The national prescription drug shortage I wrote about last year has advanced to a point where there’s now rationing of some drugs, and even reports of cancer patients being turned away when a needed drug is unavailable – sometimes right in the middle of a course of chemotherapy.
This public health crisis has also spawned a legion of sleazy gray market distributors that have been quick to jump in to sell supplies of otherwise impossible to obtain drugs, as long as health care providers are willing to pay their outrageous mark-up over what the drug would normally cost.
Gray-market vendors operate through unofficial supply channels. They are not vetted by the drug manufacturer and are also not listed by the manufacturer as an authorized distributor of record. Exactly how and where these somewhat shadowy vendors go about obtaining the scarce drugs they sell is never spelled out. But they do seem to have an uncanny ability to identify and obtain drug supplies that manufacturers and their authorized distributors can’t supply. So far, regulatory agencies have not done much at all to control this market.
Most of the cancer drugs and other drugs in short supply are less expensive generic injectables, so there’s plenty of room for profit. You can see a list of current drug shortages here and here. Many of these drugs are found in the marketing solicitations that hospitals receive every day – by fax, e-mail, and telephone, most often to the chagrin of pharmacists and hospital purchasing agents.
When applied, the medicines that come in creams, ointments, gels, sprays, lotions and patches will enter your body by penetrating through the skin and entering the bloodstream. They can cause side effects if you use too much of the medicine and it can happen even if the medicine is only intended to treat a skin condition or numb the skin before a procedure.
Several years ago, two young college students in different states died after they applied a numbing gel to their legs to prepare for a laser hair removal procedure. The gel contained high doses of two numbing medicines, lidocaine and tetracaine. The gel was intended to help ease any pain associated with the procedure. One of the students was given the gel by staff at the spa where she was planning to have the procedure, and the other woman picked up the gel from the pharmacy. Employees at the hair removal spas told the women to apply the gel to their legs before the procedure and to cover their legs in plastic wrap. Both women had a fatal reaction to the gel because too much medicine entered their bodies through the skin. One woman had a seizure in her car on the way to her appointment. She lapsed into a coma and died the next week. The other woman had a seizure and was on a ventilator (breathing machine) for 2 years before she died.
These deadly reactions were caused by high doses of the numbing medicines in the gel and applying the gel to very large areas of skin (from groin to ankle). Also, using plastic wrap over the skin heated it, which caused nearby blood vessels to dilate and blood flow to increase. That, in turn, allowed more medicine than usual to be absorbed and circulated, which eventually was toxic to the body. There are many other medicines that are applied to skin, like antibiotics, cortisone-like drugs and antifungals. All of these can be absorbed, sometimes leading to side effects.
These cases above involved prescribed medicines, but harm has also resulted from using too much over-the-counter (OTC) medicines applied to the skin. For example, the death of a 17-year-old girl was blamed on the use of too much cream for muscle aches. She was a cross country runner and had been using the cream all over her legs to soothe aching muscles after exercise. Heat and exercise can increase the amount of medicine entering your body. Her body apparently absorbed high levels of methyl salicylate, an anti-inflammatory medicine related to aspirin that is found in sports creams such as Bengay and Icy Hot. Used correctly, these creams can provide temporary relief from muscle pain but they shouldn’t be used for more than a week. Using too much over days or weeks is more dangerous than one-time use of a large amount of the cream.
If the Pharmaceutical Research and Manufacturers of America (PhRMA) has its way, a federal regulation crucial to drug safety will be repealed. The current regulation authorizes the Food and Drug Administration to screen drug names as part of the drug approval process – and to react when a proposed name could lead to medication errors due to mix-ups. FDA currently screens names and prevents use of some in order to minimize the chance post-launch that a name will be confused with that of an already available drug. FDA has told us that it rejects about 30 to 40% of names requested by drug companies.
PhRMA requested repeal of the regulation in a formal response to an April 27, 2011, Federal Register notice by FDA seeking suggestions for eliminating any existing rules perceived to be “outmoded, ineffective, insufficient, or excessively burdensome and thus may be good candidates to be modified, streamlined, expanded, or repealed.”
