Abstract
Keywords
RIVASTIGMINE (TRANSDERMAL) No. 160
Angioedema
An 84-year-old female patient was hospitalized with nausea, vomiting, dizziness, confusion, lethargy, and swelling on lips and tongue approximately 1 month after starting a rivastigmine patch (5 cm2/day) for the treatment of Alzheimer dementia. The dosage had been increased to 10 cm2/day at 3 days prior to admission, with symptoms occurring after starting the third dose. Concurrent medications included lisinopril (20 mg/day) plus hydrochlorothiazide (25 mg/day), nifedipine (30 mg/day), escitalopram (10 mg/day), calcium carbonate (2500 mg/day) with vitamin D3 (880 IU/day), and alendronate (70 mg/week). No additional changes had been made in the medication regimen with the exception of the initiation of rivastigmine therapy. A physical examination revealed a swollen lower lip and tongue and mild swelling of the upper and lower eyelids. She was not able to ambulate independently. Laboratory values were within normal limits. The patient was diagnosed with angioedema due to rivastigmine patch. Treatment included the discontinuation of the patch and the initiation of intravenous pheniramine maleate (45.5 mg), intravenous methylprednisolone (60 mg), 5% dextrose (100 mL), and nasal oxygen (2 L/min). The patient experienced a full recovery within 2 days. A follow-up over a 1-year period demonstrated no further cases of recurrence.
The authors concluded that this patient experienced angioedema related to rivastigmine patch therapy based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms. According to the Naranjo causality algorithm, this reaction was classified as probable.
Rivastigmine, Transdermal [“Exelon”]
Naharci MI & Tasci I (M Naharci, Division of Geriatrics, Gulhane Medical Faculty, Health Sciences University, Ankara, Turkey; e-mail:
ACETYLCYSTEINE No. 161
Adverse Effects
A cohort study including 1011 paracetamol poisonings was performed to compare the rate of adverse events related to acetylcysteine antidote when infused as a traditional 3-bag protocol (150 mg/kg over 1 hour, then 50 mg/kg over 4 hours, and then 100 mg/kg over 16 hours) or a modified 2-bag protocol (first bag: 200 mg/kg over 4 hours; and second bag: 100 mg/kg over 16 hours). A total of 476 poisonings required acetylcysteine, 313 of which received the 3-bag protocol and 163 received the 2-bag protocol. The majority of paracetamol poisonings occurred in females (78% and 71% in the 3- and 2-bag protocols, respectively), were deliberate self-poisonings (59% and 58% in the 3- and 2-bag protocols, respectively), and nearly 60% involved co-ingestion of other agents. The median age was lower in patients receiving the 3-bag protocol (25 years vs 31 years, P = .006). The median ingested paracetamol dose was 245 mg/kg and 235 mg/kg for the 3-bag and 2-bag protocol recipients, respectively. The acetylcysteine infusion was started at a median of 8 hours postingestion in both groups. Median time to first paracetamol concentration was taken at 6 and 5 hours postingestion in the 3-bag and 2-bag recipients, respectively, and were similar (810 mmol/L vs 824 mmol/L, P = .31). Significantly fewer anaphylactoid reactions (5% vs 14%, P = .002) and severe reactions (2% vs 8%, P = .007) occurred in recipients of the 2-bag protocol compared with the 3-bag protocol. Fewer anti-allergy medications were prescribed to patients that received the 2-bag protocol (4% vs 11%, P = .01). No differences were observed in rate of nausea/vomiting, skin reactions, and hepatotoxicity. In the 3-bag protocol, the median paracetamol concentrations were significantly lower in patients who experienced an anaphylactoid reaction than those that did not (332 µmol/L vs 709 µmol/L, P = .005); however, concentrations were not significantly different in the 2-bag protocol.
The authors concluded that the results of this study demonstrated a lower rate of adverse reactions when acetylcysteine was administered as a modified 2-bag protocol than the traditional 3-bag protocol. The proposed mechanism was the reduced infusion rate of the initial infusion.
