How soon should serum potassium levels be monitored for patients started on diuretics?

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How soon should serum potassium levels be monitored for patients started on diuretics?
EVIDENCE-BASED ANSWER

Case series show that hypokalemia following initiation of diuretic therapy occurs in most patients within 2 to 8 weeks. However, no studies are available that adequately predict the risk of this complex and multifactorial condition. Patients taking diuretics should have a potassium level checked in the first 2 to 8 weeks after initiating therapy. Mild hypokalemia (3.1 to 3.4 mmol/L) may be transient, so a repeat measurement may be considered before initiating potassium replacement. Dietary sodium restriction may also help to conserve potassium, because this will decrease urinary flow rate and potassium loss. The frequency with which to check potassium levels should be guided by the patients’ underlying clinical conditions and dietary potassium and sodium intake. (Grade of Recommendation: C, based on case series)

 

Recommendations from others

The National Council on Potassium in Clinical Practice issued a set of guidelines for potassium replacement in September 2000.1 The authors recommend using thiazide diuretics at a low dose only (eg, 12.5-25 mg of hydrochlorothiazide daily) and adding a potassium-sparing diuretic drug when higher diuretic doses are needed. For patients with asymptomatic hypertension they recommend trying to maintain a serum potassium level of at least 4.0 mmol/L. The University of Iowa Family Practice Handbook2 states: “Maximal decrease in serum K+ concentration is usually seen after 7 days of treatment. Serum K+ concentration should be measured before initiation of a diuretic and 1 week after initiation of increase in dose of the diuretic.”

Evidence summary

Hypokalemia is defined as a serum potassium level less than 3.5 mmol/L (3.5 mEq/L); hypokalemia at levels between 3.1 and 3.4 mmol/L is considered mild. The incidence of hypokalemia reported for patients on diuretic therapy is broad (7.2% to 56%),3-6 and the time period required to develop hypokalemia varies (1 week6 to >1 year7). Factors including the type of diuretic used, dosage, duration of use, dietary potassium, and so forth, make predicting an individual patient’s progression nearly impossible. Widmer and coworkers5 found that the risk of hypokalemia was greatest with concomitant glucocorticoid use, polypharmacy (greater than 12 medications administered), and female sex. The latter risk factor may be related to a higher dose-to-weight relationship.

Lemieux and colleagues8 followed 50 patients receiving a variety of diuretic regimens (hydrochlorothiazide 50 to 100 mg daily or every other day with or without reserpine 0.25 mg daily). Only 3 patients in this group had potassium levels below 3.5 mmol/L, and all decreases were only transient. Peters and coworkers6 documented potassium levels below 3.5 mEq/L in 6 of 19 patients taking hydrochlorothiazide 25 or 50 mg for 20 weeks. Three of these patients normalized without therapy. One of these transiently hypokalemic patients was also taking triamterene, a potassium-sparing diuretic.

Potassium-sparing diuretics may not free the clinician from checking a potassium level, however. Penhall and coworkers9 found hypokalemia in 24 of 54 patients receiving a fixed-combination diuretic (hydrochlorothiazide 50 mg and potassium-sparing amiloride 5 mg). Note that the dose of hydrochlorothiazide was higher in this study than is generally used today. Most recent studies have found that hydrochlorothiazide in doses above 12.5 to 25 mg do not result in significantly lower blood pressure and only lead to more electrolyte abnormalities.10

Morgan and Davidson11 performed an analysis of the published data available in 1980. They found that the average fall in potassium is less for patients taking furosemide (0.3mmol/L) than on thiazide diuretics (0.6mmol/L) and that this fall was only slightly influenced by dose or duration of treatment.

Clinical Commentary

Allen F. Shaughnessy, PharmD
Harrisburg Family Practice Residency Pennsylvania

Few hypertensive patients started on low-dose diuretics will become hypokalemic, and most of those who do will have serum levels greater than or equal to 3.0 mEq/L. In patients with heart failure or renal disease, potassium should be monitored shortly after the initiation of a diuretic because of potentially more rapid electrolyte and fluid shifts. However, many of these patients will also be taking an ACE inhibitor or spironolactone: 2 drugs that may increase serum potassium levels. In the absence of heart failure or renal disease checking a potassium level a month or so following initiation, as recommended by this review, seems reasonable.

References

1. Cohn JN, Kowey PR, Whelton PK, Prisant M. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med 2000;160:2429-36.

2. Schlichtman J, Graber MA. University of Iowa family practice handbook. 3rd ed. Chapter 5 Hematologic, electrolyte, and metabolic disorders: potassium.

3. Franse LV, Pahor M, Di Bari M, Somes GW, Cushman WC, Applegate WB. Hypokalemia associated with diuretic use and cardiovascular events in the systolic hypertension in the elderly program. Hypertension 2000;35:1025-30.

4. Schnaper HW, Freis ED, Friedman RG, et al. Potassium restoration in hypertensive patients made hypokalemic by hydrochlorothiazide. Arch Intern Med 1989;149:2677-81.

5. Widmer P, Maibach R, Kunzi UP, et al. Diuretic-related hypokalaemia: the role of diuretics, potassium supplements, glucocorticoids and -adrenoceptor agonists. Eur J Clin Pharmacol 1995;49:31-36.

6. Peters RW, Hamilton J, Hamilton BP. Incidence of cardiac arrhythmias associated with mild hypokalemia induced by low-dose diuretic therapy for hypertension. South Med J 1989;82:966-69.

7. Penhall RK, Frewin DB. Plasma potassium levels in hypertensive patients receiving fixed-combination diuretic therapy. Med J Aust 1980;1:376-78.

