Ann Pharmacother

Primary induction with mycophenolate mofetil and corticosteroids in a liver transplant recipient with hepatorenal syndrome.

Carr RR. Yoshida EM. Chung SW. Partovi N.
Vancouver Hospital and Health Sciences Centre, British Columbia, Canada.
OBJECTIVE: To report the use of mycophenolate mofetil for primary induction in a liver transplant recipient to avoid the nephrotoxicity of cyclosporine/tacrolimus. CASE SUMMARY: A 47-year-old white man in a hepatic coma with anuric hepatorenal syndrome received a liver transplant, and was given mycophenolate mofetil and corticosteroids as primary induction immunosuppression with the addition of low-dose cyclosporine 13 days later. His renal function improved and he remains rejection-free after 13 months of follow-up. CONCLUSIONS: This case suggests that mycophenolate mofetil may be used as a primary induction agent in liver transplant recipients with renal failure to avoid the additional nephrotoxicity of the standard immunosuppressants, cyclosporine and tacrolimus. Low-dose cyclosporine/tacrolimus may be introduced later as the renal function improves.

Zinc acetate treatment in Wilsons disease.

Anderson LA. Hakojarvi SL. Boudreaux SK.
Multum Information Services, Inc., Denver, CO 80209, USA. leigha@multum.com
OBJECTIVE: To briefly review the pathophysiology and diagnosis of Wilson's disease, and to evaluate the pharmacology, pharmacokinetics, clinical utility, adverse effects, dosing regimens, and pharmacoeconomics of zinc acetate therapy in Wilson's disease. DATA SOURCES: A MEDLINE search (December 1966-December 1996) of the English-language literature using the terms zinc and Wilson's disease was conducted to identify pertinent clinical trials, review articles, and case reports. Additional articles were selected from bibliographies of the reviewed literature. STUDY SELECTION AND DATA EXTRACTION: Due to the rarity of the disease, all articles were considered for possible inclusion in this review. Single case reports are referenced, but were not selected for evaluation. DATA SYNTHESIS: Wilson's disease, an inherited disorder of copper metabolism, is fatal if untreated. The chelating drugs penicillamine and trientine have been the mainstay of therapy; however, adverse reactions of chelators often interfere with successful treatment. Recently, zinc acetate was approved in the US for maintenance therapy in patients initially treated with a chelating agent. Although studies evaluating large populations are lacking zinc therapy has demonstrated exceptional safety and efficacy over a period of 40 years. Zinc acetate can be used during pregnancy and for the treatment of presymptomatic patients, although data do not support its use as monotherapy in patients with acute neurologic or hepatic disease. CONCLUSIONS: Zinc acetate is an effective maintenance therapy for patients with Wilson's disease. Negligible toxicity, compared with that of previously approved treatments, is a major advantage.

Clostridium difficile toxin-induced colitis after use of clindamycin phosphate vaginal cream.

Year 1998
Meadowcroft AM. Diaz PR. Latham GS.
School of Pharmacy, University of North Carolina, Chapel Hill 27599, USA.
OBJECTIVE: To report a case of toxin-positive Clostridium difficile-induced colitis (CDIC) after use of clindamycin phosphate vaginal cream. CASE SUMMARY: A 25-year-old postpartum white woman developed multiple watery stools and abdominal cramping on day 6 of therapy with clindamycin vaginal cream for bacterial vaginosis. She received no other concomitant medications. The patient's stool sample was found to be positive for the C. difficile toxin. Due to the costs and risks of standard therapy, we decided to manage the patient supportively. Complete resolution of the diarrhea occurred shortly thereafter. DISCUSSION: No published clinical studies in patients receiving clindamycin vaginal cream for bacterial vaginosis have documented C. difficile toxin in stool samples of patients with diarrhea. Approximately 5-6% of intravaginal clindamycin is absorbed in the bloodstream, making systemic effects possible. CONCLUSIONS: This report indicates clindamycin phosphate vaginal cream as the most probable cause of CDIC due to the temporal relationship between the occurrence of diarrhea and clindamycin administration, lack of concomitant medications, and documentation of C. difficile toxin.

