Abstract
Keywords
Labetalol (Intravenous) No. 324
Hyperkalemia (First Report*)
A 23-year-old pregnant female patient developed severe hyperkalemia during a labetalol infusion for the management of pre-eclampsia. Intravenous labetalol was administered as an infusion of 20 mg/h, increased to 40 mg after 30 minutes to a maximum of 160 mg/h. Simultaneous medications included magnesium sulfate (1 g/h and continued for 24 hours). Concurrent medications included intravenous betamethasone (12 mg every 12 hours for 48 hours), folic acid (1 mg daily), and iron fumarate (65 mg elemental iron 3 times daily). Although blood pressure readings improved with therapy, the serum potassium was highly elevated (6.4 mmol/L) approximately 7 hours after receiving the labetalol infusion. Treatment included soluble insulin (8 units) and calcium gluconate 10% (10 mL). The labetalol infusion was stopped and hydralazine infusion was initiated (2 mg/h to a maximum of 10 mg/h). The patient underwent an emergency caesarean surgery. On postoperative day 3, the serum potassium level was within normal limits (0.5 mmol/L). Oral labetalol (200 mg twice daily) was initiated for elevated blood pressure with a recurrence of hyperkalemia (5.6 mmol/L) by therapy day 4. Oral hydralazine was substituted for labetalol and resulted in rapid decrease in serum potassium levels (4.5 mmol/L) by 6 hours. Nifedipine was later substituted for hydralazine with optimal lowering of blood pressure. The patient was eventually discharged with serum potassium levels within normal limits. At follow-up 19 days postdischarge, serum potassium levels were within normal limits (4.9 mmol/L).
The authors noted that this case is the first report of severe hyperkalemia associated with intravenous administration of labetalol in a pregnant patient. According to the Naranjo probability scale, the relation of the drug as a causative agent was rated as probable.
Labetalol [“Normodyne”]
Thomas B et al (B Thomas, Hamad Medical Corporation, Doha, Qatar; e-mail:
Adverse Drug Events No. 325
Hospitalized Adult Patients
A meta-analysis including 28 articles was performed to review observational studies examining the frequency of adverse drug events and adverse drug reactions and to examine factors associated with between-study heterogeneity in adult hospitalized patients. Quality of the studies varied. Of the studies included, 60% met criteria for low-risk of bias, and 26 described how participants were selected. Thirteen studies identified and assessed avoidable events separately, 3 studies included only adverse drug reactions, 4 did not assess avoidability, and in the remaining studies it was unclear whether such events were included. The majority of the studies were performed in internal medicine wards and in teaching hospitals. The proportion of hospitalized patients that experienced an adverse drug event could not be calculated for 3 of the studies and were excluded from the quantitative analysis. In the quantitative analysis, the types of reporting included stimulated reporting (n = 4), retrospective monitoring (n = 6), and prospective monitoring (n = 15). The stimulated reporting subgroup included 1501 to 9311 participant patients, and the proportion of patients experiencing an adverse drug event ranged from 1.6% (95% confidence interval = 1.3-1.8) to 4.4% (95% confidence interval = 3.5-5.6). The summary proportion was 2.3% (95% confidence interval = 1.6-4.5), Q = 78.61, P < .001, I2 = 96%. Results were similar when a sensitivity analysis excluding more active mechanisms of reporting was performed. The proportion in the retrospective monitoring subgroup ranged from 1.7% (95% confidence interval = 1.4-2.2) to 15.6% (95% confidence interval = 10.3-23.0), and the summary proportion was 8.7% (95% confidence interval = 4.8-15.3), Q = 207.98, P < .001, and I2 = 98%. Results were similar for sensitivity analyses that excluded studies utilizing the adverse drug reaction definition and those that used less comprehensive trigger mechanisms. The results of the prospective monitoring subgroup varied widely with proportions ranging from 4.7% (95% confidence interval = 3.1-7.1) to 57.3% (95% confidence interval = 53.4-61.2). The summary proportion was 21.3% (95% confidence interval = 15.7-28.3), Q = 829.86, P < .0001, I2 = 98%. Results remained similar in sensitivity analyses excluding studies that differed regarding identification methods and that used the adverse drug event definition. A univariate meta-regression analysis identified 2 variables associated with study results, year of publication (regression coefficient = 0.134, P = .04), and method used as the information source for obtaining events. Methods included event identification by patient interview (reference), event identification by patient interview and chart review (coefficient = 1.555, P = .016), event identification by health team interview and chart review (coefficient = 0.991, P = .156), and event identified by patient and health team interview plus chart review (coefficient = 1.713, P = .008). Additional variables including sample size, inclusion of avoidable events, and event definition were not associated with the study results.
