Preparing small doses of medications from syringes can be inaccurate and lead to dangerous dosing errors for infants and small children, warns a new study.

The problem is that small doses of potent drugs for young patients are often prepared from stock of less than 0.1 millileter (mL) in size, but the equipment does not permit the accurate measurement of volumes that small, explained study author Dr. Christopher Parshuram, of the University of Toronto.

And medications that most often require small doses include powerful narcotics and sedatives such as morphine, lorazepam and fentanyl, as well as immunosuppressants, noted Parshuram, who works in the Department of Pediatrics at The Hospital for Sick Children and directs Pediatric Patient Safety Research at the University of Toronto Center for Patient Safety.

It’s a Catch-22, he and his colleagues acknowledge. “The safe administration of medications requires formulations that permit accurate preparation and administration, but current equipment does not permit the accurate measurement of volumes less than 0.1 mL,” said Parshuram in a Canadian Medical Association Journal news release.

In both hypothetical and clinical studies, he and his colleagues looked at 71,218 intravenous doses given to 1,531 infants and children admitted to an intensive care unit in 2006. Of those doses, 7.4 percent of the children and babies needed preparations of less than 0.1 mL of stock solution, and 17.5 percent needed preparations of less than 0.2 mL.

“Our findings indicate a substantial source of dosing error that involved potent medications and affected more than a quarter of the children studied,” the researchers wrote.

“Small volumes of stock solution are required because of the relatively low doses needed for infants and young children and the relatively high concentrations of commercially available stock solutions,” they added. “The clinical [consequences] of errors occurring as a result of preparing doses from small volumes will be compounded by incomplete safety data, errors in medication orders, and errors in preparation or administration.”

Since the preparation of small doses of medication is common in pediatric hospitals across North America, there is a need to review preparation methods, regulatory requirements and manufacturing processes, the researchers concluded.

The study appears in the current issue of the Canadian Medical Association Journal.

Technorati Tags: lorazepam, Small Doses of Medication

Hundreds of Kenyans living with HIV protested outside EU offices in Nairobi on Thursday against a deal they say may block access to cheap life-saving AIDS drugs.

The European Union and India are due to discuss a free-trade agreement in Brussels on Friday which campaigners say will cause shortages of generic antiretroviral (ARV) drugs. A U.N. study found that the proposed deal could make generics more expensive.

Under the proposed deal, patent terms would be extended beyond 20 years while data exclusivity provisions would force Indian manufacturers to carry out their own clinical trials instead of using existing data.

This would delay registration of generic ARVs for several years, according to the U.N.

“Unless the attacks by the European Commission on the future of generic production in India are stopped, costs will rise, ARV access will be rationed and patients will die,” said Hussein Kerrow of the advocacy group Medecins sans Frontieres.

Generic ARVs cost about $137 per person per year, a fraction of the price of patented ARVs used to treat the human immunodeficiency virus (HIV) that causes AIDS, and are sold by Western pharmaceutical companies.

Only a third of the 14.6 million people around the world who need ARVs are currently receiving them. More than 80 percent of those using them, as well as patients in developing countries, get their generic drugs from India, activists say.

“We depend on these drugs from India because they are cheap and they are very good,” said Tom Osongo, 62, a demonstrator.

The placard-waving protestors presented a petition to Eric van der Linden, the EU’s head of delegation in Kenya, who said that he would pass on their message but gave no promises.

“I am not a magician,” he said.

HIV positive Osongo said he had been suffering from tuberculosis, pneumonia and typhoid, until six years ago, when he started on the life-enhancing drugs.

“If they (generic ARVs) are not available, the first thing that would happen is me to go back down with the disease and maybe even die,” he said.

(Editing by Wangui Kanina)

Technorati Tags: AIDS drugs, antiretroviral drugs, drugs from India, generic drugs

Examining data on drug prescriptions to more than 5 million Americans over six months, the researchers found that just over 3 percent were filled but not picked up from the pharmacy.

Although that overall figure is low, the results suggest that such prescription “abandonment” contributes to the larger problem of patients’ non-adherence to their medication regimens.

“I’d say it’s a small but meaningful contribution,” said lead researcher Dr. William H. Shrank, of Harvard Medical School and Brigham and Women’s Hospital in Boston. That’s partly because certain patients had increased odds of not picking up their prescriptions, Shrank noted in an interview.

He and his colleagues found that those prescribed drugs with higher price tags were more likely to leave the medications unclaimed at the pharmacy, as were those receiving first-time prescriptions for a particular type of medication.