Antacid-induced hypermagnesemia in a patient with normal renal function and bowel obstruction.

Year 1998
McLaughlin SA. McKinney PE.
Department of Emergency Medicine, University of New Mexico Health Sciences Center, Albuquerque 87131, USA.
OBJECTIVE: To report a case of severe hypermagnesemia caused by magnesium hydroxide in a woman with normal renal function. CASE SUMMARY: A 42-year-old Hispanic woman with schizophrenia and bipolar affective disorder was transported from jail to the emergency department with confusion, abdominal pain, vomiting, and constipation. She had been treated in jail with magnesium hydroxide, ordered as milk of magnesia 30 mL po each night and Maalox 30 mL po three times daily. Additional medications included lithium carbonate 300 mg po three times daily, chlorpromazine 150 mg po three times daily, benztropine mesylate 1 mg po twice daily, and docusate sodium 100 mg po each morning. Her temperature was 35.1 degrees C, blood pressure 108/58 mm Hg, heart rate 112 beats/min, and respiratory rate 24 breaths/min. She would respond only briefly to voice or painful stimuli. Her abdomen was distended and diffusely tender. Laboratory tests included serum magnesium concentration 9.1 mEq/L (normal 1.3-2), blood urea nitrogen 16 mg/dL (8-22), creatinine 0.9 mg/dL (0.5-1.1), calcium 3.9 mEq/L (4.2-5.2), and lithium 1.0 mEq/L. A laparotomy was performed, and an adhesive band from a previous oophorectomy was found to be compressing the sigmoid colon. Hypermagnesemia, hypothermia, and hypotension continued in the intensive care unit. Despite successful treatment of the hypermagnesemia with calcium, intravenous fluids, and furosemide, the patient's cardiac rhythm degenerated into fatal, pulseless electrical activity on postoperative day 2. DISCUSSION: This case of severe hypermagnesemia from magnesium hydroxide ingestion illustrates many of the risk factors for hypermagnesemia in patients with normal renal function. People using magnesium-containing medications for relief of gastrointestinal distress may be at increased risk for hypermagnesemia. A brief review of magnesium physiology, clinical effects, and treatment is provided. Frequent use of the laboratory to identify hypermagnesemia is encouraged because it is often a clinically unexpected finding and responds well to early treatment.

Continuous fentanyl infusion: use in severe cancer pain.

Year 1998
Lenz KL. Dunlap DS.
Department of Pharmacy Practice, Medical University of South Carolina, Charleston 29425, USA. lenzk@musc.edu
OBJECTIVE: To describe the use of a continuous fentanyl infusion in an adult cancer patient. CASE SUMMARY: A 66-year-old white woman diagnosed with metastatic pancreatic carcinoma required hospital admission for pain control after receiving five different chemotherapy regimens. Morphine 2 mg/h i.v. was initiated and the dosage was titrated upward to a total of 6613 mg/d by hospital day 16. As hospital supplies of opioids became depleted over a holiday weekend, therapy was changed to a continuous infusion of hydromorphone 70 mg/h on hospital day 17, then changed to a continuous fentanyl infusion beginning with a dosage of 500 micrograms/h. The fentanyl dosage was titrated to 4250 micrograms/h by hospital day 20. She died comfortably on hospital day 22 while receiving this dosage. DISCUSSION: Continuous infusions of opioids, particularly morphine and hydromorphone, are frequently used for control of cancer pain and are safe and effective when administered by this route. Transdermal fentanyl has been shown to effectively manage chronic cancer pain, and use of continuous subcutaneous fentanyl has been reported. However, reports of continuous intravenous fentanyl infusion in the cancer pain literature are limited. Our patient achieved good pain control with a continuous infusion of fentanyl 4250 micrograms/h. CONCLUSIONS: Continuous fentanyl infusion should be considered for the treatment of cancer pain in patients requiring high doses who become refractory to other opioids, when other opioids cause intolerable adverse effects, when patients have a true morphine allergy, or when high-dose requirements threaten to deplete existing stock of alternate opioids.

