Abstract
Keywords
Lenalidomide No. 74
Eosinophilia
A 50-year-old female inpatient developed eosinophilia shortly after starting cyclic treatment with lenalidomide (25 mg daily for 21 days; 7 days off), dexamethasone (40 mg every 7 days), and cyclophosphamide (50 mg daily for 28-day cycles) for the management for POEMS syndrome. In addition, an antiinfective prophylaxis with acyclovir and trimethoprim/sulfamethoxazole was started. Medications on admission included ramipril (10 mg daily), prednisone (5 mg daily), levothyroxine (50 mg daily), folic acid (5 mg daily), aspirin (300 mg daily), omeprazole (20 mg daily), cyanocobalamin (1 mg monthly), and pyridoxine (300 mg daily). The eosinophil count remained high during lenalidomide treatment, but it decreased during the 7 days of off-time lenalidomide according to the protocol. This sequence repeated itself during the first 3 cycles, suggesting that lenalidomide was the causative agent. Screenings for immunological, allergic, and infectious etiologies were negative. The drug was not discontinued as the clinical course was favorably associated with treatment and treatment modification was not needed. The patient was discharged 4 months after admission and treatment was continued as an outpatient without further event.
The authors concluded that this patient developed eosinophilia related to lenalidomide therapy based on the temporal relationship between the administration of the agent and appearance and resolution of symptoms. According to the Naranjo causality nomogram, this reaction was classified as a probable cause of lenalidomide therapy.
Lenalidomide [“Revalamid”]
Escudero-Vilaplana V et al (V Escudero-Vilaplana, Pharmacy Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain; e-mail:
Fluphenazine Decanoate No. 75
Persistent Extrapyramidal Symptoms
A 62-year-old woman developed acute persistent dysphagia, lead-pipe rigidity, and aspiration pneumonitis 24 weeks after initiating fluphenazine decanoate (titrated to 25 mg every 2 weeks) for treatment of schizophrenia. Significant findings on physical examination included a slight fever (37.4°C), tachycardia (heart rate 115 beats/min), and hypertension (150/100 mm Hg). Peripheral oxygen saturation was maintained at 96% via a reservoir mask at a rate of 4 L/min of oxygen. Serum analysis revealed elevated C-peptide immunoreactivity (6.99 mg/dL), and tests for neuroleptic malignant syndrome were negative. Chest computed tomography revealed moderate pneumonia in the bilateral lungs. Tracheostomy was performed due to obstruction atelectasis in the lower right lung. Additional treatment included administration of oral bromocriptine (titrated to 20 mg/day). Dysphagia, lead-pipe rigidity, and oral dyskinesia began to improve, and Drug Induced Extra-Pyramidal Symptoms Scale total score declined 28 days after initial symptom evaluation. Tracheostomy was weaned at day 63. Additional treatment included rehabilitation and discharge occurred after 104 days.
The authors concluded that this case described acute and persistent extrapyramidal symptoms induced by fluphenazine. The proposed mechanism was persistent remaining plasma concentrations of fluphenazine decanoate.
Fluphenazine Decanoate [“Prolixin Decanoate”]
Omi T et al (T Omi, Department of Psychiatry, Osaka General Medical Center, Osaka, Japan; e-mail:
Enoxaparin, Unfractionated Heparin No. 76
Delayed-Onset Thrombocytopenia
A 73-year-old female developed delayed-onset heparin-induced thrombocytopenia and bilateral pulmonary emboli after receiving enoxaparin (daily, dose not reported) and unfractionated heparin during 3 hospitalizations in the 2 months prior to symptom onset. Enoxaparin was administered daily for 5 days for thromboprophylaxis during the first hospitalization, and enoxaparin and unfractionated heparin were administered 6 weeks later for an inferior ST-elevation myocardial infarction. At that hospitalization, thrombocytopenia was present (76 × 109/L) and platelets declined further (41 × 109/L) before stabilizing at 70 × 109/L despite ongoing enoxaparin administration and no specific treatment. One day later pulmonary emboli was discovered, and initial treatment included administration of tenecteplase and unfractionated heparin. Significant laboratory analyses included a positive screening test for antibodies to heparin/platelet factor 4. Subsequent functional whole blood impedance aggregometry assay confirmed the diagnosis of heparin-induced thrombocytopenia. Further treatment included discontinuation of heparin and initiation of danaparoid. Platelets declined to a nadir of 25 × 109/L before gradually improving over the following 2 weeks.
