FDA Pulls Heartburn Drug Zantac From Market

All versions of the heartburn drug Zantac (ranitidine) have been pulled from the U.S. market due to possible contamination with a probable cancer-causing chemical, the U.S. Food and Drug Administration said Wednesday.

This is the latest step in an ongoing investigation of N-Nitrosodimethylamine (NDMA) in ranitidine medications, the agency noted.

In some ranitidine products, NDMA increases over time and when the drugs are stored at higher temperatures, which may result in people being exposed to unacceptable levels of the chemical, according to the FDA.

The agency’s order for immediate withdrawal of all ranitidine products means they won’t be available either by prescription or over-the-counter (OTC) in the United States.

“Today’s action requesting companies to withdraw all remaining ranitidine products the U.S. market is being taken out of an abundance of caution,” Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said in an agency news briefing on Wednesday.

“Even though these products when they come off the factory line don’t contain unacceptable levels of (NDMA), we don’t know if they’re stored under various conditions what will end up at the end of the day,” she explained.

According to Woodcock, storage temperature appears to be key to the accumulation of NDMA in ranitidine.

“With ranitidine, the NDMA does not appear to be formed during manufacturing, but instead appears over time in storage, especially when stored at higher than room temperature,” she said. Packaging or specific formulations of the drug might play a role, too.

All of that means that the buildup of NDMA in stored Zantac “may be a fixable problem,” she told reporters. “We’re open to companies demonstrating that they’ve reformulated their product in a way that is stable.”

But for now, consumers taking OTC ranitidine should stop taking any tablets or liquid they have, dispose of them properly and not buy more. Those who want to continue treating their condition should consider using other approved OTC products, the FDA recommended.

Patients taking prescription ranitidine should talk with their health care provider about other treatment options before they stop taking the medicine, the FDA said. There are multiple drugs approved for the same or similar uses as ranitidine that don’t have risks from NDMA.

FDA tests have not found NDMA in famotidine (Pepcid), cimetidine (Tagamet), esomeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec).

Due to the current coronavirus pandemic, people shouldn’t take their ranitidine medications to a drug take-back location, the FDA noted. Follow the disposal instructions in the medication guide or package insert, or follow the FDA’s recommendations on how to safely dispose of the medications at home, the agency said.

NDMA is an environmental contaminant that can be found in water and foods and has been classified as a “probable human carcinogen” by the World Health Organization.

The presence of NDMA in minute quantities has already led to the recall of many types of blood pressure medications, such as valsartan and losartan.

NDMA’s potential presence in Zantac and generic versions of ranitidine was first reported in September 2019.

Source: HealthDay


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FDA Approves New Type of Drug to Treat Migraines

Amy Norton and E.J. Mundell wrote . . . . . . . . .

Migraine sufferers who cannot get relief from existing medications have a new treatment option, the U.S. Food and Drug Administration announced Monday.

The pill, called ubrogepant (Ubrelvy) is for the immediate treatment “of migraine with or without aura [a sensory phenomenon or visual disturbance] in adults,” the agency said in a news release.

Ubrogepant is not to be used to prevent migraines, the FDA said, only to treat an attack once it strikes.

“Migraine is an often disabling condition that affects an estimated 37 million people in the U.S.,” said Dr. Billy Dunn, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “Ubrelvy represents an important new option for the acute treatment of migraine in adults, as it is the first drug in its class approved for this indication.”

According to the FDA, approval came after the results of two studies involving more than 1,400 adults.

“In both studies, the percentages of patients achieving pain freedom two hours after treatment [defined as a reduction in headache severity from moderate or severe pain to no pain] and whose most bothersome migraine symptom (nausea, light sensitivity or sound sensitivity) stopped two hours after treatment, were significantly greater among patients receiving Ubrelvy at all doses compared to those receiving placebo,” the FDA said.

The drug is not without side effects however. In the two trials, potential side effects included nausea, fatigue and dry mouth.