Acetylcysteine [“Actedote”]
McNulty R et al (R McNulty, Western Sydney Toxicology Service, Westmead, Australia; e-mail:
ACNE, ANALGESIC PRODUCTS (TOPICAL) No. 162
FDA Safety Alert: Bacterial Contaminant
On May 29, 2018, the US Food and Drug Administration announced that certain topical acne and analgesic products may be contaminated with bacteria and should not be used, particularly in immunocompromised patients.
Acne Products [“Acne Shave Moisturizer and Kit”]
Analgesic Products [“X-Jow Pain Gel”]
FDA Safety Communication: X-Jow and Acne Shave Products by Shadow Holdings: Voluntary recall—Due to possible bacterial contamination. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm609019.htm (May 29) 2018
IMMUNOTHERAPY, ALLERGY (SUBCUTANEOUS) No. 163
Anaphylaxis
A 51-year-old female patient developed shortness of breath, loss of visual acuity, tremors, and loss of consciousness approximately 2 months after initiating allergy shots (including trees, grasses, weeds, ragweeds, molds, and environmental allergens administered 1 to 3 times a week with initial dose 1:2000 000 dilution and a target maintenance dose of 1:2000). Concurrent medications included albuterol, desloratadine, loratadine, progesterone cream, testosterone, dienogest, and montelukast. Treatment included diphenhydramine (100 mg once) and albuterol inhalation (180 µg once). Allergy shots were continued with smaller titration increments. Approximately 6 months later, severe shortness of breath occurred immediately after her regularly scheduled injection. Additional treatment included oxygen (4 L via nasal cannula) and epinephrine injection (0.3 mg twice). Resuscitation efforts were initiated due to unresponsiveness, and 4 consecutive seizures with associated urinary incontinence and tongue lacerations occurred. Treatment ultimately included transfer to the emergency department and intubation. Computed tomography and magnetic resonance imaging revealed no abnormalities, and an electroencephalogram was negative for underlying seizure disorder. The patient’s condition improved gradually, and extubation was performed the following day. After recovery, handwriting and vision changes as well as short-term memory loss was noted and did not resolve.
The authors concluded that the occurrences of anaphylaxis described in this case were related to subcutaneous allergy immunotherapy. The proposed mechanism of neurologic sequela was significant global hypoperfusion and hypoxia.
Immunotherapy, Allergy (Subcutaneous) [Immunotherapy]
Mangold M & Qureshi M (M Mangold, 112 Huckleberry Ln, Henderson, NV 89074; e-mail:
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS No. 164
Risk of Gastrointestinal Bleeding in Elderly People
A retrospective hospital-based review evaluated the risks of gastrointestinal bleeding associated with nonsteroidal anti-inflammatory drugs in 4728 elderly people (over 60 years old) in Beijing. A total of 928 patients had gastrointestinal bleeding; 3800 did not demonstrate bleeding. In multivariate analysis, risk factors associated with an increased risk of bleeding included family history of gastrointestinal bleeding (odds ratio = 3.348; P = .000), history of peptic ulcers (odds ratio = 4.068; P = .000), history of cardiovascular and cerebrovascular disease (odds ratio = 1.476; P = .001), diabetes mellitus (odds ratio = 1.408; P = .000), antiplatelet drugs (odds ratio = 3.106; P = .000), Helicobacter pylori infection (odds ratio = 1.312; P = .001), cholesterol level (odds ratio = 0.516; P = .000), upper abdominal discomfort (odds ratio = 3.467; P = .000), anorexia (odds ratio = 2.038; P = .000), and nonsteroidal anti-inflammatory drugs therapy for 0.5 to 3 months (odds ratio = 0.780; P = .000). The top 5 factors associated with gastrointestinal bleeding were melena, hematemesis, antiplatelet drugs, cholesterol level, and upper abdominal discomfort.
