Tag Archives: Drugs

How Does a $575 Life-Saving Drug Jump to $4,500? Blame a Perverse System

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Your friend is on the floor unconscious. The culprit: a heroin overdose. You panic, but then remember a gadget that can save her life. She told you where it would be if this ever happened, didn’t she? You run to her bedside table, fling open the drawer, and grab the compact purple and yellow injector. After you pull off the lid, the device speaks, telling you to place the plastic case on your friend’s thigh, press down, and dispense the life-saving drug inside. You do what it says, and a few seconds later, your friend’s eyes open wide. She’s alive.

That’s the scenario pharmaceutical company Kaleo envisioned when it developed the Evzio auto-injector. The phone-sized gadget is new, but the drug it administers—naloxone—is an old and inexpensive chemical that works immediately to reverse the effects of opioid overdoses. In 2014, it got FDA approval and hit the market for a list price of $575, an exciting new tool to battle the country’s overwhelming opioid epidemic.

But three years after Evzio came out, its cost has exploded to $4,500 per prescription. Like the pharma company Mylan did with Epi-Pen—another simple, life-saving drug—Evzio’s maker has raised its price as high as the market will bear.

If you have a friend or loved one who’s addicted to painkillers or heroin, they likely won’t pay anything for the device. That’s not how Kaleo makes money. Insurance holders can get the medication for $0. Same if you make less than $100,000 a year; if you pay cash, it’s just $360. Typically, pharma companies set the highest retail price they can get insurance companies to pay and then work out rebates with individual payers. But with Evzio, there’s yet another third party to bilk, one with a government mandate to buy the drug in bulk: law enforcement agencies.

In the past few years, state legislatures responded to the growing opioid epidemic by passing laws requiring first responders to carry naloxone. President Obama even signed a law last summer to provide $181 million in funding for naloxone programs. “There was this major push to get cops access,” says Leo Beletsky, a professor of public health at Northeastern University who helped the Department of Justice write guidelines for naloxone. “Now thousands of law enforcement agencies have equipped their officers with naloxone.” That created an entirely new market for the drug.

To drive awareness of the product, Kaleo has handed out 200,000 Evzio devices free to groups that work with addicts, including to law enforcement, though the company hasn’t released information on how many agencies negotiated deals or what they paid. When Beletsky was working with one nonprofit group in New Mexico, people asked for Evzio directly. “They call them talkies. It’s a cool, sleek compact gadget,” says Beletsky. It’s the perfect example of tech taking something clunky but critical and making it sleek and accessible.

Except for the whole price thing. Now that the New Mexico group has run out of talkies, they can’t afford to buy any more. That doesn’t mean the opioid-addicted people in New Mexico are stuck high and dry; they still have access to the old-school syringe options or the nasal spray Narcan, which just got FDA approval last year and offers bulk deals to harm reduction groups at $37.50 a dose.

But lawmakers want families and first responders to have the easiest-to-use version of naloxone—and when states started passing laws to increase access to naloxone, Kaleo benefited. Florida, Ohio, and Louisiana passed laws in the last three years that required first responders to carry FDA-approved versions of naloxone—which, until last year, only included Evzio. Beletsky says Kaleo actively lobbied to have the laws written that way. (Kaleo did not comment.) Legislators in Florida and Ohio later rewrote the laws so cheaper options are allowed. But other states continue to push for brand names. State Senator Royce West introduced a bill in Texas last year which would limit naloxone options to Evzio and Narcan.

Senator Claire McCaskill, along with 30 other Democratic senators, sent a letter to Kaleo earlier this month demanding an explanation for the price increase. In response, CEO Spencer Williamson pointed out all the outreach programs and rebates the company offers. “To support our enhanced patient access program and to ensure that as many patients as possible have access to Evzio for $0, the list price was increased,” he wrote in a letter sent back to lawmakers and the press. In other words, the people who do pay—insurance companies and some government agencies—are footing the bill for people who pay nothing. “It’s kind of like a game that pharmaceutical companies play,” says Beletsky. “[Kaleo] is trying to make up as much profit as they can before they get scooped.”