Ubrogepant belongs to a new class of medications called CGRP inhibitors that has come to the market in the past year.

CGRP is a small protein released by the trigeminal nerve during migraine attacks. It’s believed to play a key role in generating migraine misery, explained Dr. Richard Lipton, who directs the Montefiore Headache Center at the Albert Einstein College of Medicine in New York City.

The three approved CGRP inhibitors are all injection drugs that are used regularly, to prevent migraine attacks.

Ubrogepant is different because it’s a tablet that treats migraines in progress. Another oral “gepant,” called rimegepant, is also in the pipeline. Data on both drugs have been submitted to the FDA for approval, according to the companies developing them.

Lipton’s group published its own study on the drug, released last month.

The study involved nearly 1,700 patients and found that the pill worked better than a placebo pill at halting migraines in progress. Ubrogepant beat placebo treatment in easing pain and other migraine symptoms, such as nausea and sensitivity to light or sound.

Of patients who used the real drug to treat a migraine attack, 22% of those on a higher dose were pain-free within two hours. That compared with 14% of the placebo group. Similarly, 39% of ubrogepant users were free of their “most bothersome” symptom within two hours, versus 27% of placebo users.

The study, funded by drug’s maker, Allergan, was published in the Journal of the American Medical Association.

According to Lipton, the new gepants could make a “big difference” for certain migraine patients.

They include people who do not get relief from current acute treatments, and those who cannot take the medications because of side effects or safety concerns, Lipton said.

Right now, medications called triptans are the standard treatment for more severe migraine attacks. The drugs, which came out in the 1990s, stop migraines by stimulating receptors for the brain chemical serotonin, which reduces inflammation and constricts blood vessels.

But not everybody responds to the medications. And because of the blood vessel constriction, people at high risk of heart attack or stroke cannot take them.

Triptans also have side effects — like numbness, dizziness and sleepiness — that can make them difficult to take.

Gepants work through a “novel mechanism,” Lipton said, which means they might help some patients who do not respond to triptans. And they do not constrict blood vessels.

Lipton has financial ties to both Allergan and Biohaven Pharmaceuticals, maker of rimegepant.

It will be “exciting” to have new options for patients who cannot take triptans, said a neurologist who was not involved in the study.

“There haven’t been any new acute treatments in a long time,” Dr. Rachel Colman, of Mount Sinai’s Icahn School of Medicine in New York City, said in November.

Questions do remain, Colman pointed out. The latest trial tested the effects of only a single treatment, and it’s not clear how consistent patients’ responses will be over time, she said.

Long-term safety and side effects are also unknowns — though, Colman said, “so far, the tolerability data looks good.”

Nausea was the most commonly reported side effect in the JAMA study, affecting 2% of ubrogepant patients within two days of taking the drug.

In the United States alone, more than 37 million people suffer from migraines, according to the American Migraine Foundation. People with milder migraines may find relief with general pain relievers like naproxen and acetaminophen.

But for some migraine sufferers, Colman noted, “there’s a significant need” for new tactics.

Source: Healthday


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FDA Gives Expanded Approval to Prescription Fish Oil for Heart Patients

Dennis Thompson wrote . . . . . . . . .

The U.S. Food and Drug Administration on Friday gave expanded approval to a prescription form of fish oil called Vascepa, to help prevent heart trouble in people at high risk who are already taking statins.

Vascepa (icosapent ethyl) was already FDA-approved for a small percentage of patients with exceptionally high blood levels of triglycerides, a type of blood fat.

The new approval greatly expands the potential pool of patients, because it now includes people with simply high levels of triglycerides — at or above 150 milligrams per deciliter — and multiple risk factors for heart disease and diabetes.

“Today’s approval will give patients with elevated triglycerides and other important risk factors, including heart disease, stroke and diabetes, an adjunctive treatment option that can help decrease their risk of cardiovascular events,” Dr. John Sharretts said in an FDA news release. He’s acting deputy director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research.