The authors concluded that the thrombocytopenia described in this case was related to heparin administration and was of delayed onset. The proposed mechanism was high levels of platelet factor 4/heparin antibodies that activated platelets and caused thrombocytopenia and thrombosis after heparin cessation.
Enoxaparin [“Lovenox”]
Heparin [Heparin]
Balendran S et al (C Forsyth, Department of Medicine, Wyong Hospital, Sydney, New South Wales, Australia) Delayed-onset heparin-induced thrombocytopenia complicated by arterial and venous thromboses. Intern Med J 48:98–100 (Jan) 2018
Clomiphene Citrate No. 77
Hepatotoxicity
A 31-year-old male patient was hospitalized with brown urine and severe upper abdominal pain that started approximately 3 days after starting clomiphene citrate (50 mg daily) for the management of oligozoospermia. The patient denied alcohol abuse. A physical examination revealed icterus and sclera but no rash. Abnormal laboratory values were indicative of liver injury and included aspartate aminotransferase (247.08 IU/L), alanine aminotransferase (419.61 IU/L), glutamyl aminopeptidase (490.6 IU/L), total bilirubin (73.53 µmol/L), and direct bilirubin (44.21 µmol/L). An abdominal computed tomography revealed cholecystitis. Clomiphene citrate was discontinued. Symptomatic support (not defined) and analgesics (not specified) were initiated, and within 5 days of hospitalization, a decrease in jaundice occurred with complete resolution by day 10. By day 10, some laboratory values had normalized, including aspartate aminotransferase, total bilirubin, and direct bilirubin. The remainder of the patient’s recovery was uneventful.
The authors concluded that this patient experienced livery injury related to clomiphene therapy based on the temporal relationship between the administration of the agent and appearance and resolution of symptoms and abnormal laboratory values. According to the Naranjo causality algorithm, this reaction was rated as probable in relation to drug therapy. The authors suggested that liver function should be assessed in patients who develop upper abdominal pain while taking clomiphene citrate.
Clomiphene Citrate [“Clomid”]
Zhang HM et al (LR Sun, Department of Pharmacy, The First Hospital, Jilin University, Changchun, China; e-mail:
Bisoprolol No. 78
Thrombocytopenia
A 52-year-old male inpatient developed sudden thrombocytopenia (6000 platelets/L) shortly after starting bisoprolol a few days after a stent implantation. Concurrent medications included a statin (not specified), oral antidiabetic drugs (not specified), and aspirin. The patient had no previous episodes of thrombocytopenia. A bone marrow biopsy revealed no abnormalities. Serological screenings for infectious etiologies were negative. An abdominal ultrasound was normal. A treatment course with intravenous immune globulin (1 g/kg/day for 2 days) had no effect on platelet counts. As bisoprolol was the last drug added to the patient’s regimen, it was suspected. A test for platelet antibodies related to bisoprolol was positive, and bisoprolol was discontinued. Treatment included a course of prednisolone (80 mg/day), and within approximately 1 month, the total platelet count normalized and the glucocorticoid was stopped.
The authors concluded that this patient developed thrombocytopenia related to bisoprolol therapy based on the temporal relationship between the administration of the drug and the appearance and resolution of the abnormal platelet count levels. They noted that bisoprolol is not commonly associated with this event.
Bisoprolol [Bisoprolol]
Mousinho F et al (AP Azevedo, Estrada Forte do Alto Duque, Lisboa, Portugal; e-mail:
Idarucizumab No. 79
Incomplete Dabigatran Reversal
Two cases of incomplete reversal of dabigatran by idarucizumab were described.