8. Lemieux G, Beauchemin M, Vinay P, Gougoux A. Hypokalemia during the treatment of arterial hypertension with diuretics. CMAJ 1980;122:905-07.

9. Penhall RK, Frewin DB. Plasma potassium levels in hypertensive patients receiving fixed-combination diuretic therapy. Med J Aust 1980;1:376-78.

10. Lumme JAJ, Jounela AJ. Left ventricular mass, serum electrolyte levels and cardiac arrhythmias in patients with mild hypertension treated with cilazapril or hydrochlorothiazide. Int J Cardiol 1993;42:71-78.

11. Morgan DB, Davidson C. Hypokalemia and diuretics: an analysis of publications. BMJ 1980;280:905-08.

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EVIDENCE-BASED ANSWER

Case series show that hypokalemia following initiation of diuretic therapy occurs in most patients within 2 to 8 weeks. However, no studies are available that adequately predict the risk of this complex and multifactorial condition. Patients taking diuretics should have a potassium level checked in the first 2 to 8 weeks after initiating therapy. Mild hypokalemia (3.1 to 3.4 mmol/L) may be transient, so a repeat measurement may be considered before initiating potassium replacement. Dietary sodium restriction may also help to conserve potassium, because this will decrease urinary flow rate and potassium loss. The frequency with which to check potassium levels should be guided by the patients’ underlying clinical conditions and dietary potassium and sodium intake. (Grade of Recommendation: C, based on case series)

 

Recommendations from others

The National Council on Potassium in Clinical Practice issued a set of guidelines for potassium replacement in September 2000.1 The authors recommend using thiazide diuretics at a low dose only (eg, 12.5-25 mg of hydrochlorothiazide daily) and adding a potassium-sparing diuretic drug when higher diuretic doses are needed. For patients with asymptomatic hypertension they recommend trying to maintain a serum potassium level of at least 4.0 mmol/L. The University of Iowa Family Practice Handbook2 states: “Maximal decrease in serum K+ concentration is usually seen after 7 days of treatment. Serum K+ concentration should be measured before initiation of a diuretic and 1 week after initiation of increase in dose of the diuretic.”

Evidence summary

Hypokalemia is defined as a serum potassium level less than 3.5 mmol/L (3.5 mEq/L); hypokalemia at levels between 3.1 and 3.4 mmol/L is considered mild. The incidence of hypokalemia reported for patients on diuretic therapy is broad (7.2% to 56%),3-6 and the time period required to develop hypokalemia varies (1 week6 to >1 year7). Factors including the type of diuretic used, dosage, duration of use, dietary potassium, and so forth, make predicting an individual patient’s progression nearly impossible. Widmer and coworkers5 found that the risk of hypokalemia was greatest with concomitant glucocorticoid use, polypharmacy (greater than 12 medications administered), and female sex. The latter risk factor may be related to a higher dose-to-weight relationship.

Lemieux and colleagues8 followed 50 patients receiving a variety of diuretic regimens (hydrochlorothiazide 50 to 100 mg daily or every other day with or without reserpine 0.25 mg daily). Only 3 patients in this group had potassium levels below 3.5 mmol/L, and all decreases were only transient. Peters and coworkers6 documented potassium levels below 3.5 mEq/L in 6 of 19 patients taking hydrochlorothiazide 25 or 50 mg for 20 weeks. Three of these patients normalized without therapy. One of these transiently hypokalemic patients was also taking triamterene, a potassium-sparing diuretic.

Potassium-sparing diuretics may not free the clinician from checking a potassium level, however. Penhall and coworkers9 found hypokalemia in 24 of 54 patients receiving a fixed-combination diuretic (hydrochlorothiazide 50 mg and potassium-sparing amiloride 5 mg). Note that the dose of hydrochlorothiazide was higher in this study than is generally used today. Most recent studies have found that hydrochlorothiazide in doses above 12.5 to 25 mg do not result in significantly lower blood pressure and only lead to more electrolyte abnormalities.10

Morgan and Davidson11 performed an analysis of the published data available in 1980. They found that the average fall in potassium is less for patients taking furosemide (0.3mmol/L) than on thiazide diuretics (0.6mmol/L) and that this fall was only slightly influenced by dose or duration of treatment.

Clinical Commentary

Allen F. Shaughnessy, PharmD
Harrisburg Family Practice Residency Pennsylvania

Few hypertensive patients started on low-dose diuretics will become hypokalemic, and most of those who do will have serum levels greater than or equal to 3.0 mEq/L. In patients with heart failure or renal disease, potassium should be monitored shortly after the initiation of a diuretic because of potentially more rapid electrolyte and fluid shifts. However, many of these patients will also be taking an ACE inhibitor or spironolactone: 2 drugs that may increase serum potassium levels. In the absence of heart failure or renal disease checking a potassium level a month or so following initiation, as recommended by this review, seems reasonable.