Which, given that Adapt Pharma’s Narcan nasal spray now has FDA approval and costs much less, won’t be long. In fact, in Vermont, which has been hard-hit by the opioid epidemic, pharmacies can now sell Narcan over the counter. It may not be as flashy as Evzio—it doesn’t talk—but it’s nearly as simple to use and it works. And most importantly, it doesn’t cost $4,500.

Read more: https://www.wired.com/2017/02/575-life-saving-drug-jump-4500-blame-perverse-system/

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It was all yellow: did digitalis affect the way Van Gogh saw the world?

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Extracted from foxgloves, digitalis was once used as a treatment for epilepsy. Could a side effect have triggered the artists yellow period?

It was recently the 127th anniversary of the tragic death of Vincent van Gogh. His short life came to an untimely end two days after he shot himself in the chest; he had experienced mental health issues through much of his life. In the absence of a definitive diagnosis, speculation as to the true nature of his illness fills volumes.

Although he came under the care of several doctors during his life time, knowledge of diseases of the mind was in its infancy in the late nineteenth century. As a result, many of the treatments used at the time would have been ineffective if not potentially dangerous. From our point of view, however, one drug that might have been given to Van Gogh is particularly interesting.

Towards the end of his life, under the care of Dr Gachet, it seems that Van Gogh may have been treated with digitalis for the epileptic fits he experienced. Digitalis, extracted from foxglove plants, is a powerful medicine still in use today as a treatment for certain heart conditions, but not epilepsy. In Van Goghs day, and for a long time before then, digitalis was known to be an effective treatment of dropsy, or accumulation of fluid in the body. Dropsy could have been caused by inefficient beating of the heart or because of liver disease. But with little understanding of the underlying causes of many diseases, almost anything shown to have an effect on the body even if that was simply to induce vomiting was considered a medical benefit. If the treatment for one disease was successful, it was often tried out on a host of others, just in case it proved to be a panacea. Extracts of foxglove really would have been effective in treating dropsy caused by heart failure, but would have done nothing for Van Goghs epilepsy. However, it is just possible it may have contributed to his artistic output.

Portrait
Portrait of Dr Gachet, by Vincent van Gogh. Gachet holds a foxglove, seen by some to suggest that he treated Van Gogh with digitalis. Photograph: DEA / G. DAGLI ORTI/De Agostini/Getty Images

Digitalis is, in fact, a mixture of several different compounds that today are separated and used individually to treat heart conditions. One of the compounds, digoxin, is listed by the World Health Organisation as an essential medicine because of its huge benefit in the treatment of abnormal heart rhythms such as atrial fibrillation. Digoxin has two effects on the heart. Firstly, it helps to control the electrical signals that are sent across the heart to trigger the cells to beat in a coordinated way producing a heartbeat. Secondly, it makes the individual heart cells contract more slowly and strongly, improving the efficiency of the pumping action to move blood round the body.

To achieve these effects on the heart, digoxin and related compounds interact with the enzyme Na+/K+ ATPase. Digoxin is a very potent drug, the therapeutic dose is miniscule, and it is very close to the level that can also produce digitalis intoxication. Such a narrow gap between a therapeutic and potentially harmful dose would simply not be tolerated in a new drug being brought to market. However, the undoubted benefit of digoxin and its long history of use means it is a vital part of modern medicine. Because the drug has been in use for so long over 200 years, since the physician William Withering advocated its use in 1775 we have had plenty of time to understand how the drug works and the potential side-effects. Patients taking digoxin are carefully monitored and a number of antidotes have been developed to treat overdoses.

The problem, as with all drugs, is side-effects. To achieve its effects on the heart, digoxin and related compounds interact with the enzyme Na+/K+ ATPase.Digoxins strong interaction with the enzyme means it is very potent, but Na+/K+ ATPase is distributed throughout the body. It is therefore the interaction between the drug and the enzymes located elsewhere in the body that is the cause of side-effects. The most common problems associated with digoxin are nausea and loss of appetite, but its other effects are more intriguing.

Particularly high concentrations of digoxins target enzyme are found in the cone cells in retina of the eye. These are the cells that give us our colour perception. It is very rare, but some people taking digoxin and related drugs can experience haziness to their vision, or a yellow tinge to everything they see, known as xanthopsia. Occasionally, points of light may appear to have coloured halos around them. Rarer still are effects on pupil size, such as dilation, constriction or even unequal-sized pupils.