The authors concluded that the results of this study demonstrated that the proportion of inpatients with adverse drug events was high and was dependent on the method used to identify them. Suggestions to enable more reliable and precise event estimates were offered including recording information on the event identification method, the characteristics of the events, and the conduct of the study.
Adverse Drug Events [Adverse Drug Events]
Martins ACM et al (ACM Martins, National Regulatory Agency for Private Health Insurance/Agência Nacional de Saúde Suplementar, Av Augusto Severo, 84, CEP 20021-040, Rio de Janeiro, RJ, Brazil; e-mail:
Mycophenolate Mofetil No. 326
Neutropenia
An 8-year-old girl developed neutropenia approximately 3 months after initiating mycophenolate mofetil for renal transplantation due to human immunodeficiency virus–associated nephropathy. Human immunodeficiency virus was transmitted vertically. Concurrent medications included lopinavir/ritonavir, lamivudine, abacavir, isoniazid, co-trimoxazole, azithromycin, fluconazole, tacrolimus (0.1 mg daily 4 times per week), and corticosteroids. Laboratory analyses revealed a CD4 count consistently greater than 200/mm3, undetectable human immunodeficiency virus and cytomegalovirus viral loads, and no concurrent hepatitis B or hepatitis C infection. Treatment included discontinuation of mycophenolate mofetil and transition to azathioprine. Rapid and sustained recovery of neutrophil count occurred. No evidence of opportunistic infection or human immunodeficiency virus–associated complications was present and lymphocytic interstitial pneumonitis remained dormant. At 8 months posttransplantation, Epstein–Barr virus reactivation occurred and was managed by reducing tacrolimus dose (target serum concentration = 6-8 µg/L). At 18 months posttransplantation, good renal allograft function was present without donor-specific antibodies, trough tacrolimus levels were maintained in target range, and mild hypertension was the only adverse reaction present. No human immunodeficiency virus–related complications occurred, human immunodeficiency virus load remained undetectable, and CD4 count remained greater than 1000/mm3 at evaluation 2 years later.
The authors concluded that the neutropenia experienced by this patient was related to mycophenolate mofetil therapy. No mechanism was proposed.
Mycophenolate Mofetil [“Cellcept”]
Shroff RC et al (SD Marks, Department of Paediatric Nephrology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London WC1N 3JH, UK; e-mail:
Peglitocase No. 327
Methemoglobinemia, Hemolysis
A 38-year-old male patient developed fatigue, shortness of breath, and dark-colored urine approximately 48 hours after receiving his first infusion of pegloticase infusion. Concurrent medications included colchicine. Previous medications included allopurinol, which was discontinued 5 weeks prior to this event. Baseline qualitative glucose-6-phosphate dehydrogenase testing was within normal limits approximately 5 months prior to pegloticase administration. On admission, abnormal laboratory values included oxygen saturation (80%), hemoglobin (8.3 g/dL), lactate dehydrogenase (1878 IU/L), serum creatinine (2.32 mg/dL), and indirect bilirubin (7.0 mg/dL), and total bilirubin (7.8 mg/dL). Symptoms included jaundice and hematuria. Methemoglobinemia was 10.1% (arterial blood O2 saturation of 97%). A quantitative glucose-6-phosphate dehydrogenase test was normal. A diagnosis of methemoglobinemia and severe hemolysis with subsequent renal dysfunction was made. Treatment with packed red blood cell transfusions, plasmapheresis, and oral ascorbic acid resulted in rapid clinical improvement.
Follow-up at 2 months postdischarge revealed renal function within normal limits and other tests consistent with glucose-6-phosphate dehydrogenase deficiency.
The authors concluded that this patient developed hemolysis and methemoglobinemia related to peglitocase infusion. His glucose-6-phosphate dehydrogenase deficiency status was a factor in the development of the complications. However, the authors noted that it was unclear why the initial glucose-6-phosphate dehydrogenase testing was within normal limits and later lower. The authors encourage glucose-6-phosphate dehydrogenase status evaluation in all patients scheduled to receive peglitocase regardless of ancestry.