EVIDENCE-BASED ANSWER

Case series show that hypokalemia following initiation of diuretic therapy occurs in most patients within 2 to 8 weeks. However, no studies are available that adequately predict the risk of this complex and multifactorial condition. Patients taking diuretics should have a potassium level checked in the first 2 to 8 weeks after initiating therapy. Mild hypokalemia (3.1 to 3.4 mmol/L) may be transient, so a repeat measurement may be considered before initiating potassium replacement. Dietary sodium restriction may also help to conserve potassium, because this will decrease urinary flow rate and potassium loss. The frequency with which to check potassium levels should be guided by the patients’ underlying clinical conditions and dietary potassium and sodium intake. (Grade of Recommendation: C, based on case series)

 

Recommendations from others

The National Council on Potassium in Clinical Practice issued a set of guidelines for potassium replacement in September 2000.1 The authors recommend using thiazide diuretics at a low dose only (eg, 12.5-25 mg of hydrochlorothiazide daily) and adding a potassium-sparing diuretic drug when higher diuretic doses are needed. For patients with asymptomatic hypertension they recommend trying to maintain a serum potassium level of at least 4.0 mmol/L. The University of Iowa Family Practice Handbook2 states: “Maximal decrease in serum K+ concentration is usually seen after 7 days of treatment. Serum K+ concentration should be measured before initiation of a diuretic and 1 week after initiation of increase in dose of the diuretic.”

Evidence summary

Hypokalemia is defined as a serum potassium level less than 3.5 mmol/L (3.5 mEq/L); hypokalemia at levels between 3.1 and 3.4 mmol/L is considered mild. The incidence of hypokalemia reported for patients on diuretic therapy is broad (7.2% to 56%),3-6 and the time period required to develop hypokalemia varies (1 week6 to >1 year7). Factors including the type of diuretic used, dosage, duration of use, dietary potassium, and so forth, make predicting an individual patient’s progression nearly impossible. Widmer and coworkers5 found that the risk of hypokalemia was greatest with concomitant glucocorticoid use, polypharmacy (greater than 12 medications administered), and female sex. The latter risk factor may be related to a higher dose-to-weight relationship.

Lemieux and colleagues8 followed 50 patients receiving a variety of diuretic regimens (hydrochlorothiazide 50 to 100 mg daily or every other day with or without reserpine 0.25 mg daily). Only 3 patients in this group had potassium levels below 3.5 mmol/L, and all decreases were only transient. Peters and coworkers6 documented potassium levels below 3.5 mEq/L in 6 of 19 patients taking hydrochlorothiazide 25 or 50 mg for 20 weeks. Three of these patients normalized without therapy. One of these transiently hypokalemic patients was also taking triamterene, a potassium-sparing diuretic.

Potassium-sparing diuretics may not free the clinician from checking a potassium level, however. Penhall and coworkers9 found hypokalemia in 24 of 54 patients receiving a fixed-combination diuretic (hydrochlorothiazide 50 mg and potassium-sparing amiloride 5 mg). Note that the dose of hydrochlorothiazide was higher in this study than is generally used today. Most recent studies have found that hydrochlorothiazide in doses above 12.5 to 25 mg do not result in significantly lower blood pressure and only lead to more electrolyte abnormalities.10

Morgan and Davidson11 performed an analysis of the published data available in 1980. They found that the average fall in potassium is less for patients taking furosemide (0.3mmol/L) than on thiazide diuretics (0.6mmol/L) and that this fall was only slightly influenced by dose or duration of treatment.

Clinical Commentary

Allen F. Shaughnessy, PharmD
Harrisburg Family Practice Residency Pennsylvania

Few hypertensive patients started on low-dose diuretics will become hypokalemic, and most of those who do will have serum levels greater than or equal to 3.0 mEq/L. In patients with heart failure or renal disease, potassium should be monitored shortly after the initiation of a diuretic because of potentially more rapid electrolyte and fluid shifts. However, many of these patients will also be taking an ACE inhibitor or spironolactone: 2 drugs that may increase serum potassium levels. In the absence of heart failure or renal disease checking a potassium level a month or so following initiation, as recommended by this review, seems reasonable.

References

1. Cohn JN, Kowey PR, Whelton PK, Prisant M. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med 2000;160:2429-36.

2. Schlichtman J, Graber MA. University of Iowa family practice handbook. 3rd ed. Chapter 5 Hematologic, electrolyte, and metabolic disorders: potassium.

3. Franse LV, Pahor M, Di Bari M, Somes GW, Cushman WC, Applegate WB. Hypokalemia associated with diuretic use and cardiovascular events in the systolic hypertension in the elderly program. Hypertension 2000;35:1025-30.

4. Schnaper HW, Freis ED, Friedman RG, et al. Potassium restoration in hypertensive patients made hypokalemic by hydrochlorothiazide. Arch Intern Med 1989;149:2677-81.

5. Widmer P, Maibach R, Kunzi UP, et al. Diuretic-related hypokalaemia: the role of diuretics, potassium supplements, glucocorticoids and -adrenoceptor agonists. Eur J Clin Pharmacol 1995;49:31-36.

6. Peters RW, Hamilton J, Hamilton BP. Incidence of cardiac arrhythmias associated with mild hypokalemia induced by low-dose diuretic therapy for hypertension. South Med J 1989;82:966-69.

7. Penhall RK, Frewin DB. Plasma potassium levels in hypertensive patients receiving fixed-combination diuretic therapy. Med J Aust 1980;1:376-78.

8. Lemieux G, Beauchemin M, Vinay P, Gougoux A. Hypokalemia during the treatment of arterial hypertension with diuretics. CMAJ 1980;122:905-07.

9. Penhall RK, Frewin DB. Plasma potassium levels in hypertensive patients receiving fixed-combination diuretic therapy. Med J Aust 1980;1:376-78.

10. Lumme JAJ, Jounela AJ. Left ventricular mass, serum electrolyte levels and cardiac arrhythmias in patients with mild hypertension treated with cilazapril or hydrochlorothiazide. Int J Cardiol 1993;42:71-78.

