Antibiotics for everyone!

Posted on April 13, 2013 by pharminpt

Azm.001A report this week in the New England Journal of Medicine suggests that, whether you knew it or not, lots (really, lots) of your patients are/were/will be taking antibiotics.1 Patients might not consider these medications relevant to their rehabilitation, but there are concerns for rehabilitation professionals when these medications are prescribed. The authors reported on data from a huge database of prescribing information. The database accounts for 70% of all prescriptions written in the U.S. in 2010 and the authors projected what the prescribing patterns would look like for all of the prescriptions. Providers wrote 258 million prescriptions for antibiotics in 2010. That works out to 883 prescriptions for every 1000 people. We don’t  know how many unique individuals this represents – perhaps there are some antibiotic-superusers out there, but it’s hard to argue that we’re not talking about lots of antibiotics. If you practice in the southern U.S. (Louisiana, Mississippi, Alabama, Arkansas, Tennessee, Kentucky), you’re working where prescription rates are the highest (936 prescriptions per 1000 people). Those of you out west are less likely to encounter patients to whom antibiotics have been prescribed (639 per 1000 people).

Penicillins, macrolides, cephalosporins, and quinolones accounted for around 70% of all the prescriptions. The top 5 individual drugs were:

1. azithromycin (Zithromax®), a macrolide, to the tune of 51.5 million prescriptions. That’s a lot of barely legible handwriting.

2. amoxicillin, a pencillin and β-lactam, otherwise known in my house as “the pink medicine”, was a close second with 51.4 million prescriptions.

3. amoxicillin/clavulanate, otherwise known as Augmentin® tallied 21.5 million prescriptions. This drug combines the antibiotic with potassium clavulanate, an inhibitor of an enzyme that some bacteria produce rendering them at least partially resistant to drugs like amoxicillin.

4. ciprofloxacin, a quinolone, 20.4 million prescriptions.

5. cephalexin, more commonly known as Keflex®, a cephalosporin, 20.1 prescriptions.

Why do these drugs matter to us? The most common adverse effects of antibiotics are gastro-intestinal or dermatologic in nature. While nausea, diarrhea, and abdominal discomfort GI upset may be important to your patient, the real impact they might have on your clinical decision making is minimal. Rashes and other dermatologic concerns are common reactions and may or may not represent true hypersensitivity to the medications. Given that we often observe the skin of the extremities or trunk or our patients, we may notice the development of a skin eruption before the patient does. If the patient has not yet reported any of these issues to his prescriber, he should be encouraged to do so ASAP. Some adverse reactions and forms of hypersensitivity are essentially benign and others, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, though rare, can be fatal.  Additionally, I hope it’s obvious that we should certainly not be telling patients to discontinue medications.

Whenever your patient returns from an encounter with a prescribing provider, you should re-visit that patient’s medications. Seemingly benign additions, such as these antibiotics, can have an impact on rehabilitation decision making. For example, cephalexin can increase the effects of warfarin, a common anti-coagulant, making bleeding more likely.

The number 4 antibiotic, ciprofloxacin, is the most notable in a rehabilitation context. Back in 2008, the FDA informed manufacturers of this drug and others like it, the fluoroquinolones, of the need for the addition of a so-called “black box warning” to the prescribing information. This is the strongest warning that the FDA requires drug manufacturers to provide, and in the case of the fluoroquinolones, the warning pertains to an elevated risk of tendinopathy and tendon rupture in those taking the antibiotics.  The risk is greatest in those over 60, those also taking corticosteroids, or in patients who have undergone cardiac, pulmonary, or renal transplantation. The Achilles tendon is most commonly involved, though dysfunction of the tendons of the rotator cuff, the hand, biceps, and thumb has been reported.2 The mechanism is not clearly understood. Theories include ischemia, degradation of the extracellular matrix, and direct toxicity of these agents on tenocytes.3 Symptoms have been reported as soon as 6 hours after the initiation of a fluoroquinolone and as late as 6 months after discontinuation.4 Tendon pain is the most common presentation and bilateral involvement is frequent. Exercise and physical activity are frequently associated with symptom onset.5

The bottom line in rehabilitation – antibiotics are frequently prescribed, but might not be considered significant by patients and therefore not disclosed without careful questioning. Whenever a patient returns from a physician encounter, an inquiry should be made into any medication changes. GI symptoms, rashes and other skin eruptions, and any tendon-related pain or swelling during or within the 6 months following fluoroquinolone exposure, should be reported to the prescribing provider.

Lots of your patients take antibiotics and antibiotics do things to your patients besides treat their bacterial infection. Keep your eyes, and mind, open.

References

1 Hicks DO, Taylor TH, Hunkler RJ. US outpatient antibiotic prescribing, 2010. NEJM 2013;368:1461-1462.
2 Ganske CM, Horning KK. Levofloxacin-induced tendinopathy of the hip. Ann Pharmacother. 2012;46:e13.
3 Childs SG. Pathogenesis of tendon rupture secondary to fluoroquinolone therapy. Orthop Nurs. 2007;26:175-182.
4 Khaliq Y, Zhanel GG. Fluoroquinolone-associated tendinopathy: a critical review of the literature. Clin Infect Dis. 2003;36:1404-1410.
5 1. Hall MM, Finnoff JT, Smith J. Musculoskeletal complications of fluoroquinolones: guidelines and precautions for usage in the athletic population. PM R. 2011;3:132-142.

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NMEs of 2012

Posted on January 8, 2013 by pharminpt

Green PillsBefore much more of  2013 slips by, here’s a review of the newly-FDA approved drugs of 2012. More specifically, we’re talking about NMEs or “new molecular entities”, as opposed to old drugs repackaged for new indications or reformulated for new routes of administration. The FDA defines an NME as “an active ingredient that has never before been marketed in the United States in any form.” There were 39 approved in 2012, a 30% increase over 2011, and the most since 1996. Fourteen of these 39 drugs are used to treat one form of cancer or another, or address consequences of the disease.We’ll do this in several parts, 39 is a lot of medications! Here are the first 10:

