Tag Archives: amlodipine

Many Seniors at Risk For Supplement-Drug Interactions

Millions of seniors that take herbal supplements in addition to prescription drugs may be at risk for potentially serious supplement-drug interactions.

Researchers in the UK polled older adults 65 and older, finding that about one-third of them take at least one supplement in addition to their regular medications. Based on an evaluation of those supplements and drugs, researchers say that one-third of that group are at risk for potentially serious adverse events, they reported in the British Journal of General Practice.

Some of the adverse events are a risk of bleeding, an increase in blood sugar concentration and reducing the effectiveness of the medication an individual is taking.

Researchers identified three supplement-drug combinations they say pose a “significant” hazard: calcium and the underactive thyroid drug levothyroxine; peppermint and Prevacid (lansoprazole), which is used for acid reflux; and St. John’s wort and amlodipine, a blood pressure-lowering medication. In the first combination, the efficacy of levothyroxine can be reduced by calcium. Antacids like Prevacid can eat away at protective coatings on peppermint oil pills, potentially leading to nausea and heartburn. And St. John’s wort can reduce the levels of amlodipine in the blood.

Other potentially serious combinations include fish oil pills and bisoprolol, a beta blocker, as well as glucosamine, a supplement used for arthritis relief, and the diabetes drug metformin. The first combination can lead to a potentially unsafe lowering of blood pressure, while the second can increase blood sugar.

The study authors conclude that doctors should ask senior patients about supplement use to potentially avoid interactions with medications.

Is that New Drug Better? Safer? There’s Really No Way to Know

In order for a drug to be approved by the FDA, a pharmaceutical company must demonstrate that the drug is safe and effective. But the company does not need to show that the drug is any more effective  — or even as effective — than other drugs on the market for the same condition. Not requiring what is known as “comparative effectiveness” studies as part of the drug approval process is a mistake as doctors and the public are left to guess how effective or safer newer drugs are compared with ones that are already available, and likely much cheaper.

For the most part, when a new drug goes through the FDA approval process, it only has to demonstrate it is more effective than a placebo and it won’t kill you. Side effects are often a footnote. While this is important, more practical information is needed. Doctors and patients have the right to know what the best drug is for which condition. For example, say a new cholesterol-lowering drug has been approved. In weighing whether to prescribe that drug to a patient, a doctor would want to know how that drug fared both in terms of efficacy and side effects compared to existing cholesterol-lowering drugs on the market.

Why not just always go with the newer drug? newer is better, right? No, not in the medical world. Older drugs which have been used for a longer time have a much more complete safety profile which means doctors and the FDA have a better idea of what the actual side effects are and how many adverse effects are happening with that drug. All that is not tested yet on the new drug. The patient taking the new drug is the guinea pig.

Comparative effectiveness studies are just as important to consumers. If, say, that new drug was only marginally better – if at all – than existing cholesterol-lowering meds, they would likely choose to stick with a generically available, lower-cost med rather than the newer – and more expensive – drug.

The importance of comparative effectiveness studies for drugs was made well in a recent New York Times article by pediatrician Aaron Carroll, MD, who is also a professor at the Indiana University School of Medicine. In the piece, Carroll mentions a 2002 comparative effectiveness trial that was published in JAMA that looked at various medications used for hypertension. The primary outcomes investigators were looking were fatal and non-fatal coronary heart disease.

The 4 drugs examined were chlorthalidone — a diuretic; amlodipine, known as a calcium channel blocker; doxazosin; and lisinopril, an angiotensin-converting enzyme (ACE) inhibitor.

While results showed they were all equally effective in regards to coronary heart disease, chlorthalidone was better in lowering systolic blood pressure, preventing heart failure and stroke, and lowering cardiovascular disease rates.

The results tell “us what drug is best to start if you have someone over 55 with high blood pressure and at least one risk factor for coronary heart disease,” Carroll wrote. “That’s exactly the kind of question that only a comparative effectiveness trial can answer.”

As it stands now, patients could potentially be harmed by getting a new treatment that has a safety and side effect profile that is worse than established products that have been on the market for a long time. And they could also spend more on newer drugs than don’t work as well. Consumers deserve to know how drugs in the same therapeutic class compare against each other so that they can make the most informed decision about what medication to take for a condition.

My advice: Always take the older drug for a condition unless it doesn’t work for you or you experience strong side effects.

