Annals of Pharmacotherapy

Rublein, John C; Eron, Joseph J; Butts, John D; Raasch, Ralph H

doi: 10.1345/aph.18260pmid: 10492487

OBJECTIVE:A retrospective study was performed to determine whether twice-daily ritonavir 400 mg plus twice-daily saquinavir 400 mg (ritonavir 400/saquinavir 400) was better tolerated than ritonavir 600 mg twice daily (ritonavir 600). A secondary objective was to determine whether the rate of discontinuation due to therapeutic failure differed between the two ritonavir regimens.DESIGN:The study was a retrospective chart review. Data collected included ritonavir dose; length of ritonavir therapy; reason for discontinuation; HIV-1 RNA prior to and at discontinuation of ritonavir therapy; CD4+ count; and antiretroviral therapy prior to, concomitant with, and initiated after ritonavir therapy.SETTING:Patient charts were reviewed in a university teaching hospital clinic.PATIENTS:Patients were identified through a search of the pharmacy database from December 18, 1995, to December 18, 1997. Patients were >18 years old, but not restricted by gender or race.MAIN OUTCOME MEASURES:The main outcome measures were frequency of discontinuation of ritonavir due to intolerance or due to lack of therapeutic efficacy.RESULTS:The search identified 116 patients, including 57 patients taking ritonavir 400/saquinavir 400 and 54 patients taking ritonavir 600. Five patients on other ritonavir regimens were excluded. Significantly fewer patients receiving ritonavir 400/saquinavir 400 (14%) discontinued ritonavir due to intolerance compared with ritonavir 600 (37%; p = 0.002). Discontinuations due to therapeutic failure were not significantly different: 8.8% for ritonavir 400/saquinavir 400 and 7.4% for ritonavir 600, despite the fact that ritonavir/saquinavir therapy followed another protease inhibitor in 41 patients (73.2%) compared with 12 patients (24.5%) for ritonavir 600 (p = 0.001).CONCLUSIONS:Ritonavir 400/saquinavir 400 is better tolerated than ritonavir 600.

Williamson, John C; Volles, David F; Lynch, PL Mark; Rogers, P David; Haverstick, Doris M

doi: 10.1345/aph.18336pmid: 10492488

OBJECTIVE:To determine the stability of cefepime in peritoneal dialysis solution.DESIGN:Cefepime HCl was added to premade bags of Delflex peritoneal dialysis solution with 1.5% dextrose to produce a cefepime concentration of approximately 100 μg/mL. Peritoneal dialysis solution bags were stored at 4, 25, and 37 °C to simulate refrigeration, room temperature, and body temperature, respectively. Samples were drawn at scheduled times up to 336, 168, and 48 hours, respectively, after the addition of cefepime HCl. Cefepime concentrations were measured by HPLC.SETTING:This study was performed at a university-affiliated tertiary care hospital.OUTCOME MEASURE:If the mean concentration of the samples at a given time and condition was >90% of the initial concentration, cefepime was considered stable at that time and condition.RESULTS:The mean HPLC results for samples drawn at each time and condition were all >90%.CONCLUSIONS:Cefepime is stable in peritoneal dialysis solution with dextrose 1.5% for 14 days refrigerated, seven days at room temperature, and 48 hours at 37 °C.

Tsuyuki, Ross T; Johnson, Jeffrey A; Teo, Koon K; Ackman, Margaret L; Biggs, Rosemarie S; Cave, Andrew; Chang, Wei-Ching; Dzavik, Vladimir; Farris, Karen B; Galvin, Donna; Semchuk, William; Simpson, Scot H; Taylor, Jeff G