And that, Shrank said, points to areas where there is room for improvement. A number of studies have shown that people with chronic health problems, including high blood pressure, diabetes and heart disease, commonly fail to take their medications as prescribed.

To find out why, Shrank’s team wanted to look at one aspect of the larger picture: how often patients simply never pick up their prescriptions from the pharmacy. Their study, published in the Annals of Internal Medicine, also looked for clues that might explain the patients’ behavior and flag problems that doctors and pharmacists could address.

The researchers used data from CVS Caremark, a national retail pharmacy chain and pharmacy benefits manager that also funded the study. They focused on 10.3 million prescriptions filled by more than 5 million patients in 2008.

Of those prescriptions, 3.3 percent were abandoned — meaning the medication was bottled but returned to stock when the patient did not pick it up after two weeks.

Not all those patients necessarily went untreated. In just under half of cases, the patient bought a prescription for another medication in the same drug class within 30 days, sometimes at a different pharmacy.

But 1.8 percent of all prescriptions were returned to stock and apparently not replaced with an alternative.

Certain prescriptions had a higher likelihood of not being picked up: New prescriptions were nearly three times as likely as others to go unclaimed, for instance. Patients with complex prescription regimens for multiple health problems were more likely to abandon one or more of their medications.

And prescriptions for opiate drugs were least likely to be abandoned — perhaps because patients’ need for painkillers is more acute, the authors speculate, or the drugs’ potential for resale is greater.

The strongest predictor of prescription abandonment, however, was price: Drugs that cost more than $50, and those with a co-payment of $40 to $50, were three to five times more likely to go unclaimed than medications with no patient co-payment.

It’s not surprising that patients were more likely to abandon higher cost drugs, according to Shrank. “I think this is telling us that ‘sticker shock’ is real,” he said.

“Patients often don’t know the cost of a drug until they arrive at the pharmacy.” To help avoid that, Shrank suggested that when patients are given a new prescription, they ask the doctor about the price.

A lower cost alternative might be available. Pharmacists could also work more closely with doctors to make them aware of drug prices and lower cost alternatives, the authors write.

As for the greater likelihood of new prescriptions being abandoned, that could signal that some patients do not fully understand why they are being put on a new drug, according to Shrank.

He again advised people to talk to their doctors, and ask questions any time they do not understand the reasons for a drug prescription.

Shrank and his colleagues also found that prescriptions sent to the pharmacy electronically had a 64 percent greater chance of abandonment than those prescribed the old-fashioned way — either hand-delivered by patients or phoned or faxed in by the doctor.

But, Shrank said, “that does not mean that electronic prescriptions are bad.”

One reason for their higher likelihood of abandonment is that, unlike paper prescriptions brought in by patients, electronic prescriptions arrive at the pharmacy regardless of a patient’s intention to ultimately pick up the drug.

But it’s also possible that patients not given a paper prescription are more apt to forget about the medication.

Shrank said that it might be helpful for doctors who use electronic prescribing to give patients written reminders to make sure they remember that their medication will be awaiting them at the pharmacy.

Overall, the study findings “shed light on an important component of medication non-adherence,” according to an editorial published with the report.

One remaining question is how such prescription abandonment ultimately affects people’s health, write Drs. Michael D. Murray, of Purdue University College of Pharmacy in Indianapolis, and Jeff Harrison of the University of Auckland in New Zealand.

In some cases, they note, a patient’s decision not to pick up a drug — out of concern for side effects, for instance, or because he or she already has an adequate supply — may turn out to have positive effects, or none at all.

On the flip side, Murray and Harrison point out, the fact that a patient picks up a prescription does not necessarily mean that he or she ends up taking it.

Shrank said that studies need to keep investigating the various and complex reasons that people do not use their medications as prescribed.

“We need to have a better understanding of how we can help patients adhere to their medications,” he said.

SOURCE: Annals of Internal Medicine, online November 15, 2010.

Technorati Tags: Abandoned prescriptions, drug prescriptions, new prescriptions

A good night’s sleep when you’re pregnant may help keep your blood pressure levels normal, new research suggests.

Pregnant women who got less than six hours of nightly sleep during early pregnancy had systolic blood pressure readings in their last trimester that were nearly 4 mm/Hg higher than women who slept nine hours nightly, the study found. And women who got less than five hours of sleep increased their odds of developing preeclampsia — a serious pregnancy complication related to high blood pressure — more than ninefold.

On the other hand, getting too much sleep could also be a problem: women who reported sleeping more than 10 hours a night in their first trimester had more than a twofold increase in the risk of developing preeclampsia, according to the study published in the October issue of the journal Sleep.