Fulyzaq® (crofelemer)    This drug is indicated for use to manage diarrhea in patients with HIV/AIDs when the diarrhea is not caused by an infection. In the clinical trials used to bring the drug to market, 2.6% of patients experienced back pain, 2.6% experienced arthralgia, and 2.2% experienced muscle pain, all symptoms that could certainly have patients seeking physical therapy services. Before we get too concerned, we should look more closely at these numbers, and the information provided on the drug label. The adverse effect data reported on the drug label is derived from 3 placebo-controlled clinical trials in which 696 patients with HIV received the drug at various doses and who were followed for a mean of 78 days, and, because adverse effects reported did not differ by dose, the data are more specifically derived from 229 patients who received 125 mg twice daily and 274 patients who received placebo. Now, this is not a drug that many rehabilitation professionals will encounter frequently, but it highlights the importance of understanding the data one is trying to apply to an individual patient. Given the above percentages, a rehabilitation professional might be inclined to consider this drug as a contributor to a patient’s back pain, arthralgias, or myalgias, and it may be. However, 2.6% of 229 is 6. Six patients in the treatment arm reported back pain. So what? The “so what” is that 4 patients, or 1.5% of the 274 patients who received a placebo also reported back pain. Yes, 2.6% is more than 1.5%, but is there really a difference between the groups? This isn’t reported, so we don’t really know. Looking at rates of adverse effects in the placebo arm of a trial takes a bit more digging, but might help in deciding how likely it is that a medication is contributing to your patient’s current symptoms. Interestingly, given that 95% of adverse drug reactions are amplification effects, constipation is not reported at all in this data.1 Moving on…

Sirturo® (bedaquiline)    Approved on December 28th, 2012, Sirturo® is an oral antimycobacterial agent indicated in the treatment of multi-drug resistant tuberculosis when no other alternatives exist.

Eliquis® (apixaban)    Here we have one of the new generation of anticoagulants, an orally-administered direct inhibitor of factor Xa, very specifically indicated to reduce the risk of stroke, and embolism in general, in patients with atrial fibrillation that is not a result of cardiac valve dysfunction. This one should be on your radar related to an increased bleeding risk, although this risk is generally less than that of warfarin.

Juxtapid® (lomitapide)    This molecule inhibits a protein in liver and intestinal cells whose function is necessary for the synthesis of VLDL and chylomicrons, ultimately lowering plasma LDL concentration. Rather than being routinely prescribed for dyslipidemia, it is indicated only for use in homozygous familial hypercholesterolemia, a genetic form of severe hypercholesterolemia. Use of the orally administered medication carries a significant risk of hepatotoxicity, limiting it’s usefulness in the general population. Gastrointestinal side effects occurred almost universally in study participants – diarrhea, nausea, dyspepsia, and vomiting occurred in 93% of subjects in the clinical trial used to bring the drug to market.

Gattex® (teduglutide)    Administered by injection only, teduglutide is an analog of human glucagon-like peptide-2 (GLP-2). It is indicated to enhance the absorption of parenteral nutrition in adults with short bowel syndrome.

Signifor® (pasereotide)    This new drug is injected subcutaneously in order to control Cushing’s disease when surgical treatment is not possible or is ineffective. Hyperglycemia  occurs almost universally during the first 2 weeks of treatment, regardless of the patient’s baseline glucose tolerance.

raxibacumab    An injectable intended to treat inhalational anthrax.

Iclusig® (ponatinib)    We’re moving into the large number of new options in cancer treatment with this agent. It is an injected drug indicated for the treatment of adults with chronic myeloid leukemia and a certain type of acute lymphoblastic leukemia.

Cometriq® (cobozantinib)    It will be used to treat metastatic medullary thyroid cancer.

Xeljanz® (tofacitinib)    You might see this one – it is a tablet that will be prescribed to patients with moderate to severe rheumatoid arthritis who have responded to or do not tolerate methotrexate. It may be used alone or in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs. It is a Janus kinase (JAK) inhibitor. These enzymes function in signaling pathways related to hematopoiesis and immune cell function. Serious infections, such as pneumonia, cellulitis, herpes zoster, and urinary tract infections, occurred more commonly in patients taking tofacitinib than in patients taking placebo.

There you have it, 10 of the new approvals from last year. Look for ten more at the end of the week.

References (Back to Text)
1. Pirmohamed M et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004;329:15.

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Lorcaserin approved by FDA

Posted on June 28, 2012 by pharminpt

Yesterday, the U.S. Food and Drug Administration approved the weight loss drug lorcaserin (Belviq®, Arena Pharmaceuticals). This is the first approval for an obesity treatment since orlistat (Xenical®) in 1999. The effect on weight loss is modest (3-5%) and the drug was studied versus placebo in combination with changes in diet and physical activity. Clearly not a miracle drug, but hopefully another useful tool in the management of this complex and extremely important issue.

At a glance, the most significant effect of the drug on patient management in rehabilitation appears to be an increase in hypoglycemia in patients with type 2 diabetes. Additionally, low back pain is listed as an adverse effect in the same population, though the mechanism for this is unclear. The drug appears to have its effect through activation of serotonin 2C receptors in the central nervous system. This means that other medications that activate serotonin receptors or increase serotonin levels may be problematic when taken in combination with lorcaserin, potentially producing a constellation of adverse effects known collectively as serotonin syndrome. Some antidepressants, drugs used to treat migraine headaches, and even herbal supplements such as St. John’s Wort and Panax ginseng are guilty as charged in this regard. Serotonin syndrome is characterized by

  • cognitive signs & symptoms – headache, agitation, confusion, hallucinations
  • autonomic signs & symptoms – hypertension, tachycardia, shivering, sweating, nausea, diarrhea
  • neuromuscular signs & symptoms – tremor, myoclonus/twitching, hyperreflexia.

There is a case report in the physical therapy literature of a patient presenting with serotonin syndrome misdiagnosed as fibromyalgia. 

Neither the FDA nor Arena Pharmaceutical’s websites provided a date that the drug would be available for prescription. As with all new medications, we’ll have to wait and see how lorcaserin is used and what effects it has on individuals in the real world, outside of more carefully controlled clinical trials used to bring the drug to market. Come back and post in the comments if/when you see your patients taking it.

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Oh, the Medicines You’ll Take!

Posted on June 28, 2012 by pharminpt

An Update on Pediatric Drug UtilizationChildren and Pills

Drugs aren’t just for grown ups, but it would appear that kids are being prescribed fewer medications than they used to be back in the day, all the way back in 2002.1 The data, published online in the journal Pediatrics, and reported on by Reuters news service, was generated through what I am sure was many joyous hours of sifting through large prescription databases. This allowed the FDA researchers access to about half of all the retail prescriptions written in the U.S. between 2002 and 2010. The database included prescriptions paid for with cash, those filled by Medicaid beneficiaries, and those for participants in commercial insurance plans.  According to the authors, this is the first time the prescription drug use of U.S. children has been described in this way in children. It’s important to recognize that this database didn’t (and still doesn’t) take into account over-the-counter (OTC) medications, supplements that don’t require a prescription, and any prescriptions filled by mail. It also doesn’t tell anyone whether or not any of the drugs were actually taken (probably some were, don’t you think?). When all of the fun was through being had, there were a couple of findings for us to note.