Vascepa is a drug derived from fish that contains pure EPA, a key nutrient in fish oil. A month’s supply of Vascepa costs roughly $300.

Friday’s approval follows on the positive results of a study on Vascepa presented in November at the annual meeting of the American Heart Association (AHA). Early findings from the clinical trial found that the drug slowed the development of artery-clogging plaques.

In the study, Vascepa appeared to put the brakes on key aspects of plaque formation in vessels after nine months of use, lead researcher Dr. Matthew Budoff, a professor at UCLA’s David Geffen School of Medicine, said at the time.

“We found significant slowing of progression among four different plaque markers, including total plaque,” Budoff noted in a presentation at the AHA’s annual meeting, in Philadelphia.

These early results provide some tantalizing hints why icosapent ethyl was found to reduce risk of heart-related disease and death by 25% in another study released last year, said Dr. Donald Lloyd-Jones, chair of preventive medicine at Northwestern University Feinberg School of Medicine.

EVAPORATE, the clinical trial reported on last month, is ongoing and will report final results after 18 months. Experts hope more data from the trial will show which aspect of the drug’s effect on plaque is reducing heart risk.

The EVAPORATE trial placed 40 people on high doses of icosapent ethyl and another 40 on a placebo. All participants were already taking statins and had developed at least one artery-clogging plaque. Amarin Corp., which makes Vascepa, paid for the trial.

Participants underwent CT scans at the beginning of the study and at nine months to track progression of arterial plaque in their bodies. They’ll undergo a final CT scan at 18 months.

Compared to the control group, people on icosapent ethyl experienced a slowdown in plague growth at nine months, including:

  • 42% less progression in total plaque,
  • 89% less new calcified plaque,
  • 57% less new fibrous plaque,
  • 19% less new non-calcified plaque.

Notably, the fish oil drug did not appear to actually melt away plaques, but only slowed down their growth, said Dr. Stephen Nicholls, a professor of cardiology at Monash University in Queensland, Australia.

“There was no evaporation. They all continued to progress,” said Nicholls.

There are several possible explanations why icosapent ethyl slows buildup of plaque in the arteries, Nicholls said.

The drug has been shown to reduce triglyceride levels, which contribute to plaque formation. In this study, triglycerides declined, Budoff said.

But the antioxidant and anti-inflammatory effects of the fish oil drug should also be considered as potential contributors, Nicholls said.

Newer trials have tended to support the value of fish oil drugs in controlling arterial plaques, after years of mixed results, Lloyd-Jones and Nicholls said. Both experts were not involved with the new trial.

That’s probably because earlier trials did not have people on high enough doses of purified fish oil supplements, Nicholls said.

Other high-dose fish oil clinical trials are ongoing, and will provide further evidence in the near future, Lloyd-Jones said.

Source: HealthDay

The FDA’s New EPA/DHA Health Claim

Jessica Levings wrote . . . . . . . . .

Fish and seafood packaging may now boast qualified health claims stating that omega-3s can help reduce risk of hypertension and coronary heart disease and lower blood pressure.

In June, the FDA approved the use of certain qualified health claims on foods and dietary supplements containing the omega-3 fatty acids EPA and DHA relating to their ability to reduce the risk of hypertension and coronary heart disease, as well as lower blood pressure. The decision was in response to a 2014 petition submitted by the Global Organization for EPA and DHA Omega-3 (GOED).

According to Harry Rice, PhD, GOED’s vice president of regulatory and scientific affairs, who spearheaded the health claim petition on behalf of the organization and its members, “The new qualified health claims provide what many, including GOED, consider to be long overdue acknowledgement from the FDA about the blood pressure–lowering benefits associated with EPA/DHA, the primary long-chain omega-3 fatty acids found in fatty fish. Linking EPA/DHA intake to blood pressure reduction provides consumers a benefit to which they can relate.”