Based on the results of this hospital-based retrospective review, the authors concluded that several independent factors were associated with an increased risk of gastrointestinal bleeding with the use of nonsteroidal anti-inflammatory drugs in elderly hospital patients, including a family history of gastrointestinal bleeding, history of peptic ulcers, history of cardiovascular and cerebrovascular disease, diabetes mellitus, antiplatelet drugs, Helicobacter pylori infection, hypocholesterolemia, and nonsteroidal anti-inflammatory drugs used for 0.5 to 3 months.
Nonsteroidal Anti-Inflammatory Drugs [“Ibuprofen,” “Indomethacin,” “Naproxen,” “Tolmetin”]
Chi TY et al (Zhang M, Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing 100053, China; e-mail:
VALPROIC ACID, CLOZAPINE No. 165
Drug Interaction: Increased Clozapine Metabolism
A retrospective case-control analysis of 45 adult hospitalized patients receiving both clozapine and valproic acid and 45 matched controls receiving only clozapine was performed to evaluate a potential pharmacokinetic interaction between clozapine and valproic acid. The controls were matched for age, sex, smoking status, concurrent medication use, and markers of inflammation. The median number of comedications in both groups was 3 (P = .191). Median dose-corrected serum concentrations for clozapine’s main metabolite, norclozapine (0.44 [25th percentile, 0.27; 75th percentile, 0.58] (ng/mL)/(mg/d) vs 0.78 [0.60-1.07] (ng/mL)/(mg/d); P = .000) and norclozapine to clozapine ratio (0.40 [0.36-0.47] vs 0.71 [0.58-0.84]; P = .000) were significantly lower in the group receiving both valproic acid and clozapine; however, the median dose-corrected serum concentration of clozapine was not significantly different between the 2 groups. Serum concentrations were similarly reduced in analyses specific for smoking and sex. The reductions in median dose-corrected norclozapine serum concentration were larger among nonsmokers (0.49 [0.38-0.60] vs 1.02 [0.63-1.29]) compared with smokers (0.39 [0.23-0.54] vs 0.68 [0.59-0.84]) and females (0.45 [0.29-0.60] vs 0.98 [0.63-1.28]) compared with males (0.44 [0.25-0.58] vs 0.69 [0.60-0.98]).
The authors concluded that results of this study suggested that valproic acid increased clozapine metabolism with a predominant effect on norclozapine metabolism. The proposed mechanism was valproic acid–induced induction of the cytochrome P450 enzymatic pathway.
Valproic acid [“Depakene”]
Clozapine [“Cloazaril,” “Fazaclo ODT,” Versacloz”]
Hommers L et al (L Hommers, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, D-97080 Würzburg, Germany; e-mail:
OPIOIDS No. 166
FDA Communication: Warning Letter to Illegal Sales of Opioids on the Internet
On June 5, 2018, the US Food and Drug Administration (FDA) announced that it has warned 9 online networks, operating a total of 53 websites, that they must stop illegally marketing potentially dangerous, unapproved, and misbranded versions of opioid medications (eg, tramadol and oxycodone). The announcement stated that the FDA is taking this action to protect US consumers from illicit opioids sold illegally on the Internet. As part of this effort, the FDA is hosting a summit with Internet stakeholders to find new methods to work collaboratively.
Opioids [“Oxycodone,” “Tramadol”]
FDA News Release: FDA takes action against 53 websites marketing unapproved opioids as part of a comprehensive effort to target illegal online sales. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm609869.htm?utm_campaign=06052018_PR_FDA%20takes%20action%20against%2053%20websites%20marketing%20unapproved%20opioids&utm_medium=email&utm_source=Eloqua (Jun 5) 2018
VACCINES No. 167
Adverse Events
In a cross-sectional study, the utility of the Harare City Adverse Events Following Immunizations surveillance system was assessed for surveilling adverse events related to immunizations. A total of 21/41 clinics were randomly selected. Interviewer-administered questionnaires were used to collect data. Of the 51 respondents, 98% knew the purpose of the adverse events following immunizations system, 94% knew at least 2 presenting symptoms of adverse events following immunizations, and 77% were aware of the correct date of form submission to the next level. Reasons associated with underreporting or lack of reporting included receiving no feedback (47.1%), fear of victimization (31.4%), and little time during the work shift (21.6%). A total of 84% were willing to continue participating. All 21 clinics included in the study had written adverse events following immunization guidelines and case definitions but only 14 clinics had adequately stocked emergency drugs. The total cost for a single notification was estimated at $22.30.