More for the Grownups. Less for the Kids.

It makes sense that adults, especially older adults, take more medication than children. As a whole, older adults have more chronic medical problems that require medications for effective management or control. Think diabetes, heart disease, hypertension, and arthritis. Those 4 alone could leave you taking half a dozen or more medications every day. And then if you’re depressed or can’t sleep, add a couple more. Just a few years ago, children (those of you under 17 years old) were a leading source of growth in the pharmaceutical industry. More than 1 in 4 insured children were taking a prescription medication for a chronic condition. This more recent study seems to indicate just the opposite. While prescription drug use by adults between 2002 and 2010 increased by 11%, outpatient prescriptions for children decreased by 9%. We could debate whether this is a good thing or a bad thing – my vote is on good, but that’s what comments are for.

Sometimes Less is Not More

The drug categories that saw significant declines in the study period were:

  • allergy medicines, 61% fewer prescriptions
  • cough and cold drugs, 42% fewer prescriptions
  • antibiotics, 14% fewer prescriptions
  • analgesics, 14% fewer prescriptions
  • antidepressants, 5% fewer prescriptions

The authors noted that the allergy medications loratidine (Claritin®) and cetirizine (Zyrtec®) transitioned from prescription medications to OTC and this could certainly account for the large decrease in this category of prescriptions. The large drop in prescriptions of cough and cold medicines can be attributed to, at least in part, a Cochrane database systematic review in 2004 and subsequent FDA advisory in 2008. Both of these documents take the view that the risks of using these products, both prescription and OTC, outweigh the benefits. The use of antibiotics remains highly prevalent, but has been curtailed to some degree. There is greater awareness among the general public that not every earache, cough, and stuffy head should be treated with antibiotics.

Wait, There’s More…

The biggest increase (93%) was seen in prescriptions for birth control pills. The authors suggest that this is likely to reflect their use for longer durations and for purposes other than preventing pregnancy, such as helping to control acne. They also mention that these drugs were prescribed relatively rarely to people who can’t get into R-rated movies without a grownup back in 2002 and their prescription doesn’t represent a large proportion of the overall number written in 2010. More remarkable is the 46% increase in prescriptions for medication used to treat attention deficit hyperactivity disorder (ADHD). This means that 800,000 more prescriptions were written for these drugs in 2010 than in 2002. Methylphenidate (Ritalin®) was the most commonly prescribed drug to adolescents 12-17 years old during the entire study period – 4.3 million prescriptions in 2010 – but overall, the rate of prescription of this drug didn’t change much. Prescription patterns for other medications in this group were more variable, based in part on new evidence becoming available and in part on newer drugs becoming the popular kids in class. Prescriptions for amphetamine/dextroamphetamine (Adderall®) decreased by 15% and dextroamphetamine (Dexedrine SR®, Procentra®) by 69%. In contrast, after 2004, prescriptions for dexmethylphenidate (Focalin®), lisdexamfetamine (Vyvanse®), and guanfacine (Intuniv®) all increased. The last member of this group, atomoxetine (Strattera®) saw an increase between 2002 and 2004 but a significant decrease between 2004 and 2010. Labeling changes in late 2004, including a black box warning and medication guide related to suicidal ideation in children and adolescents taking atomoxetine, could have contributed to the decline in it’s use. Whew – simpler version – compared to 2002, there’s always a lot of Adderall® out there, more Focalin®, Vyvase®, and Intuniv®, and less dexedrine and Strattera®. Other drug categories that saw increases include oral corticosteroids (22%), asthma medications (14%), dermal corticosteroids (10%), and seizure medications (10%).

Into the Mouths of Babes

One of the secondary objectives of the study was to examine off-label prescription in pediatric patients. Off-label prescription refers to the use of an FDA-approved medication in a way which has not been FDA-approved. This is in no way illegal (well, I suppose it could be, but most of the time it’s not) and usually occurs when there is at least some evidence supporting the non-approved application. The study authors state that off-label prescribing is fairly common in this population. Turns out they were right, at least in the case of the drug lansoprazole (Prevacid®). Of the estimated 500,000 or so prescriptions written for this proton-pump inhibitor for children in 2010, 358,000 (70%) were written for infants younger than one year of age. Guess what? Not FDA-approved, all off-label. OK, no big deal, off-label use isn’t illegal. No it’s not, but the label of the drug itself states that in a multicenter, double-blind, placebo controlled study, lansoprazole was not effective in patients younger than 1 year old with symptomatic reflux! So we’ve got no real potential for benefit, but certainly some risk in the form of potential adverse effects, both short- (abdominal discomfort, constipation, diarrhea) and long-term (questions about increased fracture risk with long-term use). The authors have this one pegged exactly correctly, this is a question that needs an answer.

The Envelope, Please

The big winners, the most commonly prescribed medications in each age group, were:

  • infants 0-23 months – amoxicillin
  • children 2-11 years – amoxicillin
  • adolescents 12-17 years – methylphenidate (Ritalin®)
One other drug deserving honorable mention – albuterol – was listed as a commonly prescribed medication for infants and children in all of these age groups, becoming more common as children age. It was the 4th most commonly prescribed for infants, 3rd most common for children, and 2nd most common for adolescents. 

Wait, Where Am I?

This is useful and all, but what’s the point? The point is that it is useful. If you are a physical or occupational therapist working in a pediatric setting, you should have a working understanding of the medications you’ve just been reading about. That way, when you notice that the way a child you’re working with feels, moves, behaves, or communicates has changed, you have a better starting point for considering whether the medications that child is taking could be playing some role in that change. And, as always, if you’re seeing something that doesn’t make sense, ask!

Reference (Back to text)

1. Chai G, Governale L, McMahon AW, Trinidad JP, Staffa J, Murphy D. Trends of outpatient prescription drug utilization in US children 2002-2010, [published online ahead of print June 18, 2012]. Pediatrics. doi:10.1542/peds.2011-2879.

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Adverse drug events in the ICU – do they happen and do they matter?