Case 1. An 86-year-old male was treated with dabigatran (150 mg twice daily) for 11 months for atrial fibrillation. During hospitalization for presumed pneumonia, concurrent medications included intravenous antibiotics and diltiazem, a digoxin load, and amiodarone for atrial fibrillation with rapid ventricular rate. Septic shock secondary to presumed toxic megacolon occurred 5 days after admission. Additional treatment included administration of vasopressors, intubation, and discontinuation of dabigatran. Surgical intervention was performed and required administration of fresh frozen plasma and packed red blood cells. Idarucizumab (5 g) and factor eight inhibitor bypass activity (21 units/kg) were administered for persistent postoperative blood loss. Significant laboratory findings at that time included a reduction in international normalized ratio (from >13.6 to 1.93) and elevated dabigatran concentration (1170 ng/mL; reference range = 40-240 ng/mL). Serum dabigatran concentration declined to 447 ng/mL; however, postoperative hemorrhage continued, and expiration occurred.
Case 2. A 62-year-old female was treated with dabigatran (150 mg twice daily) for 4 months for atrial fibrillation when she developed altered mental status and presumed mixed septic and cardiogenic shock. Concurrent medications were not reported. Significant laboratory findings included marked coagulopathy (international normalized ratio >13.6, activated partial thromboplastic time >150 seconds), elevated dabigatran concentration (2260 ng/mL), anemia (baseline hemoglobin = 16.3 g/dL; nadir = 7.5 g/dL day 2), and elevated serum creatinine (baseline = 1.13 mg/dL; peak = 1.98 day 2). Treatment included administration of fresh frozen plasma, platelets, packed red blood cells, and cryoprecipitate. Additional treatment included administration of idarucizumab (5 g) and factor eight inhibitor bypass activity (10 units/kg). Repeat dabigatran concentration declined to 1440 ng/mL; however, continuous renal replacement therapy was initiated and an additional dose of factor eight inhibitor bypass activity (10 units/kg) and idarucizumab (5 g) were administered. Dabigatran concentrations remained elevated, and care was withdrawn on day 4. Death was attributed to hemorrhagic stroke secondary to dabigatran and lactic acidosis due to ischemic bowel.
The authors concluded that these cases described incomplete reversal of dabigatran by idarucizumab. Proposed mechanisms included supratherapeutic dabigatran concentrations and elevated coagulation parameters.
Idarucizumab [“Praxbind”]
Steele AP et al (WE Dager, Department of Pharmacy Services, University of California, Davis Medical Center, 2315 Stockton Blvd, Sacramento 95817-2201, CA; e-mail:
Dietary Supplement No. 80
FDA Safety Communication: Contains Undeclared Medication
On February 27, 2018, the US Food and Drug Administration published a company notice regarding the voluntary recall of a dietary supplement that contained the pharmacologically active medication, sibutramine. Sibutramine is a diet suppressant that was removed from the US market in October 2010 related to a significant cardiovascular safety profile. Patients were advised to return the product and refrain from purchasing the product further.