Based on the results of this small study, the authors concluded that the Adverse Events Following Immunizations surveillance system was useful, simple, acceptable, timely, stable, and representative but costly. It appeared that the surveyed respondents were knowledgeable regarding procedures and reporting practices. Several factors, such as lack of time and fear of victimization, were identified as limitations in reporting.
Vaccines [Immunizations]
Zvanaka S et al (J Tsitsi, MPH Programme, Department of Community Medicine, University of Zimbabwe, Harare, Zimbabwe) Evaluation of the adverse events following immunizations surveillance system in Harare City, Zimbabwe, 2016: a descriptive cross sectional study. Pan Afr Med J 28:308 (Dec) 2017
DRUGS No. 168
Drug-Induced Liver Injury in Patients With Cutaneous Drug Reactions
The prevalence of drug-induced liver injury was evaluated in a retrospective cohort study of Australian inpatients (from 2 hospitals) with cutaneous adverse drug reactions, including characteristics of liver injury, risk factors, suspected involved medications, and outcomes. A total of 104 patients with cutaneous adverse drug reactions were identified, of which 31.7% had liver injury. Of these, 50% had a drug reaction with eosinophilia and systemic symptoms, and 30.2% had Stevens-Johnson syndrome/toxic epidermal necrolysis. The majority (69.7%) of the liver injury cases involved a cholestatic/mixed pattern; 18.2% had severe disease. Significant risk factors for the development of liver injury were not identified. A total of 59 drugs were involved in the reported cases, with the most commonly cited therapeutic drug class associated with drug induced liver injury being antimicrobials (62.7%). The median duration of hospitalization was significantly longer in patients with liver injury compared with those without liver injury (19 vs 11 days; P = .002). The mortality rate was not significantly different between the 2 groups (15.2% vs 9.9%). No patient required liver transplantation.
Based on the results of this study, the authors concluded that drug liver injury commonly occurs in patients with cutaneous adverse drug reactions. In addition, these patients experience longer hospitalization periods.
Drugs [Drugs]
Fang WC et al (WC Fang, Department of General Medicine, The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia; e-mail:
ANTIDEPRESSANTS No. 169
Clitoris Engorgement
A 39-year-old female patient complained of occasional burning, pinpricks, and swelling of the clitoris approximately 2 days after starting escitalopram (20 mg daily) for the treatment of adjustment disorder with depressed mood. Escitalopram was discontinued followed by a full recovery from symptoms within a week. Substitution with duloxetine (30 mg daily) was associated with the development of similar symptoms within 2 days after initiation of therapy. After discontinuation, there was immediate improvement and disappearance of symptoms within a few days. The patient no longer required medications due to spontaneous resolution of her psychiatric diagnosis. However, approximately 2 years later, the patient experienced similar symptoms after the initiation of venlafaxine (75 mg daily) for the management of the adjustment disorder with mood changes. As with the other events, complete resolution of the symptoms occurred within 1 week after the drug was discontinued.
The authors concluded that this patient experienced clitoris engorgement after exposure to antidepressant therapy based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms.