Peglitocase [“Krystexxa”]
Geraldino-Pardilla L et al (L Geraldino-Pardilla, Division of Rheumatology, Columbia University, College of Physicians & Surgeons, 630 W 168th Street, P&S 10-445, New York, NY 10032; e-mail:
Artesunate No. 328
Autoimmune Hemolytic Anemia
A 17-year-old female patient developed fever, anemia, and thrombocytosis approximately 8 days after receiving 3 doses of intravenous artesunate (120 mg every 12 hours) for the treatment of complicated malaria. Concurrent medications included oral artemether (80 mg twice daily), lamefantrine (480 mg daily), piperacillin/tazobactam (12 g daily), and ciprofloxacin (500 mg twice daily). Malaria improved and total clearance of parasites occurred prior to development of symptoms. Significant laboratory findings at symptom onset included decreased hemoglobin (6.3 g/dL), thrombocytosis (489 g/L), and a negative Coomb’s test. No initial treatment was administered due to the subject leaving against medical advice. Readmission occurred 6 days later due to persistent fever and asthenia. Additional laboratory findings at that time included a further decrease in hemoglobin (4.6 g/dL), a reticulocyte count of 202 000/mm3, lactate dehydrogenase of 658 units/L, undetectable haptoglobin levels, and a positive Coomb’s test for both immunoglobulin G and complement factor C3d. Analyses for malaria, glucose-6-phosphate dehydrogenase deficiency, antinuclear antibodies, and additional pathogens were negative. Drug-dependent antibody testing was positive only with artesunate. Treatment included administration of methylprednisolone (60 mg daily for 7 days) and led to gradual improvement in hemoglobin (8.8 g/dL). Treatment was continued with oral prednisone (50 mg daily) tapered gradually over the subsequent 2 months, and complete recovery occurred.
The authors concluded that the immune-mediated hemolytic anemia experienced by this patient was related to the use of artesunate. Proposed mechanisms included drug absorption (hapten-induced), immune complex formation with the drug on red blood cell surface, and auto-antibody production resulting in immunoglobulin G and immunoglobulin M positivity in direct antiglobulin test.
Artesunate [“Artesunate”]
Raffray L et al (D Malvy, Travel Clinics and Tropical Diseases Unit, University Hospital Center of Bordeaux, Bordeaux, France; e-mail:
Dimethyl Fumarate No. 329
FDA Safety Communication
On November 25, 2014, the FDA alerted health care professionals regarding a case report of fatal progressive multifocal leukoencephalopathy related to the use of dimethyl fumarate in a patient with multiple sclerosis. The patient had been taking dimethyl fumarate for more than 4 years but was not taking concurrent immunomodulators or other agents with known association with progressive multifocal leukoencephalopathy. It was noted that the patient had reduced lymphocytes, which could have been a risk factor associated with progressive multifocal leukoencephalopathy, but this relationship is not clear. The FDA noted that this is the only confirmed case of progressive multifocal leukoencephalopathy associated with dimethyl fumarate. They also noted that based on this report, product labeling will be revised to reflect this potentially serious complication.
Dimethyl Fumarate [“Tecfidera”]
FDA Drug Safety Communication: FDA warns about case of rare brain infection PML with MS drug Tecfidera (dimethyl fumarate). http://www.fda.gov/Drugs/DrugSafety/ucm424625.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Nov 25) 2014
Ibrutinib No. 330
Tumor Lysis Syndrome
A 57-year-old male patient was hospitalized for severe fatigue and generalized weakness approximately 7 days after starting ibrutinib (420 mg daily) for the treatment of chronic lymphocytic leukemia. Medications on admission included alprazolam, citalopram, oxycodone, and ranitidine. Prior to starting ibrutinib, abnormal laboratory values included hemoglobin (11-12 g/dL), platelets (110 × 109/L to 120 × 109/L), and lactate dehydrogenase (213 U/L). However, within 3 days after starting ibrutinib, the white blood cell count changed to 120 000/mm3, absolute lymphocyte count to 116 400/mm3, hemoglobin to 13.7 g/dL, platelets to 73 000/mm3, and potassium to 5.7 mEq/L. On physical examination, the patient was bradycardic and hypotensive. Abnormal laboratory values at this time included white blood cell (108 000/mm3), potassium (7 mEq/L), creatinine (3.4 mg/dL), calcium (5.8 mg/dL), phosphate (>12 mg/dL), and uric acid (30 mg/dL). The patient had severe metabolic acidosis with normal lactate levels. Screenings for infectious etiologies were negative. Treatment included the discontinuation of ibrutinib and the initiation of intravenous fluids, sodium bicarbonate infusion, calcium gluconate, insulin, dextrose 50%, sodium-polysterene, rasburicase, and piperacillin/tazobactam. Approximately 72 hours after admission, the white blood cell count was at 58 000/mm3. Discharge occurred on hospital day 8 with a white blood cell count of 39 000/mm3. At 3 weeks postdischarge, ibrutinib was restarted (420 mg daily) without further event or episodes of tumor lysis syndrome.