Posted on June 22, 2012 by pharminpt

ICU MonitorPhysical Therapists in Intensive Care

With all the talk lately about early mobilization in the ICU (a recent systematic review, Amy Pawlik’s standing room only presentation at CSM 2012), it’s evident that physical therapists and other rehabilitation professionals are only going to be more involved in critical care in the coming years. This is a challenging practice environment where an understanding of all the medical issues involved is a requirement for sound clinical decision making. Obviously, this includes your patient’s medications. Well, you say, my patient is in an ICU so the MDs and nurses must be looking really closely at this issue, right? That may be, but in spite of the frequent oversight of a team of healthcare providers, including pharmacists, there is evidence that the potential for adverse drug events is high in this environment.

One Error for Every Five Doses

In a study published in Critical Care Medicine back in 2006, investigators used a direct observation method to look for errors and adverse drug events during 4 4-day periods in a medical intensive care unit in a tertiary care academic medical center in Arizona.1 The observers, pharmacy residents specializing in critical care pharmacy practice, recorded information related to the entire medication administration process, from the writing of the prescription to the actual administration. The study detected 132 significant preventable errors or adverse drug events associated with 645 medication doses. In other words, in this study period, in this ICU, one error was made for every 5 doses of medication administered! The most common errors (23%) were those of omission. The wrong dose of the right drug (20%), prescribing, dispensing or administering the wrong drug (16%), using the wrong technique (15%), though the authors don’t make it clear what this really means, and missing potential drug-drug interactions (10%) made up the majority of these errors.

So, do medication errors happen? Looks like it, and in some pretty obvious ways – omission, wrong drug, and wrong dose being the most common types of errors (69%). Now, to be fair to the parties involved, these errors can occur throughout the process, from prescription to dispensing to administration, so it’s not just the physicians or just the nurses or just the pharmacists. And many of these errors are related to potential adverse events  – it’s not that patients are actually not getting drugs they should, being given incorrect doses, or being given incorrect drugs. Perhaps an incorrect dose is ordered by the physician, but the nurse or pharmacist catches that error and the patient is gets the correct drug at the correct dose.

Are there particular medications that are involved in these errors more frequently than others? Not really – the troublemakers are tough to pin down. The largest proportion of medications involved in adverse drug events was “other” (22%). Not helpful. Cardiovascular drugs (17%), antimicrobials (15%), and sedatives and analgesics (14%) were the only others in double digits.

The study was really more about the process of medication delivery, and where in the process errors were occurring, so we don’t have much to go on in terms of clinical outcomes and the adverse drug effects that these errors caused or could have caused. But, the authors were kind enough to provide examples of different kinds of errors, from which you should be able to extrapolate plausible clinical consequences:

  • excessive doses of sedative and antihypertensive medications
  • missed or late doses of a variety of medications
  • failure to adjust sedative doses following extubation
  • administration of antihypertensive agents to patients with low blood pressure
  • orders for patient-controlled analgesia with a lockout time of 6 hours instead of 6 minutes (ouch!)

Drug-Drug Interactions

In this study, unnoticed drug-drug interactions (DDIs) accounted for a relatively small proportion of errors leading to actual or potential adverse drug events. More recently, a study published in the June issue of The International Journal of Pharmacy Practice evaluated the frequency, severity, and drug combinations involved in DDIs in a medical intensive care unit in Pennsylvania.2 As in the study by Kopp et al, the objective here was not to track clinical outcomes, so we can’t say much about what to look for, just that we should be looking. These authors also used direct observation, evaluating 247 patient drug  profiles via 2 interaction databases over a 4 week period. The observers identified 457 DDIs, at a rate of nearly 2 per patient. Antihypertensives and anticoagulant/antiplatelet agents were most commonly involved in these interactions. About a quarter of the interactions were classified as major in at least one of the databases.

We’re not provided with any information as to how many of these interactions resulted in  any sort of clinical consequence, and just as with the errors, certainly most of them do not. Why or how do these interactions slip by? It’s always important to recognize that it’s not necessarily negligence or lack of knowledge. It may be simply that the drug’s benefit to the patient outweighs the risk of the interaction.

What, Me Worry?

Does this mean you need to input all of your patient’s medications into an interaction database and assume every order has some kind of mistake in it? No, but as they say, just because you’re paranoid doesn’t mean they’re not out to get you. As in every other setting, awareness of the potential for adverse drug events, whether they are the result of a DDI or an error in the process of medication delivery, is critical. Pun totally intended, by the way. Rehabilitation professionals practice somewhat more independently in an outpatient setting, and it makes sense that we should keep a close eye on medications. In critical care, we are far more likely to be part of a pretty effective team, one in which everyone’s role is fairly well defined. It’s at least one team member’s role to know what’s going one with medications and it’s not the PT or OT. But, as we can see in these 2 publications, mistakes slip by. We can also see that when they do, drugs that we should be familiar with (know your antihypertensives and take blood pressure, people!) are involved. We don’t have the pharmacologic knowledge of a physician or a nurse, but if something doesn’t make sense to you, it could be because it doesn’t make sense. Look at the medications. Speak up. Ask questions. You’ll make better decisions for your patients. That’s the object of all of this, isn’t it?

References (Back to text)

1. Kopp BJ, et al. Medication errors and adverse drug events in an intensive care unit: direct observation approach for detection. Crit Care Med. 2006;34:415-425.

2. Smithburger PL, Kane-Gill SL, Seybert AL. Drug-drug interactions in the medical intensive care unit: an assessment of the frequency, severity and the medications involved. Int J Pharm Pract. Published online before print, June 7, 2012 doi: 10.1111/j.2042-7174.2012.00221.x

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Twelve trillion, four hundred forty billion…

Posted on January 12, 2012 by pharminpt
Pill Sampler

© Pharmacopoeia, The British Museum

Does that number mean anything to you? Probably not, and that’s probably OK. But should it? Probably, and here’s why. That number is an estimate, a very rough estimate, of the number of medication doses, both prescription and over the counter, that the 311 million residents of the United States will consume during their cumulative lifetimes. I’ve made some big assumptions in generating that number, but it is probably safe to say that it is a big number no matter how you arrive at the final value.

My inspiration for thinking about the number comes from 2 different places. Medscape pointed me to an article in the American Journal of Pharmacy Education that pointed me to an exhibit displayed in the British Museum in 2003 called Cradle to Grave.1 The artists depicted, quite literally, the 14,000 doses of prescription medication consumed by the average British citizen during his or her lifetime. The artists estimate that the number of medication doses would increase to 40,000 if over-the-counter (OTC) medications were included. If we apply that number to the U.S. population, voilá, 12 trillion, four hundred forty billion. That’s a lot of pills, injections, ointments, and small cups full of sweet, but vile tasting, liquid.

