OTC to Rx Seems Like the Wrong Direction

It keeps happening. A common substance (two actually), available on drug store shelves everywhere, has been turned into a prescription drug. The current culprit is a drug called Diclegis, prescribed for morning sickness in pregnancy. You may recall that the drug has gained some notoriety because a famous person was shown on her Instagram account holding a bottle of the product and exclaiming over its benefits.

It turns out that Diclegis is nothing more than a combination of an antihistamine and a vitamin. A 30-day prescription runs around $350, while a 30-day supply of doxylamine succinate (aka Unisom) and pyridoxine hydrochloride (vitamin B6) will cost you about $25. Not only is it made from common ingredients, it’s a repeat of a drug that was on the market more than 30 years ago. The drug Bendectin was the only FDA-approved remedy for morning sickness. Many women had filed lawsuits claiming that the drug had caused birth defects in their babies. It wasn’t true, but the cost of defending the suits led the maker to pull the drug from the market in 1983. The only real side effect from Bendectin/Diclegis is sleepiness—not surprising considering that the main ingredient is an antihistamine.

There’s Gold In Them There Pills

As I mentioned in an earlier post, when a drug goes off patent protection the manufacturer often looks to take it to over-the-counter (OTC) status. But every now and then someone with a deep pocketed research grant sees a way to go the other direction. Another example of this transfer is a prescription fish oil. Lovaza contains 840 mg of omega-3 oils from fish, in 1 gram total of fish oil. The maker has run plenty of clinical trials showing that Lovaza provides benefits for your heart and brain. The claim is that Lovaza is better than ordinary off-the-shelf fish oil because it’s more concentrated, or because it’s standardized, or some such. I don’t believe a word of it. If your doctor recommends Lovaza, look for a good high-potency fish oil at your local grocery instead.

Another example is Niaspan. This is simply a time-release formulation of niacin, vitamin B3. A 90-day supply of 500-mg Niaspan will cost nearly $200, while the same amount of ordinary niacin is less than $10 at the grocery. (Or you can do what I do, and buy niacin as bulk powder from online sources such as www.PureBulk.com.) Not to mention that time-release formulas of niacin carry a higher risk of liver damage than the ordinary type.

Be a smart consumer. When your doctor recommends a prescription type of something ordinary, ask why the preference.

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A New Drug of Choice?

My local paper carried an article this morning about the latest series of deaths from an overdose of heroin. It seems like that’s become the drug of choice for people of all stripes. It used to be that heroin was for the junkies, the losers, the lowest of the low. No more. Now it’s the go-to option for people looking to replace prescription opioid painkillers such as oxycodone.

All the opioids—drugs that act like opium, such morphine—are excellent at relieving mild-to-moderate pain for most people. But they also all create physical addiction and mental dependence in regular users. This creates a dilemma for physicians and for society: How do you provide access to these drugs for people who truly need them, while keeping them out of the hands of those who abuse the drug? And how do you tell the difference for sure? (One of my new favorite bloggers, Jen Gunter, has an excellent article about the dilemma physicians face.)

The term diversion refers to any use of a drug outside its purpose intended by the prescribing physician. (This definition may seem a little convoluted, and it is. But diversion has a very specific meaning.) In the case of opioids, they can be diverted by theft, by black-market sales to other people, or by what’s known as doctor-shopping—going from doctor to doctor looking to get a prescription without the others being aware.

From Savior to Satan In One Easy Step

Oxycodone had been available for many years as the brands Percodan (when combined with aspirin) and Percocet (with acetaminophen [Tylenol]). But these formulations called for taking the drug every 4–6 hours to maintain effectiveness—which played hell with the sleep pattern of someone in pain. When the time-release formulation Oxycontin was approved in 1995, it was seen as a godsend for people who suffer chronic pain. Now they could take the drug only twice a day for longer-lasting pain relief.

Oxycontin packs twice as much oxycodone into a single tablet, released over time. But if you crush the tablet the time-release mechanism is defeated and all the drug is available at once. This is what made Oxycontin so attractive to addicts. For a period in the late 1990s and early 2000s, pharmacy break-ins seemed like the crime du jour. Eventually pharmacists got smart and held only enough Oxycontin in stock for that day’s needs. Now the primary source of diversion is patients, who sell what they don’t use for up to $50 per pill.

Yes, Heroin Kills

As the supply of Oxycontin has dried up, people have been turning toward heroin instead. It’s relatively cheap and easily available (so I’m told), and increasingly socially acceptable. Except when it kills.

Street heroin is cut with anything from powdered milk to kitchen cleanser, and the user can’t tell the difference. Who knows what else they’re putting in their arm, or foot, or neck, or wherever else they can pop out a vein. And the cutting leaves the drug at an uncertain strength, which is how most overdose deaths happen—the user gets an unexpectedly potent dose. Not that I’m recommending the abuse of prescription drugs, but at least with Oxycontin you know what you’re getting.

Convenient Isn’t Always Best

It seems like everywhere you look these days you see ads for anticoagulant drugs. These meds, Pradaxa, Xarelto, and Eliquis, are being promoted to reduce the risk of stroke due to the heart condition atrial fibrillation (aFib). They’re intended to replace the older warfarin (Coumadin), and are supposed to be better because they’re more convenient. But once you know the facts you’ll see that “convenient” may not be right for you.

No Salad for You Today

Warfarin reduces blood’s ability to clot by blocking the action of vitamin K—a factor in what’s known as the clotting cascade. The drug has been around since the 1950s, and works very well at thinning the blood. It has a bad reputation among patients, though, for two reasons. The first has to do with what’s known as the therapeutic index. This is the range of dosage that walks the line between too little to be effective and so much that it’s dangerous. The balance is so delicate that the brand-name drug was alone in the marketplace for more than 40 years before makers of generics could show that their warfarin was as stable as the branded medication.

Patients on warfarin need regular testing of their blood’s clotting ability, with a test called the INR (international normalized ratio, what used to be known as PT/prothrombin time). When beginning a regimen of warfarin, it can takes weeks of constant testing and adjustment to get just the right dosage. And any change in your other medications or your lifestyle can drag you back into the test/adjust phase.

This leads to the second reason. Warfarin works through the vitamin K system, so you have to keep your dietary intake of vitamin K steady. That is, if you have a salad for dinner, you have to have one pretty much every day, with the same kind of greens. (Leafy greens such as lettuce and kale are the main source of dietary vitamin K.) For just about everyone, the only way to keep your intake constant is to make that intake zero. And, um, leafy greens are good for you.

There’s So Much Blood

The risk of any blood thinner is that of excess bleeding. If you’re going in for surgery you need to stop the medication some time beforehand to avoid excessive bleeding during the procedure. And any injury poses a higher risk. I once watched a friend taking warfarin bleed almost all day from a simple shaving cut. Bumps and falls carry a higher risk of bruising. Serious injuries like those from an auto accident can cause death by bleeding out. The highest risk, though, comes from undetected bleeding such as from an ulcer.

Fortunately, for someone who’s taking warfarin there’s an antidote: vitamin K. But the newer drugs work differently, and there’s no antidote. The results are about what you’d expect. Between 2010 and 2014, there were about 9,000 anti-coagulant-related deaths reported to the FDA. Of those, only 700 were related to warfarin, even though up to 10 times as many patients are taking warfarin as are on these newer drugs. Curiously, studies on the new drugs show a lower risk of stroke compared to warfarin. But the real world doesn’t always agree with results from clinical studies.

Ads for these newer anticoagulants show people leading carefree lives, I suppose because they’re no longer burdened with all the testing. Somehow the family sitting around after a funeral doesn’t make it into those ads.

Oh, and by the way, a 90-day script of generic warfarin costs about $10, while the new guys are $500–$1,000. So much for controlling health care costs.

Antibiotic Use and Your Risk for Diabetes

For years, epidemiologists have been warning about the overuse of antibiotics. The greatest danger is that bacteria and viruses can (and do) develop resistance to the drugs. For instance, there are drug-resistant strains of TB, staph, malaria, HIV, and gonorrhea.

Certain classes of antibiotics have their own problems. As an example, the fluoroquinolones (Cipro, Levaquin, and their cousins) can weaken tendons. I know several people who have torn an Achilles tendon during or shortly after a course of one of these drugs. And Levaquin makes my knees hurt so badly I can barely get out of a chair. (And what’s with all the football players who are out for this season with tendon damage? Achilles, ACL, MCL, it seems like any tendon in the lower body is a target. Knowing how cavalierly trainers treat other drugs, I wouldn’t be surprised to hear about tubs of antibiotics in the trainer’s room.) Now there’s evidence that connects antibiotic use with diabetes.

Want a Danish With That Antibiotic?