The effects of digitalis intoxication have been suggested as the cause of Van Goghs yellow period and the spectacular sky he painted in The Starry Night. More circumstantial evidence comes from the two portraits Van Gogh produced of his doctor, Paul Gachet, showing him holding a foxglove flower. One of Van Goghs self portraits also shows uneven pupils.

All of this is very interesting but it is pure speculation. Van Gogh may not have taken digitalis, and perhaps simply liked the colour yellow and the effect of swirling colours around the stars he painted. Unequal pupil size in his self-portrait may have been the result of a simple slip of the paintbrush.

There are also many other factors to consider. Van Gogh was known to drink large quantities of absinthe (though not enough to produce yellow colour perception) as well as turpentine (which can affect vision but not colour perception). Whatever the reason for Van Goghs particular artistic choices, we can still appreciate his remarkable output from such a tragically short life.

Read more: https://www.theguardian.com/science/blog/2017/aug/10/it-was-all-yellow-did-digitalis-affect-the-way-van-gogh-saw-the-world

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Rule that patients must finish antibiotics course is wrong, study says

Experts suggest patients should stop taking the drugs when they feel better rather than completing their prescription

Telling patients to stop taking antibiotics when they feel better may be preferable to instructing them to finish the course, according to a group of experts who argue that the rule long embedded in the minds of doctors and the public is wrong and should be overturned.

Patients have traditionally been told that they must complete courses of antibiotics, the theory being that taking too few tablets will allow the bacteria causing their disease to mutate and become resistant to the drug.

But Martin Llewelyn, a professor in infectious diseases at Brighton and Sussex medical school, and colleagues claim that this is not the case. In an analysis in the British Medical Journal, the experts say the idea that stopping antibiotic treatment early encourages antibiotic resistance is not supported by evidence, while taking antibiotics for longer than necessary increases the risk of resistance.

There are some diseases where the bug can become resistant if the drugs are not taken for long enough. The most obvious example is tuberculosis, they say. But most of the bacteria that cause people to become ill are found on everybodys hands in the community, causing no harm, such as E coli and Staphylococcus aureus. People fall ill only when the bug gets into the bloodstream or the gut. The longer such bacteria are exposed to antibiotics, the more likely it is that resistance will develop.

The experts say there has been too little research into the ideal length of a course of antibiotics, which also varies from one individual to the next, depending in part on what antibiotics they have taken in the past.

In hospital, patients can be tested to work out when to stop the drugs. Outside hospital, where repeated testing may not be feasible, patients might be best advised to stop treatment when they feel better, they say. That, they add, is in direct contravention of World Health Organisation advice.

Other experts in infectious diseases backed the group. I have always thought it to be illogical to say that stopping antibiotic treatment early promotes the emergence of drug-resistant organisms, said Peter Openshaw, president of the British Society for Immunology.

This brief but authoritative review supports the idea that antibiotics may be used more sparingly, pointing out that the evidence for a long duration of therapy is, at best, tenuous. Far from being irresponsible, shortening the duration of a course of antibiotics might make antibiotic resistance less likely.

Alison Holmes, a professor of infectious diseases at Imperial College London, said a great British authority, Prof Harold Lambert, had made the same point in a Lancet article entitled Dont keep taking the tablets as early as 1999. It remains astonishing that apart from some specific infections and conditions, we still do not know more about the optimum duration of courses or indeed doses in many conditions, yet this dogma has been pervasive and persistent.

Jodi Lindsay, a professor of microbial pathogenesis at St Georges, University of London, said it was sensible advice. The evidence for completing the course is poor, and the length of the course of antibiotics has been estimated based on a fear of under-treating rather than any studies, she said. The evidence for shorter courses of antibiotics being equal to longer courses, in terms of cure or outcome, is generally good, although more studies would help and there are a few exceptions when longer courses are better for example, TB.

But the Royal College of GPs expressed concerns. Recommended courses of antibiotics are not random, said its chair, Prof Helen Stokes-Lampard. They are tailored to individual conditions and in many cases, courses are quite short for urinary tract infections, for example, three days is often enough to cure the infection.