Before the announcement of the new qualified health claims, since 2004 the FDA has allowed the following qualified health claim on certain foods and supplements: “Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.”

Following are the new qualified health claims the FDA announced, which manufacturers may voluntarily use on labels of seafood and other qualifying foods and supplements:

1. Consuming EPA and DHA combined may help lower blood pressure in the general population and reduce the risk of hypertension. However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.

2. Consuming EPA and DHA combined may reduce blood pressure and reduce the risk of hypertension, a risk factor for CHD (coronary heart disease). However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.

3a. Consuming EPA and DHA combined may reduce the risk of CHD (coronary heart disease) by lowering blood pressure. However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.

3b. Consuming EPA and DHA combined may reduce the risk of CHD (coronary heart disease) by reducing the risk of hypertension. However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.

4. Research shows that consuming EPA and DHA combined may be beneficial for moderating blood pressure, a risk factor for CHD (coronary heart disease). However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.

Dietary supplements and conventional foods bearing any of the above claims must contain at least 0.8 g EPA and DHA (combined total) per serving and meet certain other nutrient content criteria. Importantly, the requirement of 0.8 g per serving isn’t a recommended intake level but rather a level of intake the FDA observed to lower blood pressure in limited studies.

Under general health claim requirements, individual foods can’t bear a health claim if they exceed 13 g total fat, 4 g saturated fat, 60 mg cholesterol, and 480 mg sodium per reference amount customarily consumed (RACC), per labeled serving size, and per 50 g if the RACC is 30 g or less or two tablespoons or less. Furthermore, to bear a health claim, individual foods also must contain, before any nutrient addition, at least 10% DV for vitamin A, vitamin C, iron, calcium, protein (5 g), or dietary fiber per RACC.

Evidence Base for the EPA/DHA Health Claim

The FDA determined that the overall evidence relating to EPA/DHA intake and blood pressure didn’t meet the “significant scientific agreement” standard required for an authorized health claim, but it did meet the “credible evidence” standard for a qualified health claim.

To assess whether a beneficial link exists between consuming EPA and DHA together and lowering blood pressure, the FDA evaluated 104 intervention studies analyzing the effect of EPA and DHA from conventional foods, dietary supplements, and prescription drugs on blood pressure in both normotensive and hypertensive people. Only 36 of the 104 studies showed a statistically significant benefit, with durations ranging from four weeks to one year, and combined doses of EPA and DHA ranging from 390 mg per day to 15 g per day.

Based on its findings, the FDA concluded there’s “some credible evidence suggesting a relationship between the combined intake of EPA and DHA from conventional foods, dietary supplements, and prescription drugs and blood pressure reduction. However, this evidence is highly inconsistent.”

Sources of EPA and DHA, Average Intake

EPA and DHA are added to certain supplements and are naturally found or fortified in some conventional foods, including fatty fish (eg, salmon, mackerel, sardines), fish oils, seaweed, and algal oils. Studies have found that food contributes a small amount of DHA and EPA to total daily omega-3 intakes; the National Institutes of Health estimates the amounts at 40 mg in children and teenagers and about 90 mg in adults.

Dietary supplements containing omega-3s also contribute to total omega-3 intake, with fish oil as one of the most commonly used sources. According to 2012 data, 7.8% of US adults and 1.1% of US children reported taking supplements containing fish oil, omega-3s, and/or DHA or EPA. According to 2003–2008 National Health and Nutrition Examination Survey (NHANES) data, supplements add about 10 mg to average DHA intakes, and 20 mg to average EPA intakes in adults. Data from the FDA and NHANES indicate that the current average intake of EPA and DHA in the United States is only about 77 mg per day from all sources for people aged 4 and older.

