-- Back to Table of ContentsObjective. To determine if hospital-based clinical pharmacy services and pharmacy staffing continue to be associated with mortality rates.
Methods. A database was constructed from 1998 MedPAR, American Hospital Association’s Annual Survey of Hospitals, and National Clinical Pharmacy Services databases, consisting of data from 2,836,991 patients in 885 hospitals. Data from hospitals that had 14 clinical pharmacy services were compared with data from hospitals that did not have these services; levels of hospital pharmacist staffing were also compared. A multiple regression analysis, controlling for severity of illness, was used.
Results. Seven clinical pharmacy services were associated with reduced mortality rates: pharmacist-provided drug use evaluation (4491 reduced deaths, p=0.016), pharmacist-provided in-service education (10,660 reduced deaths, p=0.037), pharmacist-provided adverse drug reaction management (14,518 reduced deaths, p=0.012), pharmacist-provided drug protocol management (18,401 reduced deaths, p=0.017), pharmacist participation on the cardiopulmonary resuscitation team (12,880 reduced deaths, p=0.009), pharmacist participation on medical rounds (11,093 reduced deaths, p=0.021), and pharmacist-provided admission drug histories (3988 reduced deaths, p=0.001). Two staffing variables, number of pharmacy administrators/100 occupied beds (p=0.037) and number of clinical pharmacists/100 occupied beds (p=0.023), were also associated with reduced mortality rates.
Conclusion. The number of clinical pharmacy services and staffing variables associated with reduced mortality rates increased from two in 1989 to nine in 1998. The impact of clinical pharmacy on mortality rates mandates consideration of a core set of clinical pharmacy services to be offered in United States hospitals. These results have important implications for health care in general, as well as for our profession and discipline.
Key Words: clinical pharmacy services, pharmacy staffing, mortality rates, reduced deaths.
(Pharmacotherapy 2007;27(4):481-493)
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Study Objectives. To distinguish adverse events related to ribavirin therapy from those attributable to severe acute respiratory syndrome (SARS), and to determine the rate of potential ribavirin-related adverse events.
Design. Retrospective cohort study.
Setting. Hospitals in Toronto, Ontario, Canada.
Patients. A cohort of 306 patients with confirmed or probable SARS, 183 of whom received ribavirin and 123 of whom did not, between February 23, 2003, and July 1, 2003. Of the 183 treated patients, 155 (85%) received very high-dose ribavirin; the other 28 treated patients received lower-dose regimens.
Measurements and Main Results. Data on all patients with SARS admitted to hospitals in Toronto were abstracted from charts and electronic databases onto a standardized form by trained research nurses. Logistic regression was used to evaluate the association between ribavirin use and each adverse event (progressive anemia, hypomagnesemia, hypocalcemia, bradycardia, transaminitis, and hyperamylasemia) after adjusting for SARS-related prognostic factors and corticosteroid use. In the primary logistic regression analysis, ribavirin use was strongly associated with anemia (odds ratio [OR] 3.0, 99% confidence interval [CI] 1.5-6.1, p<0.0001), hypomag-nesemia (OR 21, 99% CI 5.8-73, p<0.0001), and bradycardia (OR 2.3, 99% CI 1.0-5.1, p=0.007). Hypocalcemia, transaminitis, and hyperamylasemia were not associated with ribavirin use. The risk of anemia, hypomag-nesemia, and bradycardia attributable to ribavirin use was 27%, 45%, and 17%, respectively.
Conclusions. High-dose ribavirin is associated with a high rate of adverse events. The use of high-dose ribavirin is appropriate only for the treatment of infectious diseases for which ribavirin has proven clinical efficacy, or in the context of a clinical trial. Ribavirin should not be used empirically for the treatment of viral syndromes of unknown origin.
Key Words: ribavirin, adverse events, severe acute respiratory syndrome, SARS, hemolytic anemia.
(Pharmacotherapy 2007;27(4):494-503)
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Study Objectives. To characterize the immunomodulatory response in a pressure overload model of heart failure, and to further validate this animal model of human heart failure.
Design. Randomized, controlled, animal study.
Setting. Large university research facility.