We are concerned about the concept of patients stopping taking their medication midway through a course once they feel better, because improvement in symptoms does not necessarily mean the infection has been completely eradicated. Its important that patients have clear messages and the mantra to always take the full course of antibiotics is well known. Changing this will simply confuse people.

The UKs chief medical officer, Prof Dame Sally Davies, said: The message to the public remains the same: people should always follow the advice of healthcare professionals. To update policies, we need further research to inform them.

[The National Institute for Health and Care Excellence] is currently developing guidance for managing common infections, which will look at all available evidence on appropriate prescribing of antibiotics.

The Department of Health will continue to review the evidence on prescribing and drug-resistant infections, as we aim to continue the great progress we have made at home and abroad on this issue.

Read more: https://www.theguardian.com/society/2017/jul/26/rule-patients-must-finish-antibiotics-course-wrong-study-says

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People taking heartburn drugs could have higher risk of death, study claims

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Research suggests people on proton pump inhibitors are more likely to die than those taking different antacid or none at all

Millions of people taking common heartburn and indigestion medications could be at an increased risk of death, research suggests.

The drugs, known as proton pump inhibitors (PPIs), neutralise the acid in the stomach and are widely prescribed, with low doses also available without prescription from pharmacies. In the UK, doctors issue more than 50m prescriptions for PPIs every year.

Now researchers say the drugs can increase risk of death, both compared with taking a different type of acid suppressant and not taking any at all.

We saw a small excess risk of dying that could be attributed to the PPI drug, and the risk increased the longer they took them, said Ziyad Al-Aly, an epidemiologist from the University of Washington and co-author of the study.

The team say the study suggests those who take the drugs without needing to could be most at risk. They urged people taking PPIs to check whether this was necessary.

Previous research has raised a range of concerns about PPIs, including links to kidney disease, pneumonia, more hip fractures and higher rates of infection with C difficile, a superbug that can cause life-threatening sepsis, particularly in elderly people in hospitals.

But the latest study is the first to show that PPIs can increase the chance of death. Published in the journal BMJ Open, it examined the medical records of 3.5 million middle-aged Americans covered by the US veterans healthcare system.

The researchers followed 350,000 participants for more than five years and compared those prescribed PPIs to a group receiving a different type of acid suppressant known as an H2 blocker. They also took into account factors such as the participants age, sex and conditions ranging from high blood pressure to HIV.

The results show that those who took PPIs could face a 25% higher risk of death than those who took the H2 blocker.

In patients on [H2 blocker] tablets, there were 3.3 deaths per 100 people over one year. In the PPI group, this figure was higher at 4.7 per 100 people per year, said Al-Aly.

The team also reported that the risk of death for those taking PPIs was 15% higher than those taking no PPIs, and 23% higher than for those taking no acid suppressants at all.

Similar levels of increased risk were seen among people who used PPIs but had no gastrointestinal conditions, a result which the authors speculated might be driving the higher risk seen overall.

Gareth Corbett, a gastroenterologist from Addenbrookes hospital in Cambridge who was not involved with the study, cautioned against panic, pointing out that in most cases the benefits of PPI far outweighed any risk. What was more, he said, while the increased risk sounded high, it was still very low for each person.

PPIs are very effective medicines, proven to save lives and reduce the need for surgery in patients with bleeding gastric and duodenal ulcers and several other conditions, he said.

The studys authors said it was important that PPIs were used only when necessary and stopped when no longer needed.

Corbett agreed that many people take PPIs unnecessarily. They could get rid of their heartburn by making lifestyle changes, such as losing weight and cutting back on alcohol, caffeine and spicy foods, he said.

The authors said the study was observational, meaning it did not show that PPIs were the cause of the increased risk of death, and that it was unclear how the drugs would act to affect mortality. They said the drugs could affect components within cells, known as lysosomes, that help break down waste material, or shortening protective regions at the end of chromosomes, known as telomeres.

Aly said people on PPIs should check with their GP whether the drugs were still needed, adding: In some cases we expect that PPIs can be safely stopped, particularly in patients who have been taking them for a long time.

Read more: https://www.theguardian.com/science/2017/jul/04/people-taking-heartburn-drugs-could-have-higher-risk-of-death-study-claims

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