Combining Smaller Doses of Blood Pressure Drugs Lowers Side Effects

Using lower doses of a combination of blood pressure medications is as effective and has far fewer side effects than taking a standard dose of a single hypertension drug, according to a new review.

Researchers, examining data from 42 prior trials that involved more than 20,000 people with high blood pressure, found that taking a quarter dose of 2 different hypertension drugs was as effective as taking a single pill at the standard dose. Also, the side effects experienced from this dual quarter-dose therapy were about the same as those taking a placebo, according to the meta-analysis published in the journal Hypertension.

Results also showed that taking a combination of quarter doses of 4 different medications was almost twice as effective as a standard dose of just one medication.

The drugs included in the review covered 5 of the main categories of blood pressure-lowering drugs: ACE inhibitors, angiotensin receptor blockers, beta blockers, calcium channel blockers and thiazides. Side effects associated with them include dizziness, nausea, lack of energy and unexplained weight gain or loss.

Researchers cautioned that the evidence is not yet strong enough to recommend using a combination of lower doses of hypertension meds and that larger trials would need to be conducted before doing so.

Some Blood Pressure Meds May Boost Risk for Mood Disorders

People who take certain blood pressure-lowering medications may be at an elevated risk of developing mood disorders, including depression and bipolar disorder.

Researchers examined data on more than 144,000 adults with an average age of 56. Just over 32,000 of them were taking one of 4 types of drug to treat their hypertension: angiotensin agonists (ACE inhibitors and angiotensin receptor blockers), beta blockers, calcium channel blockers and thiazide diuretics.

Common angiotensin agonists include Cozaar (losartan), Diovan (valsartan), Lotensin (benazepril) and Altace (ramipril); common beta blockers are Lopressor (metoprolol), Coreg (carvedilol) and atenolol; common calcium channel blockers include Norvasc (amlodipine) and Cardizem (diltiazem); and common thiazide diuretics include hydrochlorothiazide (HCTZ, HCT, HCZ).

Over a 5-year period, those on a beta blocker or calcium channel blocker were twice as likely to have been hospitalized for a mental illness (mostly depression) compared to those on an angiotensin agonist, the researchers reported in the journal Circulation.

People on an angiotensin agonist were also 50% less likely to be hospitalized with a mood disorder compared to those who weren’t on any hypertension drug. And those taking a thiazide diuretic had no impact on risk for hospitalization.

It’s important to note that the study was observational in nature, meaning the researchers aren’t sure exactly what led to the increase in mood disorders with some of these drugs. However, the results may indicate that patients with high blood pressure that are at risk for mood disorders could be better off with an angiotensin agonist.

Be Aware of Potential Interactions With Statins and Heart Drugs

Doctors and patients need to be aware of drug-drug interactions between medications used to lower cholesterol and those used to treat heart disease, according to new recommendations from the American Heart Association (AHA).

Statins, which are used to lower cholesterol, are among the most popular drugs prescribed to American adults. They are also prescribed to patients who have clogged arteries, a condition known as atherosclerosis, or those at risk for it. In many cases, these people are also taking other heart meds.

The AHA published a list of drugs often given to heart patients that can often interact with statins. These include:

  • Blood pressure-lowering medications known as calcium channel blockers. These include Norvasc (amlodipine), Cardizem (diltiazem) and Calan (verapamil).
  • Drugs to treat irregular heartbeat, such as Multaq (dronedarone), Cordarone (amiodarone) and Digox (digoxin)
  • Heart failure medications, including Entresto (sacubitril/valsartan) and Corlanor (ivabradine)
  • Drugs known as fibrates which are used to lower triglycerides, another type of lipid (fat) in the blood, such as Lopid (gemfibrozil)
  • Blood thinners, such as Coumadin (warfarin) and Brilinta (ticagrelor)

The most common interaction when taking these drugs in combination with a statin is that it can increase the level of the statin in the blood, which can lead to muscle weakness or pain. However, the benefits of taking the medications outweigh the risks, which are relatively minor, the recommendations state. To minimize the risks, a doctor should adjust the dose of the statin.

But there are some drug combinations that should be avoided. For example, Lopid should never been taken with the statins Mevachol (lovastatin), Pravachol (pravastatin), and Zocor (simvastatin).

