain heart-related conditions continue to outweigh their potential risks.
- Do not stop taking your ARB unless told to do so by your healthcare professional.
- Talk to your healthcare professional if you have concerns about your medicine.
- Report any side effects you experience to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of the page.
Additional Information for Healthcare Professionals
- The meta-analysis by Sipahi et al. concluded that there was an increase in new cancer diagnoses in patients randomized to an ARB.1
- FDA has not concluded that angiotensin receptor blockers (ARBs) increase the risk of cancer. The Agency is reviewing information related to this safety concern and will update the public when additional information is available.
- FDA believes the benefits of ARBs continue to outweigh their potential risks.
- Report adverse events involving ARBs to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of this page.
Data Summary
The meta-analysis included data from over 60,000 patients in several long-term, randomized, controlled clinical trials evaluating angiotensin receptor blockers (ARBs) for which adverse events related to cancer were captured during the study. The mean duration of follow-up ranged from 1.7 to 4.8 years.
The study reported the frequencies of new cancer occurrence to be 7.2% for patients receiving ARBs compared to 6.0% for those not receiving ARBs (risk ratio = 1.08, 95% Confidence Interval: 1.01-1.15). No statistically significant difference in cancer deaths was noted.
The meta-analysis had several limitations that make it difficult to determine the validity of the findings without further examination of the underlying data. The limitations include:
- The analysis included data from trials where there was no adjudication of cancer-related adverse events. In these trials, there was no way to determine whether the events represented new diagnoses of cancer, or events related to a preexisting cancer. Thus, the actual number of new cancer occurrences is unknown.
- The analysis may not have included all relevant clinical trials of ARBs.
- The analysis is not based on patient-level data. Knowledge of the specific timing and nature of events in individual patients would aid in interpretation of the findings.
- The majority of patients included in the studies reviewed were receiving the ARB telmisartan; therefore the applicability of the cancer-related findings to all ARBs is uncertain.
- The meta-analysis was planned to examine a hypothesis raised by cancer-related trends in three outcome studies. Because the meta-analysis included two of these studies, the results of the meta-analysis do not provide a fully independent confirmation of the hypothesis raised by the earlier studies.
Approved Angiotensin Receptor Blockers
Single Ingredient Angiotensin Receptor Blockers
Brand Name Generic Name
Atacand candesartan
Avapro irbesartan
Benicar olmesartan
Cozaar losartan
Diovan valsartan
Micardis telmisartan
Teveten eprosartan
Combination Angiotensin Receptor Blockers
Brand Name Generic Names
Atacand HCT candesartan and hydrochlorothiazide
Avalide irbesartan and hydrochlorothiazide
Azor olmesartan and amlodipine
Benicar HCT olmesartan and hydrochlorothiazide
Diovan HCT valsartan and hydrochlorothiazide
Exforge valsartan and amlodipine
Exforge HCT valsartan, amlodipine, and hydrochlorothiazide
Hyzaar losartan and hydrochlorothiazide
Micardis HCT telmisartan and hydrochlorothiazide
Teveten HCT eprosartan and hydrochlorothiazide
Twynsta telmisartan and amlodipine
Valturna valsartan and aliskiren
References:
1. Sipahi I, Debanne SM, Rowland DY, Simon DI, Fang JC. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. The Lancet Oncolology 2010;11(7), 627-36.
Source: FDA
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Commonly used blood pressure drugs 'increase cancer risk'
Commonly used blood pressure drugs significantly increase the risk of developing cancer, according to a new study.
By Kate Devlin, Medical Correspondent
Published: 7:30AM BST 14 Jun 2010
Researchers found significantly increased rates of all cancers among patients taking the drugs.
The class of drugs, called Angiotensin-receptor blockers (ARBs), are widely used to treat high blood pressure as well as heart failure and kidney damage caused by diabetes.
The drugs work by blocking a hormone known to increase blood pressure.
But previous research suggested that they might also affect the risk of developing cancer.
The new review looked at 13 trials of the drugs which involved more than 150,000 patients.