11. Morgan DB, Davidson C. Hypokalemia and diuretics: an analysis of publications. BMJ 1980;280:905-08.

References

1. Cohn JN, Kowey PR, Whelton PK, Prisant M. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med 2000;160:2429-36.

2. Schlichtman J, Graber MA. University of Iowa family practice handbook. 3rd ed. Chapter 5 Hematologic, electrolyte, and metabolic disorders: potassium.

3. Franse LV, Pahor M, Di Bari M, Somes GW, Cushman WC, Applegate WB. Hypokalemia associated with diuretic use and cardiovascular events in the systolic hypertension in the elderly program. Hypertension 2000;35:1025-30.

4. Schnaper HW, Freis ED, Friedman RG, et al. Potassium restoration in hypertensive patients made hypokalemic by hydrochlorothiazide. Arch Intern Med 1989;149:2677-81.

5. Widmer P, Maibach R, Kunzi UP, et al. Diuretic-related hypokalaemia: the role of diuretics, potassium supplements, glucocorticoids and -adrenoceptor agonists. Eur J Clin Pharmacol 1995;49:31-36.

6. Peters RW, Hamilton J, Hamilton BP. Incidence of cardiac arrhythmias associated with mild hypokalemia induced by low-dose diuretic therapy for hypertension. South Med J 1989;82:966-69.

7. Penhall RK, Frewin DB. Plasma potassium levels in hypertensive patients receiving fixed-combination diuretic therapy. Med J Aust 1980;1:376-78.

8. Lemieux G, Beauchemin M, Vinay P, Gougoux A. Hypokalemia during the treatment of arterial hypertension with diuretics. CMAJ 1980;122:905-07.

9. Penhall RK, Frewin DB. Plasma potassium levels in hypertensive patients receiving fixed-combination diuretic therapy. Med J Aust 1980;1:376-78.

10. Lumme JAJ, Jounela AJ. Left ventricular mass, serum electrolyte levels and cardiac arrhythmias in patients with mild hypertension treated with cilazapril or hydrochlorothiazide. Int J Cardiol 1993;42:71-78.

11. Morgan DB, Davidson C. Hypokalemia and diuretics: an analysis of publications. BMJ 1980;280:905-08.

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Evidence-based answers from the Family Physicians Inquiries Network

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Physicians, Pharmaceutical Representatives, and Patients: Who Really Benefits?

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Physicians, Pharmaceutical Representatives, and Patients: Who Really Benefits?

Dr Jones, would you use these Wompicillin drug samples if I take you to a baseball game in a luxury box catered by Alfredo’s?

Sure, I love drug samples. I’ve been wanting to try Wompicillin.

Dr Jones, would you use these drug samples if I bring lunch to your office?

Okay, as long as you bring enough lunch for the nurses.

Dr Jones, would you use these drug samples if I just leave some pens in your waiting room?

What kind of physician do you think I am?

Dr Jones, I know what kind of physician you are… we’re just haggling over the price.

The pharmaceutical industry spends billions of dollars each year on drug promotion. A common method of promotion is through drug detailing, in which an individual pharmaceutical representative meets with one or more physicians to discuss their products. These meetings may include travel, sporting or cultural events, conferences, or meals, and often involve gifts from the drug representative to the physician. Gifts may include pens, pads, clocks, watches, bags, calendars, golf balls, shotgun shells, mugs, books, or artwork. These meetings also typically involve the exchange of information verbally and through printed material about the drug. Although the mock dialogue presented above may overstate the problem with interactions between physicians and pharmaceutical representatives, there is genuine concern that these are ethically problematic relationships.

In this issue of the Journal Backer and colleagues1 provide evidence for a wide range of community family physician behaviors involving drug representatives, gifts from pharmaceutical companies, and use of medication samples. Interactions between drug representatives and physicians varied between and within the practices studied. A large number of the practices had formal methods for meeting with these representatives, and several scheduled patient appointment times to meet with them. Gifts varied from pens and candy to meals and tickets to a musical. Medication sample use varied between physicians, but, on average, samples were given in nearly 1 in 5 patient visits.

I contend that the relationship between the physician and the drug representative has more to do with changing physicians’ prescribing patterns than with providing good patient care. However, the language used in this article provides the subtle message that drug samples, gifts, meals, treats, and educational materials are beneficial, but I believe each of these particular benefits is loaded with problems.

Drug samples

The use of medication samples varied widely between and within practices in the study by Backer and colleagues. Although the authors describe physicians who distribute more samples as sensitive to the needs of their patients, they did not measure physician sensitivity or the needs of the patients or the community. The sample types that were distributed represent a wide range of treatments; antibiotics, anti-inflammatory drugs, and antihypertensives were among the most frequently dispensed samples. A quick review of the samples in an office I visited last week revealed only the newest and most expensive formulations of these medicines. There was no sulfamethoxazole-trimethoprim, amoxicillin, hydrochlorothiazide, or ibuprofen. There was plenty of cefuroxime, valsartan, and rofecoxib. Indiscriminant use of the newest antibiotics will certainly exacerbate the crisis of drug-resistant bacteria. Of particular concern is the distribution of samples for chronic illness. For example, a newly diagnosed hypertensive patient is started on amlodipine therapy because there is an “ample supply” in the drug cabinet. However, the evidence still recommends b-blockers and diuretics as first-line therapy for hypertension. A recent study found that despite the evidence and the recommendations of the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure3 the number of prescriptions for b-blockers and diuretics have dropped, while the number of prescriptions for calcium channel blockers have increased. Calcium channel blockers now represent 38% of antihypertensive medication prescriptions compared with 11% for b-blockers and 8% for diuretics.3

Are drug samples really the best method for providing medicine to those with low income? If samples are given according to what is in the closet, what happens to the hypertensive patient when the amlodipine samples run out? Does she have to buy more pills? Or does she change treatment every few months on the basis of what sample is in? For low-income patients there are better methods for obtaining necessary medicines. Many of the proven therapies are reasonably priced. A 1-month supply of hydrochlorothiazide is $7.92 and sulfamethoxazole-trimethoprim is $9 to $12 for a 2-week course, compared with amlodipine at $74 per month. For those physicians who want to use the newer medicines or brand names, nearly all the major drug companies have programs to supply medicine to low-income patients. These programs are indexed at www.phrma.org/patients/index.html.