Are these drugs our problem? Selena Horner, writing on the blog MyPhysicalTherapySpace.com, agrees with me and the APTA House of Delegates that they are, but she’s greatly concerned. She’s concerned about “how the mix of medications” will affect a patient. She’s concerned about inappropriate medication use. It turns out that this does not mean medications being used inappropriately by patients, it means inappropriate medications are being prescribed by physicians. More on that another time. She’s concerned that physical therapists are not equipped to discuss medications with physicians. She concerned that the issue feels out of the scope of her expertise. Is understanding how diabetes affects a patient out of the scope of physical therapist practice? What about systemic lupus erythematosus? Don’t physical therapists need to understand the effects of this very complex disorder?

A patient’s medications are very much like the rest of the medical history. Drugs change physiology, just as disease does. We need to understand the impact of those changes, when they relate to the reasons patients seek our care and when they affect the decisions we need to make about caring for our patients. Ms. Horner is concerned about putting herself and her patients in an uncomfortable position by questioning the decisions of the physicians caring for her patients. Physical therapists need to recognize that medications might be interfering with treatment, creating or contributing to symptoms, or limiting a patient’s progress. And when we think this is happening, hopefully we have enough confidence in our professional judgement  to discuss this with our patient and then call the physician or other prescriber, describe what we are seeing, clearly state our concern that medications may be contributing to the issue, and ask what options the patient has.

It’s not simple. There is no way for anyone to know exactly how 4 or 5 different medications will affect an individual, let alone what 14 or 15 drugs will do to each other and to the patient. But our patients are taking drugs, and drugs change physiology. We have no real choice but to give it a shot.

Reference (Back to text)

1. Anderson CA, Bates I, Brock T. Seven billion humans and 98 trillion medication doses. Am J Pharm Educ. 2011;75:1-2.

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Enough (acetaminophen) is enough

Posted on July 29, 2011 by pharminpt

Extra-strength acetaminophen bottleAs of yesterday, it got a little harder to take too much Tylenol®.  NPR reported on their Health blog Shots, that McNeil Consumer Healthcare, a division of Johnson & Johnson , is going to change the labeling on Extra Strength Tylenol® this fall. The active ingredient in Tylenol®, acetaminophen , sometimes abbreviated APAP,  is generally regarded as safe, but is associated with liver damage at high doses.

How high is high?

Of course the answer is it depends. On what you ask? It depends primarily on the health of your liver. This is influenced greatly by the amount of ethanol one consumes on a regular basis. In general, toxicity is associated with a single dose of 150 mg/kg of body weight. This works out to somewhere between 7-10 grams for most adults. If an extra-strength Tylenol® capsule/caplet/tablet has 500 mg, 14-20 pills can do the job. This number is lower if you’re a chronic alcohol consumer or have poor nutrition. Less than this, but more than the recommended (until yesterday) 4 gms/day over some period of time can also be toxic – liver failure toxic enough for ya?

Why do bad things happen?

Well, not in general, but with acetaminophen anyway – APAP is absorbed quickly from the stomach and small intestine and metabolized in the liver via a processcalled conjugation. Basically, this involves attaching an additional molecule or part of a molecule to the APAP molecule. This usually inactivates it and, very conveniently, makes it water soluble so it can be removed by the body in the urine. But, if you take too much all at once, or more than enough often enough, the liver’s ability to conjugate the APAP is overwhelmed. Instead the APAP molecule is changed chemically, oxidized this time, by another enzyme into a toxic product or metabolite. Normally this breakdown product is very quickly conjugated itself via a substance in the liver called glutathione.

Here’s the problem – if you have too much of this toxic compound, or not enough glutathione (because it all got used up taking care of all this toxic goo in the liver, for example), the liver is damaged. That damage can lead to severe liver failure, severe enough to  result in the need for a liver transplant. It can be fatal. In fact, APAP overdose is the leading cause of acute liver failure in the US.(source)

The Solution Might Be Part of the Problem

Given that liver failure is a thing most our patients would want to avoid, what should they do? Simple. They should know that they are taking APAP and then make sure they are not taking too much. Unfortunately, it turns out that the trick for average folks is knowing that APAP is in what they are taking in the first place. A study in the American Journal of Preventive Medicine in May of this year looking at patient knowledge of over-the-counter (OTC) pain reliever ingredients, and specifically APAP, showed that while most people (75%) knew aspirin was the active ingredient in Bayer® aspirin (I would hope so!), only 31% new that APAP was the active ingredient in Tylenol®.1 To be fair, only 19% of subjects knew naproxen was in Aleve® and ibuprofen was in Advil®.1 Less than half of the subjects said that they routinely read ingredient information when purchasing OTC meds.1

What about prescription pain relievers with APAP in them? There are quite a few of those, too. How many can you name?  Click three times in the blank space below and you’ll find 4 common ones.

Vicodin® , Percocet® , Ultracet® , and Lortab®

are common prescription pain relievers that also have APAP in them – up to 750 mg in one form of Vicodin®. Patients then might take OTC APAP if their prescription medications don’t provide adequate relief, thinking that it would be safe given that it’s available OTC. Many other cough, cold,  and allergy medications – over 600 prescription and non-prescription medications have APAP as an ingredient. (source)

All of these common OTC medications have one version or another that contains APAP:

  • Anacin®
  • Excedrin®
  • Alka-Seltzer®
  • Triaminic®
  • Sudafed®
  • Comtrex®
  • DayQuil®
  • NyQuil®
  • Vicks® Forumula 44

Change is in the Wind (on the bottle, really)

Yesterday’s press release states that, beginning this fall,  the maximum daily dose recommended on the packaging of Extra Strength Tylenol® will be decreased from 4000 mg (8 pills) to 3000 mg (6 pills). The recommended maximum daily dose for regular strength Tylenol® will be reduced sometime next year. McNeil Consumer Healthcare has started a consumer website called Get Relief Responsibly in an effort to  educate consumers of APAP-containing products. Finally, beginning in 2012, they will be introducing Bottle Cap Messaging – a message printed on the top of the bottle of some Extra Strength Tylenol® products.