The authors concluded that this patient developed tumor lysis syndrome with ibrutinib monotherapy and that clinicians should be aware of tumor lysis syndrome as a possible complication.
Ibrutinib [“Imbruvica”]
Kaur V et al (V Kaur, Division of Hematology/Oncology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205; e-mail:
Pregabalin No. 331
Neuropsychiatric Symptoms, Thrombocytopenia
A 28-year-old female inpatient developed fever, dizziness, confusion, and disorganized speech approximately 1.5 hours after receiving a single dose of pregabalin (75 mg) for the management of neuralgia. On admission, laboratory values were within normal limits, including platelet counts (131 × 109/L). Other therapies administered during the hospitalization included tramadol (2 doses), topiramate (50 mg twice daily), neurotropin (8 neurotropin units twice daily), and compound vitamin B (2 tablets every 8 hours). Though the fever subsided after treatment with loxoprofen sodium (60 mg), the neuropsychiatric symptoms did not improve until the next morning. On reassessment, it was noted that the platelet counts were decreased (85 × 109/L). On redosing with pregabalin, similar neuropsychiatric symptoms and fever recurred within 1 hour after administration. Fever again responded within 36 hours after the administration of loxoprofen and discontinuation of pregabalin. Improvement in neuropsychiatric symptoms occurred over a 2-day period. Platelet count levels remained low (73 × 109/L) prior to discharge. At follow-up 2 weeks postdischarge, the platelet count was within normal limits (102 × 109/L).
The authors concluded that this patient developed neuropsychiatric symptoms with thrombocytopenia related to the administration of pregabalin. According to the Naranjo probability scale, this relationship was rated as probable.
Pregabalin [“Lyrica”]
Qu C et al (C Qu, Department of Clinical Pharmacy, The Third Affiliated Hospital of Sun Yat-Sen University, 600, Tianhe Road, Guangzhou 510630, China; e-mail:
Statins No. 332
Cough
A review of several international adverse drug event reporting systems were reviewed for reports of statin-associated cough during the period of 2004 to 2012. A total of 995 spontaneous reports of statin-related cough were identified, including atorvastatin, rosuvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, and pitavastatin. It is recognized that statins may be associated with interstitial lung disease, which may initially manifest as a persistent nonproductive cough. In addition, statins may be related to cough without association of lung injury. Reports reviewed from the Canadian and Australian databases indicated that 88% of statin-associated coughs occurred in the absence of lung injury. It was not possible to detect statin-induced cough without lung injury in the US database. The total number of reports of statin-related cough are provided in descending order: rosuvastatin (n = 425), atorvastatin (n = 344), simvastatin (n = 144), pravastatin (n = 39), fluvastatin (n = 34), lovastatin (n = 9), and pitavastatin (n = 0).
The authors concluded that a review of several national adverse drug reaction databases for reports of statin-induced cough suggested that statins are involved with iatrogenic dry cough as a class effect.