 

 

The authors also found that little instruction was provided to patients who received samples; side effects and drug interactions were rarely discussed. Office personnel use of samples was observed, and in one office patients had unsupervised access to the storage closet. Personal use of drug samples has numerous medical and ethical concerns that have been fully outlined elsewhere.4 Patients having unsupervised access to samples is inappropriate and dangerous. Prescribing medications on the basis of convenience (ie, the drug on the top shelf of the sample cabinet) may not be the best medicine for the patient.

Gifts, meals, and treats

Chren and Landefeld5 found that physicians who ate more meals paid for by drug representatives were more likely to request new drugs be added to their hospital formulary. Orlowski and Wateska6 found that use of 2 intravenous drugs significantly increased at the hospital after a large number of the physicians attended an all-expense-paid trip to a medical conference sponsored by the pharmaceutical companies that manufactured the 2 drugs. Blake and Early7 found that although many patients did not disapprove of their physician receiving medical books or ballpoint pens, nearly half disapproved of physicians receiving meals from drug companies. Chren and colleagues8 also point out that physician gifts are ultimately paid for by the patient who must buy the medicine. At a time when so many physicians loudly decry for-profit medicine, it is surprising that so many are willing to profit from the pharmaceutical industry.

Educational materials

Are the education materials from drug representatives truly balanced and evidence based, or are they simply another type of promotional or advertising handout? Stryer and Bero9 found that 42% of the printed material distributed by drug representatives did not comply with Food and Drug Administration requirements, and 33% did not provide a balanced presentation of the benefits and risks. Ziegler and coworkers10 reported that more than 10% of the information provided by drug representatives was flatly inaccurate. And all this inaccurate information was favorable toward that particular medication. How does false information benefit the patient or the physician? Continuing medical education (CME) is a very specific term, and the American Medical Association and American Academy of Family Physicians have strict guidelines about how, when, and where prescribed CME can be obtained, and the extent to which pharmaceutical companies can offer CME. The type of informal meeting between the drug representative and the physician that the authors describe is not CME, and it should not be construed as taking the place of formal educational endeavors.

A problematic relationship

Backer and coworkers state that interactions between physicians and drug representatives represent a complex symbiosis. That symbiotic relationship is exactly the problem. In the physician-patient interaction it is the patient who should benefit. Yet, the complex relationship between drug representatives and physicians benefits the pharmaceutical company and the physician only; the patient gains nothing. Problems with interaction between the physician and the drug representative are also emblematic of the larger interaction of the pharmaceutical industry and medical science. Recent editorials have questioned the close nature of the involvement of academic medical centers, their physicians, residents, and medical scientists with the pharmaceutical industry that provides money for drug studies in addition to gifts, samples, and promotional handouts.11,12

We practice medicine in a difficult era. Physicians are assailed by insurance companies who want us to cut costs while providing more care, and by patients who hope insurance incentives or monetary arrangements will not cloud our professional judgment. Many patients still trust us to do the right thing, but their trust may be fading. We can not afford the perception that physicians can be bought for baseball tickets, lunch, and a few pens.

References

1. EL, Lebsack JA, Van Tonder RJN, Crabtree BF. The use of pharmaceutical representatives and medication samples in community-based family practices. J Fam Pract 2000;49:811-16.

2. Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Institutes of Health publication no. 98-4080; 1997.

3. D, Lopez J. Trends in antihypertensive drug use in the United States: do the JNC V recommendations affect prescribing? JAMA 1997;278:1745-48.

4. JM, McCabe J, Nicholas RA. Personal use of drug samples by physicians and office staff. JAMA 1997;278:141-43.

5. MM, Landefeld CS. Physicians’ behavior and their interaction with drug companies. JAMA 1994;271:684-89.

6. JP, Wateska L. The effects of pharmaceutical firm enticements on physician prescribing patterns: there’s no such thing as a free lunch. Chest 1992;102:270-73.

7. RL, Early EK. Patients’ attitudes about gifts to physicians from pharmaceutical companies. J Am Board Fam Pract 1995;8:457-64.

8. MM, Landefeld CS, Murray TH. Doctors, drug companies, and gifts. JAMA 1989;262:3448-51.

9. D, Bero LA. Characteristics of materials distributed by drug companies: an evaluation of appropriateness. J Gen Intern Med 1996;11:575-83.

10. MD, Lew P, Singer BC. The accuracy of drug information from pharmaceutical sales representatives. JAMA 1995;273:1296-98.

11. M. Is academic medicine for sale? N Eng J Med 2000;342:1516-18.

12. T. Uneasy alliance: clinical investigators and the pharmaceutical industry. N Eng J Med 2000;342:1539-44.

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Dr Jones, would you use these Wompicillin drug samples if I take you to a baseball game in a luxury box catered by Alfredo’s?

Sure, I love drug samples. I’ve been wanting to try Wompicillin.

Dr Jones, would you use these drug samples if I bring lunch to your office?

Okay, as long as you bring enough lunch for the nurses.

Dr Jones, would you use these drug samples if I just leave some pens in your waiting room?