“Women, in general, need about seven to nine hours of sleep during pregnancy, preferably nine hours. Getting less than that amount can have health affects,” said study author Michelle Williams, a professor of epidemiology and global health at the University of Washington, and co-director of the Center for Perinatal Studies at the Swedish Medical Center in Seattle.

“Women generally already know that they’re eating well and getting enough exercise for two during pregnancy. Our study suggests that women should also aspire to sleep well for two,” said Williams.

But, she added, because the current study is one of the first to show this association, its findings need to be confirmed by other researchers before any recommendations can be made.

The study included 1,272 healthy pregnant women who were recruited for the study during prenatal care visits to the Swedish Medical Center in Seattle between December 2003 and July 2006.

All the women reported information on their lifestyles and health characteristics, as well as sleeping habits, in an initial interview done around 14 weeks’ gestation. Blood pressure was measured periodically throughout pregnancy.

Sleep duration didn’t appear to have an effect on blood pressure levels in the first and second trimesters of pregnancy. However, during the third trimester, women who slept less than six hours a night had an average systolic (that’s the top number in a blood pressure reading) blood pressure that was 3.72 mm/Hg higher than women who slept nine hours. Even women who slept seven to eight hours a night had systolic blood pressure readings that were 2.43 mm/Hg higher than women who slept nine hours.

The study also found that systolic blood pressure was 4.21 mm/Hg higher in women who slept more than 10 hours each night.

To better assess what such differences in blood pressure might mean to pregnant women, the researchers also looked at the effect of sleep time on the risk of developing preeclampsia, which can have significant health consequences for both the mother and the baby.

The researchers found that women who slept less than five hours a night increased their odds of developing preeclampsia more than 9.5 times, and those who stayed in bed more than 10 hours had more than a twofold increased risk of preeclampsia.

Williams said the current study wasn’t designed to find the cause behind these associations, but that the researchers theorize that changes in the body’s circadian rhythm may occur when sleep habits change during pregnancy, and that these changes may cause hormonal changes that affect blood pressure levels.

“This is a very important study, but it’s just a beginning,” said Dr. Mary Rosser, an obstetrician and gynecologist at Montefiore Medical Center in New York City. Rosser said that there are numerous changes that occur during pregnancy that could affect blood pressure levels, such as the weight gain that’s typical during pregnancy. Even if weight alone doesn’t affect blood pressure levels, Rosser said that the extra weight could cause sleep apnea, which is known to raise blood pressure.

But, Rosser added, it’s definitely a good idea for women to get a good night’s sleep, although doing so often becomes difficult as a pregnancy progresses.

“Women often take care of other people, but pregnant women need to carve out time to rest, either at night or with naps during the day,” she said. Rosser also recommended avoiding caffeinated beverages altogether, and making sure you get enough water during the day. Women may also sleep better if they exercise during the day, she said.

Technorati Tags: high blood pressure, High Blood Pressure risk, Lack of Sleep, Sleep During Pregnancy, systolic blood pressure

Federal health regulators have approved the first pill to treat the underlying causes of multiple sclerosis, a debilitating nervous system disorder that has traditionally been treated with injectable drugs.

The Food and Drug Administration approved Swiss drugmaker Novartis’ treatment Gilenya to reduce relapses in patients with multiple sclerosis, who experiences loss of balance, muscle spasms and other movement problems.

There is no cure for the disease, but steroids can reduce the duration and severity of symptoms in the short term, and seven treatments on the market have had success in reducing recurrence of symptoms.

All involve daily or regular injections, which doctors say discourages some patients from keeping up with their treatment.

“One of the things Gilenya offers is an alternative to injection or infusion administration,” said Dr. Nick LaRocca, of the National Multiple Sclerosis Society. “Many people prefer to take a capsule because they don’t like to stick needles into themselves.”

Multiple sclerosis causes the body’s immune system to attack the protective coatings of the brain and spinal cord. Gilenya works to reduce a type of white blood cell that often attacks the nervous system.

The FDA reviewed the drug under a priority timetable reserved for groundbreaking therapies.

In June, an FDA panel voted 25-0 that Gilenya helps reduce relapses of multiple sclerosis.

Despite the overwhelming endorsement, panelists also had questions about side effects and said patients should receive their first dose under doctor supervision because of the possibility of sudden heart irregularities.

Additionally, panelists said patients should receive routine lung function tests.

Those side effects were less common when patients received the lower of two doses tested by Novartis.

Novartis said Wednesday the FDA approved a 0.5-milligram daily dose of Gilenya.