Young, Melissa D; Stilling, William J; Munger, Mark A

doi: 10.1345/aph.18467pmid: 10492490

OBJECTIVE:This 10-year follow-up study of previously published surveys of pharmacy practice acts examines 50 state and the District of Columbia pharmacy practice acts to assess the range of statutory definitions and determine the direction and magnitude of statutory changes since 1988.DATA SOURCES:State codes for 50 states and the District of Columbia, with attention focused on the pharmacy practice acts; Puerto Rico and the Virgin Islands were excluded.DATA EXTRACTION:The focus on each statute was the statutory definition of the “practice of pharmacy.”DATA SYNTHESIS:Comparing 1998 with 1988, codification of interpreting and evaluating prescriptions increased 22% (1998; 39/47, four states contain no definition of the practice of pharmacy), compounding 8% (47/47), consultation 19% (41/47), dispensing 2.5% (47/47), drug administration threefold (24/47), drug product selection twofold (45/47), drug utilization review 70% (35/47), patient assessment 6.5-fold (6/47), pharmacokinetic services threefold (3/47), pharmacist prescribing 4.6-fold (15/47), and participation in drug research 10.5-fold (10/47).CONCLUSIONS:Since 1988, state pharmacy practice acts have increased the codification of pharmaceutical care services as integral pharmacy functions. Although substantial progress has been made over the past decade, a number of states have not incorporated definitions of pharmaceutical care functions into their state statutes. Enactment of the National Association Boards of Pharmacy Model State Pharmacy Act is one way for pharmacists' practice to expand with the evolution of the practice of pharmacy.

Brooks, Joseph C

doi: 10.1345/aph.18341pmid: 10492491

OBJECTIVE:To report the case of a rare, potentially preventable, immediate noncardiogenic pulmonary edema reaction to the rapid administration of protamine during coronary artery bypass graft (CABG) surgery.CASE SUMMARY:A 74-year-old white man was administered a 250-mg bolus of protamine sulfate toward the end of CABG surgery to reverse the heparin anticoagulation. Immediately following the administration of protamine, oxygen saturation declined, pink frothy sputum was suctioned from the trachea, and 1500 mL of serous fluid was removed from the airway. The patient was stabilized, but the surgeons were unable to close his chest because of the profound edema. Chest closure occurred on hospital day 6, with discharge from the intensive care unit on hospital day 28.DISCUSSION:Noncardiogenic pulmonary edema is a rare adverse event that occurs in 0.2% of cardiopulmonary bypass patients, with mortality rates approaching 30%. Complement activation or direct pharmacologic release of histamine by high concentrations of protamine is the suspected cause. High concentrations of protamine in the lungs may directly release histamine, with significant vasodilating effects.CONCLUSIONS:Immediate reversal of heparin anticoagulation with protamine is necessary to control bleeding; however, rapid protamine injection can be associated with life-threatening pulmonary edema. Slower, cautious administration and accurate calculation of protamine doses may prevent such an event.

Yolles, Jennifer C; Armenta, Wendy A; Alao, Adekola O

doi: 10.1345/aph.18418pmid: 10492492

OBJECTIVE:To describe the first reported case of serum sickness induced by exposure to bupropion.CASE SUMMARY:Bupropion was administered to a 45-year-old white man being treated for depression with psychosis. Within 24 hours after his first dose of bupropion, the patient became delirious and then developed fever, myalgia, arthralgia, and a rash. Bupropion was discontinued after the second dose. With supportive measures, symptoms remitted over two weeks.DISCUSSION:A thorough search for other etiologies of the patient's symptoms was unrevealing, and a clinical diagnosis of serum sickness was made. Given the temporal association between the illness and the introduction of bupropion, this was felt to be the causal agent. No previous reports of serum sickness induced by bupropion were found in the literature.CONCLUSIONS:The previously unreported adverse drug reaction of serum sickness associated with the use of bupropion is demonstrated by this case, based on the temporal relationship and the results of stopping the drug, in light of no other identifiable etiology.

Rivera, José O

doi: 10.1345/aph.18350pmid: 10492493

OBJECTIVE:To report a case of angioedema associated with losartan administration.CASE SUMMARY:A 45-year-old white man with a history of hypertension and gout was treated with losartan/hydrochlorothiazide, allopurinol, and colchicine. The patient experienced two episodes of angioedema within a 10-hour period. On both occasions the symptoms resolved after treatment.DISCUSSION:Angiotensin-converting enzyme (ACE) inhibitors are associated with a relatively high incidence of angioedema. The incidence of angioedema secondary to losartan, an angiotensin II receptor antagonist, is unknown. The patient reported in this case differs significantly from the two cases reported in the literature because he had normal renal function, no previous exposure to ACE inhibitors, the reaction was of late onset, and the symptoms recurred.CONCLUSIONS:This case suggests that losartan can induce late-onset angioedema in patients with normal renal function and that the reaction can recur after initial resolution of the symptoms.