Community pharmacists assessments and recommendations for treatment in four case scenarios.

Year 1998
Lamsam GD. Kropff MA.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, PA 15261, USA.
OBJECTIVE: To evaluate community pharmacists' interpersonal skills, ability to make appropriate assessment of a patient' s drug-related problems, and ability to propose an appropriate therapeutic plan. DESIGN: A disguised shopper design was used. Four different case scenarios were designed, with input from a five-member community/primary care pharmacist advisory committee. Two different cases were assigned to each of two shoppers. One hundred and one pharmacies were shopped twice, totaling 202 shopping experiences. A three-member evaluation committee made up of clinical faculty members in ambulatory care and internal medicine assessed the appropriateness of the recommendations. SETTING: The study was conducted in 101 randomly selected community pharmacies in the Pittsburgh area, including both chain and independent pharmacies. MAIN OUTCOME MEASURES: Main outcome measures included the quality of the pharmacists' interpersonal skills, patient assessment skills, and recommendations. RESULTS: The majority of pharmacists demonstrated acceptable to good interpersonal skills. Overall, 31.7% of the recommendations were appropriate, while 39.1% were poor (i.e., recommendations that would likely worsen the patient's condition or potentially harm the patient). In 33.2% of the cases, recommendations were made without prior assessment of the patient's problems. CONCLUSIONS: A lack of clinical knowledge and skills should be considered as a barrier that must be overcome if the provision of pharmaceutical care is to become a reality in community practice.

Pemoline therapy resulting in liver transplantation.

Year 1998
Adcock KG. MacElroy DE. Wolford ET. Farrington EA.
University of North Carolina Hospitals and Clinics, Chapel Hill 27514, USA.
OBJECTIVE: To describe a case of pemoline-induced liver failure resulting in liver transplantation. CASE SUMMARY: A 9-year-old white boy, diagnosed with attention deficit/hyperactivity disorder (ADHD) and treated with pemoline, developed signs and symptoms of liver failure. Pemoline therapy was discontinued, but the patient's liver function continued to decline. Ultimately, a liver transplantation was required. DISCUSSION: Pemoline, an agent used in ADHD treatment, has been associated with hepatotoxicity with the majority of cases occurring in pediatric patients. To our knowledge, this is the second reported case of pemoline-induced liver failure resulting in liver transplantation. The mechanism of action remains unclear, with several hypotheses being postulated including hypersensitivity reactions, dose-related phenomena, and autoimmune-mediated reactions. CONCLUSIONS: With increasing evidence linking pemoline to liver failure, this agent should not be considered first-line therapy for ADHD. Prior to initiating therapy, baseline liver function tests should be obtained and closely monitored, and parents and patients should be educated on the signs and symptoms of liver toxicity.

Azathioprine hypersensitivity reaction in a patient with ulcerative colitis.

Year 1998
Garey KW. Streetman DS. Rainish MC.
Department of Pharmacy, Bassett Healthcare, Cooperstown, NY 13326, USA.
OBJECTIVE: To describe a case of azathioprine hypersensitivity in a patient with ulcerative colitis. CASE SUMMARY: A 40-year-old white man with ulcerative colitis, treated with chronic mesalamine and occasional steroids, was admitted to the hospital with a 3-day history of fever, nausea, vomiting, and a rash. Fourteen days prior to admission, the patient had been started on azathioprine for ulcerative colitis. Upon admission, azathioprine therapy was temporarily withheld, resulting in resolution of his signs and symptoms. Symptoms returned when azathioprine was restarted. It was decided that these signs and symptoms were most likely caused by azathioprine hypersensitivity, and the agent was discontinued. DISCUSSION: To our knowledge, this is the first reported case of azathioprine hypersensitivity in a patient with ulcerative colitis. The time course and presenting signs and symptoms support the diagnosis of azathioprine hypersensitivity, as does the patient's response to rechallenge. The mechanism of this hypersensitivity reaction is unclear, but may involve the nitroimidazole portion of the azathioprine molecule. CONCLUSIONS: Azathioprine hypersensitivity often presents with signs and symptoms resembling a systemic infection such as fever, leukocytosis, and evidence of end organ dysfunction. The diagnosis of azathioprine hypersensitivity should be considered in patients who have recently either initiated or increased their dosage of azathioprine.