The Bottom Line

Especially with growing concerns about NSAIDs and current recommendations for older adults to seek initial relief from musculoskeletal pain with APAP, its important that physical therapists  help physicians help patients use APAP safely. So, know what your patients are taking, including their OTC medications. Help them know what they are taking – it takes some time, but knowing what your patients know about their medications, can be a useful medication safety tool. Of course, we would ask our patients about pain, but if pain relief is inadequate, at a minimum encourage patients to communicate this to prescribers. If necessary, make contact with the prescribing provider yourself, ideally with your patients’ knowledge and consent.

Reference (Back to text)

1. King JP et al. Developing consumer-centered, nonprescription drug labeling: a study in acetaminophen. Am J Prev Med. 2011;40:493-498.

Posted in musculoskeletal | Tagged , , , | 1 Comment

NSAIDs, even over-the-counter, not to be taken lightly

Posted on July 27, 2011 by pharminpt

heart
Have you ever suggested that a patient take an over-the-counter (OTC) anti-inflammatory or analgesic? Aside from the fact that prescribing medication is outside of the scope of physical therapist practice, the number of reasons against making a casual recommendation that a patient take an OTC medication is growing, almost daily.

The Basics

On July 14th, at theheart.org, Lisa Nainggolan reported on a study published in the July 2011 issue of The American Journal of Medicine. The study was a post-hoc analysis of data from the the INVEST trial. Here we go again with the catchy acronyms. In any case, the purpose of INVEST (the INternational VErapamil Trandolapril STudy) was to compare effects of a calcium channel blocker-based strategy to a beta-blocker based strategy in the control of hypertension (HTN) in patients with stable coronary artery disease (CAD). Trandolapril, an angiotensin-converting enzyme inhibitor and/or hydrochlorothiazide, a diuretic, were added to achieve BP control. Subjects, who were at least 50 years old and had both HTN and stable CAD, were followed for 2 years. The authors of the present study followed subjects for an additional 5 years to investigate the relationship between chronic non-steroidal anti-inflammatory (NSAID) use, blood pressure, and adverse outcomes in people with coronary artery disease and hypertension. The primary outcome was all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke, whichever came first. Secondary outcomes were all-cause mortality (after a non-fatal MI or stroke), total MI, and total stroke. Outcomes were evaluated by a panel blinded to the NSAID-using status of the subjects. Chronic NSAID users reported NSAID use at baseline and at every follow up visit. Non-chronic users only reported use at some visits, or not at all. Chronic users were matched with non chronic users by risk for the outcomes of interest and risk was calculated using Cox regression analysis for the 2 groups. Most subjects were using NSAIDs to manage rheumatoid arthritis, osteoarthritis, or low back pain.

NSAIDs and Rehabilitation

We started to get the message a few years ago, courtesy of Vioxx, that NSAIDs probably create cardiovascular issues for folks, especially older adults who are already at risk because of their age, blood pressure, lipids, smoking history, and, most important for us, a lack of physical activity. Other large studies have since shown that this is probably a class effect, with diclofenac users typically having a higher rate of cardiovascular events, and naproxen and ibuprofen users having a risk not very different from non-users, but the findings have not been consistent across studies.1,2,3 NSAIDs are important in rehabilitation, if for no other reason than lots of older adults with chronic musculoskeletal symptoms use these drugs, either by prescription or OTC. There is evidence that a large proportion of patients who are in the care of a physical therapist use them, anywhere from 20-80%.4,5,6 The most recent look at this issue was a multi-center study by Boissonnault and Meek almost 10 years ago, so we don’t really know where things stand right at this moment. But, in their survey of 2311 physical therapy outpatients, 79% were using an anti-inflammatory (ibuprofen, naproxen, and others) or aspirin, either OTC or prescribed. Surprisingly, almost 20% of patients were using duplicate therapy – a prescribed NSAID with an OTC NSAID or prescribed aspirin and OTC aspirin.

So, to recap what we’ve got so far:

  • a lot patients seeking rehabilitation are dealing with rheumatoid arthritis, osteoarthritis, or low back pain
  • up to 80% of these patients are using NSAIDs, maybe OTC, maybe by prescription
  • 20-40% of these patients may be using NSAIDs and/or aspirin inappropriately by taking more than one NSAID, in some combination of OCT and prescription
  • many of these patients are also older, have stable CAD, and HTN

Take a second now, and estimate the proportion of patients in your practice that fit those criteria. If your estimate is 10% or less, there’s probably no need for you to read the rest of this post, but if you treat adults over 50 years old with musculoskeletal issues, you’re kidding yourself if you think this doesn’t apply to your patients.

Chronic NSAID Users are at Risk

Of the 22,576 subjects who participated in the study, 882 were chronic NSAID users. As a group, the chronic users were younger, more likely to be female, more likely to have diabetes and peripheral arterial disease, and were less likely to be using aspirin and lipid-lowering medications. The primary outcomes occurred at a rate of 4.4 events per 100 patient years vs. 3.7 events per 100 patient years in the non-chronic users. The adjusted hazard ratio was 1.47 (95% CI 1.19-1.82, p=.0003). So where’s the bad news for NSAIDs here? As usual, it’s in the details. Yes there was a 47% increase in all-cause mortality, non-fatal MI or non-fatal stroke for the chronic NSAID users over the non-users. But, much of that difference was driven by a 90% increase in all-cause mortality, a difference that persisted between the two groups over 5 years of follow-up. And the largest difference between the 2 groups was within the secondary outcomes, a 126% increase in cardiovascular mortality.

Two additional findings were surprising. First, the rate of gastrointestinal bleeding was very low in both groups (0% of chronic users vs. 0.8% of non-chronic users). The authors propose that subjects had been taking the drugs before entry into the study and events could also have occurred before study entry. Or, perhaps chronic users were chronic users because they could tolerate chronic use. They also note that bleeding was not a targeted outcome in the trial, and events may have been missed. Second, both systolic and diastolic blood pressure were lower in the chronic group at baseline and throughout follow-up. The common wisdom, derived from short-term data, is that NSAIDs uniformly increase SBP by about 5 mm Hg.7
The authors were unable to explain this finding other than to say that NSAID-induced increases in BP have not been shown in long term studies. Additionally, when subjects’ BP was poorly controlled (SBP > 150 mm Hg), the rate at which adverse events occurred was even greater than that seen among the chronic users as a whole. This hazard ratio was only reported in a figure, so it is difficult to establish what the hazard ratio and increased risk really was.