What kind of physician do you think I am?

Dr Jones, I know what kind of physician you are… we’re just haggling over the price.

The pharmaceutical industry spends billions of dollars each year on drug promotion. A common method of promotion is through drug detailing, in which an individual pharmaceutical representative meets with one or more physicians to discuss their products. These meetings may include travel, sporting or cultural events, conferences, or meals, and often involve gifts from the drug representative to the physician. Gifts may include pens, pads, clocks, watches, bags, calendars, golf balls, shotgun shells, mugs, books, or artwork. These meetings also typically involve the exchange of information verbally and through printed material about the drug. Although the mock dialogue presented above may overstate the problem with interactions between physicians and pharmaceutical representatives, there is genuine concern that these are ethically problematic relationships.

In this issue of the Journal Backer and colleagues1 provide evidence for a wide range of community family physician behaviors involving drug representatives, gifts from pharmaceutical companies, and use of medication samples. Interactions between drug representatives and physicians varied between and within the practices studied. A large number of the practices had formal methods for meeting with these representatives, and several scheduled patient appointment times to meet with them. Gifts varied from pens and candy to meals and tickets to a musical. Medication sample use varied between physicians, but, on average, samples were given in nearly 1 in 5 patient visits.

I contend that the relationship between the physician and the drug representative has more to do with changing physicians’ prescribing patterns than with providing good patient care. However, the language used in this article provides the subtle message that drug samples, gifts, meals, treats, and educational materials are beneficial, but I believe each of these particular benefits is loaded with problems.

Drug samples

The use of medication samples varied widely between and within practices in the study by Backer and colleagues. Although the authors describe physicians who distribute more samples as sensitive to the needs of their patients, they did not measure physician sensitivity or the needs of the patients or the community. The sample types that were distributed represent a wide range of treatments; antibiotics, anti-inflammatory drugs, and antihypertensives were among the most frequently dispensed samples. A quick review of the samples in an office I visited last week revealed only the newest and most expensive formulations of these medicines. There was no sulfamethoxazole-trimethoprim, amoxicillin, hydrochlorothiazide, or ibuprofen. There was plenty of cefuroxime, valsartan, and rofecoxib. Indiscriminant use of the newest antibiotics will certainly exacerbate the crisis of drug-resistant bacteria. Of particular concern is the distribution of samples for chronic illness. For example, a newly diagnosed hypertensive patient is started on amlodipine therapy because there is an “ample supply” in the drug cabinet. However, the evidence still recommends b-blockers and diuretics as first-line therapy for hypertension. A recent study found that despite the evidence and the recommendations of the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure3 the number of prescriptions for b-blockers and diuretics have dropped, while the number of prescriptions for calcium channel blockers have increased. Calcium channel blockers now represent 38% of antihypertensive medication prescriptions compared with 11% for b-blockers and 8% for diuretics.3

Are drug samples really the best method for providing medicine to those with low income? If samples are given according to what is in the closet, what happens to the hypertensive patient when the amlodipine samples run out? Does she have to buy more pills? Or does she change treatment every few months on the basis of what sample is in? For low-income patients there are better methods for obtaining necessary medicines. Many of the proven therapies are reasonably priced. A 1-month supply of hydrochlorothiazide is $7.92 and sulfamethoxazole-trimethoprim is $9 to $12 for a 2-week course, compared with amlodipine at $74 per month. For those physicians who want to use the newer medicines or brand names, nearly all the major drug companies have programs to supply medicine to low-income patients. These programs are indexed at www.phrma.org/patients/index.html.

 

 

The authors also found that little instruction was provided to patients who received samples; side effects and drug interactions were rarely discussed. Office personnel use of samples was observed, and in one office patients had unsupervised access to the storage closet. Personal use of drug samples has numerous medical and ethical concerns that have been fully outlined elsewhere.4 Patients having unsupervised access to samples is inappropriate and dangerous. Prescribing medications on the basis of convenience (ie, the drug on the top shelf of the sample cabinet) may not be the best medicine for the patient.

Gifts, meals, and treats

Chren and Landefeld5 found that physicians who ate more meals paid for by drug representatives were more likely to request new drugs be added to their hospital formulary. Orlowski and Wateska6 found that use of 2 intravenous drugs significantly increased at the hospital after a large number of the physicians attended an all-expense-paid trip to a medical conference sponsored by the pharmaceutical companies that manufactured the 2 drugs. Blake and Early7 found that although many patients did not disapprove of their physician receiving medical books or ballpoint pens, nearly half disapproved of physicians receiving meals from drug companies. Chren and colleagues8 also point out that physician gifts are ultimately paid for by the patient who must buy the medicine. At a time when so many physicians loudly decry for-profit medicine, it is surprising that so many are willing to profit from the pharmaceutical industry.

Educational materials

Are the education materials from drug representatives truly balanced and evidence based, or are they simply another type of promotional or advertising handout? Stryer and Bero9 found that 42% of the printed material distributed by drug representatives did not comply with Food and Drug Administration requirements, and 33% did not provide a balanced presentation of the benefits and risks. Ziegler and coworkers10 reported that more than 10% of the information provided by drug representatives was flatly inaccurate. And all this inaccurate information was favorable toward that particular medication. How does false information benefit the patient or the physician? Continuing medical education (CME) is a very specific term, and the American Medical Association and American Academy of Family Physicians have strict guidelines about how, when, and where prescribed CME can be obtained, and the extent to which pharmaceutical companies can offer CME. The type of informal meeting between the drug representative and the physician that the authors describe is not CME, and it should not be construed as taking the place of formal educational endeavors.