PhRMA wants FDA to prove that name reviews actually prevent medication errors. They argue that FDA’s program is “burdensome and disruptive without showing that it is effective in reducing medication errors.” They also contend that there are no validated measures for identifying brand names that are similar enough to be confused. Given the debt-reduction climate in Washington, even some important public health programs might be cut. This sure shouldn’t be one of them.
Without a doubt, drug name confusion is one of the most common causes of medication errors reported to the National Medication Errors Reporting Program operated by the Institute for Safe Medication Practices (ISMP). Drugs like Celebrex and Celexa, for example, can sound similar when prescribed over the telephone - but Celebrex is for pain while Celexa is for anxiety and depression. A more recent example of this is the warning that FDA sounded last month about potentially dangerous errors resulting from mix-ups between risperidone (Risperdal) and ropinirole (Requip).
Most pharmacies in our area provide an important patient safety tool right on their prescription labels: a description of the shape, color and imprint code of the medication that should be inside. Yet few patients may realize this and fewer still use it. Independent pharmacies, mail order pharmacies and major national chains like CVS, Walgreens, Rite Aid and Target all have added this safety feature. With so much information on prescription labels, however - including patient and doctor name, drug name, instructions and warnings - the added information can easily be missed. But it’s important, so look for it and put it to use.
Exactly why this tool is important was illustrated this past week, when we heard from a patient who used the description to find out that her pharmacist accidentally dispensed the wrong strength of medication. When she got home after picking up a prescription for her heart and blood pressure medication, she read the pill description on the label before taking any. Immediately, she saw that the description didn’t match the appearance of the pills in the bottle. She called the pharmacy to question why the mismatch occurred - and learned that instead of 25 mg tablets of atenolol as prescribed, the tablets were actually 50 mg. That strength had caused side effects in the past, so she returned it and got the correct strength.
At the Institute for Safe Medication Practices, my colleagues and I have always encouraged patients to avoid taking or administering medications that look different than expected without first verifying that the medication is correct. That’s easy to do if you are renewing a prescription for a brand name drug, which is almost always available from a single manufacturer. Generic drugs, however, rarely if ever look like the brand name version, even though they are equivalent in safety and effectiveness. An example is the antidepressant Prozac (fluoxetine), which is widely used and available from 10 generic manufacturers; each is different in appearance.
In case you missed it, Johnson & Johnson's McNeil Consumer Healthcare Division announced Thursday that it’s reducing the maximum daily dose of its Extra Strength Tylenol pain reliever in order to lower the risk of accidental overdoses of acetaminophen, the main ingredient. Whereas labeling allowed 4,000 mg daily in the past, it’s now down to 3,000 mg or 6 tablets of 500 mg apiece. Although the drug is quite safe when taken as labeled, too much Tylenol can be toxic to the liver and in some cases has caused liver failure and even the need for a liver transplant. While they’re changing extra strength labeling now, regular Tylenol tablet labels will soon receive a dosage change as well.
I’d like to personally thank McNeil for taking action on acetaminophen dosage levels, which to my knowledge was done outside of any Food and Drug Administration requirement. Most cases of acetaminophen-related liver failure has been due to intentional overdoses during suicide attempts. But it has also happened accidentally, such as when people take Tylenol along with another containing product that contains acetaminophen, like Nyquil or Theraflu, and therefore go over the recommended dosage limit without realizing it. McNeil says it reduced the dosage to prevent this type of accident. I wrote about a situation like that back in February, after I received a report about a Mom who almost gave her kid a cold medicine called Triaminic liquid but also bought a bottle of store brand acetaminophen for fever and sore throat. There are over 600 over-the-counter (OTC) acetaminophen products on pharmacy shelves, so be sure to a read the dosage facts label carefully on cough and cold medicines to make sure you aren’t duplicating dosages. It’s my understanding that other OTC acetaminophen products besides Tylenol will also make these changes.
Acetaminophen is also an ingredient in many prescription analgesic medications like Percocet, Lortabs and Vicoden. That’s been a problem, too, since pharmacy labels often aren’t clear about that and you usually can’t tell from the drug name. Also, instead of spelling out “acetaminophen,” prescription labels sometimes just say “APAP.” That common abbreviation for it might be well-known to pharmacists and doctors but not to patients.