Dietary Supplement [“Bella All Natural”]
FDA Safety Communication: Bella Diet Capsules by Bella All Natural: Recall—presence of sibutramine. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm598464.htm (Feb 27) 2018
Anti–Tumor Necrotizing Factor Agents No. 81
Autoimmune Hepatitis
In a retrospective cohort study, the medical records of 659 pediatric patients with inflammatory bowel disease who were receiving anti–tumor necrosis factor between 2000 and 2015 were assessed for the incidence and characteristics of drug-induced liver injury. This study was precipitated by the discovery of an index case in a 17-year old female patient with suspected drug-induced liver injury and autoimmune features after infliximab exposure (after 6 infusion cycles). The injury resolved entirely within 4 months after the discontinuation of infliximab without additional therapy. In the retrospective review, patients were included if alanine aminotransferase values were at least greater than twice the upper limit of normal. Of the 659 patients included in the review, more than half (62%) were male and had Crohn’s disease (73%). The median follow-up duration was 2.8 (interquartile range = 1.7-4.3) years. Median age at anti–tumor necrosis factor therapy initiation was 14.2 (interquartile range = 12.3-15.8) years. The majority of patients (n = 570) received a single anti–tumor necrosis factor agent, 80 received 2 agents, and 9 patients received 3 agents. The first anti–tumor necrosis factor agent used in most patients was infliximab (84%). Overall, 7.7% of the patients developed new alanine aminotransferase elevations while on anti–tumor necrosis factor. Most alanine aminotransferase elevations were mild and transient and attributable to alternate etiologies. Biochemically, all cases had a hepatocellular pattern of injury without cholestasis, coagulopathy, or hypoalbuminemia. The median latency to alanine aminotransferase elevation was 12.6 weeks. Median time to alanine aminotransferase normalization was 18.1 weeks. No additional clear cases of autoimmune hepatitis were identified. Alanine aminotransferase normalized in the majority of patients (93%). In addition to the index case, 5 liver biopsies were performed in patients with alanine aminotransferase elevation. Application of the Roussel-Uclaf Causality Assessment Method identified 12 patients with a score ≥3 (at least “possible” causality). In 5 of the cases identified with the Roussel-Uclaf Causality Assessment Method, an alternate drug was identified as the causative agent.
The authors concluded that the use of anti–tumor necrosis factor agents in pediatric patients is commonly associated with transient liver enzyme abnormalities.
Infliximab [“Remicade”]
Adalimumab [“Humira”]
Goliumamb [“Simponi”]
Riccuito A et al (AM Griffiths, Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada; e-mail:
Oxcarbazepine No. 82
Stevens-Johnson Syndrome
A 6-year-old male patient was hospitalized with a body-wide red maculopapular rash that started approximately 10 days after starting oxcarbazepine (12 mg/kg/day for 5 days, then increased to 18 mg/kg/day) for the treatment of uncontrolled seizures. The rash had started around the mouth and lips and spread to other areas of the body. Laboratory values were within normal limits. No other medications were noted. Stevens-Johnson syndrome was diagnosed and treatment included the administration of topical corticosteroid. Peeling of the lesions on the cheeks and arms occurred on hospital day 3, but significant improvement had occurred by day 7 with discharge from the hospital. Two months postdischarge, a patch test with carbamazepine and oxcarbazepine were negative.
The authors concluded that this patient experienced drug-induced Stevens-Johnson syndrome.
Oxcarbazepine [“Trilepta”]
Beken B et al (B Beken, Department of Pediatric Allergy and Immunology, Trakya University Medical School, Edirne, Turkey; e-mail:
Glucocorticoids No. 83
Cataracts, Glaucoma
A systematic review and meta-analysis including 28 randomized controlled trials and 10 observational studies was performed to determine the association between systemic glucocorticoid use and the risk of developing cataracts and/or glaucoma in patients with rheumatoid arthritis. Cataracts and glaucoma were reported in 3 of 28 randomized controlled trials. A significant difference in the risk of developing cataracts and glaucoma for glucocorticoid exposed versus unexposed rheumatoid arthritis patients was not observed (risk difference 0.01 events/patient, 95% confidence interval CI = –0.01 to 0.03, and risk difference 0.01 events/patient, 95% confidence interval = –0.02 to 0.04, respectively). The cumulative 2-year incidence of cataracts in randomized controlled trials reporting cataract occurrence was 2.0% (95% confidence interval = 0.6 to 6.6), which is less than the expected population cumulative incidence in patients under the age of 75 years (6% over 1 year and 12% over 2 years). In observational studies, the combined risk of developing cataracts in glucocorticoid-exposed patients was 0.07 events per person (95% confidence interval = 0.04 to 0.10) and the odds ratio was 2.1 (95% confidence interval = 1.5 to 2.9). No significant association between glucocorticoid use and glaucoma was found in the 3 observational studies that reported glaucoma (combined risk difference 0.00, 95% confidence interval = 0.01 to 0.02).