There are certainly things this study doesn’t tell us. There was no information gathered about the specific NSAIDs the subjects were taking and the authors propose that this increase in adverse events, primarily cardiovascular mortality, is a class effect of all NSAIDs until shown otherwise. It’s also possible that NSAID use serves as a marker for other conditions that also increase the risk for adverse events, rheumatoid and osteoarthritis, in particular. Finally, keep in mind that the data regarding NSAID use is all generated through self-report. If subjects did not report NSAID use at each follow-up visit, they were classified as non-chronic users. Subjects may have reported NSAID use when they were not , but it is probably more likely that subjects used NSAIDs and not reported it. In either case, subjects would be misclassified.

The authors reach the conclusion that chronic NSAID use should be avoided with older adults. We don’t know where this increase in cardiovascular mortality comes from. One would think an increase in BP might account for the difference in a large population of individuals. Not that a 5 mm Hg in SBP is deadly, but SBP correlates with cardiovascular mortality risk, so in a large enough group, a small change in BP has a large effect. However, in this cohort of subjects, chronic NSAID users had lower SBPs, so we can’t lay the blame there. As reported on theheart.org, Dr. Anthony A. Bavry, the lead author of the study, recommends that patients not discontinue these medications on their own. Communication with prescribers, a recurring theme here at Pharmacology in Physical Therapy, is the key. He tells his patients that there is evidence of harm. At the least, he makes an effort to decrease the frequency or dose of NSAID use, and attempts to make a switch to acetaminophen. But, he says, “ultimately, it’s up to them if this potential risk is worth taking depending upon the indication for their use.”

The Take Home Message

The bottom line for us in rehabilitation: we can and should play an important role in pain relief, especially when that pain is musculoskeletal in origin, Yes, exercise and physical modalities have risks, but it is likely those risks, in whatever form, are lower than the risks of chronic NSAID use. Rehabilitation professionals need to be extremely cautious with OTC medications. Just because they are available over the counter does not mean that they are benign. We should always ask patients about their medications, and not just prescription medications. It would appear that, with NSAIDs, duplication (more than one NSAID) is common and this may increase overall exposure to the drugs and possible increase the risk of an adverse event. We know – and you’ll hear it over and over here – it is outside of the scope of PT practice (except in the military) to prescribe. Avoid making recommendations about medications in response to a patient’s question. In patients who have had an MI, it appears that the risk increases for any NSAID over any duration, making this an especially concerning situation.8 Your response should be to encourage your patient to speak to his physician or to ask patient if you can contact the provider yourself.

References (Back to text)
1. Graham DJ et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005;365:475-481.

2. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006;296:1633-1644.

3. Trelle S et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086. doi: 10.1136/bmj.c7086.

4. Boissonnault WG, Koopmeiners MB. Medical history profile: orthopaedic physical therapy outpatients. J Orthop Sports Phys Ther. 1994;20:2-10.

5. Boissonnault WG. Prevalence of comorbid conditions, surgeries, and medication use in a physical therapy outpatient population: a multicentered study. J Orthop Sports Phys Ther. 1999;29:506-525.

6. Boissonnault WG, Meek PD. Risk factors for anti–inflammatory-drug- or aspirin-induced gastrointestinal complications in individuals receiving outpatient physical therapy services. J Orthop Sports Phys Ther. 2002;32:510-517.

7. Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med. 1994;121:289-300.

8. Schjerning Olsen, AMB et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: a nationwide cohort study.

Posted in cardiovascular, musculoskeletal | Tagged , , , , , , , , , , , | 2 Comments

ARISTOTLE says “nyah nyah – nah nah nah” to warfarin

Posted on June 23, 2011 by pharminpt

AristotleThe search for an alternative to the pain-in-the-### that is warfarin goes on. There are some promising candidates. The FDA approved dabigatran (Pradaxa™), a direct thrombin inhibitor, back in November of last year. It has its pros and cons. In short, it is more effective than warfarin in preventing stroke in patients with non-valvular atrial fibrillation and is 74% less likely to cause serious bleeding than warfarin. No monitoring needed, either. Rivaroxaban(Xarelto™) is hot on its heels. Yesterday, as reported on theheart.org, Bristol-Myers Squibb reported that their new entry into the anti-coagulant quagmire, apixaban (Eliquis™), a factor Xa inhibitor, is “noninferior” to warfarin in preventing stroke in atrial fibrillation.

This is just a preliminary report and there is no real data to look at right now. If you happen to be in Paris (yes, France) on August 28th, you can catch a detailed report at the European society of Cardiology Congress. The press release goes on to report that not only is apixaban noninferior to warfarin, it is also superior to warfarin in both stroke prevention and bleeding risk. Noninferiority and superiority aren’t the same thing, apparently, and it’s kind of a big deal, or so it appears.

The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects with Atrial Fibrillation) – where do you get ARISTOTLE out of that? – enrolled over 18000 subjects at more than 1000 centers in 40 countries. The subjects received either twice per day apixaban or “dose-adjusted” warfarin. I’m assuming that means a dose of warfarin necessary to achieve an international normalized ratio (INR) of no less than 2.0.

Bristol-Meyers Squibb is working with Pfizer and the companies hope to have FDA approval by the end of this year. The drug is already approved in Europe, but for the prevention of deep vein thrombosis in adults after elective hip or knee arthroplasty rather than stroke prevention in atrial fibrillation.

Beyond recognizing that patients taking these new drugs are at risk for bleeding, the implications in rehabilitation are largely unknown. There is no antidote for these medications, and there is no readily available monitoring that will tell health care providers whether or not the drugs are working. If these drugs are taken, they work. But we know that most people don’t take their meds as prescribed, especially over the long term. We’ll have to wait and see on this one, and on rivaroxaban, and on dabigatran. Keep an eye out right here for more info in the future – once I know something, I’ll make sure you know it, too.

Posted in bleeding | Tagged , , , , , | 3 Comments

Dodo birds and 80 mg of simvastatin

Posted on June 23, 2011 by pharminpt

dodoHigh doses of simvastatin have gone the way of those famous birds from Mauritius as of two weeks ago. The FDA released a statement on June 8th recommending that the cholesterol-lowering drug simvastatin not be prescribed at the 80 mg dose except when a patient has been taking the drug at that dose for more than 12 months without muscle symptoms. The FDA advises that no new 80 mg prescriptions should be written, either for patients initiating treatment with the drug or for patients already taking lower doses. A 40 mg dose of simvastatin can reduce low-density cholesterol (LDL-C) by 41%, but doubling the dose to 80 mg only decreases LDL-C by another 6%. Subjects in the SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) trial were more likely to experience muscle damage when taking high-dose simvastatin.1 These findings triggered the FDA alert. I have no idea why a study published in 2007 is triggering an FDA alert in 2011, but this is what was reported on theheart.org (free registration probably required to view).