Animals. Twenty-seven, male, Sprague-Dawley rats.
Intervention. The rats underwent either aortic constriction or a sham procedure.
Measurements and Main Results. Six months after the surgical procedure, echocardiographic measurements were obtained, the animals were sacrificed, and plasma samples were taken to measure concentrations of biomarkers. As six (40%) of the 15 rats in the aortic-constriction group died before the 6 months, only nine rats from this group underwent immunomodulatory evaluation. Compared with the sham procedure, aortic constriction increased the left ventricle:body weight ratio in the rats (p=0.0016) It also decreased the velocity of circumferential shortening (p=0.08) and increased myocardial expression of atrial natriuretic factor, b-myosin heavy chain, and fibronectin (p<0.05). Concentrations of the proinflammatory mediator interleukin (IL)-1b and the counterregulatory mediator IL-10 also significantly increased (p<0.04) in the group that underwent aortic constriction compared with the group that underwent the sham procedure. Nonsignificant increases (mean change ~50-180%) were also observed for IL-2, IL-6, and leptin concentrations.
Conclusions. In this classic animal model of heart failure, a systemic immunomodulatory response was evaluated after 6 months of pressure overload resulting in myocardial decompensation and, in some cases, mortality. The findings are similar to the immunomodulatory response that may be observed in human heart failure. These novel results further define this model of heart failure and suggest another aspect of its relevance to human heart failure with regard to pressure overload and the immuno-modulatory response.
Key Words: aortic constriction, heart failure, cytokines, chemokines, interleukin, leptin, animal study.
(Pharmacotherapy 2007;27(4):504-509)
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Study Objective. To compare outcomes of treating alcohol withdrawal delirium (AWD) with a symptom-driven benzodiazepine protocol versus nonprotocol benzodiazepine infusions in the intensive care unit (ICU).
Design. Retrospective observational study of a quality improvement project.
Setting. Medical intensive care unit at a Veterans Affairs medical center.
Patients. Thirty-six patients who had 40 ICU admissions for AWD between January 1, 1994, and May 31, 2003. Sixteen episodes (15 patients [historical controls]) occurred before implementation of the symptom-driven protocol in 1998, and 24 episodes (21 patients) occurred after implementation.
Measurements and Main Results. Outcomes evaluated were time to reach symptom control, total dose of benzodiazepine, amount of time receiving continuous benzodiazepine infusion, length of ICU and hospital stay, polypharmacy (use of multiple benzodiazepines), and complications of treatment. The historical control group was treated according to physician preference, which consisted of continuous-infusion midazolam without a protocol. The symptom-driven protocol used lorazepam administered initially as intermittent intravenous doses, progressing to a continuous intravenous infusion according to a locally developed symptom scale. The mean ± SD values for the outcomes in the historical control group versus the protocol group were as follows: time to control symptoms 19.4 ± 9.7 versus 7.7 ± 4.9 hours (p=0.002), cumulative benzodiazepine dose in lorazepam equivalents 1677 ± 937 versus 1044 ± 534 mg (p=0.014), time receiving benzodiazepine continuous infusion 122.1 ± 64.4 versus 52.0 ± 35.1 hours (p=0.001), length of stay in the ICU 7.7 ± 6.3 versus 5.6 ± 1.7 days (p=0.21), and length of hospital stay 15.3 ± 8.9 versus 11.2 ± 3.4 days (p=0.43).
Conclusions. Use of a symptom-driven protocol was associated with significantly decreased time to symptom control, amount of sedative required, and time spent receiving benzodiazepine infusion compared with historical controls. The use of the protocol is effective but requires close monitoring to ensure protocol compliance and to avoid potential propylene glycol toxicity.
Key Words: alcohol withdrawal delirium, AWD, alcohol withdrawal syndrome, treatment protocol, benzodiazepine, lorazepam, midazolam, intensive care.
(Pharmacotherapy 2007;27(4):510-518)
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Study Objective. To describe the dose-concentration relationship of a continuous intravenous infusion of valproic acid (VPA) in pediatric patients when a dosing protocol is used.
Design. Retrospective and concurrent chart review.