The authors concluded that an association between glucocorticoid use and the development of cataracts in rheumatoid arthritis patients was observed in observational studies but not randomized controlled trials and that there was no association with regard to the development of glaucoma. The authors suggested that significant underreporting may have been present in the randomized controlled trials.
Glucocorticoids [Glucocorticoids]
Black RJ et al (RJ Black, Discipline of Medicine, The University of Adelaide, Adelaide, Australia; e-mail:
Gentamicin No. 84
Adverse Effects
A systematic review including 36 studies was performed to identify the frequency and type of adverse events associated with a single dose of gentamicin (intravenous or intramuscular) in adults aged 16 years and older for any indication. The review included randomized controlled trials (n = 11), cohort studies (n = 18), a retrospective survey, pharmacokinetic studies (n = 3), and quasi-experimental studies (n = 3). A total of 24 107 participants received a single dose of gentamicin (dose range = 1 mg/kg to 480 mg). Indications for use included prophylaxis during surgery, cystogram, transrectal prostate biopsy, sepsis, gonorrhea, and urinary tract infection. Concurrent antibiotics included flucloxacillin, metronidazole, a broad-spectrum β-lactam antibiotic, amoxicillin/clavulanate, aztreonam, cefazolin, clindamycin, vancomycin, azithromycin, fluoroquinolones, teicoplanin, dicloxacillin, or no concurrent antibiotic. Due to study heterogeneity, a meta-analysis was not performed. Reported adverse events in patients receiving gentamicin included increased creatinine or acute kidney injury (n = 2599), the majority of which were reversible cases; dizziness (n = 7); and elevated serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase. No cases of ototoxicity were reported.
The authors concluded that this review suggested that a single dose of gentamicin can affect renal function; however, it was usually mild and transient. The proposed mechanism of nephrotoxicity was reuptake of gentamicin in the proximal renal tubule cells resulting in high drug concentrations within the tubule cells.
Gentamicin [“Garamycin”]
Hayward RS et al (RS Hayward, Whittall Street Clinic, University Hospitals Birmingham NHS Trust, Birmingham B4 6DH, UK; e-mail:
Methadone No. 85
Poisoning
A systematic review and meta-analysis including 12 studies was performed to describe the causes and clinical symptoms of methadone poisoning in children admitted to hospitals in Iran. A total of 7 articles were included in the meta-analysis, and the prevalence of symptoms in referred patients was 44% (95% confidence interval = 0.288-0.609; I2 = 93%). The most frequently reported symptoms of methadone poisoning included loss of consciousness (80%, event rate 95% confidence interval = 0.612-0.928), meiotic pupils (76%, event rate 95% confidence interval = 0.690-0.827), drowsiness (72% event rate 95% confidence interval = 0.323-0.934), vomiting (56%, event rate 95% confidence interval = 0.357-0.754), apnea (48%, event rate 95% confidence interval = 0.383-0.589), nonapneic breathing (41%, event rate 95% confidence interval = 0.223-0.634), and cyanosis (25%, event rate 95% confidence interval = 0.117-0.460). In 4 studies, a significant positive relationship was observed between methadone poisoning in children and family’s income level (P < .05). The most frequently reported reasons for methadone poisoning included accidental ingestion by children (69.7%), storage in inappropriate containers (62.91%), parents’ mistake in feeding the drug to children (60.67%), parents’ addiction (50.21%), parents’ low level of education (38%), history of child poisoning (29.1%), parents’ psychological disorders (21%), and intentional poisoning by parents or other family member (9.7%).
The authors concluded that methadone poisoning in children may be limited by storing in a suitable container away from children. They also stated it was essential to educate parents on health issues of their children.