Antidepressants [“Escitalopram,” “Duloxetine,” “Venlafaxine”]
Raudino F & Buono G (F Raudino, Department of Neurology, Valduce Hospital, Como, Italy; e-mail:
ANTIMICROBIALS (PARENTERAL) No. 170
Catheter Complications in Outpatient Parenteral Therapy
The associations between intravenous antimicrobial agent(s) and catheter complications was evaluated in a prospective cohort study of 339 adult patients requiring home-based outpatient parenteral antimicrobial therapy. The patients were discharged from 2 academic medical centers. The mean age was 52 years, with approximately half of the patients (46.9%) being female. Patients had catheters in place for a median of 33 days. Vesicant antimicrobials were not associated with an increased rate of catheter complications (adjusted incidence rate ratio = 1.63; 95% confidence interval = 0.89-2.96). In contrast, drugs associated with an increased rate of catheter complications included vancomycin and daptomycin (adjusted incidence rate ratio = 2.32, 95% confidence interval = 1.20-4.46); and adjusted incidence rate ratio = 4.45, 95% confidence interval = 1.02-19.41, respectively). Other nondrug factors associated with an increased risk of catheter complications included Staphylococcus aureus infections (adjusted incidence rate ratio = 2.13; 95% confidence interval = 1.09-4.19) and midline catheters (adjusted incidence rate ratio = 9.44; 95% confidence interval = 2.12-41.97).
The authors concluded that, in this study, antimicrobial agents falling into standard definitions of vesicants as extremes of pH are not associated with catheter complications. However, vancomycin (classified as a vesicant antimicrobial) and daptomycin (should be considered as a vesicant antimicrobial) were associated with an increased risk of catheter complication.
Antimicrobials, Parenteral [“Daptomycin,” “Vancomycin”]
Keller SC et al (SC Keller, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, 1800 E Monument St, 4th Floor, Baltimore, MD 21287; e-mail:
DIAZOXIDE No. 171
Study Stopped Due to Intolerance
A randomized, double-blind, placebo-controlled, crossover study conducted by the National Institute of Mental Health to assess the efficacy and safety of a 3-week course of diazoxide (200-400 mg daily) in 6 participants with treatment-refractory major depressive disorder was stopped prematurely related to severe adverse events. The primary clinical outcome measure was change in Montgomery-Asberg Depression Rating Scale score from baseline to posttreatment. Adverse events documented in the trial included but were not limited to elevated liver function tests, hypotension, headache, edema, muscle/bone/joint pain, tachycardia, nausea, and dizziness. The events were significant enough to cause all the patients to withdraw from the study.
The authors concluded that the adverse effects that were associated with the use of diazoxide were significant to cause patient withdrawal from the study. The authors also stated that despite the fact that these results are negative, they are an important addition to the literature.
Diazoxide [Diazoxide]
Kadriu B et al (B Kadriu, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Room 7-5545, Bethesda, MD 20892; e-mail:
QUETIAPINE No. 172
Delayed Seizures After Overdose
A 21-year-old female patient was hospitalized 22 hours after an intentional ingestion of quetiapine (1400 mg) with alcohol (5 drinks). Symptoms included somnolence and sleeping for 19 hours. Prescribed medications included bupropion XL (300 mg) and quetiapine (50 mg), which was started 4 days previously as part of a regimen for major depressive disorder. On admission, a 12-lead electrocardiogram was normal, and urine toxicology screen was negative for illicit drug use. Approximately 6 hours after admission to the psychiatry ward and approximately 28 hours after the overdose, the patient experienced a generalized tonic-clonic seizure that lasted 30 seconds with spontaneous resolution. Symptoms following the seizure included somnolence, tachycardia, and altered mental status. Treatment included the administration of magnesium sulfate, and the postictal symptoms gradually resolved over several hours. No additional seizure activity was noted during the remainder of her hospital stay, and the patient was discharged 8 days later.
The authors concluded that this patient experienced a delayed-onset seizure related to the overdose of quetiapine. The authors noted that this is a rare effect with only 2 other published case reports in the literature. The authors cautioned clinicians who are caring for similar patients to monitor for delayed effects.
Quetiapine [“Seroquel”]
Chen JA et al (EH Cheung, Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine, Los Angeles, CA 90095; e-mail:
RANITIDINE No. 173
Sleep Disturbance
A 40-year-old male patient developed difficulty falling asleep, disturbing dreams, and nighttime awakenings approximately 3 days after starting ranitidine (150 mg twice daily). Concurrent medications included topical imiquimod 5% cream. Previous therapy was topical 40% salicylic acid pad, which was not successful for a verrucous plaque on the right foot. Additional symptoms included gastroesophageal reflux disease-like with a constant full sensation in the middle of his chest, sleep talking, and bizarre dreams. After 3 weeks of ranitidine therapy, he self-discontinued the medication; all symptoms promptly resolved. Approximately 3 weeks later, the patient restarted ranitidine, and within 1 day, similar symptoms recurred. After discontinuing ranitidine again, all symptoms stopped and did not recur.