Overall, those taking the significantly more likely to develop cancer over four years than those on a placebo, the findings show.
However, there was no significant difference in the risk of dying from cancer and, overall, the chances of developing the disease still remained modest.
According to the researchers “The increased risk of new cancer occurrence is modest but significant …[However] the finding of a 1.2 per cent increase in absolute cancer risk over an average of 4 years needs to be interpreted in view of the estimated 41 per cent background lifetime cancer risk.”
Writing in the same journal Steven Nissen from the Cleveland Clinic, said that the findings raised crucial questions about drug safety.
He called for further research to establish the exact link between the drugs, for which there were 15 million prescriptions written in England last year, and the risk of cancer.
But experts warned that the findings, by a team at Case Western Reserve University in Cleveland, Ohio, and published online by The Lancet Oncology journal, were based on limited research.
Judy O’Sullivan, senior cardiac nurse at the British Heart Foundation, said: “This analysis of previous research is inconclusive and anyone taking ARBs to treat their heart disease, or risk of developing it, shouldn’t stop based on this alone.
“The benefits of taking the drug are well established and it remains an effective treatment for many of the 2.6 million people in the UK living with coronary heart disease.
“We need more research to look specifically into any potential risks of developing cancer when taking ARBs.”
Martin Lerwick, from Cancer Research UK, said: "It’s important that we try to understand all the side effects of drugs so that people can make an informed choice about their treatment.
“At the moment there isn’t enough evidence to draw any firm conclusions about how blood pressure drugs might affect cancer risk and this will need further investigation.
“People shouldn’t stop taking these drugs on the basis of this research, if they’re concerned they should speak to their GP."
Dr Tim Chico, an expert in blood pressure drugs from the University of Sheffield, said: "This study does not prove that these drugs cause cancer, although it is certain that lowering blood pressure save lives by preventing strokes and heart attacks.”
Source: Daily Telegraph
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FDA Recall of Cleviprex an injectable medication that is used to treat high blood pressure (hypertension) in people who cannot take medicine by mouth.
The Medicines Company (NASDAQ: MDCO) announced today that it is voluntarily expanding the recall of Cleviprex ® (clevidipine butyrate) injectable emulsion due to the potential presence of visible particulate matter which has been observed in some vials. Four (4) additional lots of Cleviprex are being recalled. The four additional Cleviprex lots are 68-407-DJ, Exp. 08/2010; 68-408-DJ, Exp. 08/2011; 71-101-DJ and 71-106-DJ, Exp. 11/2011. The previously recalled lots were 61-978-DW, 61-979-DW, and 61-980-DW, Exp. 01/2010; 68-404-DJ, 68-405-DJ, and 68-406-DJ, Exp. 08/2010; 69-830-DJ, 63-385-DJ, 63-386-DJ, and 63-266-DJ, Exp 03/2011; and 64-453-DJ, Exp. 04/2011. The Company is cooperating with the U.S. Food and Drug Administration on this recall. The visible particulate matter is primarily made up of sub visible inert stainless steel particles of around 2.5 microns in diameter. Experimental animal and human data indicate that these particles are scavenged by macrophages and other cells of the reticuloendothelial system. Particles could theoretically reduce blood flow in capillaries, cause mechanical damage to some tissues, or initiate acute or chronic inflammatory reactions. Reduced blood supply to tissues may lead to ischemia or organ insufficiency in the brain, kidney, liver, heart or lungs.
Anyone with inventory from the affected lots of Cleviprex should arrange for its return through their pharmaceutical wholesaler/distributor.
For medical inquiries, adverse event reporting or quality issues related to Cleviprex, please contact The Medicines Company Medical Information at 1-888-977-6326 Monday to Friday 8:00am-5:30pm EST or [email protected].
Any adverse reactions associated with the use of Cleviprex may also be reported to the FDA’s MedWatch Program by fax at 1-800-FDA-0178, by mail at MedWatch, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or on the MedWatch website at www.fda.gov/medwatch1.
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