Chromium picolinate toxicity.

Year 1998
Cerulli J. Grabe DW. Gauthier I. Malone M. McGoldrick MD.
Nutrition Support, Division of Pharmacy Practice, Albany College of Pharmacy, NY 12208, USA.
OBJECTIVE: To describe a case of toxicity secondary to chronic ingestion of 6-12 times the recommended daily allowance of over-the-counter (OTC) chromium picolinate. CASE SUMMARY: A 33-year-old white woman presented with weight loss, anemia, thrombocytopenia, hemolysis, liver dysfunction (aminotransferase enzymes 15-20 times normal, total bilirubin 3 times normal), and renal failure (serum creatinine 5.3 mg/dL; blood urea nitrogen 152 mg/dL). She had ingested chromium picolinate 1200-2400 microg/d for the previous 4-5 months to enhance weight loss. The patient had chromium plasma concentrations 2-3 times normal. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome were ruled out by clinical findings, peripheral blood smears, and a bone marrow biopsy. The patient was managed with supportive measures and received blood product transfusions and hemodialysis. Hemolysis stabilized and liver function improved over 6 days. Liver function returned to normal prior to discharge. Renal function began to return on day 12 and her serum creatinine on discharge was 1.3 mg/dL. One year later, all laboratory values were within normal limits. DISCUSSION: Trivalent chromium is an essential trace element that is considered safe when ingested in normal quantities. Trivalent chromium compounds are used by patients to enhance weight loss, increase lean body mass, and/or improve glycemic control. Information regarding the toxicity of chromium picolinate is limited. CONCLUSIONS: Chromium supplements may cause serious renal impairment when ingested in excess. Medication histories should include attention to the use of OTC nutritional supplements often regarded as harmless by the public and lay media.

Leukocytoclastic vasculitis associated with clarithromycin.

Year 1998
Gavura SR. Nusinowitz S.
Department of Pharmacy Services, Mount Sinai Hospital, Toronto, Ontario, Canada. scott.gavura@utoronto.ca
OBJECTIVE: To report a possible case of leukocytoclastic vasculitis associated with clarithromycin therapy. CASE SUMMARY: An 83-year-old white woman was prescribed clarithromycin for pneumonia. Six days after her initial presentation, she developed lesions on her palms. Clarithromycin was discontinued at that time. The following day she developed purpuric eccymotic nonblanching lesions that primarily appeared on the lower extremities, buttocks, and abdomen. Colonoscopy revealed generalized erythema and edema of the bowel mucosa. Gastroscopy revealed duodenitis and gastritis, but no bleeding or ulceration. Skin biopsy of the lesions was compatible with leukocytoclastic vasculitis. Renal function was not affected, although hematuria was noted. All symptoms resolved after drug withdrawal and a short course of corticosteroids. DATA SOURCES: Searches were performed on MEDLINE, Embase, International Pharmaceutical Abstracts, and major adverse drug reaction databases to identify reports and articles discussing clarithromycin- and macrolide-induced leukocytoclastic vasculitis. DISCUSSION: Leukocytoclastic vasculitis is one category of drug hypersensitivity reactions characterized by distinctive patterns of perivascular inflammation. The case described here is consistent with the diagnosis of leukocytoclastic vasculitis, and is similar to the other single published case report associated with clarithromycin. CONCLUSIONS: Leukocytoclastic vasculitis induced by clarithromycin is a rare but serious potential adverse effect.