Setting. Tertiary care, 473-bed, academic medical center with a 120-bed, dedicated children’s hospital.
Patients. Twenty-six pediatric patients (< 18 yrs old) who received VPA according to the protocol for continuous intravenous infusions between January 1, 2004, and March 31, 2006, identified by using a pharmacy order-entry system.
Measurements and Main Results. Patient demographics, VPA treatment regimens, clinical responses, and safety data were recorded and analyzed. Median patient age was 8.5 years (range 1.4-16 yrs). Approximately two thirds received VPA for seizures, and one third for migraines. Patients were given a mean ± SD VPA loading dose of 28.5 ± 5.2 mg/kg followed by a continuous infusion rate of 1 ± 0.2 mg/kg/hour. Mean ± SD serum concentration measured 4.5 ± 1.6 hours after the loading dose was 83.3 ± 22.8 µg/ml. Steady-state concentration at 23.3 ± 3.0 hours after the start of the continuous infusion was 80.0 ± 26.0 µg/ml. Postload and steady-state serum concentrations were within the target concentration of 50-100 µg/ml in 77% and 69% of patients, respectively. On further analysis, when the target range was expanded to 50-125 µg/ml (125 µg/ml was deemed acceptable if no adverse effects were noted), 89% and 92% of patients, respectively, had postload and steady-state VPA serum concentrations within this range. The response rate was excellent, with nearly 85% of patients achieving a complete or partial response to therapy. Adverse effects were generally mild and uncommon.
Conclusions. The continuous-infusion protocol permitted rapid intravenous loading of VPA in pediatric patients while minimizing adverse events and achieving concentrations in the upper region of the therapeutic range.
Key Words: valproic acid, VPA, continuous intravenous infusion, migraine, childhood epilepsy.
(Pharmacotherapy 2007;27(4):519-525)
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Study Objective. To examine the class effect of angiotensin II receptor blockers (ARBs) on mortality in patients with heart failure who were aged 65 years or older.
Design. Retrospective population-based study.
Data Source. Administrative database that stores information on hospital discharge summaries for the Canadian provinces of Quebec, Ontario, and British Columbia.
Patients. A total of 6876 patients aged 65 years or older who were discharged with a primary diagnosis of heart failure between January 1, 1998, and March 31, 2003, and who filled at least one prescription for an ARB within 90 days of discharge.
Measurements and Main Results. Times to all-cause death in patients receiving individual ARBs were compared. Models were adjusted for demographic, clinical, physician, and hospital characteristics; models were also adjusted for dosage categories, which were represented by time-dependent variables. The cohort of 6876 patients had a mean ± SD age of 78 ± 7 years, and most (62%) were women. Losartan was the most frequently prescribed ARB (61%), followed by irbesartan (14%), valsartan (13%), candesartan (10%), and telmisartan (2%). Irbesartan, valsartan, and candesartan were associated with better survival rates than losartan (adjusted hazard ratios [HRs] and 95% confidence intervals [CIs] 0.65 [0.53-0.79], 0.63 [0.51-0.79], and 0.71 [0.57-0.90], respectively). No difference was noted in mortality in patients prescribed telmisartan compared with those receiving losartan (HR 0.92 [95% CI 0.55-1.54]).
Conclusions. Elderly patients with heart failure who were prescribed losartan had worse survival rates compared with those prescribed other commonly used ARBs. The absence of a class effect for ARBs is consistent with data showing pharmacologic differences among the drugs.
Key Words: angiotensin II receptor blockers, ARBs, class effect, heart failure, mortality.
(Pharmacotherapy 2007;27(4):526-534)
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Study Objective. To compare the effectiveness of darbepoetin alfa with epoetin alfa (recombinant human erythropoietin [rHuEPO]) for achieving transfusion independence and increasing hemoglobin concentrations in critically ill patients.
Design. Retrospective, descriptive study.
Setting. Level I trauma center intensive care units.
Patients. Seventy-two patients who spent at least 3 days in the cardio-thoracic, medical, or surgery-trauma intensive care units and received at least one weekly dose of rHuEPO 40,000 units (33 patients) or darbepoetin alfa 100 µg (39 patients).
Measurements and Main Results. Number of rHuEPO and darbepoetin alfa doses, hemoglobin concentrations, and cumulative number of transfusions were recorded for up to 28 days after the first dose was given, and the data were statistically analyzed. Beginning a median of 10 days after the patients were admitted to the intensive care unit, they received a median of 3.5 doses of darbepoetin alfa or 4 doses of rHuEPO. Mean hemoglobin concentrations at which treatment with darbepoetin alfa and rHuEPO were started were 8 and 8.2 g/dl, respectively (p=0.41). Transfusion independence was achieved in 44% of patients in the darbepoetin alfa group compared with 36% of patients in the rHuEPO group (p=0.63). Patients in both groups received a mean of 2.7 units of packed red blood cells during the 28-day study period. The mean change in hemoglobin levels from baseline over time did not significantly differ between groups (p=0.75).
Conclusions. Patients receiving darbepoetin alfa 100 µg/week and those receiving rHuEPO 40,000 units/week for anemia of critical illness achieved similar rates of transfusion independence and increases in hemoglobin concentrations from baseline at 28 days. Compared with previously published studies, erythropoietic agents were administered late in the course of critical illness in response to low hemoglobin concentrations.
Key Words: anemia, critical illness, darbepoetin alfa, epoetin alfa, recombinant human erythropoietin, rHuEPO, transfusion, transfusion independence, hemoglobin.
(Pharmacotherapy 2007;27(4):535-541)
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Drug-induced anaphylaxis remains a relatively infrequent event. However, penicillin and associated b-lactam antibiotics remain a primary cause of anaphylaxis. Penicillin allergies are undoubtedly overreported, and patients with suspected penicillin allergy can be treated with antibiotic alternatives. Penicillin allergy skin testing is a simple and effective way to identify true penicillin allergy. Skin testing involves testing for both major and minor determinants and should be conducted in a facility with available life-support equipment. The commercial major determinant product, benzylpenicilloyl-polylysine, was removed from the market in 2004; this action compromised the ability of clinicians to evaluate a patient’s likely response to penicillin therapy. Alternatives to skin testing include laboratory synthesis of major determinants, use of the radioallergosorbent test (RAST), or a combination of RAST and minor determinant skin testing. Patients with suspected penicillin allergy can undergo desensitization if they require penicillin therapy. The planned return of a commercial major determinant will hopefully resolve this issue.
Key Words: PrePen, benzylpenicilloyl-polylysine, penicillin allergy, skin test, radioallergosorbent test, RAST.
(Pharmacotherapy 2007;27(4):542-545)
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Pharmacotherapy for depression is often necessary during pregnancy. The information available about use of the newer antidepressants in pregnant women is limited by trial design and lack of long-term follow-up of exposed infants. Selective serotonin reuptake inhibitors (SSRIs) are not generally thought to be major teratogens. Some recent studies, however, have suggested that paroxetine may be associated with a small increase in risk of congenital abnormalities, particularly cardiac defects. Data on the effect of SSRIs on the incidence of preterm birth, spontaneous abortion, and fetal death are conflicting. Third-trimester exposure to newer antidepressants, including SSRIs and serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine), has been associated with a poor neonatal adaptation syndrome. In addition, SSRI use may be associated with an increased risk of persistent pulmonary hypertension of the newborn. Preliminary evidence suggests that SSRI exposure in utero does not have significant long-term effects on cognition or behavior. Based on limited information, mirtazapine, bupropion, and venlafaxine do not appear to be major teratogens. Little or no information is available on duloxetine.
Key Words: pregnancy, antidepressants, safety, selective serotonin reuptake inhibitors, SSRI, venlafaxine, duloxetine, mirtazapine, bupropion.
(Pharmacotherapy 2007;27(4):546-552)
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Antiplatelet therapy is a cornerstone in the management of acute coronary syndromes. Clopidogrel produces irreversible inhibition of the platelet adenosine diphosphate receptor, thereby attenuating activation and aggregation of platelets. Clopidogrel has been shown to prevent stent thrombosis in patients undergoing percutaneous coronary intervention (PCI) and reduces major adverse cardiovascular events in patients with unstable angina or non-ST-segment elevation myocardial infarction (non-STEMI). Recent studies have left clinicians with many questions regarding the role and dosing regimens of clopidgrel in STEMI, PCI, and primary or secondary prevention. Based on an analysis of the data, clopidogrel should be given in addition to aspirin and fibrinolytic therapy to patients with STEMI. In patients undergoing PCI, a loading dose of clopidogrel 600 mg should be given if the procedure needs to be performed within 15 hours of initial presentation. If PCI can be delayed for 15 hours or more, a loading dose of 300 mg can be used. Evidence also suggests that clopidogrel should not be prescribed for primary prevention in high-risk patients.
Key Words: clopidogrel, acute coronary syndromes, ACS, antiplatelet therapy, percutaneous coronary intervention, PCI, ST-segment elevation myocardial infarction, STEMI, non-ST-segment elevation myocardial infarction, non-STEMI, unstable angina.
(Pharmacotherapy 2007;27(4):553-563)
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Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse effect that typically manifests several days after the start of heparin therapy, although both rapid- and delayed-onset HIT have been described. Its most serious complication is thrombosis. Although not all patients develop thrombosis, it can be life threatening. The risk of developing HIT is related to many factors, including the type of heparin product administered, route of administration, duration of therapy, patient population, and previous exposure to heparin. The diagnosis of HIT is typically based on clinical presentation, exposure to heparin, and presence of thrombocytopenia with or without thrombosis. Antigen and activation laboratory assays are available to support the diagnosis of HIT. However, because of the limited sensitivity and specificity of these assays, bedside probability scales for HIT were developed. When HIT is suspected, prompt cessation of all heparin therapy is necessary, along with initiation of alternative anticoagulant therapy. Two direct thrombin inhibitors -- argatroban and lepirudin -- are approved for the management of HIT in the United States, and bivalirudin is approved for use in patients with HIT who are undergoing percutaneous coronary intervention. Other agents, although not approved to manage HIT, have also been used; however, their role in therapy requires further evaluation. A comprehensive HIT management strategy involves the evaluation of numerous factors. Many patients, including those undergoing coronary artery bypass surgery, those with acute coronary syndromes, those with hepatic or renal insufficiency, and children, require special attention. Clinicians must become familiar with the available information on this serious adverse effect and its treatment so that optimum patient management strategies may be formulated.
Key Words: heparin-induced thrombocytopenia, HIT, argatroban, lepirudin, danaparoid, bivalirudin, fondaparinux, warfarin, unfractionated heparin, UFH, low-molecular-weight heparin, LMWH.
(Pharmacotherapy 2007;27(4):564-587)
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Delirium is common in acutely ill patients and can result in substantial morbidity if left untreated. Atypical antipsychotics have been postulated to be safer and more effective than haloperidol for treatment of this condition. To evaluate the role of atypical antipsychotics versus haloperidol for treatment of delirium in hospitalized acutely ill adults, we searched MEDLINE (1977-September 2006) and International Pharmaceutical Abstracts (1997-September 2006) for English-language publications of clinical trials that compared atypical antipsychotics and haloperidol. Four comparative studies were identified: one double-blind, randomized study (risperidone vs haloperidol), one single-blind, randomized study (olanzapine vs haloperidol), and two retrospective studies (olanzapine vs haloperidol and quetiapine vs haloperidol). These studies demonstrated that atypical antipsychotics are as efficacious as haloperidol. In addition, they appear to be associated with a lower frequency of extrapyramidal effects, and thus are safer than haloperidol. However, these conclusions are based on a limited number of studies; larger comparative trials are needed to elucidate the role of atypical antipsychotics for treating delirium in this population.
Key Words: critical illness, delirium, atypical antipsychotic, haloperidol, quetiapine, risperidone, olanzapine, intensive care unit, ICU.
(Pharmacotherapy 2007;27(4):588-594)
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Diabetes mellitus is the sixth leading cause of death in the United States, and most patients with the disease have type 2 diabetes. The effectiveness of cinnamon supplementation in patients with type 2 diabetes has received a great deal of media attention after a study was published in 2003. Although the efficacy of cinnamon in patients with diabetes has not been established, many patients seek other therapies and supplement their prescribed pharmacologic therapy with cinnamon. We conducted a literature search, limited to English-language human studies, using MEDLINE (1966-August 2006), EMBASE (1980-August 2006), International Pharmaceutical Abstracts (1970-August 2006), and Iowa Drug Information Service (1966-August 2006). References from articles and clinical trials were reviewed for additional sources; no abstracts were reviewed. We found two prospective, randomized, double-blind, placebo-controlled, peer-reviewed clinical trials and one prospective, placebo-controlled, peer-reviewed clinical trial that evaluated the efficacy of cinnamon supplementation in patients with type 2 diabetes; a total of 164 patients were involved in these trials. Two of the studies reported modest improvements in lowering blood glucose levels with cinnamon supplementation in small patient samples. One trial showed no significant difference between cinnamon and placebo in lowering blood glucose levels. Overall, cinnamon was well tolerated. These data suggest that cinnamon has a possible modest effect in lowering plasma glucose levels in patients with poorly controlled type 2 diabetes. However, clinicians are strongly urged to refrain from recommending cinnamon supplementation in place of the proven standard of care, which includes lifestyle modifications, oral antidiabetic agents, and insulin therapy.
Key Words: cinnamon, diabetes mellitus, type 2, dietary supplements, glucose.
(Pharmacotherapy 2007;27(4):595-599)
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A 68-year-old woman developed eosinophilic pleural effusion and systemic eosinophilia 2 months after starting antihypertensive therapy with diltiazem. Several drugs are known to cause this disorder; however, the only other drug the patient had been taking was clonidine, which she had taken for the past 3-4 years. She was evaluated for all other possible causes of eosinophilia and eosinophilic pleural effusion, including malignancy, infection, and autoimmune disorders. Her symptoms resolved after diltiazem was discontinued, and no recurrence was noted on follow-up. To our knowledge, this is the first case report of eosinophilic pleural effusion caused by diltiazem. According to the Naranjo adverse drug reaction probability scale, a probable relationship existed between diltiazem and the patient’s eosinophilia and pleural effusion. Although numerous drugs have been associated with eosinophilia and eosinophilic pleural effusion, the spectrum may actually be wider than is commonly thought and may include such unrecognized agents as diltiazem.
Key Words: eosinophilia, diltiazem, pleural effusion.
(Pharmacotherapy 2007;27(4):600-602)
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Two men, aged 83 and 78 years, who received stable therapy with simvastatin 80 mg/day were hospitalized 1-2 weeks after completion of short-term treatment with erythromycin and clarithromycin, respectively. Both patients were admitted with myalgia, muscle weakness, functional disability (inability to raise arms and legs), and serum creatine kinase levels more than 60 times the upper limit of normal (ULN). Substantial elevations in aspartate aminotransferase (> 30 times the ULN) and alanine aminotransferase (> 7 times the ULN) levels were also observed. Rhabdomyolysis was diagnosed in both patients. Both recovered, but the combined events resulted in almost 40 days of hospitalization, the cost of which is considerable. According to the Naranjo adverse drug reaction probability scale, the likelihood that the rhabdomyolysis was secondary to a simvastatin-macrolide interaction was probable. Four cases of rhabdomyolysis after therapy with combined simvastatin and clarithromycin have been reported previously, but this is apparently the first report of rhabdomyolysis after coadministration of erythromycin. The interacting mechanism likely was inhibited cytochrome P450 (CYP) 3A4 metabolism and possibly P-glycoprotein transport of simvastatin as well. Previous reports of simvastatin-clarithromycin-related events involved additional drugs that inhibited CYP3A4 and P-glycoprotein. However, this was not the situation with our two patients. To prevent future events, it is crucial that clinicians recognize the interaction risk associated with concurrent use of simvastatin and clarithromycin or erythromycin. The risk could be managed by temporary interruption of simvastatin treatment or administration of a noninteracting antimicrobial agent.
Key Words: simvastatin, erythromycin, clarithromycin, rhabdomyolysis, drug interactions.