Atorvastatin [“Lipitor”]
Fluvastatin [“Lescol”]
Lovastatin [“Mevacor”]
Pitavastatin [“Livalo”]
Pravastatin [“Pravachol”]
Rosuvastatin [“Crestor”]
Simvastatin [“Zocor”]
Carnovale C et al (E Clementi, Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, Consiglio Nazionale delle Ricerche Institute of Neuroscience, University Hospital “Luigi Sacco,” Via GB Grassi, 74-20157 Milan, Italy; e-mail:
Amisulpride No. 333
Mania
A 19-year-old male patient with cerebral palsy developed acute mania after being switched from risperidone to amisulpride for the treatment of schizophrenia. The patient had been taking risperidone for 12 weeks when the decision to switch to amisulpride was made. A tapering risperidone schedule was employed over a 3-day period (6 mg, 4 mg, and 2 mg, respectively) and then discontinued, while amisulpride was initiated (400 mg daily on days 1 to 8). On day 4, the patient developed symptoms of euphoria, persistent laughing, exaggerated self-esteem, extreme talkativeness, flight of ideas, and psychomotor agitation. On day 8, the amisulpride dose was increased (800 mg daily) but his Young Mania Rating Scale score (16) was indicative of a hypomanic or manic episode. By day 15 the Young Mania Rating Scale score was 21, indicating a more severe progression. Treatment included the discontinuation of amisulpride, and risperidone was restarted (4 mg daily). By day 20, the manic symptoms had reversed (Young Mania Rating Scale score of 3) and clinical condition remained uneventful during follow-up of 6 months.
The authors concluded that this patient experienced rapid-onset mania related to amisulpride therapy based on the temporal relationship between the appearance and resolution of symptoms with drug administration.
Amisulpride [“Amazeo,” “Amipride”]
Chuang WC et al (YW Yeh, Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; e-mail:
Omega-3-Acid Fish Oils No. 334
Allergy
A 65-year-old female patient developed an unrecognized allergic reaction approximately 4 days after starting treatment with omega-3-acid ethyl esters (2 g twice daily). Concurrent medications included rizatriptan, albuterol, ramipril, furosemide, carvedilol, clonazepam, spironolactone, raloxifene, lispro/lispro protamine, sitagliptan/metformin, lactulose, pregabalin, sertraline, monteleukast, topiramate, simvastatin/ezetimibe, rifaximin, bifantis probiotic, calcium citrate with vitamin D, magnesium, cetirizine, and niacin. Noted allergies included celecoxib, adhesive, shellfish, olives, and tuna. Four days after starting therapy with fish oil, the patient developed chest tightness, flushing, shortness of breath, tingling of upper extremities, pruritus, abdominal pain, and nausea. Prior to emergency department admission, the patient took nonprescription diphenhydramine (100-150 mg in a single dose followed by 25-50 mg every 2 hours) with some relief of pruritic symptoms. Eosinophil levels were within normal limits, and the patient was discharged with instructions for primary care follow-up. Approximately 9 days after starting fish oil therapy, the patient discontinued taking the agent, with mild improvement in symptoms. The patient continued to take medications from a pill box organizer that had previously contained the fish oil products. She was instructed to discard or clean the container and contents. At this visit, immunoglobulin E concentrations were elevated (132 IU/mL) with eosinophils still at normal levels. At follow-up 1 week later, the patient reported that all symptoms had resolved within 3 days of implementing the above-mentioned practices. A further follow-up at 3 weeks later revealed a decrease in immunoglobulin E to 117 IU/mL. Fish oil was not restarted.
The authors concluded that a patient with fish allergies developed an allergic reaction related to the initiation of omega-3-acid fish oil therapy. Reactions to other medications were ruled out. According to the Naranjo probability scale, this reaction was rated as probable in relation to fish oil administration. The authors encouraged clinicians to inquire about food allergies when prescribing omega-3-acid fish oil therapy.
Omega-3-Acid [“Lovaza”]
Howard-Thompson A et al (A Howard-Thompson, Department of Clinical Pharmacy and Family Medicine, University of Tennessee Health Science Center, Memphis, TN; e-mail:
Metformin, Verapamil No. 335
Drug Interaction: Decreased Effectiveness of Metformin
In a prospective study, the pharmacokinetics and efficacy of metformin (via oral glucose tolerance testing) was evaluated in 12 healthy subjects (mean age = 27 years) at baseline (day 1) and after metformin administration (day 2), and after concurrent administration with verapamil (days 15 and 16). Metformin was administered as 1000 mg on day 1 and 750 mg on days 2, 15, and 16. Verapamil (180 mg sustained release daily) was administered on days 14 to 16. Prior to the first metformin dose, verapamil did not affect baseline serum glucose concentrations. However, verapamil affected the ability of metformin to reduce maximum blood glucose concentrations by 62.5% and decreased the area under the curve of glucose concentrations by 238%. Verapamil did not alter the pharmacokinetics of metformin.