FDA recently told prescription drug manufacturers to reduce acetaminophen dosage strength in combination products for the same reason that McNeil reduced the OTC dose. And under its Safe Use Initiative, FDA has been working with state pharmacy boards and others to have the word “acetaminophen” spelled out on pharmacy labels.
The Food and Drug Administration recently alerted the public about reports of mix-ups between risperidone (Risperdal) and ropinirole (Requip). Some of the reported incidents involved patients who required hospitalization.
FDA evaluated 226 errors involving confusion between these drugs, all of which were reported either to FDA’s MedWatch adverse event reporting system or the National Medication Errors Reporting Program operated by my organization, the Institute for Safe Medication Practices.
Risperidone is a drug used for psychiatric conditions like schizophrenia or bipolar disorder. Ropinirole is used in Parkinson’s disease and a condition called restless legs syndrome, in which people can’t resist an urge to move their legs.
The reasons for confusion between these drugs are many. Besides having somewhat similar names, they include illegibly handwritten prescriptions, and similar product strengths and dosages. Among the available forms, each comes in tablets of 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg and they are also prescribed by doctors at the same dosing intervals – once or twice a day. In pharmacies, since the drug names are spelled similarly, the manufacturer’s containers are usually stored next to one another. Also, since drug names are listed alphabetically on computer screens, doctors and pharmacists sometimes choose the wrong name when processing prescriptions.
When you get a prescription filled at the pharmacy, if the medication you receive doesn’t look right, there’s always the possibility that an error has made. Yet, sometimes people ignore the clues.
A 56-year-old man with diabetes went to the pharmacy to refill his prescription for Glucophage (metformin). This medication helps people with diabetes maintain a healthy blood sugar level. Mistakenly, the man was given 850 milligram tablets instead of 500 milligram tablets. Right away, he recognized that the tablets looked different, but he didn’t say anything. The error was discovered two months later when he refilled his prescription. Luckily, he suffered no permanent harm; however, he lacked energy and felt weak because he took too much medicine.
Why didn’t this patient speak up? Some consumers may worry that questioning a health professional could be insulting. Others may think that the medicine looks different because it’s a generic drug. Too many people may dismiss their concerns because they feel they don’t know as much about medications as health professionals. Even the slightest hint of anxiety can stop many from speaking up.
Healthcare workers face the same dilemma. A nurse may hesitate to point out a possible medication error to a well-respected physician. Even when people speak up, they may accept an unsatisfactory explanation or easily be convinced that no mistake has been made. This sad truth is clearly seen when my organization is called upon to investigate deadly medication errors. In most cases, someone had a feeling that something was not right, but failed to speak up or was convinced by others that there was no problem.
Parents, grandparents, and anyone else wearing a medicine patch all need to be extra cautious when they’re around children and pets. Everyone’s familiar with medicine bottle labels that warn, “Keep out of reach of children” when medications are stored. But not many think of that when it comes to medication patches they’ve already worn. Yet, all too often we learn about tragedies where kids have been exposed medicine patches that fell off a family member or that they find in a trash can, discarded after use.
Some potentially dangerous medicines come in patches that you attach to your skin. Examples include nicotine patches to help people quit smoking, drugs for motion sickness like scopolamine, and drugs for pain, like the narcotic fentanyl. Lidocaine, a local anesthetic that’s used for nerve pain for patients who’ve had shingles, also comes in a patch and contains potentially lethal amounts of drug if accidentally ingested. Patches are designed to give a constant amount of medicine over a certain period of time, usually several days. New patches contain lots of medicine, but used patches can still contain medicine after you take them off. So both new and used patches can be dangerous if kids or small animals somehow find them and apply or ingest them.
Earlier this month, one of the pharmacy technicians I work with alerted me to a report she’d just received through our reporting program from a doctor who wanted us to put out a warning after an accidental ingestion of a used medicine patch nearly caused an 8-month-old baby’s death. At home, the child found a once lost fentanyl patch and placed it into his mouth where it became affixed to the roof of his mouth (called the palate). Later a grandparent thought he looked sleepy so the baby was placed into his crib for a nap.