(Pharmacotherapy 2007;27(4):603-607)
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A 28-year-old man with schizophrenia intentionally ingested a lethal dose of acetaminophen and an unknown quantity of ibuprofen. He arrived at the hospital with acute renal and fulminant liver failure complicated by rhabdomyolysis. His creatine kinase level was 20,306 U/L on admission, which increased to 245,595 U/L by hospital day 2, and subsequently decreased to 339 U/L by day 16. The patient underwent liver transplantation on day 3; necrotic bowel was found during surgery. Rhabdomyolysis associated with acetaminophen overdose has been described only in a few case reports, but rarely in association with acetaminophen taken alone. The literature does not provide a clear association between acetaminophen and rhabdomyolysis because of other possible traumatic and nontraumatic causes. In this case, the Naranjo adverse drug reaction probability scale indicated a probable adverse reaction of rhabdomyolysis associated with acetaminophen overdose. In addition, nonsteroidal antiinflammatory agents (NSAIDs) are well known to be ulcerogenic in the upper gastrointestinal tract, but potential effects on the lower tract are less well known. Only a few NSAID-induced cases of ischemic colitis have been reported. Several mechanisms of action have been proposed, such as direct mucosal damage and inhibition of intestinal prostaglandin production. In this patient, the Naranjo scale indicated a probable adverse reaction of ischemic colitis associated with ibuprofen overdose. Patients who have taken an acetaminophen overdose should be assessed for rhabdomyolysis as a possible complication. In addition, an evaluation of ibuprofen-induced bowel necrosis in these patients may be warranted.
Key Words: rhabdomyolysis, necrotic bowel, acetaminophen, ibuprofen.
(Pharmacotherapy 2007;27(4):608-612)
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A 67-year-old woman with iron deficiency anemia required parenteral iron therapy and was treated with intravenous ferric gluconate. She tolerated the first dose, but after the second dose, she developed a tingling feeling all over her body, along with swelling in her hands and feet, and a rash with hives over most of her body. It was thought that she had likely experienced a hyper-sensitivity reaction to ferric gluconate. The decision was made to continue therapy; however, two modifications were made. The patient was given dexamethasone, diphenhydramine, and ibuprofen 1 hour before administering the third dose, and the infusion time was prolonged by 1 hour. Approximately 45 minutes after the infusion was completed, the patient developed hives on her arms and legs. At the patient’s next clinic visit, it was decided that continuation of parenteral iron repletion was necessary, and the decision was made to attempt a challenge with iron sucrose. The patient was given dexamethasone 8 mg to be taken the night before and the morning of treatment. She successfully completed the iron repletion therapy with iron sucrose. Three parenteral iron products are available in the United States: iron dextran, sodium ferric gluconate complex, and iron sucrose. Iron dextran, the oldest of these products, carries the highest risk for hypersensitivity reactions. Available data suggest that either iron sucrose or ferric gluconate can be safely administered to patients with known hypersensitivity to iron dextran. Our patient’s experience implies that it may be possible to safely administer iron sucrose to a patient with hypersensitivity to ferric gluconate. This finding has clinical implications and warrants confirmation in a larger population.
Key Words: iron dextran, ferric gluconate, iron sucrose, hypersensitivity reaction.
(Pharmacotherapy 2007;27(4):613-615)
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Cyclophosphamide is a chemotherapeutic agent with the potential to cause pulmonary toxicity, most commonly in the form of diffuse alveolar damage. Cyclophosphamide-induced pulmonary toxicity is extremely rare and often difficult to recognize because of presence of confounding factors, including use of other cytotoxic drugs, radiation pneumonitis, oxygen toxicity, pulmonary infections, and malignancies. The lung toxicity caused by cyclophosphamide is accelerated when cyclophosphamide is combined with amiodarone, an antiarrhythmic agent also capable of lung toxicity. We describe a patient with non-Hodgkin’s lymphoma who developed fatal pulmonary toxicity after a single dose of cyclophosphamide in the setting of long-term amiodarone use.
Key Words: cyclophosphamide, drug toxicity, amiodarone.
(Pharmacotherapy 2007;27(4):616-618)
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