The authors concluded that this patient experienced sleep disturbances related to ranitidine therapy based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms. In addition, the patient had a positive rechallenge with the drug.
Ranitidine [“Zantac”]
Werbel T & Cohen PR (T Werbel, School of Medicine, University of California, San Diego Moores Cancer Center, San Diego, CA; e-mail:
ENZALUTAMIDE No. 174
Rash
An 87-year-old male patient developed erythematous macules on his trunk and extremities approximately 2 weeks after starting daily enzalutamide for castration-resistant prostate cancer. A physical examination revealed a diffuse erythematous maculopapular eruption on his trunk and extremities. A skin biopsy revealed a dermal and perivascular infiltration. Treatment included the discontinuation of the drug and the administration for topical betamethasone butyrate propionate ointment. Enzalutamide was restarted again at a lower dose with the recurrence of similar symptoms approximately 2 days later. He continued the drug with continued topical steroid therapy.
The authors concluded that this patient experienced a maculopapular eruption related to enzalutamide therapy based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms. In addition, the patient had a positive rechallenge with the drug.
Enzalutamide [“Xtandi”]
Saito-Sasaki N et al (Y Sawada, Department of Dermatology, University of Occupational and Environmental Health, 1-1 Isei-gaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan; e-mail:
JANUARY–JUNE 2018 INDEX
A
Adverse effects, 161
FDA safety communication: bacterial contamination, 162
Methods to determine direct costs, 1
Compulsive gambling behaviour, 124
Bezoars resulting in small bowel obstruction, 17*
Liver failure, 68
Severe adverse events, 45
Clitoris engorgement, 169
Meta-analysis: risk of epithelial ovarian cancer, 111
Autoimmune hepatitis, 81
Catheter complications in outpatient parenteral therapy, 170
Poisoning exposures in young children, 51
Neonatal congenital malformations associated with use during pregnancy, 158, 159
Acute open angle glaucoma, 55
Hyperprolactinemic galactorrhea, 154
Weight gain, 134
Poison exposures in pediatric patients, 102
Immune-mediated necrotizing myopathy, 16
Rhabdomyolysis, 4
B
Dependence after high-dose therapy, 128
Allergic contact dermatitis, 19
FDA safety alert: not be used in children less than 2 years of age, 156
Safety comparison, 147
Interaction with laboratory measurement of thyroid hormones, 21
Thrombocytopenia, 78
Severe adverse reactions, 149
Long-term effects in neonates, 42
Suicide ingestions in adolescents, 100
Drug interaction: decreased busulfan clearance, 115
C
Noncholestatic acute hepatocellular injury, 27
Cannabinoid hyperemesis syndrome, 7
Cardiotoxicity, 104
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
FDA safety alert: bacterial contaminant, 148
Hepatotoxicity, 77
Cardiotoxicity, 9
Microscopic colitis, 129
FDA safety communication: restriction to use in adults, 14
FDA safety communication, 88
Death, 93
Opsoclonus syndrome, 94
Drug interaction: increased trough cyclosporine concentrations, 25
D
False elevation of international normalized ratio, 90
Study stopped due to intolerance, 171
Adverse event reports, 137
FDA safety communication: contains undeclared medication, 80
FDA safety communication: possible salmonella contamination, 31, 35
FDA safety communication: undeclared ingredient, 130, 132, 152
Heart failure exacerbation, 109
Respiratory-related morbidity and mortality, 69
FDA safety communication: neural tube defects, 150
Anemia, metabolic acidosis, 101
Elevations in coagulation laboratory tests, 98