Methadone [“Dolophine,” “Methadose”]
Allameh Y et al (M Babakhanian, Social Determinants of Health Research Center, Semnan University of Medical Sciences, Semnan, Iran; e-mail:
Erlotinib No. 86
Conjunctivitis
A 72-year-old male patient developed pain, photophobia, and epiphora in both eyes shortly after taking a double dose of erlotinib (300 mg daily) for 4 days. The patient had been taking the medication at a dose of 150 mg once daily for approximately 2 weeks for metastatic non–small cell lung cancer. A physical examination, revealed xerosis cutis on the face, particularly near the nose and eyes. Ectropion of the lower eyelids and lid margin hyperaemia (++) of both eyes was also observed. The corneas of both eyes were normal. Treatment included the discontinuation of erlotinib with levofloxacin and pranoprofen eye drops, which resulted in resolution of the skin and ocular symptoms within 1 week. Once erlotinib was reinitiated, no further recurrences occurred at the regular dose (150 mg once daily).
The authors concluded that this patient’s conjunctivitis was related to an overdosing of erlotinib and that clinicians should be aware of this potential adverse event associated with the use of the drug.
Erlotinib [“Tarceva”]
Sun P et al (S Li, Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; e-mail:
Warfarin, Enzalutamide No. 87
Drug Interaction: Increased International Normalized Ratio Values
A 77-year-old male patient developed an increased international normalized ratio shortly after starting enzalutamide (160 mg daily) therapy. Concurrent medications included amlodipine, multivitamin, ergocalciferol, cyanocobalamin, gabapentin, duloxetine, and warfarin. Initially, the patient’s international normalized ratio was relatively stable on weekly warfarin doses of 42 to 45 mg. At the most recent visit, the international normalized ratio was 3.5 during warfarin 45 mg per week. The patient was subsequently hospitalized for decreased appetite and increased weakness as well as shortness of breath. On hospital day 2, the patient’s international normalized ratio was 2. During hospitalization and a rehabilitation facility stay, the patient’s international normalized ratio was never greater than 1.5. At a follow-up clinic appointment, the international normalized ratio was 1.4 on a 56 mg weekly dose of warfarin. Due to a lack of rise in international normalized ratio after 3 doses of warfarin 8 mg, the patient’s dose was increased to 63 mg per week (50% increase from 42 mg weekly dose; 40% increase from initial 45 mg weekly dose). At the patient’s next visit, the international normalized ratio was 2.1, despite reporting one missed dose that week. The patient also had developed a full body rash of unknown origin. All medications were stopped. Due to the discontinuation of enzalutamide, the warfarin dose was decreased to 42 mg/week, and at weekly follow-up visits, the international normalized ratios were therapeutic at 2.6 and 2.1, respectively. After enzalutamide was restarted, the warfarin dose was increased to 63 mg/week, resulting in an international normalized ratio of 3.2 and 3.8 at the next 2 clinic visits. The warfarin dose was subsequently reduced to 57 mg/week. The international normalized ratio was therapeutic at the next clinic visit.
The authors concluded that this patient’s changing international normalized ratio patterns were related to a drug interaction between warfarin and enzalutamide based on the temporal relationship between the administration of the drugs and the international normalized ratio patterns. They noted that though this interaction was potentially identified in a phase I study, this is the first published case report. They recommended that patients receiving warfarin and concurrent enzalutamide may require approximately 30% to 50% adjustment in their warfarin dosage to maintain a therapeutic international normalized ratio. According to the Naranjo Adverse Drug Reaction probability scale, this reaction was classified as probable in relationship to the drug interaction. The proposed mechanism of action was enzalutamide’s activity on CYPC29 substrates such as warfarin.
Warfarin [“Coumadin”]
Enzalutamide [“Xtandi”]
Parret JL et al (RE Owens, Wingate University School of Pharmacy, Department of Pharmacy Practice, Hendersonville, NC; e-mail:
Compounded Drug Products No. 88
FDA Safety Communication
On March 2, 2018, the US Food and Drug Administration altered health care professionals and patients not to use drug products produced by Cantrell Drug Company of Little Rock, Arkansas, due to serious deficiencies in the sterility practices in the compounding operations that put patient safety at risk. Administration of contaminated or otherwise poor-quality drug products can result in serious and life-threatening injury or death.