The authors concluded, based on these results, that verapamil reduces the ability of metformin to reduce glucose concentrations without influencing its pharmacokinetic profile. The suggested mechanism of interaction was the possible verapamil action as an organic cation transporter-1 competitive inhibitor, preventing metformin transport into the liver. The authors suggested that further study is needed regarding this interaction in patients with diabetes.
Metformin [“Diabex”]
Verapamil [“Isoptin SR”]
Cho SK et al (JY Chung, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam, Kyounggi 463-707, Korea; e-mail:
Allopurinol, Febuxostat No. 336
Inappropriate Prescribing and Risk of Adverse Events in Elderly
In a cross-sectional, prospective study, the prevalence and appropriateness of xanthine oxidase inhibitor prescriptions were evaluated in elderly inpatients in 95 Italian hospital wards. Based on this analysis, predictors of inappropriate prescriptions at discharge with adverse events at 3 months postdischarge were examined. The initial study sample was 4035 elderly patients (at least 65 years) at admission and 3502 at discharge. Among these patients, 467 (11.6%) and 461 (13.2%) were treated with allopurinol or febuxostat at hospital admission and discharge, respectively. Allopurinol was the most frequently used xanthine oxidase inhibitor, with 2 patients each receiving febuxostat at admission and discharge. Inappropriate treatment with a xanthine oxidase inhibitor was noted in 428 patients (91.6%) and 418 patients (90.7%) at hospital admission and discharge, respectively. In 286 patients (66.8%) these drugs were inappropriately prescribed at both admission and discharge. The mean duration of xanthine oxidase inhibitor therapy was 3.3 years. Predictors of inappropriate xanthine oxidase inhibitor prescribing were determined via comparison of patients receiving such therapy (n = 418) with those not receiving xanthine oxidase inhibitor therapy (controls; n = 3024). For those inappropriately treated, hyperuricemia, polypharmacy, chronic renal failure, diabetes, obesity, ischemic cardiomyopathy, heart failure, and cardiac dysrhythmias were associated with greater prescription of xanthine oxidase inhibitors. In addition, patients inappropriately treated with xanthine oxidase inhibitors at discharge were associated with a higher risk of an adverse event at 3-month follow-up (odds ratio = 1.68; 95% confidence interval = 1.10-2.58; P = .02) but there was no difference between the groups for risk of readmission (odds ratio = 0.84; 95% confidence interval = 0.57-1.23; P = .36), or all-cause mortality (odds ratio = 1.30; 95% confidence interval = 0.80-2.12; P = .30).
The authors concluded that based on this study, there was a high prevalence of inappropriate prescribing xanthine oxidase inhibitors in elderly patients at both hospital admission and discharge. Inappropriate treatment with these agents was primarily related to therapy of asymptomatic hyperuricemia in patients with cardiovascular disease. Inappropriate prescribing at discharge was associated with an increased risk of adverse events at follow-up.
Allopurinol [“Zylporim”]
Febuxostat [“Adenuric”]
Pasina L et al (L Pasina, Drug Information Service for the Elderly, IRCCS—Istituto di Ricerche Farmacologiche “Mario Negri,” Via Giuseppe La Masa, 19, 20156 Milan, Italy; e-mail:
Pemetrexed No. 337
Thrombocytopenic Thrombotic Purpura
A 70-year-old male patient developed severe thrombocytopenic thrombotic purpura approximately 7 days after receiving a single dose of pemetrexed (1000 mg). Concurrent medications included omeprazole (20 mg daily) and furosemide (25 mg daily). White blood cell count was 1460 cells/µL with neutrophil count at 840 cells/µL. At 21 days posttherapy, the white blood cell and neutrophil counts normalized with platelet counts decreased to 47 000/µL and hemoglobin to 10.7 g/dL. Lactate dehydrogenase was increased to 520 U/L, and bilirubin was increased to 1.7 mg/dL. On day 27 posttherapy, platelets had increased to 67 000. Further therapy with pemetrexed was postponed and treatment with recombinant erythropoietin (40 000 units) was initiated. Despite treatment, the patient’s clinical condition continued to deteriorate with eventual death. The last platelet count documented was 9000/µL.
The authors concluded that this patient developed acute and fatal thrombocytopenic thrombotic purpura related to pemetrexed therapy. An exact mechanism of action was not elucidated.
Pemetrexed [“Alimta”]
Albasio I et al (C Baratelli, AOU San Luigi Gonzaga, Orbassano, Torino, Italy; e-mail: