Another Metoprolol Recall Reveals the Dark Side of Generic Drugs

Here we go again: another generic metoprolol recall from an Indian drug company. The FDA announced problems with Dr. Reddy's metoprolol succinate 25 mg extended release tablets and the company is in the process of recalling 1,356,000 pills.

What is going on with this heart medicine?

Toprol-XL (metoprolol) is a beta blocker in the same family as atenolol and propranolol. Tens of millions of people swallow beta blockers every day to control heart rate, reduce the risk of a second heart attack, prevent migraines and ease the pain of angina. These medications may also lower blood pressure.

The original brand name medicine was developed under the name Lopressor and was an immediate release product. That means it had to be taken up to four times daily. That was inconvenient for many people. The extended-release formulation, Toprol-XL, was approved in 1992 and was given once daily, making it far more patient friendly.

We first suspected that there might be problems with generic extended release metoprolol succinate in 2007. Readers of our newspaper column and visitors to our website began reporting therapeutic failures when they were switched from Toprol-XL to metoprolol succinate. Here are just a few of their reports:

"After taking Toprol XL with good results for three years to control cardiac arrhythmias, I was given a generic substitute three weeks ago when I switched pharmacies.

"After taking the daily dosage for five days, I began having more and more arrhythmias to the point of having to be admitted to the hospital. There were no other differences in my daily life.

"After discharge, I returned to the unused brand name drug (Toprol XL) and have had no further problems." Nancy, March 20, 2007

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"I have been taking brand name Toprol XL for quite some time without any problems. Last week, I ran out and my doctor phoned in the refill for a generic prescription. I received metoprolol ER.

"I took it for 7 days. This is absolutely NOT the same. I have a blood pressure cuff that records my last 100 readings. During about the first 12 hours after taking it, my blood pressure was way too low. During about the last 12 hours, my blood pressure was much higher than it ever was. I am on my way now to pick up a new prescription for the brand name, at an additional cost to me, of course." Debbie, July 5, 2007

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On October 21, 2007, we wrote to alert the FDA and its Office of Generic Drugs about the problems patients were reporting with this medication. We were told, in essence, "We'll get back to you." We heard nothing more.

Over the last several years there have been a number of recalls of generic metoprolol. In 2008 the FDA warned Sandoz that its formulation of metoprolol succinate had not been properly validated. There were dissolution problems. In other words, it didn't dissolve properly in a test solution. Sandoz recalled its generic formulation of metoprolol that year.

In 2009, Ethex, a subsidiary of KV Pharmaceutical, also got into trouble with its extended-release metoprolol. The company eventually pleaded guilty to felonies of failing to notify the FDA about manufacturing problems with a variety of medications.

Fast forward to 2014. In May, a large Indian drug manufacturer called Wockhardt had to recall 109,744 bottles of its metoprolol succinate. This company had two of its manufacturing plants shunned by FDA in 2013. Violations in manufacturing meant that products from these facilities could not be exported to the U.S. One of the plants made metoprolol succinate. Until these discoveries, Wockhardt provided one fourth of the metoprolol swallowed by Americans.

Now we are told that another Indian drug company, Dr. Reddy's Laboratories, also has problems with its metoprolol succinate. It is in the process of recalling 13,560 bottles from the U.S. market. This involves 25 mg tablets from lots C206578 and C207415 (NDC 55111-466-01). In both the Wockhardt and Dr. Reddy's recall of metoprolol the problem was dissolution. That is, the formulations were not releasing the active ingredient according to FDA specifications.

But here is the rub. Although the FDA considers the Dr. Reddy's recall important (Class II, which means "a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences") it is doing little to alert patients. Pharmacies are supposed to stop dispensing such products and return them to the company. But patients who have Dr. Reddy's metoprolol succinate 25 mg pills, even if they are in the recalled lots, are supposed to keep taking them. Huh? Does that make any sense?

Even if you wanted to check on your bottle of pills to see if it was included in the recall, the chances are very good that you would not find a lot number. That's because most state pharmacy rules do not require lot numbers on repackaged pill bottles. Why is it that there are lot numbers on all over-the-counter medications, soup cans and cereal boxes but rarely on a prescription bottle of generic pills? Does that make any sense to you?

Here are some more recent complaints about metoprolol from visitors to our website:

"My metoprolol was usually a small, white, tapered pill. My prescription was refilled with one that was white and aspirin-shaped. After taking only a couple, I experienced an irregular heartbeat.

"I called the pharmacist and she exchanged the round pills. The problem stopped. When I told my previous doctor what had happened, she said, 'That couldn't happen.' I said, 'The pharmacist said it could.'

"Later my drugstore ran out of the small white tapered pill. I was sent to another drug store to get it refilled. I told the pharmacist what had happened and he said, 'Of course that happened; the round pill is not time release.'"  E.T., May 16, 2014

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"After having a bad reaction to a generic metoprolol in 2007, I began using the AstraZeneca original (Toprol-XL) and then switched to the PAR extended release generic, which is the one authorized by AstraZeneca. It's more expensive than other generics but I've always done well with it (50mg/day), so for me it's well worth the money. To my knowledge there's never been an issue with this generic, but I look forward to PP corroborating that." Gerald, May 16, 2014

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"I too had cardiac problems after being on metoprolol for a few years. My GP refused to believe I had problems from the medication. Eventually I was hospitalized. The cardiologist stated that if I had not come to the hospital via 911, I would not have survived."Marjorie, RN, BA, May 26, 2014

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Were this the only generic drug recall in recent years we would not be terribly worried. Unfortunately, dozens of different generic drugs have been recalled. We were instrumental in identifying the problems with generic versions of the antidepressant Wellbutrin XL 300. A generic product called Budeprion XL 300 was eventually withdrawn after we bugged the FDA for years because of reports of generic drug failures by visitors to this website. A different bupropion XL 300 was also withdrawn with little fanfare from the FDA.

To learn more about this tale of woe and intrigue, check out of book, Top Screwups Doctors Make and How to Avoid Them. It provides our "Top 10 Tips for Taking Generic Drugs," since insurance companies virtually force most Americans to buy generics. We're not against generic drugs, but we wish the FDA would do a better job both approving bioequivalency and monitoring foreign manufacturers. In the meantime, people will have to take steps to protect themselves. We hope our tips for using generic drugs safely will help.

Share you own generic drug story, positive or negative, below.

http://www.peoplespharmacy.com/2014/06/22/another-metoprolol-recall-reveals-the-dark-side-of-generic-drugs/

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Sodium Chloride

Today's Shortages

ASHP/FDA
Heparin Sodium Inj.

Shortage Of Saline Solution Has Hospitals On Edge

Hospitals across the country are struggling to deal with a shortage of one of their essential medical supplies.

Manufacturers are rationing saline solution — essentially pharmaceutical-grade salt water. The stuff is used all around hospitals to clean wounds, mix medications or treat dehydration. Now drug companies say they won’t be able to catch up with demand until next year.

That leaves San Francisco General Hospital’s materials manager, Reid Kennedy, in a fix. Kennedy is in charge of managing all the gloves, bandages, bedpans and IV solutions for the emergency room, medical floors and operating room.

He got a call last year from his vendor telling him it might not be able to deliver his full order.

“We were put on notice that it was going to be tight,” he says, walking through the basement warehouse.

Then things got worse in January. The flu season hit much harder than expected, and sick people flooded into hospitals. Saline bags flew off the shelves to treat dehydration. Demand far outstripped supply.

But it’s difficult to ramp up production, explains Capt. Valerie Jensen, the director of the drug shortage program at the Food and Drug Administration.

“To make one of these drugs is very complex, even though the drug itself is simple,” she says. “It takes about three weeks to make one batch of normal saline from start to finish.”

She says it’s challenging to make sure saline products are sterile. If you swallow a pill with a little bit of dirt on it, you’ll probably be fine. But contaminated saline injected into your vein could cause a big problem.

That’s why the FDA sets strict quality standards for the facilities that manufacture saline and other IV drugs, but the agency has to find a delicate balance between safety and supply.

Some suppliers suggest keeping up with the FDA’s standards is too onerous and may be playing a part in the shortage.

“A lot of variables came together to create this,” said Scott Crandall, director of medical supply contracts at Novation, a group buying organization in Texas that manages contracts for San Francisco General and 2,000 other hospitals across the country. He’s been hearing from manufacturers that increased FDA scrutiny is interfering with drug production.

“During the last year, all suppliers had issues in their facilities where they had to correct certain things the FDA found,” he says.

Some of those things were serious. Hospira, one manufacturer of saline, issued a recall earlier this year because of leaks in its saline bags. Manufacturer Baxter found particles in saline vialsand had to recall four lots. Both companies say the recalls had no bearing on the current shortage.

But Crandall says inspections and maintenance require shutting down machines. Last winter, he says, maintenance closures “slowed production down, 10 to 20 percent.”

Colin Carthen is the procurement director for Satellite Healthcare, which runs 70 dialysis centers. He says Baxter told him winter weather was also a problem. Snow and ice storms in the Midwest delayed trucks headed for California.

“As the weather got worse, we began to see more and more back-order issues,” he says. Each dialysis patient needs about four liters of saline every week to help clean his or her blood. At the worst of the shortage, Carthen felt like the lives of all 6,000 patients depended on him to find them saline.

“I called up a clinical person that I knew at like 11:30 at night and said, ‘Well, what happens if we run out of saline?’ Because I was really afraid,” he remembers. “And they were just like, ‘Yeah, it gets ugly, fast.’ ”

If supplies were to get really low, clinics would have to triage patients so the sickest could get treatment first. Without any dialysis treatment, toxins accumulate in the blood and patients can die. So every day, Carthen spent hours juggling and rerouting supplies so everyone had enough.

Hospitals have developed new clinical protocols to conserve supplies during the shortage. Nurses at San Francisco General are using smaller saline bags when possible, and transitioning patients who still need hydration to drink water from cups a little sooner than they did in the past.

The FDA is trying to mitigate the shortage by importing salinefrom Spain and Norway.

Both Baxter and Hospira, the top two saline producers in the country, say they are doing all they can to maximize production. Each points a finger at other suppliers for contributing to the shortage.

“We saw increased demand amid decreased product availability from competitors as the main driver,” a Baxter spokesman writes in an email.

A Hospira spokesman says: “Hospira began seeing stronger demand for its saline products in late 2013 when another manufacturer began to experience manufacturing issues.”

Hospira reported a 20 percent increase in U.S. sales of its injectable drugs between January and March, citing “increased volume due to competitor supply issues,” in its latest quarterly financial report.

For now, the price of saline is steady. Hospitals have contracts that keep rates locked in through next year. But when those contracts expire, it’s possible hospitals will pay two or three times as much.

This story is part of a partnership between NPR, KQED and Kaiser Health News.

Copyright 2014 KQED Public Media. To see more, visithttp://www.kqed.org.

Transcript :

LYNN NEARY, HOST:

Hospitals across the country are struggling to deal with a shortage of one of their most essential medical supplies – saline solution. It’s a product used throughout the hospital during surgery, for dialysis, with medications. Drug companies are rationing it and say they won’t be able to catch up with demand until next year. From member station KQED in San Francisco, reporter April Dembosky explains why saltwater is so hard to come by.

APRIL DEMBOSKY: Reid Kennedy walks through the basement of San Francisco General Hospital. He’s in charge of managing all of the gloves and bandages and bedpans that pass through here. He stops at a special backroom with a combination lock.

REID KENNEDY: IV solutions are under lock and key because they go in people’s bodies.

DEMBOSKY: This is where the hospital keeps its precious saline supply.

KENNEDY: And saline is huge – hugely popular. It’s just used everywhere. It’s used in wound management. It’s used in medication delivery. It’s used hydration. It’s used just everywhere.

DEMBOSKY: The patients upstairs wouldn’t know it, but Kennedy is dealing with a serious shortage of saline. He first got a call last year from his supplier telling him they might not be able to deliver his full order.

KENNEDY: We were just put on notice that it was going to be tight.

DEMBOSKY: Then things got worse in January when the flu season hit.

KENNEDY: It knocked us out.

(SOUNDBITE OF DOOR SLAMMING)

DEMBOSKY: But we’re talking about salty water here. Can’t drug companies just whip up some more?

VALERIE JENSEN: To make one of these drugs is very complex, even though the drug itself is very simple.

DEMBOSKY: That’s Valerie Jensen, the director of the drug shortage program at the FDA. She says drug companies are already making as much saline as they can.

JENSEN: They only have so many lines that can produce these drugs. And those lines are running 24/7, but they’re just not able to meet the total demand.

DEMBOSKY: What makes saline production so complicated is making sure it’s sterile. Injecting saline into a vein with the slightest contamination can cause big problems. But the FDA has to strike a delicate balance between safety and supply. The shortage seems to be caused by multiple factors. Scott Crandall is with Novation, a group buyer in Texas that manages saline contracts for San Francisco General and 2,000 other hospitals. He’s been hearing from manufacturers that increased FDA scrutiny is interfering with drug production.

SCOTT CRANDALL: During last year, all of the suppliers had issues within their facilities where they had to correct certain things the FDA found.

DEMBOSKY: Some of those things were tiny technical infractions. But some of those things were serious. Hospira, one manufacturer of saline, issued a recall earlier this year because of leaks in its saline bags. Before that, drug company Baxter found particles in its saline and had to recall four lots. Both companies say recalls had nothing to do with the shortage. But Crandall says inspections and maintenance require shutting down machines.

CRANDALL: It slowed their production down 10 to 20 percent – are the numbers we’re being told.

DEMBOSKY: Winter weather was a factor, too. Colin Carthen is Satellite Healthcare’s procurement director. He says Baxter told him that snow and ice storms in the southeast were delaying trucks headed for California.

COLIN CARTHEN: As the weather got worse, we began to see more and more backorder issues.

(SOUNDBITE OF MEDICAL EQUIPMENT)

DEMBOSKY: Carthen oversees the saline supply for 70 dialysis centers across the U.S., including this one near San Francisco. This afternoon, a handful of patients sit in rows of vinyl recliners receiving treatment for kidney failure. Each dialysis patient needs about four liters of saline each week to help clean their blood. At the worst of the shortage, Carthen felt like the lives of all 6,000 patients depended on him to find a way around the shortage.

CARTHEN: So I called up a clinical person at 11:30 at night and said what happens if we were to run out of saline because I was really afraid about what might happen. And they were just like yeah. It gets ugly fast.

DEMBOSKY: If supplies got really low, clinics would have to triage patients so the sickest got treatment first. Without any dialysis treatment, toxins accumulate in the blood and patients can die. That’s why Carthen says every day he spent hours juggling and re-routing supplies so everyone had enough. The FDA is trying to mitigate the shortage by importing saline from Spain and Norway. For most hospitals, the price of saline is a steady. Hospitals have contracts that keep rates locked through next year. But when those contracts expire, it’s possible hospitals will pay two or three times as much. For NPR News, I’m April Dembosky in San Francisco.

Dr Reddy's Lab recalls 13,560 bottles of heart drug in US

Dr Reddy`s Laboratories Ltd is recalling 13,560 bottles of its high blood pressure drug metoprolol succinate in the United States after it failed a dissolution test - a measure to check the amount of time it takes the active ingredient to release into the body - the US Food and Drug Administration said.

Metoprolol succinate extended release is a cheaper generic form of AstraZeneca Plc`s Toprol XL and the dissolution test was meant to help predict the drug's performance inside the body.

Metoprolol is used alone or in combination with other medications to treat high blood pressure. It also is used to prevent angina (chest pain) and to improve survival after a heart attack.
Another Indian drug maker Wockhardt Ltd also recalled 109,744 bottles of the same drug last month on the same reason.

- See more at: http://www.domain-b.com/companies/companies_d/Dr_Reddys_Labs/20140621_heart_drug.html#sthash.cbBetSMV.dpuf

Rye Pharmacist Sued For Negligence In Student Extern's Death

RYE, N.Y. – A Rye pharmacist is being sued for negligence in the death of a St. John’s University graduate student, who worked as an extern at his pharmacy and was exposed to a dangerous drug his first week on the job.

James Yoo, 22, was last seen by workers at Rockwell Compounding Associates putting away inventory, including fentanyl – a powerful painkiller. He was later found collapsed on the floor, the family’s lawyer Joshua Grobber said, citing the police report.

The autopsy report showed Yoo, of Queens, died of transdermal absorption, indicating he came into contact with the fentanyl, which can be transmitted through the skin.

Gropper said he had been working there three or four days starting the first week of February 2013 and the lawsuit, filed in late May, says Pharmacist Steven Cosentino should have offered better supervision.

He was exposed to the fentanyl Feb. 7, 2013 and died six days later, according to the suit. 

In addition to Cosentino and Rockwell Compounding Associates, St. John’s University (College of Pharmacy and Health Services) is named as a defendant. 

Its doctorate students must complete an externship to graduate. The suit claims it did not place Yoo in a “safe and properly supervised work environment with competent and responsible pharmacists and personnel.”

Consentino was put on probation for one year in 2002 for “selling drugs to physicians who are not the ultimate user for whom said drugs were intended.” Since Yoo’s death, Consentino and his pharmacy’s licenses were suspended in January 2014 for compounding drugs without patient prescriptions. 

The lawsuit states that St. John’s should have known placing Yoo and its other students as externs with Consentino was “reckless and improper.”

“The lawsuit is against the pharmacist and the pharmacy for improper training and supervision,” Gropper said. “But, also against St. John’s for not properly vetting the pharmacy, which not only had a prior history of problems, but were currently under investigation when Mr. Yoo was placed there.”

A call was placed to Rockwell Compounding, which has a recorded message that seems to gone unchanged since last year. It said it's clean rooms was temporarily out of order due to recent storms and local power outages. St. John's did not immediately return a call for comment. 

Yoo’s family seeks punitive damages in an amount to be determined at trial, together with interest and the costs of taking this action.

“The family is more concerned about not so much getting rich but deterring other schools and other pharmacies from this kind of practice and trying to make sure this kind of thing doesn’t happen again,” Gropper said.

http://rye.dailyvoice.com/news/rye-pharmacist-sued-negligence-student-externs-death-0

Health Canada seeks input on drug shortages

Health Canada is seeking input from Canadian physicians and members of the public on the current approach to notifications about drug shortages in Canada.

Addressing the problem of drug shortages has been a priority issue for the Canadian Medical Association and its specialty affiliate organizations since such shortages were identified in 2010. Many specialty groups feel the shortages of prescription drugs in Canada are so severe that they are having an impact on the delivery of appropriate patient care

“It is very important that the views of individual physicians are heard by Health Canada,” said CMA President Dr. Louis Hugo Francescutti.

At its recent meeting, the CMA Board of Directors established of a Drug Shortages Working Group to develop an action plan to address the issue of the ongoing shortages. The working group will define the scope and goals of CMA advocacy efforts on this topic which has global dimensions.

A policy adopted by the CMA a year ago notes “the escalation in shortages of prescription drugs in the past few years and the ongoing disruptions to supply experienced in Canada and globally are matters of grave concern to the Canadian Medical Association (CMA) and its members.”

“Currently there are more than 400 drugs listed on the Health Canada website documenting the shortages,” said Francescutti.

“While the CMA cannot resolve the complex issue of drug shortages in Canada we are committed to advocating for reducing the impact of these shortages on physicians and their patents.”

Physicians are urged to complete the online Health Canada survey consisting of nine questions on the best approach to drug shortage notification. A pdf version of the consultation is also available to those who wish to submit the survey by email or regular mail.

http://www.cma.ca/healthcanadaseeksinputondrugshortages