Current Drug Safety - Volume 12, Issue 3, 2017

Background: The prevalence of adverse drug reactions is reported to be high in critical care units. We conducted a systematic review to study the prevalence, drugs implicated, preventability, predictability, severity and determinants of adverse drug reactions in critical care settings. Methods: We searched MEDLINE, EMBASE, PROQUEST and OVID (January 1995 to June 2015) using pre-specified appropriate medical subject heading terms. Of 1552 studies, 34 studies were included for data extraction and synthesis. Results: Overall, the prevalence of adverse drug reactions was 0.3% to 17% in paediatric intensive care units and 4.5% to 34.1% in adult intensive care units. The highest prevalence reported among critical care settings was 117.4 per 1000 patient days. The most common drug classes implicated were antimicrobials in the medical intensive care units, cardiovascular drugs and anticoagulants in the coronary care units, and analgesics and sedatives in the surgical care units. The prevalence of fatal and severe adverse drug reactions ranged from 0.9 to 19% and 5.7 to 28.6% respectively. The predictable and preventable adverse drug reactions ranged from 74.3 to 90.2% and 8.6 to 62.8% respectively. Only 8 studies reported patient outcomes. About 5.6% to 25.5% of patients died. Conclusion: There is wide variation in prevalence, characteristics and drug classes implicated in the occurrence of adverse drug reactions by type of intensive care unit. Findings of this study would help health care professionals to optimise pharmacotherapy in critical care settings.

Background: Infectious and malignant events are responsible for morbidity and mortality in patients with Immune-Mediated Inflammatory Diseases (IMIDs). Anti-tumor necrosis factor (Anti-TNF) agents appear to have an impact, however the individual effect of these agents in the different conditions is still unclear. Objective: The aim of this study is to estimate the Incidence Rates (IR) of infections and malignancies in patients treated with anti-TNFs across different IMIDs, as well as potential risk factors. Methods: IR/100 patient-years were evaluated in adult patients treated for any IMID with an anti-TNF between January 2000 and December 2014. Predictors were tested with bivariate and multivariate statistical analysis. Results: The IR/100 patient-years of serious infections was 4.02 (95% CI 3.20-5.04) with significant differences across IMIDs and anti-TNF agents. The most frequent site of serious infection was the gastrointestinal system. Five cases [IR of 0.28 (95% CI 0.12-0.66) /100 patient-years] of tuberculosis were diagnosed, exclusively in patients treated with monoclonal antibodies. Three (60%) of those were extrapulmonary. The IR/100 patient-years of malignancy was 1.75 (95% CI 1.24-2-47). Conclusion: There is significant variability in the IR of infections across indications and agents. Thus, physicians should be thoughtful when generalizing data from literature regarding the use of an anti-TNF agent in a specific IMID. Further studies are necessary to clear aspects regarding the safety of individual anti-TNF biologics and to clarify their impact in the different IMIDs.

Introduction: Drug treatment may be related to the development of adverse drug reactions (ADRs). Aim: In this paper, we evaluated the ADRs in patients admitted to Catanzaro Hospital. Methods: After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April 30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. Results: During the study period, we analyzed 2870 clinical records containing a total of 11,138 prescriptions, and we documented the development of 770 ADRs. The time of hospitalization was significantly higher (P<0.05) in women with ADRs (12.6 ± 1.2 days) with respect to men (11.8± 0.83 days). Using the Naranjo score, we documented a probable association in 78% of these reactions, while DIPS revealed that about 22% of ADRs were related to DDIs. Patients with ADRs received 3052 prescriptions on 11,138 (27.4%) having a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) with respect to patients not experiencing ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and were treated as new diseases. Conclusion: Our results indicate that drug administration induces the development of ADRs also during the hospitalization, particularly in elderly women. Moreover, we also documented that ADRs in some patients are under-diagnosed, therefore, it is important to motivate healthcare to report the ADRs in order to optimize the patients' safety.

Background: Poor quality antimalarial medicines still represent a threat to the public health, especially in Sub-Saharan Africa which bears a disproportionate share of the global burden of malaria. It is essential and urgent to strengthen mechanisms against counterfeit medicines. One of the approaches is regular market surveillance through quality controls. Methods: 12 samples of artemether/lumefantrine were collected from formal and informal drug sellers in Cotonou (Benin) as well as additional other similar samples from Rwanda (13 samples) and from D.R. Congo (9 samples). Thin Layer Chromatography (TLC) as classical and simple identification test was applied in Benin while an analytical chemistry laboratory in Belgium (ULg, Pharmacy Department) was asked for further analyses with HPLC and Raman spectroscopy using a developed and validated HPLC method for rapid analysis of artemether/lumefantrine. Results: The results obtained in Belgium confirmed the lack of the two active ingredients in the suspected sample of ACT medicine from Benin whereas some samples from Rwanda and D.R. Congo were found to present risk of substandard drugs either for under-dosing or over-dosing. Conclusions: Counterfeit/falsified of artemisinin-based combination therapy (ACT) medicines are really scourge that needs to be fought through strong collaboration between public health authorities and appropriate quality control laboratories.