The grandparent caring for the child was not aware that the baby had somehow found and ingested a used fentanyl patch. After sometime, the caregiver heard "gurgling" sounds coming from the child's crib. The child was lifted from the crib and was flaccid. His lips were blue, indicating that he wasn’t breathing well. CPR was administered, 911 was called, and the child was transported to the emergency room for treatment, where the patch was noticed and removed from his mouth. A reversal drug called naloxone was administered in the ED, and the baby’s breathing, which had slowed to dangerous levels, rebounded within minutes. Fortunately the patient awakened and became more alert although a second dose of naloxone was required 30 minutes later. The patient was admitted to the ICU for further treatment and observation. While he was unconscious, the baby breathed in some particles from his mouth causing aspiration pneumonia (lung inflammation.) The patient was treated with antibiotics and thankfully did fine thereafter.
A doctor prescribed doxepin (Sinequan) 50 mg daily for a young man with depression. This medicine is available in a 50 mg capsule. But the pharmacy where the man had the prescription filled carried only 10 mg and 100 mg capsules. Sinequan treats depression and anxiety but it can also be used for other reasons. The lower dose (10 mg) is often used to treat patients with chronic itching. A higher dose (50 mg or more) is the usual dose to treat depression.
The pharmacist intended to fill the man’s prescription using the 10 mg capsules, with a label directing him to take 5 capsules daily. But when entering the prescription into the pharmacy computer, the pharmacist accidentally chose 100 mg capsules on the computer screen. Since the directions on the prescription bottle instructed the man to take 5 capsules daily, he took a total of 500 mg of doxepin every day for a month—ten times more than the prescribed dose!
The young man experienced a rapid heartbeat, headache, drowsiness, dizziness, and nausea during the month. He did not contact his doctor since he was told that he might initially experience some of these symptoms, and they would decrease over time.
The error was eventually discovered when the prescription was transferred to a different pharmacy. The pharmacist at the new pharmacy called the doctor because she was concerned about such a high dose of the medicine. (Doses for this drug should not exceed 300 mg daily.) After recognizing the error, the young man’s doctor had to slowly decrease the dose, as rapid dose changes are not recommended. The young man continued to be drowsy and fatigued for some time, even after the dose was finally adjusted to 50 mg daily.
The good news from our standpoint as a medication safety organization is that prescriptions that are handwritten are quickly becoming a thing of the past. According to a report last month form the nation’s leading router of electronic prescriptions, Surescripts, the number of doctors who now prescribe electronically has grown from 74,000 at the end of 2008 to 234,000 by the end of 2010. This represents 36 percent of office-based physicians. This is indeed good news. Mix-ups due to bad handwriting, look-alike drug names and other medical errors, are expected to decline along with growth in “e-prescribing.” But as with almost any kind of advance, along with the expected improvements come some unintended consequences.
One issue that’s arisen is something that’s akin to doctor’s calling prescriptions to the pharmacy without telling you what's being prescribed, which leaves you clueless about what to expect. With e-prescribing, we’ve been noticing is that consumers may be leaving the doctor’s office without anything in hand. In the past, you at least got a handwritten prescription, where you could usually make out the drug name. With e-prescribing, if you don’t get anything in writing, you may not know what to expect at the pharmacy. If the pharmacist hands you something that doesn’t seem right based on your expectations, then it might just be that an error has happened. Now you may not even have a chance.
A colleague told us about an experience he had at the doctor’s office with e-prescribing. He and his wife took their daughter to a doctor for a skin rash. The doctor prescribed a topical corticosteroid, using a handheld device to send the order electronically to the pharmacy. The doctor asked the couple which pharmacy they’d like to use, which, all in all, seemed very efficient. Except the doctor never told the family exactly WHAT drug he was prescribing or how it should be taken. He just instructed the parents to pick up the medication at their community pharmacy.
My colleague left for the pharmacy, but while in transit he and his wife began to realize that since they had no idea what the doctor prescribed, they also didn’t have anything to go by to know if they were getting the right prescription for their daughter. No error happened, but my colleague warned that this lack of information secondary to electronically prescribing directly to the pharmacy could eventually lead to some patients getting the wrong medication. They might just accept anything the pharmacist handed to them.