Denmark has a nationalized medical care system, so it’s possible to gather very complete records on populations. A recent review looked at the records of every person in Denmark who had been diagnosed with type 2 diabetes during the period 2000–2012. They then case-matched each of these records with another person who did not have diabetes. When the results of the 2 groups were compared, it turned out that any antibiotic use within the previous 15 years raised the risk of developing diabetes by about 30%. The risk was higher the more recent the use had been, and rose with the number of prescriptions for antibiotics.

We don’t know what the cause is here. It’s possible that as diabetes is developing you’re more susceptible to infections, or that somehow antibiotics interfere with blood sugar metabolism. The only theory the researchers could reject was that gut bacteria are somehow involved. They came to that conclusion because all types of antibiotics created the effect. Different types of drugs affect gut bacteria differently, so if that were the source of the problem you would expect there to have been more of a difference between drug classes. At any rate, the connection is there.

Antibiotics in Your Life

You can control your antibiotic intake. Obviously if you have pneumonia an antibiotic could save your life. But people go to their doc asking for an antibiotic for almost any upset, and it’s been this way for many years. Antibiotics don’t help colds or flu, so don’t you be that person. And be careful about the meat you eat. Conventionally raised meat of all types has had antibiotics used in the process to support the animal’s growth.

You may not be able to eliminate the use of all antibiotics, but if you do need a course or if you’ve been on a regimen in the past keep in mind your increased risk of diabetes. Pay more attention to your food intake and activity level. Do the things we should all be doing already to maintain good health.

Statin Use in the Elderly

Statin drugs, prescribed to lower cholesterol levels, are among the most widely prescribed drugs. Ads for the various brands used to be inescapable, but now that most of them have come off patent protection Crestor is the only one you’ll still see promotions for.

There’s no doubt that statin drugs do what they are intended to do: lower blood levels of cholesterol. The question ever since the first of these drugs was introduced, though (Mevacor/lovastatin in 1987) has been, “So what?” That is, what’s the benefit to the patient? The claim was that, because high cholesterol was associated with heart disease and heart attacks, lowering a person’s cholesterol level ought to reduce their risk of heart trouble. Except that, well, it didn’t work out that way. Patients on cholesterol-lowering medications tend to have roughly the same risk of heart disease as patients not taking the drug.

Overuse of Statins Is a Chronic Problem

Given that statins in general don’t seem to have much of an effect on their main endpoint (reduction of heart disease), there’s been lots of concern about their overuse. There’s extra concern about use of the drugs in populations that typically haven’t been included in clinical trials, namely the very young and the very old.

Now the use of drugs to lower cholesterol in children is shocking in itself, and a topic for another time. But a report published this week in the online version of JAMA Internal Medicine says that statin use among the very elderly—those age 80 and above—has increased significantly between 1999 and 2012, rising from 8.8% in 1999–2000 to 34.1% in 2011–12. As I said, there’s been little research into the benefits and—especially—the risks of statin use in this age group. (By the way, both my parents turned 81 this year. They finally consider themselves elderly. I’m not so sure about very elderly.)

For those of you in this age group, or who are caring for someone who is, it may be time to ask the doctor if this drug is necessary. As we age our bodies process drugs differently. In addition, we begin to lose our ability to cope with stresses, such as the effects of drugs. And data from the CDC shows that more than a third of all people over age 60 are taking 5 or more prescription drugs. That’s quite a load on a body.

If I had to guess, I’d say that the increase in use among this age group has more to do with inertia than anything else. They were given a script for a statin 20 years ago, and they’re still on it because nobody has said, “That’s enough.”

Here Come Those Seasonal Allergies

(Part 1 of 3)

It’s hard to believe that fall is almost here. School starts today where I live, and evenings are getting cool (thank goodness). And with the fall comes another bout of seasonal allergies for those who are sensitive. (Though really, any season is allergy season. While most people think of blooming flowers and trees in the spring and ragweed in the fall as the worst culprits when it comes to allergens, we’re always surrounded by things that can make us sneeze, itch and, wheeze. Dust, mold, pet dander, and tobacco smoke know no season. )

Watery eyes, runny nose, and sneezing are the body’s way of trying to get rid of whatever is bothering you at the moment. Together, these symptoms are called allergic rhinitis (that’s hay fever to you and me), and they’re a gold mine for the medical industry. The top-selling prescription drug for nasal allergies, Nasonex, brought in more than a billion dollars in 2013 for its manufacturer.

But for most people, drugs are not the best solution. Depending on their category, prescription drugs either provide symptom relief or interfere with the function of your immune system. Whichever kind you use, the benefits are overwhelmed by the adverse effects.