In other instances, the AHA recommends limiting the dose of a statin when taken together with another heart drug. People who take Norvasc should be limited to 20 mg a day or less of Mevachol or Zocor. Patients on Cordarone should take, at most, 20 mg a day of Zocor or 40 mg a day of Mevachol. Zocor should also be limited to 10 mg a day when given in combination with Multaq.

High Blood Pressure Med May Increase Risk of Low White Blood Cell Count

A common drug used to treat high blood pressure may elevate the risk in some patients of a condition in which a person’s white blood cell count is severely diminished, leaving them more susceptible to infection.

A recent case study discussed in the American Journal of Case Reports described a 61-year-old man who went to the emergency room with severe throat pain and difficulty swallowing that lasted over a week. He said he was being treated for hypertension, and was taking Norvasc (amlodipine) and Lotensin (benazepril) for it.

At the hospital, the patient was diagnosed with neutropenia, an abnormally low level of neutrophils, a type of white blood cell. He was admitted and given antibiotics for the pharyngitis he also had.

Given that the patient started Lotensin 2 months before symptoms started, and neutropenia is rarely seen with Norvasc, doctors suspected Lotensin to be the cause of his drug-induced agranulocytosis (DIAG). After he was taken off Lotensin, the patient achieved a quick recovery in white blood cell count. And after 3 weeks, the patient’s white blood cell count remained in the normal range.

Drugs to treat cancer and antibiotics are the most common causes of DIAG, and there have been prior instances of trial subjects taking Lotensin, which is considered an ACE inhibitor, a common class of high blood pressure drugs, who developed the condition.

“Because [ACE inhibitors] are commonly employed drugs, we report this case to increase awareness among prescribers about this rare but potentially lethal side effect of benazepril,” the authors concluded.

FDA Warns Against Tablet Splitting to Save Money

While many consumers split pills in half in order to save money, even if the tablets are not scored down the middle, the FDA is warning against the practice as the dose in each half can vary significantly, potentially leading to taking too much medicine.

FDA researchers tested whether a score on a tablet impacted the uniformity of the dose in drugs, Norvasc (amlodipine), which is used to treat high blood pressure, and Neurontin (gabapentin), an anticonvulsant used to treat seizures.

Tablets were purchased from 5 amlodipine and 6 gabapentin drug manufacturers, Monthly Prescribing Reference reported. Both drugs are available as a generic.

When unscored amlodipine tablets were split, the variability in the dose of the two halves were significant. In addition, none of the split tablets met established criteria for “content uniformity.”

With gabapentin, the fully scored tablets met criteria for acceptable weight and dose of the active ingredient.

Overall, splitting tablets produced more variability in doses in both of the drugs, though the change in amolodipine was more significant.

The FDA warns against splitting tablets to save money, and in its own guidance, says that splitting “can affect how much drug is present in the split tablet and available for absorption.”

Do Statin Drugs Need a Re-Think?

Have you heard of PCSK9 inhibitors? If you read our FDA Watch post about them, you know that this new class of medication just received preliminary FDA approval as a cholesterol-lowering agent.

In a 2015 study published in the New England Journal of Medicine, participants taking PCSK9 inhibitors had LDL or “bad” cholesterol levels that were 60% lower than those who took a placebo. And indications are that side effects are minimal.

Does that mean they’ll replace statins as the go-to treatment for high LDL cholesterol? Quite the opposite, at least for now.

Still, the emergence of PCSK9 (proprotein convertase subtilisin kexin 9) inhibitors is of great interest, because there are good reasons to seek alternatives. Even with new guidelines for statins, released in 2013, widespread use of the cholesterol-lowering medications (Lipitor, Crestor, and so on) remains controversial. Those guidelines advise statin therapy for all adults with heart disease or diabetes. They also encourage adults between the ages of 40 and 75 who have at least a 7.5 percent risk of heart attack or stroke over the next 10 years, regardless of their cholesterol levels, to take a statin. (The previous guidelines prescribed statin use for adults with a 10-year risk of heart disease over 20% or LDL or “bad” cholesterol levels were above 130).

That said, even given the controversial nature of statins, they do have some benefits that are not present in the new PCKS9 medications. Statins, for example, reduce inflammation and act as anti-coagulants, reducing the risk of developing blood clots, according to David Diamond, MD, a professor of molecular pharmacology and physiology at the University of South Florida.

Then there’s the fact that that the evolocumab or alirocumab — the 2 approved PCSCK9s — are injected drugs rather than daily pills and are, at least for now, far more expensive than statins.