Cha, Yoon Ju; Pearson, Vincent Earl

doi: 10.1345/aph.18396pmid: 10492494

OBJECTIVE:To report a case of angioedema associated with the angiotensin II receptor antagonist losartan.CASE SUMMARY:A 62-year-old African-American woman was admitted to the hospital for acute renal failure and uncontrolled hypertension. After attempting blood pressure control with three different agents, captopril was combined with metoprolol. The patient noted swelling of the lips combined with shortness of breath after four days of captopril. Losartan was substituted for captopril, which then produced similar swelling of the lips (without shortness of breath) after only one dose. These symptoms resolved after discontinuation of losartan and administration of antihistamines.DISCUSSION:Losartan, like other angiotensin II receptor antagonists, blocks the action of angiotensin II at the receptor level. Five published case reports involved patients with a prior history of intolerance to the angiotensin-converting enzyme inhibitors. Two published case reports of similar reactions also occurred in patients with renal compromise. The mechanism for this reaction from losartan is not known, but may not be due to bradykinin excess.CONCLUSIONS:Clinicians should be aware that angiotensin receptor antagonists may not be safe alternatives in patients who have a history of angioedema secondary to the angiotensin-converting enzyme inhibitors.

Zeolla, Mario M; Carson, John J

doi: 10.1345/aph.18435pmid: 10492495

OBJECTIVE:To report a case of successful clopidogrel use in a patient who developed suspected ticlopidine-induced hepatotoxicity during therapy for a cerebrovascular accident.CASE REPORT:A 79-year-old white woman with a history of hypertension, type 2 diabetes, Alzheimer disease, and coronary artery disease started receiving ticlopidine 250 mg twice daily three days after hospital admission for a cerebrovascular accident. Medications prior to admission included quinapril, furosemide, insulin, atorvastatin, conjugated estrogen, medroxyprogesterone, donepezil, and vitamin E. The estrogen, medroxyprogesterone, and donepezil were discontinued on admission. Laboratory tests on admission revealed that total bilirubin, alkaline phosphatase, and aspartate aminotransferase (AST) were within normal limits. On day 39 of hospitalization, laboratory tests showed marked increases in alkaline phosphatase, AST, alanine aminotransferase, γ-glutamyl-transferase, and 5' nucleotidase. Physical examination revealed no signs of jaundice or hepatomegaly, and laboratory tests for viral hepatitis were negative. A presumptive diagnosis of ticlopidine-induced hepatotoxicity was made and ticlopidine was discontinued. The following day, clopidogrel 75 mg/d was initiated. Liver function tests returned to baseline over the following four months with ongoing clopidogrel therapy.DISCUSSION:Ticlopidine-induced hepatotoxicity is well documented in the literature. In the present case, clopidogrel, a structurally similar thienopyridine, was substituted for ticlopidine following the development of presumptive ticlopidine-induced hepatotoxicity. Serum liver enzyme concentrations returned to baseline with continued clopidogrel therapy, suggesting that clopidogrel is a suitable alternative in patients who develop ticlopidine-induced hepatotoxicity.CONCLUSIONS:Clopidogrel may be a suitable alternative for patients who develop ticlopidine-induced hepatotoxicity.

Kethu, Sripathi R; Rukkannagari, Sireesha; Lansford, Charles L

doi: 10.1345/aph.18408pmid: 10492496

OBJECTIVE:To describe a case of symptomatic hepatotoxicity attributed to oxaprozin use.CASE SUMMARY:A 41-year-old white woman was admitted to the hospital with malaise, anorexia, and right upper quadrant pain. The patient was found to have severe jaundice with liver enzyme elevation. Laboratory test results for potential etiologies were negative, except for the use of oxaprozin for the preceding six weeks. Diagnosis of drug-induced hepatotoxicity was made by liver biopsy. The patient's symptoms resolved and liver enzymes normalized after oxaprozin was discontinued.DISCUSSION:Symptomatic hepatic effects attributable to most nonsteroidal antiinflammatory drugs (NSAIDs) are rare and usually mild. Oxaprozin has been shown to cause mild elevation of liver enzymes in clinical studies. This is the second reported case of presumed oxaprozin-induced icteric hepatitis. The mechanism of oxaprozin-induced hepatotoxicity is unclear, but is thought to be due to metabolic idiosyncrasy. Most NSAID reactions are hepatocellular and occur because of individual susceptibility (idiosyncrasy). In general, people aged >40 years and women are more predisposed to NSAID-induced liver injury.CONCLUSIONS:Although this toxicity is rare, clinicians should be aware of the potential for oxaprozin to cause hepatotoxicity and use caution when prescribing this medication. This case also stresses the importance of careful inquiry regarding drug or toxin exposure in cases of unexplained hepatitis.