Many people turn to over-the-counter medications for relief. Older antihistamines, such as diphenhydramine (Benadryl) and chlorpheniramine (Chlor-Trimeton), are infamous for their adverse effects—especially drowsiness, but also rapid heartbeat, dry mouth, and problems emptying the bladder.

The second-generation antihistamines, including cetirizine (Zyrtec) and loratadine (Claritin), are less likely to have negative side effects, but users still report dry mouth, headache, and occasional rapid heartbeat. The newest antihistamines available aren’t really new at all; they’re just modifications of older drugs. While there does seem to be a slightly smaller risk of side effects, the drugs aren’t any more effective than their older brothers.

What’s Going On Inside

The human body is set up to reject unfamiliar invaders. Your immune system is constantly on the alert for bacteria and viruses that can cause infection if left unchallenged. A well-tuned immune system will know the difference between non-threatening newcomers and true stranger danger. But if something goes awry, in either genes or experience, your immune system goes after harmless substances such as dust and pollen.

The first time your immune system encounters something new, it creates specific antibodies that then attach themselves to specialized cells known as mast cells. When the newcomer shows up again, the mast cells release histamine—the chemical that causes the classic allergy symptoms.

Most drugs for allergy relief, including all the ones available over the counter, address the receptors for histamine—meaning that your immune response is still going haywire but the desired result, getting rid of the offenders, is blocked. A smaller class of drugs works to stabilize mast cells, so they don’t release so much histamine. Drugs in a third class disrupt the immune response entirely. Almost all of the drugs in this group are steroids, and are prescription-only.

That’s the background on allergies. Over the next couple days I’ll give you the rundown on allergy treatments that work—and ones that don’t.

The Travels of a Prescription Drug

Prescription drugs can take a winding path to market. It takes much investigation and pre-clinical work before the first molecule enters a human subject’s body. After that there are still years of clinical trials ahead before a new drug makes it to market. Many candidates fail at some stage along the way.

Drugmakers invest huge amounts of money to get that new wonder drug into patients’ hands. Our patent system gives the maker 17 years to sell as much of the drug as they can for as much money as they can before other makers are allowed to produce their own generic version. The generics have to undergo their own testing and approval before coming on the market, but initial costs are much lower and the price of a brand-name drug tends to come down significantly once generics are available.

Unfortunately for the makers of the original drug, the patent clock starts as soon as they’ve identified their molecule, and keeps running while the trials are underway. This means that the competition-free time for a new drug is significantly less than 17 years. But sometimes the maker has a backup strategy.

Extending the Life of a Drug

If you’ll recall your dusty high-school chemistry, molecules are three-dimensional objects. And many molecules come in 2 mirror-image versions of each other—left- and right-handed versions if you will. As it turns out, for many of these molecules only one of the -handed versions has an effect in the body.

So when a manufacturer finds a molecule that will work as a new drug, the first introduction might be a mixture of both the left and right versions. This is a natural result of the manufacturing process, so it’s not like the maker is adulterating their product in any way. But it does mean that only half of the molecules of product X are doing you any good.

Here’s where the backup comes in. The patent was originally granted on the left-and-right mixture. The 17-year limit is coming up, and voila! here’s a “new” version that’s really only the active half of the original. There’s still patient trials to conduct, but no investigative work to be done, and the trials can typically be shorter and smaller (and so cheaper) because the original drug has already been shown to be safe and effective.

When Drugs Do the Splits

Here’s an example of how that works. In 1989 the FDA approved the drug Prilosec for the treatment of frequent heartburn and GERD (gastroesophageal reflux disease). Prilosec is the molecule omeprazole. In 2002 the FDA approved generic omeprazole. It’s no coincidence that in February of 2001 the FDA had approved Nexium to treat the same conditions—Nexium’s molecule is esomeprazole, the left-handed version of omeprazole.

While Prilosec had market exclusivity for 13 years, for Nexium it was 14 years (generic esomeprazole was approved earlier this year). One more year of protection might not seem like much, but in 2013 Nexium was the #2-selling prescription drug in the US, with sales of more than $6 billion.

I want to emphasize that there’s nothing underhanded about this process. The manufacturer simply adds a step to separate the two -handed versions, and packages the one that’s effective. And I’m not picking on Nexium, it just happens to be one I have data for at hand. But keep in mind that, in this example if Nexium works for you at whatever it’s costing you for your prescription, then the drugstore’s generic OTC version of Prilosec will probably work just as well.