The drug comes in several forms – by itself in generic form and as Zocor™, in combination with ezetimibe as Vytorin™, and in combination with niacin as Simcor™. More importantly, physical therapists should know that HMG-CoA reductase inhibitors, more commonly known as statins can and do cause muscle symptoms. There have been 2 articles published in Physical Therapy addressing scope and presentation of this problem, one in 2005 and another last October.2,3 They are recommended reading for anyone in rehabilitation who treats patients with muscle symptoms. That’s everyone in rehabilitation, you say? Exactly my point. Weakness, pain, and tenderness are common symptoms of statin-induced myopathy. These are all symptoms that may bring a patient to see a physical therapist, or that a patient might experience during the course of rehabilitation, or both. The key for us would be the lack of a reasonable mechanism or explanation for these symptoms. For example, your patient has exercised and might expect some soreness, but this discomfort should resolve over a few days following the exercise. When it doesn’t, and the patient is taking a statin, questions need to be asked.

It turns out that not all statins are created equal. This is true for most drug classes. Drugs are biochemically similar enough to be grouped together, but differences in molecular structure produce different effects. In the case of the statins, one difference may be the lipid solubility of the molecule. Statins that are more lipid soluble (lovastatin and simvastatin are 2 of the most lipid soluble statins) can easily cross the cell membrane of muscle and other cells. It also turns out that the statins are toxic to muscle cells. Well, embryonic precursors to muscle cells anyway. And they’re not all toxic to the same extent. When Kobayashi et al looked at this in 2008, they found that it took more than 1000 times less simvastatin than pravastatin to kill 50% of the cells in their culture.4 The only statin more toxic to the cells in this experiment was cerivastatin, once upon a time known as Baycol™, which was voluntarily withdrawn from the market in the U.S. in 2001 because of an excess number of cases of severe, fatal, muscle damage. Keep in mind, of course, that these results reflect what happens in a cell culture and not necessarily in human muscle.

The risk of muscle damage in the SEARCH trial was greatest during the first year of statin treatment, hence the recommendation that patients who have already been taking simvastatin 80 mg for more than a year without symptoms probably don’t need a medication change. The risk for muscle damage also increased with increasing age and female sex, consistent with previously described risk-factors for statin-induced myopathy.

The FDA has also mandated labeling changes for all doses of simvastatin, providing us with some clues, in the form of drug combinations, that increase the risk for muscle damage. Simvastatin is contraindicated with azole antifungals (metronidazole or Flagyl™ is one of the most common); the antibiotics erythromycin and clarithromycin; protease inhibitors, used in the management of HIV infection; gemfibrozil, another lipid-lowering agent; and cyclosporine, a common immunosuppressant used after solid organ transplantation. This is not a complete list of contraindicated drugs, but these are the most commonly prescribed and drugs that most rehabilitation professionals should be familiar enough with to recognize by name. Three cardiovascular drugs, verapamil, diltiazem, and amiodarone,  should not be used with more than 10 mg of simvastatin. Amlodipine and ranolazine should not be taken with more than 20 mg of simvastatin. Both of these are also cardiovascular medications. The FDA recommendation to limit grapefruit juice intake to less than 1 quart per day remains in place.

Now, according to Dr. Steven Nissen on theheart.org, this is old news as far as “knowledgeable lipid experts” are concerned. These experts stopped writing prescriptions for high-dose simvastatin years ago, says Dr. Nissen. But the FDA says, and Dr. Nissen agrees, that in 2010 more than 2 million prescriptions were written for 80 mg simvastatin, an unsafe dose of this drug, when there are safer, equally effective alternatives readily available.

So if you encounter a patient tomorrow who is taking 80 mg of simvastatin, what do you say? Clearly, we’re not pharmacists or physicians, but I think we can safely tell them what the FDA would tell them if the patient were to go looking for the FDA’s guidance:

  • don’t stop taking the medication unless told to do so by a prescribing health care provider (ie, we shouldn’t be telling patients to stop!)
  • review your medications with a prescribing provider to make sure there are no contraindicated medications being taken
  • immediately report any symptoms of muscle pain, tenderness, weakness, unexplained fatigue, or dark or red colored urine
The dark or red urine is produced when myoglobin, a protein found in muscle, makes its way into the blood and then the kidneys, and finally into urine. A lot of muscle needs to break down for this to happen. This protein causes damage to the kidneys and can cause kidney failure. Kidney failure is often the cause of death in rhabdomyolysis, which is just another name for the most severe form of muscle damage.

So while knowing dosing information is not usually critical for rehabilitation professionals, the take home message here is that seeing an 80 mg dose of simvastatin should provoke you to ask some questions, if not of the patient, at least in your mind:

  • First, how long has the patient been taking this drug at this dose?
  • What other drugs does the patient take (see the lists above for those that might cause problems)
  • Has the patient had any communication with the prescribing provider about this drug at this dose?
  • Does the patient have any muscle symptoms right now, for which there is not a good explaination?

If the answer to first question is < 12 months, or the patient is taking drugs that are contraindicated with simvastatin (at any of the above mentioned doses), or the patient has not spoken with the prescriber, or especially if the patient has current muscle symptoms, you need to either strongly encourage the patient to contact the prescriber or contact the prescriber yourself to discuss your concerns. Certainly describe muscle symptoms if there are any. From there, rather than question the appropriateness of the medication or the dose, it might be best (with the patient’s knowledge and consent before) to ask some questions of the prescriber for the patient. Be on the lookout!

Back to text
1. SEARCH Study Collaborative Group. Study of the effectiveness of additional reductions in cholesterol and homocysteine (SEARCH): characteristics of a randomized trial among 12064 myocardial infarction survivors. Am Heart J. 2007;154:815-823.
2. Tomlinson SS, Mangione KK. Potential adverse effects of statins on muscle. Phys Ther. 2005;85:459-465.
3. Di Stasi SL, MacLeod TD, Winters JD, Binder-MacLeod SA. Effects of statins on skeletal muscle: a perspective for physical therapists. Phys Ther. 2010;90:1530-1542.
4. Kobayashi M, wt al. Association between risk of myopathy and cholesterol-lowering effect: a comparison of all statins. Life Sciences. 2008;82:969-975.

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