Grant E. Sklar

Acetylcysteine Treatment for Non–Acetaminophen-Induced Acute Liver Failure:

OBJECTIVE To evaluate the effectiveness of intravenous acetylcysteine in the treatment of non–acetaminophen-induced acute liver failure (ALF). DATA SOURCES A search of MEDLINE (1966–March 2003), International Pharmaceutical Abstracts (1970–2003), and Cochrane Library (2003, issue 3) databases was conducted, using the search terms acetylcysteine, non–acetaminophen-induced hepatic failure, liver failure, intravenous, and treatment. DATA SYNTHESIS All of the studies found were small and do not provide conclusive evidence that acetylcysteine benefits this subgroup of patients. Microvascular regional benefits were seen, but clinical outcomes have not been studied. CONCLUSION Intravenous acetylcysteine should not be used routinely for treatment of non–acetaminophen-induced ALF. Further large-scale studies are needed to evaluate clinical outcomes.

Possible Pharmacokinetic Interaction with Quinidine: Ciprofloxacin or Metronidazole?

OBJECTIVE: To discuss a potential pharmacokinetic interaction between quinidine, ciprofloxacin, and metronidazole. CASE SUMMARY: A 51-year-old black woman was admitted for shortness of breath, abdominal pain, and atrial fibrillation. Procainamide and diltiazem were begun for the atrial fibrillation and ciprofloxacin and metronidazole for suspected diverticulitis. The therapy was switched to quinidine on day 5 because of adverse events associated with procainamide. A trough serum quinidine concentration (SQC) on day 7 was 6.3 μg/mL (normal 2–5) with normal QT and QTc intervals. On day 8, the patient was discharged in normal sinus rhythm. She took her last doses of antibiotics on day 15 and a follow-up SQC on day 18 was 2.3 μg/mL. DISCUSSION: The possible explanations for the changes in SQCs include: (1) laboratory error, (2) compliance with medication regimen, and (3) altered hepatic metabolism. The first two are not likely in this case. The laboratory verified the elevated SQC and the patient had her prescriptions refilled within appropriate time limits. The third explanation seems more plausible. Quinidine is metabolized by the hepatic mixed-function oxidase system, specifically cytochrome P450 (CYP) 3A4. We found that metronidazole has been shown to inhibit CYP3A activity and ciprofloxacin has been shown to inhibit certain isozymes in the cytochrome P450 system as well. CONCLUSIONS: When metronidazole and ciprofloxacin are administered concomitantly with quinidine, clinicians should be aware of this potential interaction. Quinidine concentrations should be monitored and patients should be assessed for signs and symptoms of quinidine toxicity.

A cost analysis of Outpatient Parenteral Antibiotic Therapy (OPAT): an Asian perspective

The concept of Outpatient Parenteral Antibiotic Therapy (OPAT) is relatively new in Asia. This study compared the actual costs and outcomes of care involving OPAT with conventional inpatient-only care at a university hospital in Singapore. Actual costs were obtained for selected patients enrolled in OPAT after 1 January 2005 and these costs were directly compared with those of age-, gender- and diagnosis-matched patients managed as inpatients only prior to the availability of OPAT in the preceding 12 months. Outcomes of patients were also considered. The OPAT and inpatient-only groups comprised 72 and 93 enrollments, respectively. Mean treatment duration for OPAT patients was 42.5 days versus 19 days for those receiving inpatient-only care (P < 0.001). The mean total treatment cost for OPAT and inpatient-only care was US

Hemolysis as a Potential Complication of Acetaminophen Overdose in a Patient with Glucose‐6‐Phosphate Dehydrogenase Deficiency

12 736 and

Fluosol : therapeutic failure in severe anemia

12 403, respectively (P = 0.706). Mean cost per day for care including an OPAT episode was US

Pentoxifylline-Induced Thrombocytopenia A Case Report

278 versus

Erythema Multiforme Secondary to Dimenhydrinate in a Patient With Previous Similar Reactions to Pamabrom

457 per day for inpatient-only care (P < 0.001). There was no difference in outcomes between the two groups. OPAT is a viable alternative to inpatient care as it is safe, effective and results in lower daily costs. The trend to longer treatment courses is worthy of further review.

Identification and evaluation of pharmacists' commonly used drug information sources.

A 21‐year‐old Chinese man who took an overdose of acetaminophen was hospitalized. His medical history was significant for glucose‐6‐phosphate dehydrogenase (G6PD) deficiency. On admission, physical examination was unremarkable and laboratory results were within normal limits. During his hospitalization, the patient experienced a decrease in hemoglobin concentration of almost 4 g/dl and an increase in unconjugated bilirubin consistent with the development of hemolysis. Acetaminophen was the most likely cause of the hemolysis. Clinicians must be aware of this potential complication after acetaminophen overdose in G6PD‐deficient patients.

Identification and physicians' views of their commonly-used drug information sources in Singapore.

OBJECTIVE: To report the use of Fluosol in the management of a severe anemia and to review the literature regarding the use of Fluosol. CASE REPORT: A 40-year-old woman, at 40.5 weeks gestation, was admitted for induction of labor. Her hospital course was complicated by a postpartum hemorrhage and severe anemia. Because the patient was a Jehovahs Witness, she received non-blood products including hetastarch, iron dextran, and erythropoietin, and a total of 33 mL/kg of Fluosol, but she did not survive. DISCUSSION: Fluosol is an oxygen-carrying, perfluorochemical blood substitute. It was administered to our patient, who presented with the lowest hemoglobin (Hb) (11 g/L) and hematocrit (0.31 fraction of 1.00) of all reported cases. Almost all patients with an Hb <20 g/L do not survive. CONCLUSIONS: Although the use of Fluosol as a blood substitute appears theoretically promising, its use in the management of severe anemia cannot be recommended.

An evaluation of the completeness of drug-drug interaction-related information in package inserts

Pentoxifylline-induced thrombocytopenia is rare, and information is lacking about its presentation. We describe a 72-year-old Chinese male who developed thrombocytopenia after initiation of pentoxifylline for the treatment of chronic lower limb ischemia due to peripheral artery disease. Venous thromboembolism had been ruled out with an ultrasound. Vascular surgeons had also determined there was no indication for surgical intervention. Four days after initiation of pentoxifylline, he developed thrombocytopenia, and his platelets were 68 × 103/μL. He was not in overt disseminated intravascular coagulation (DIC), based on his International Society for Thrombosis and Hemostasis (ISTH) DIC score of 4. Dengue fever, which is endemic in Singapore, was ruled out. Pseudothrombocytopenia was also excluded with a peripheral blood film. When his platelets continued to fall, pentoxifylline was discontinued on the fifth day of treatment, and platelets normalized 48 hours after discontinuation. Pentoxifylline was a probable cause of thrombocytopenia using the Naranjo Adverse Drug Reaction Probability Scale (score = 7). The patient did not receive further doses of pentoxifylline. Prescribers should be aware of the risk of thrombocytopenia with pentoxifylline therapy and discontinue its use promptly if it is suspected.