A problematic relationship

Backer and coworkers state that interactions between physicians and drug representatives represent a complex symbiosis. That symbiotic relationship is exactly the problem. In the physician-patient interaction it is the patient who should benefit. Yet, the complex relationship between drug representatives and physicians benefits the pharmaceutical company and the physician only; the patient gains nothing. Problems with interaction between the physician and the drug representative are also emblematic of the larger interaction of the pharmaceutical industry and medical science. Recent editorials have questioned the close nature of the involvement of academic medical centers, their physicians, residents, and medical scientists with the pharmaceutical industry that provides money for drug studies in addition to gifts, samples, and promotional handouts.11,12

We practice medicine in a difficult era. Physicians are assailed by insurance companies who want us to cut costs while providing more care, and by patients who hope insurance incentives or monetary arrangements will not cloud our professional judgment. Many patients still trust us to do the right thing, but their trust may be fading. We can not afford the perception that physicians can be bought for baseball tickets, lunch, and a few pens.

Dr Jones, would you use these Wompicillin drug samples if I take you to a baseball game in a luxury box catered by Alfredo’s?

Sure, I love drug samples. I’ve been wanting to try Wompicillin.

Dr Jones, would you use these drug samples if I bring lunch to your office?

Okay, as long as you bring enough lunch for the nurses.

Dr Jones, would you use these drug samples if I just leave some pens in your waiting room?

What kind of physician do you think I am?

Dr Jones, I know what kind of physician you are… we’re just haggling over the price.

The pharmaceutical industry spends billions of dollars each year on drug promotion. A common method of promotion is through drug detailing, in which an individual pharmaceutical representative meets with one or more physicians to discuss their products. These meetings may include travel, sporting or cultural events, conferences, or meals, and often involve gifts from the drug representative to the physician. Gifts may include pens, pads, clocks, watches, bags, calendars, golf balls, shotgun shells, mugs, books, or artwork. These meetings also typically involve the exchange of information verbally and through printed material about the drug. Although the mock dialogue presented above may overstate the problem with interactions between physicians and pharmaceutical representatives, there is genuine concern that these are ethically problematic relationships.

In this issue of the Journal Backer and colleagues1 provide evidence for a wide range of community family physician behaviors involving drug representatives, gifts from pharmaceutical companies, and use of medication samples. Interactions between drug representatives and physicians varied between and within the practices studied. A large number of the practices had formal methods for meeting with these representatives, and several scheduled patient appointment times to meet with them. Gifts varied from pens and candy to meals and tickets to a musical. Medication sample use varied between physicians, but, on average, samples were given in nearly 1 in 5 patient visits.

I contend that the relationship between the physician and the drug representative has more to do with changing physicians’ prescribing patterns than with providing good patient care. However, the language used in this article provides the subtle message that drug samples, gifts, meals, treats, and educational materials are beneficial, but I believe each of these particular benefits is loaded with problems.

Drug samples

The use of medication samples varied widely between and within practices in the study by Backer and colleagues. Although the authors describe physicians who distribute more samples as sensitive to the needs of their patients, they did not measure physician sensitivity or the needs of the patients or the community. The sample types that were distributed represent a wide range of treatments; antibiotics, anti-inflammatory drugs, and antihypertensives were among the most frequently dispensed samples. A quick review of the samples in an office I visited last week revealed only the newest and most expensive formulations of these medicines. There was no sulfamethoxazole-trimethoprim, amoxicillin, hydrochlorothiazide, or ibuprofen. There was plenty of cefuroxime, valsartan, and rofecoxib. Indiscriminant use of the newest antibiotics will certainly exacerbate the crisis of drug-resistant bacteria. Of particular concern is the distribution of samples for chronic illness. For example, a newly diagnosed hypertensive patient is started on amlodipine therapy because there is an “ample supply” in the drug cabinet. However, the evidence still recommends b-blockers and diuretics as first-line therapy for hypertension. A recent study found that despite the evidence and the recommendations of the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure3 the number of prescriptions for b-blockers and diuretics have dropped, while the number of prescriptions for calcium channel blockers have increased. Calcium channel blockers now represent 38% of antihypertensive medication prescriptions compared with 11% for b-blockers and 8% for diuretics.3

Are drug samples really the best method for providing medicine to those with low income? If samples are given according to what is in the closet, what happens to the hypertensive patient when the amlodipine samples run out? Does she have to buy more pills? Or does she change treatment every few months on the basis of what sample is in? For low-income patients there are better methods for obtaining necessary medicines. Many of the proven therapies are reasonably priced. A 1-month supply of hydrochlorothiazide is $7.92 and sulfamethoxazole-trimethoprim is $9 to $12 for a 2-week course, compared with amlodipine at $74 per month. For those physicians who want to use the newer medicines or brand names, nearly all the major drug companies have programs to supply medicine to low-income patients. These programs are indexed at www.phrma.org/patients/index.html.

 

 

The authors also found that little instruction was provided to patients who received samples; side effects and drug interactions were rarely discussed. Office personnel use of samples was observed, and in one office patients had unsupervised access to the storage closet. Personal use of drug samples has numerous medical and ethical concerns that have been fully outlined elsewhere.4 Patients having unsupervised access to samples is inappropriate and dangerous. Prescribing medications on the basis of convenience (ie, the drug on the top shelf of the sample cabinet) may not be the best medicine for the patient.