Clinical decision support system to identify drug-related problems, 116
Drug-induced liver injury in patients with cutaneous drug reactions, 168
Inpatient deaths related to drugs, 71
Intensive care unit admissions related to drug overdose, 145
E
Septic shock, pyelonephritis, bacteremia, 2*
Delayed-onset thrombocytopenia, 76
Rash, 174
Conjunctivitis, 86
F
Cardiovascular safety outcomes in patients with gout, 117
Poisoning, 131
Drug-induced liver injury, 13
Amnestic syndrome, 58
Pancytopenia, 127
Hepatotoxicity, 57
Anaphylaxis, 18*
Accidental ingestion by pediatric patient, 29
QTc interval prolongation, torsades de pointes, 54
Persistent extrapyramidal symptoms, 75
Drug interaction: rhabdomyolysis, 153
G
Trypophobia, 125
FDA safety communication: prolonged residual body storage, 8
Adverse effects, 84
Cataracts, glaucoma, 83
Hypertensive crisis, 107
Risk of liver cancer reduced, 20
Epidermal desquamation, 12
H
Non–immediate allergic cutaneous reactions, 23
Priapism, 133
Neurocognitive impairment, death, 120
FDA news release: risk-based evaluation, 11
Methemoglobinemia, 97
Restrictive cardiomyopathy, 67
I
Incomplete dabigatran reversal, 79
Anaphylaxis, 163
Discontinuation, 34
Pericarditis in pediatric patient, 64
Sarcoid-like granulomatosis, 140
K
Adverse drug and medication error events in Japanese hospital, 114
Risk of liver disease, 39
FDA safety communication: illegal sale of unapproved product, 155
FDA safety communication: recall and update on kratom contamination with Salmonella, 105
FDA safety communication: recall due to Salmonella contamination, 91, 112, 126, 138
Salmonella contamination, 103
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
Gastrointestinal bleeding, 143
Cholestatic jaundice, 24
Macular toxicity, 26
FDA safety alert: infection associated with bacterial contamination, 135
N
Central sleep apnea, 123*
Acute pneumonitis, 62
FDA news release: instructions for discontinuation, 5
Fatal myocarditis and rhabdomyolysis, 157
Risk of gastrointestinal bleeding in elderly people, 164
O
Boxed warning: dosing clarification, 46
Toxicity, 146
QTc prolongation after single-dose intravenous use, 99
Rash, 121
FDA news release: illegal marketing of unapproved products, 53
Deaths associated with overdose in the United States, 106
FDA communication: warning letter to illegal sales of opioids on the Internet, 166
Use and risk of pneumococcal disease, 95
Thrombocytopenia, 136
Stevens-Johnson syndrome, 82
P
Risk of melanoma, 142, 144
Fatal poisonings, 60
Risk of ischemic stroke, myocardial infarction, 73
Q
Delayed seizures after overdose, 172
R
Disorientation, 141
Stevens-Johnson syndrome, 89*
Sleep disturbance, 173
Anaphylactic shock, 44
Henoch-Schonlein purpura, IgA nephropathy, 59
Rash, 96
Angioedema, 119
Angioedema, 160
FDA safety communication: anaphylaxis, hypersensitivity reactions, 33
Occupational allergic respiratory disease, 22*
S
Involuntary muscular movements, 122*
Reported exposures in poison centers, 37
Continuous peripheral infusion associated with phlebitis, 92
Ketoacidosis, 113
Oxalate nephropathy, 36
FDA news release: warning letters, 3
Bilateral renal infarctions, 118
T
Drug interaction: life-threatening bleeding, 10*
Coagulopathy, decreased fibrinogen, 38
Hypoglycemia, 56
Hemolytic anemia, 6
V
Adverse events, 167
Drug-induced hypersensitivity syndrome, 15
Drug interaction: increased clozapine metabolism, 165
Panic disorder, 108
Acute interstitial nephritis, 40
Drug interaction: exacerbation of neuropathic pain, 151
Drug interaction: syndrome of inappropriate diuretic hormone, 72
W
Drug interaction: increased international normalized ratio values, 87
Y
Toxicity, 139
Z
FDA safety alert: recall related to contamination, 110