Compounded Drug Products [Compounded Drug Products]
FDA Safety Communications: Compounded drug products from Cantrell Drug Company: FDA warning—serious deficiencies in quality and sterility assurance. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm599112.htm (Mar 2) 2018
January–March 2018 Index
A
Methods to determine direct costs, 1
Bezoars resulting in small bowel obstruction, 17*
Liver failure, 68
Severe adverse events, 45
Autoimmune hepatitis, 81
Poisoning exposures in young children, 51
Acute open angle glaucoma, 55
Immune-mediated necrotizing myopathy, 16
Rhabdomyolysis, 4
B
Allergic contact dermatitis, 19
Interaction with laboratory measurement of thyroid hormones, 21
Thrombocytopenia, 78
Long-term effects in neonates, 42
C
Noncholestatic acute hepatocellular injury, 27
Cannabinoid hyperemesis syndrome, 7
Fatty liver, 43*
Adverse drug reactions: rate and incidence, 48
Drug-induced liver injury, 63
No increased risk of atrial fibrillation, 47
Drug-induced immune-mediated thrombocytopenia, 70
FDA safety alert: long-term mortality risk in patients with heart disease, 61
Hepatotoxicity, 77
Cardiotoxicity, 9
FDA safety communication: restriction to use in adults, 14
FDA safety communication, 88
Drug interaction: increased trough cyclosporine concentrations, 25
D
FDA safety communication: contains undeclared medication, 80
FDA safety communication: possible salmonella contamination, 31, 35
Respiratory-related morbidity and mortality, 69
Inpatient deaths related to drugs, 71
E
Septic shock, pyelonephritis, bacteremia, 2*
Delayed-onset thrombocytopenia, 76
Conjunctivitis, 86
F
Drug-induced liver injury, 13
Amnestic syndrome, 58
Hepatotoxicity, 57
Anaphylaxis, 18*
Accidental ingestion by pediatric patient, 29
QTc interval prolongation, torsades de pointes, 54
Persistent extrapyramidal symptoms, 75
G
FDA safety communication: prolonged residual body storage, 8
Adverse effects, 84
Cataracts, glaucoma, 83
Risk of liver cancer reduced, 20
Epidermal desquamation, 12
H
Non–immediate allergic cutaneous reactions, 23
FDA news release: risk-based evaluation, 11
Restrictive cardiomyopathy, 67
I
Incomplete dabigatran reversal, 79
Discontinuation, 34
Pericarditis in pediatric patient, 64
K
Risk of liver disease, 39
L
Short-term and long-term pediatric outcomes of antenatal exposure, 32
Skin depigmentation, 28
Eosinophilia, 74
Severe hypoglycaemia, 49
Acute hepatitis, 41
Overdose, 52
FDA safety communication: packaging changes, 50
Acute liver injury, 30
Colorectal cancer, 66
M
Liver failure, 65
Poisoning, 85
Cholestatic jaundice, 24
Macular toxicity, 26
N
Acute pneumonitis, 62
FDA news release: instructions for discontinuation, 5
O
Boxed warning: dosing clarification, 46
FDA news release: illegal marketing of unapproved products, 53
Stevens-Johnson syndrome, 82
P
Fatal poisonings, 60
Risk of ischemic stroke, myocardial infarction, 73
R
Anaphylactic shock, 44
Henoch-Schonlein purpura, IgA nephropathy, 59
FDA safety communication: anaphylaxis, hypersensitivity reactions, 33
Occupational allergic respiratory disease, 22*
S
Reported exposures in poison centers, 37
Oxalate nephropathy, 36
FDA news release: warning letters, 3
T
Drug interaction: life-threatening bleeding, 10*
Coagulopathy, decreased fibrinogen, 38
Hypoglycemia, 56
Hemolytic anemia, 6
V
Drug-induced hypersensitivity syndrome, 15
Acute interstitial nephritis, 40
Drug interaction: syndrome of inappropriate diuretic hormone, 72
W
Drug interaction: increased international normalized ratio values, 87