About 2.5 million people around the world have multiple sclerosis, with an estimated 400,000 of them in the U.S. In the most common form of the disease, patients experience periods of well-being followed by periodic relapses.

Physicians who treat multiple sclerosis are mindful of safety problems with other recent treatment for the disease. Biogen Idec’s drug Tysabri was approved for the condition in November 2004 and pulled from the market the next year after cases of a rare but lethal brain inflammation in some patients. It was reintroduced in 2006 under an FDA-approved distribution program.

Novartis said it is pursuing regulatory approval in Europe and the rest of the world.

The company’s stock climbed 33 cents to $56.79 in pre-market trading Wednesday.

Technorati Tags: Gilenya, multiple sclerosis, nervous system disorder, Novartis

Freer trade could harm India’s generic drug business, which supplies the bulk of the AIDS medicines sent to developing countries, a study backed by the drug-purchasing body UNITAID said on Tuesday.

The report, written by a UNITAID official along with experts from Boston University and Harvard, warns that India’s generics could cost more and be harder to access if the country has to adhere to stricter intellectual property rules. It said trade deals India already signed up to, such as the World Trade Organization intellectual property accord known as TRIPS, have already begun to complicate efforts to get cheap, life-saving drugs to poorer countries. “The introduction of product patents in India is severely constraining generic competition and supply, particularly for newer medicines,” the report found.

“Many free trade agreements that have been concluded or are being negotiated between industrialized and developing countries contain measures that restrict access to medicines.” The study, published in the Journal of the International AIDS Society, said trade talks between India and the European Union include measures that could delay or restrict competition from generic medicines by extending patent terms, requiring data exclusivity and tightening border enforcement rules.

Such moves could drive up prices for India’s anti-retroviral treatments, limit dosage options and delay access to newer and better drugs, the report argued. “Such measures can undermine the international goal to achieve universal access to HIV/AIDS interventions.” Set up in 2006 by Brazil, Chile, France, Norway and Britain, UNITAID uses proceeds from airfare taxes and donations to fund HIV/AIDS, malaria and tuberculosis treatment in poor countries.

Jorge Bermudez, UNITAID’s executive secretary, said that 80 percent of the AIDS drugs the group now distributes come from Indian generics manufacturers. “The findings of this study raise grave concerns for us,” he said in a statement. “What we need today is a more flexible approach to scale up treatment and not the opposite.” India’s generic drug manufacturers include Cipla Ltd, Aurobindo Pharma Ltd, Strides Arcolab Ltd, Dr Reddys Laboratories and Ranbaxy Laboratories. (Editing by Stephanie Nebehay and Mark Heinrich)

Technorati Tags: AIDS drugs, generic drugs, India generic drugs, Indian generics manufacturers

Many parents give their children too large or frequent doses of non-prescription medicines for fever, coughs and colds, putting their health at risk, according to an Australian study released Monday.

“Many children are being put at risk by parents? over-use of widely-available over the counter medicines for fever, coughs and colds,” concluded the study by University of Sydney researchers presented at a conference of the International Pharmaceutical Federation.

“We were surprised and concerned to find that some people thought that medicines must be safe because you can buy them without prescription”, said Rebekah Moles, who headed up the study of 97 parents and day care centre employees.

“Taking all the scenarios together, 44 percent of participants would have given an incorrect dose, and only 64 percent were able to measure accurately the dose they intended to give”, said Moles.

Only 14 percent managed the fever scenario correctly.

The noted that 48 percent of calls in 2008 to the New South Wales Poisons Information Centre, which receives all out of hours calls from around Australia, concerned accidental overdose in children, with 15 percent needing hospitalisation.

Australia is unlikely to be a special case, the researchers said, and they believe that the inappropriate use of children’s medicines is widespread throughout the world.

“It is vital that parents worldwide should understand the proper usage of medicines so that they do not continue to put their children’s health at risk,” said Moles.

Technorati Tags: Child health, children's medicines, non-prescription drugs

Eisai Co and Pfizer Inc said they won U.S. regulatory approval for a higher dose once-daily version of Aricept, a drug that treats Alzheimer disease.

Eisai, Japan’s No. 4 drugmaker, said in March it expected annual U.S. sales of the drug, its flagship product, to fall 60 percent to $800 million from $2 billion between 2011 and 2013 with the expiration of its patent for the drug looming.

The U.S. Federal Drug Administration approved a 23 mg tablet version of the drug, which treats moderate-to-severe Alzheimer’s. About 3.5 million Americans over the age of 65 suffer from the disease.

(Reporting by Phil Wahba; editing by Carol Bishopric)

Technorati Tags: Alzheimer disease, Aricept, Eisai Co, Pfizer Inc

Clinical trials aimed at pinpointing emerging safety problems with drugs already on the market should only be conducted when other, less invasive research is not possible, a U.S. advisory group said on Friday.

The Institute of Medicine’s report, requested by U.S. Food and Drug Administration officials, comes ahead of a highly-anticipated meeting next week on GlaxoSmithKline Plc’s diabetes drug Avandia, that has come under fire for potential heart risks.

Glaxo is conducting a randomized, controlled trial called TIDE to compare Avandia to Takeda Pharmaceutical Co’s rival drug, Actos, after safety concerns emerged with Avandia that the FDA and its advisers concluded were unclear.

While the IOM did not target the Avandia trial in particular, FDA Commissioner Margaret Hamburg asked the independent, nonprofit medical group to weigh in with at least an initial finding on general ethical issues involving the safety of studying the risks of drugs already in use.

The FDA called in 2007 for the TIDE study, which aims to enroll 16,000 patients and end in 2015, although some critics say it could take longer.

Analyses of other data since then have convinced some researchers that Avandia’s risks are greater than those of Actos and have repeatedly called for the trial to be halted.

Glaxo has defended its drug, saying data overall shows it does not increase the risk of heart attack, stroke or death.

On Tuesday and Wednesday, FDA’s panel of outside experts will weigh numerous studies and analyses before recommending whether Avandia should remain on the market, be pulled from the market, or various options in between.

They also will be asked to weigh in on the TIDE trial.

In its report, the IOM said randomized controlled trials should only be done when “a responsible policy decision cannot be made based either on the existing evidence or on evidence from new observational studies.”

It also said studies of real world use of a drug — known as observational studies and often done by reviewing insurance claims and other databases — can yield strong data.

In separate FDA documents released on Friday, FDA staff scientists were split over whether the TIDE trial should continue just as they are divided over whether another major Glaxo trial, RECORD, showed excessive heart-attack risks with Avandia.

Some staff also pointed to studies done since 2007, including an FDA analysis of 52 trials on the prescription drug, as well as a review of Medicare data that showed a greater risk of heart attack and other complications with Glaxo’s drug.

“Based on these findings, any proposed head-to-head trial of rosiglitazone vs. pioglitazone is unethical and exploitative,” agency reviewers David Graham and Kate Gelperin wrote.

Rosiglitazone is the generic name for Avandia, and pioglitazone is the generic name for Actos.

Another FDA scientist, clinical reviewer Karen Mahoney, said that the TIDE trial does not have many of the limitations of the earlier RECORD study and could be illuminating.

“This trial, if it continues to completion, has the potential to address the question of the cardiovascular safety of rosiglitazone more definitively,” she wrote in a separate memo.

(Reporting by Susan Heavey; Editing by Tim Dobbyn)

Technorati Tags: Actos, Avandia, drug safety trials, pioglitazone, Rosiglitazone

The U.S. House of Representatives has approved a ban on some patent agreements between brand name and generic drug companies, deals which a federal agency says slow the arrival of cheaper generic drugs to market.

The House, voting late on Thursday, approved the measure as part of its approval of money to pay for President Barack Obama’s Afghanistan troop increase.

The measure, backed by the Federal Trade Commission, must now be considered by the Senate. The U.S. House has approved the measure previously but it has died in the Senate.

The Generic Pharmaceutical Association (GPhA) said it was disappointed in the vote.

“As this legislation moves to the Senate, GPhA will expand its efforts to point out that a curb on settlements will not hasten generic market entry, but rather will delay the launch of new and affordable generic medicines,” the group said.

“The unintended consequence of these restrictions on settlements will significantly harm the millions of Americans who rely on generic drugs,” it said in a statement.

But the House move pleased FTC Chairman Jon Leibowitz, who has made stopping the deals a centerpiece of his tenure on the commission. The FTC says the deals break antitrust law in instances where brand name drug companies essentially pay generic companies to delay entering the market.

“Congress has taken a critical step toward ending a practice that is dramatically increasing the cost of prescription drugs,” said Leibowitz.

The FTC has estimated that the deals — which often come as part of settling patent litigation — cost consumers about $3.5 billion a year by delaying access to generics.

(Reporting by Diane Bartz; Editing by Tim Dobbyn)

Technorati Tags: brand name drug, cheaper generic drugs, drug patent, generic drug, generic medicines, prescription drugs