More (and More) Statin Users

Some doctors have expressed concerns about revised statin recommendations, citing biased research and troublesome side effects. They’re far broader than former guidelines; it’s expected they’ll double the number of Americans taking the cholesterol-lowering medications to an estimated 56 million –- NEJM notes that the biggest increase is expected to be among those without cardiovascular disease. For men ages 60 to 75, the number would jump from 30% to 87%; among women in the same age group, the number of statin users would increase from 21% to 54%.

Men and women are prescribed statins in equal measure, notes John Abramson, MD, lecturer on healthcare policy at Harvard Medical School and author of Overdosed America: The Broken Promise of American Medicine. And, once statin therapy starts, patients are expected to remain on the drugs for a lifetime.

Pros and Cons of Statins

There is no question that statins do their job of lowering cholesterol. But research shows that statins might not be effective in reducing the risk of cardiac death. That is, lowering your bad (LDL) number may not actually have the desired effect of better heart-health outcomes. On that score, the research is unclear.

The authors of an article published in the February 2015 issue of Expert Review of Clinical Pharmacology criticize previous research, noting that statins are not as effective as doctors and patients have been led to believe. Nor are they as safe.

“People have been deceived and led to believe that cholesterol in the blood causes heart attacks and we need to get our cholesterol levels down to reduce our heart attack risk,” explains Diamond, the paper’s co-author, “That is untrue.”

A 2014 study published in the British Medical Journal found that people with less than a 20% risk of heart disease over the next 10 years had no significant reduction in overall mortality or cardiac mortality as a result of taking statins.

Understanding the Risks

While statins might not be effective for lowering the risk of heart disease or stroke, taking the drugs can cause significant side effects. In the BMJ study, 18% of statin users reported side effects from the medication. (A 2013 study in the Journal of Clinical Lipidology concluded that side effects, particularly muscle pain, were the most common reason people stopped taking statins.) Side effects most often associated with statin use:

  • Liver injury: According to a 2014 FDA report for consumers (PDF) liver injury is a rare but possible occurrence.
  • Diabetes: A small increased risk of developing diabetes has been shown in statin users. According to 2014 research reported in Diabetes Journal: “The risk of new-onset diabetes rises as adherence with statin therapy increases.” The FDA says that the benefits of statins outweigh that risk. That said, you should check with your doctor about having your blood sugar tested after starting statin therapy.
  • Memory loss: This side effect, also deemed rare, is often characterized as a “fuzzy” feeling, and it stops upon stopping statin use.
  • Muscle pain or weakness: In some cases, statins, particularly lovastatin, have been linked to muscle pain and a muscular weakness called myopathy.

Research has also shown a link between low cholesterol, statin use and cancer. One study found women with high cholesterol who took statins for 10 years had double the risk of an invasive form of breast cancer than those who had never taken a statin.

For those who experience side effects, Abramson suggests talking to the doctor about a “medication holiday” to see if a break from statin therapy relieves the symptoms.

“If the symptoms disappear, the doctor may want to change the dose or prescribe a different statin or even take you off of the medication altogether,” he explains.

Exploring the options

Concerns over side effects have patients exploring other options to reduce their risk of heart disease and stroke. Lifestyle changes like exercise, a healthy diet, smoking cessation and stress reduction are among the most effective.

The World Heart Federation notes that a sedentary lifestyle increases the risk of developing cardiovascular disease up to 50% while a diet high in saturated fat is responsible for about 1/3 of coronary heart disease worldwide.

Following a Mediterranean diet, which includes lots of fruits and vegetables along with healthy fats from fish, olives, avocados, seeds and nuts has been linked to a reduced risk of cardiovascular disease, according to research published in the New England Journal of Medicine.

New research shows that staying fit can help delay age-related increases in cholesterol. (Researchers defined “fit” as hitting the recommendation to engage in 150 minutes of moderate physical activity or 75 minutes of high intensity activity every week).

“In many cases, exercise, eating a healthy diet and not smoking are going to be far more effective at reducing the risk of heart disease than taking a statin,” Abramson says.

It remains to be seen if or how the PCSK9 inhibitors change the cholesterol-lowering drug market. Critics cite their so-far astronomical cost — which could reach or even exceed $10,000 a year. And while they do appear, in early results, to lower cholesterol significantly more than statins, if they also turn out to have positive effects on heart health with few or less-troubling side effects? That could be a game changer.

Further Reading