Currently, there’s no recommended intake level in the United States for EPA or DHA. However, to help improve heart health, the 2015–2020 Dietary Guidelines for Americans (DGA) recommend individuals in the general population to consume about 8 oz per week of a variety of seafood, providing about 250 mg per day of EPA and DHA. Importantly, the DGA note that this recommendation is for the total package of nutrients seafood provides, including its EPA and DHA content.

Use of the EPA/DHA Health Claim on Fish

For items sold at seafood counters in supermarkets, nutrition labeling of fresh fish and packaged single-ingredient fish is voluntary unless nutrient content or a health claim is made. Fish and packaged seafood may bear the claim if they meet all the required criteria for its use.

The FDA defines fish as “fresh or saltwater finfish, crustaceans, other forms of aquatic animal life (including, but not limited to, alligator, frog, aquatic turtle, jellyfish, sea cucumber, and sea urchin, and the roe of such animals) other than birds or mammals, and all mollusks, where such animal life is intended for human consumption.” With regard for labeling these products with the EPA/DHA qualified health claims, the FDA considers “products that are essentially all fish” to be those without any added ingredients and with an “insignificant amount” of added fat or carbohydrate. Examples of products considered all fish include raw, boiled, and broiled fish.

Source: Today’s Dietitian

Heartburn Drug May Contain Small Amounts of Known Carcinogen, FDA Says

A substance that could cause cancer has been found in some ranitidine heartburn and ulcer medicines, including the brand-name drug Zantac, and the source of this contamination is being investigated, the U.S. Food and Drug Administration says.

While preliminary tests found low levels of the nitrosamine impurity N-nitrosodimethylamine (NDMA) in some ranitidine products, the FDA said this does not mean patients taking the drugs should stop using them now.

NDMA is the same contaminant found in many brands of blood pressure and heart failure medicines during the past year, leading to recalls.

Patients who are taking prescription ranitidine and want to stop using it should discuss alternatives with their health care provider, the FDA advised. Those taking over-the-counter (OTC) ranitidine could switch to other OTC medicines.

Several drugs are approved for the same or similar uses, the FDA noted.

NDMA is an environmental contaminant found in water and foods, including meats, dairy products and vegetables. It is classified as a probable human carcinogen.

“Drug impurities remain a major national concern,” said Dr. David Robbins, associate chief of endoscopy at Lenox Hill Hospital in New York City. “While Zantac may prove safe in the long run, this latest statement adds confusion and concern, so my interim advice to patients is simple: switch to another drug … and of course, confirm with your doctor the need for an antacid.”

The FDA said it’s evaluating whether the low levels of NDMA in ranitidine pose a risk to patients and that it will post that information when it’s available.

In a statement, pharmaceutical giant Sanofi, which makes Zantac, said that it “takes patient safety seriously, and we are committed to working with the FDA. Zantac OTC (over the counter) has been around for over a decade and meets all the specified safety requirements for use in the OTC market.”

In the meantime, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said the FDA is working with international regulators and industry partners to find out where the contamination originated.

“The agency is examining levels of NDMA in ranitidine and evaluating any possible risk to patients,” she said in a news release. “The FDA will take appropriate measures based on the results of the ongoing investigation.”

Large amounts of NDMA may pose a risk, but the levels of NDMA in ranitidine found in preliminary tests barely exceed amounts found in common foods, according to the FDA.

Ranitidine decreases the amount of acid created by the stomach. OTC ranitidine is approved to prevent and relieve heartburn, and prescription ranitidine is approved for a number of uses, including treatment and prevention of ulcers of the stomach and intestines, and treatment of gastroesophageal reflux disease.

Similar contamination in heart medicines is also under investigation.

“The FDA has been investigating NDMA and other nitrosamine impurities in blood pressure and heart failure medicines called Angiotensin II Receptor Blockers (ARBs) since last year,” Woodcock said. “In the case of ARBs, the FDA has recommended numerous recalls as it discovered unacceptable levels of nitrosamines.”

Source: HealthDay


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