Gifts, meals, and treats

Chren and Landefeld5 found that physicians who ate more meals paid for by drug representatives were more likely to request new drugs be added to their hospital formulary. Orlowski and Wateska6 found that use of 2 intravenous drugs significantly increased at the hospital after a large number of the physicians attended an all-expense-paid trip to a medical conference sponsored by the pharmaceutical companies that manufactured the 2 drugs. Blake and Early7 found that although many patients did not disapprove of their physician receiving medical books or ballpoint pens, nearly half disapproved of physicians receiving meals from drug companies. Chren and colleagues8 also point out that physician gifts are ultimately paid for by the patient who must buy the medicine. At a time when so many physicians loudly decry for-profit medicine, it is surprising that so many are willing to profit from the pharmaceutical industry.

Educational materials

Are the education materials from drug representatives truly balanced and evidence based, or are they simply another type of promotional or advertising handout? Stryer and Bero9 found that 42% of the printed material distributed by drug representatives did not comply with Food and Drug Administration requirements, and 33% did not provide a balanced presentation of the benefits and risks. Ziegler and coworkers10 reported that more than 10% of the information provided by drug representatives was flatly inaccurate. And all this inaccurate information was favorable toward that particular medication. How does false information benefit the patient or the physician? Continuing medical education (CME) is a very specific term, and the American Medical Association and American Academy of Family Physicians have strict guidelines about how, when, and where prescribed CME can be obtained, and the extent to which pharmaceutical companies can offer CME. The type of informal meeting between the drug representative and the physician that the authors describe is not CME, and it should not be construed as taking the place of formal educational endeavors.

A problematic relationship

Backer and coworkers state that interactions between physicians and drug representatives represent a complex symbiosis. That symbiotic relationship is exactly the problem. In the physician-patient interaction it is the patient who should benefit. Yet, the complex relationship between drug representatives and physicians benefits the pharmaceutical company and the physician only; the patient gains nothing. Problems with interaction between the physician and the drug representative are also emblematic of the larger interaction of the pharmaceutical industry and medical science. Recent editorials have questioned the close nature of the involvement of academic medical centers, their physicians, residents, and medical scientists with the pharmaceutical industry that provides money for drug studies in addition to gifts, samples, and promotional handouts.11,12

We practice medicine in a difficult era. Physicians are assailed by insurance companies who want us to cut costs while providing more care, and by patients who hope insurance incentives or monetary arrangements will not cloud our professional judgment. Many patients still trust us to do the right thing, but their trust may be fading. We can not afford the perception that physicians can be bought for baseball tickets, lunch, and a few pens.

References

1. EL, Lebsack JA, Van Tonder RJN, Crabtree BF. The use of pharmaceutical representatives and medication samples in community-based family practices. J Fam Pract 2000;49:811-16.

2. Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Institutes of Health publication no. 98-4080; 1997.

3. D, Lopez J. Trends in antihypertensive drug use in the United States: do the JNC V recommendations affect prescribing? JAMA 1997;278:1745-48.

4. JM, McCabe J, Nicholas RA. Personal use of drug samples by physicians and office staff. JAMA 1997;278:141-43.

5. MM, Landefeld CS. Physicians’ behavior and their interaction with drug companies. JAMA 1994;271:684-89.

6. JP, Wateska L. The effects of pharmaceutical firm enticements on physician prescribing patterns: there’s no such thing as a free lunch. Chest 1992;102:270-73.

7. RL, Early EK. Patients’ attitudes about gifts to physicians from pharmaceutical companies. J Am Board Fam Pract 1995;8:457-64.

8. MM, Landefeld CS, Murray TH. Doctors, drug companies, and gifts. JAMA 1989;262:3448-51.

9. D, Bero LA. Characteristics of materials distributed by drug companies: an evaluation of appropriateness. J Gen Intern Med 1996;11:575-83.

10. MD, Lew P, Singer BC. The accuracy of drug information from pharmaceutical sales representatives. JAMA 1995;273:1296-98.

11. M. Is academic medicine for sale? N Eng J Med 2000;342:1516-18.

12. T. Uneasy alliance: clinical investigators and the pharmaceutical industry. N Eng J Med 2000;342:1539-44.

References

1. EL, Lebsack JA, Van Tonder RJN, Crabtree BF. The use of pharmaceutical representatives and medication samples in community-based family practices. J Fam Pract 2000;49:811-16.

2. Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Institutes of Health publication no. 98-4080; 1997.

3. D, Lopez J. Trends in antihypertensive drug use in the United States: do the JNC V recommendations affect prescribing? JAMA 1997;278:1745-48.

4. JM, McCabe J, Nicholas RA. Personal use of drug samples by physicians and office staff. JAMA 1997;278:141-43.

5. MM, Landefeld CS. Physicians’ behavior and their interaction with drug companies. JAMA 1994;271:684-89.

6. JP, Wateska L. The effects of pharmaceutical firm enticements on physician prescribing patterns: there’s no such thing as a free lunch. Chest 1992;102:270-73.

7. RL, Early EK. Patients’ attitudes about gifts to physicians from pharmaceutical companies. J Am Board Fam Pract 1995;8:457-64.

8. MM, Landefeld CS, Murray TH. Doctors, drug companies, and gifts. JAMA 1989;262:3448-51.

9. D, Bero LA. Characteristics of materials distributed by drug companies: an evaluation of appropriateness. J Gen Intern Med 1996;11:575-83.

10. MD, Lew P, Singer BC. The accuracy of drug information from pharmaceutical sales representatives. JAMA 1995;273:1296-98.

11. M. Is academic medicine for sale? N Eng J Med 2000;342:1516-18.

12. T. Uneasy alliance: clinical investigators and the pharmaceutical industry. N Eng J Med 2000;342:1539-44.

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