Background: Voluntary medication error reporting is an imperfect resource used to improve the quality of medication administration. It requires judgment by front-line staff to determine how to report enough to identify opportunities to improve patients’ safety but not jeopardize that safety by creating a culture of “report fatigue.” Objective: This study aims to provide information on interpretability of medication error and the variability between the subgroups of caregivers in the hospital setting. Methods: Survey participants included nursing, physician (trainee and graduated), patient/families, pharmacist across a large academic health system, including an attached free-standing pediatric hospital. Demographics and survey questions were collected and analyzed using Fischer’s exact testing with SAS v9.3. Results: Statistically significant variability existed between the four groups for a majority of the questions. This included all cases designated as administration errors and many, but not all, cases of prescribing events. Commentary provided in the free-text portion of the survey was sub-analyzed and found to be associated with medication allergy reporting and lack of education surrounding report characteristics. Conclusion: There is significant variability in the threshold to report specific medication errors in the hospital setting. More work needs to be done to further improve the education surrounding error reporting in hospitals for all noted subgroups.

Background: Topiramate is a medication that is approved as both monotherapy and adjunctive treatment of seizure disorder in adults and adolescents. It is also approved for migraine prophylaxis. It has been associated with many side effects, including weight loss and the development of renal stones. It has also been associated with various central nervous system side effects such as dizziness, nervousness, parasthesias, and fatigue. Less commonly, it has been associated with the development of psychotic symptoms such as hallucinations. Objective: To describe the relationship between the administration of topiramate and the development of hallucinations in this patient. Methods: We will now present the case of a 32-year-old man who developed auditory hallucinations after initiating a relatively low dose of topiramate (25mg twice daily) for the treatment of chronic pain. We will review the prior cases of topiramate induced hallucinations, and discuss how these cases compare to the case we have described. We will review the treatment of these hallucinations. Results: In this case, there was a close temporal relationship between the initiation of topiramate and the onset of auditory hallucinations. Conclusion: This case supports the previous reports describing the association between the use of topiramate and the developmenrt of hallucinations. Although the average daily topiramate dose associated with the development of hallucinations in previously reported cases was 150 mg in women and 181 mg in men, hallucinations can occur at lower doses (as low as 50 mg daily) as well.

Background: Hypersensitivity reactions due to Proton pump inhibitors (PPIs ) are rare, and further anaphylaxis to a PPI with cross-reactivity to all commercially available PPIs is very rare. Objective: To present a case of anaphylaxis to pantoprazole with cross-reactivity to all commercially available PPIs. Methods: Skin prick tests (SPTs), intradermal tests (IDTs) and oral provocation tests (OPTs) were performed with available PPIs according to the method described in previous studies. Results: All tested PPIs except lansoprazole were positive on skin tests either SPT or IDT. The patient was challenged with lansoprazole at increasing doses (7.5 mg, 15 mg, 30 mg capsule) every 60 minutes and she reacted with urticaria to 52.5 mg cumulative dose of lansoprazole. She could tolerate ranitidine and famotidine tablets via OPT. Conclusion: In our best knowledge, our case was the first case in this regard and that points the possibility of all cross-reactive pattern in patients with pantoprazole anaphylaxis and the importance of a thorough drug allergy work-up for finding safe alternatives. H2 receptor antagonists are used as safe alternatives in cases with PPI hypersensitivity.

Background: Lithium is known to cause certain neurological deficits. However, reports of aphasia secondary to lithium toxicity are scant. We report the case of a 70 year old African American woman with a history of schizoaffective disorder and mild dementia who developed transient intermittent aphasia secondary to lithium toxicity. Methods: Patient was admitted because of agitation, delusional behavior, and pressured speech. Her previous medications included divalproex sodium 500 mg po bid, valproic acid 250 mg po qd, risperidone 3.5 mg po bid, lorazepam 1 mg po bid, amlodipine besylate 5 mg po qd, levothyroxine sodium 25 mcg po qd, gabapentin 300 mg po qd, amantadine HCl 100 mg po bid, and aspirin 81 mg po qd. Since patient's symptoms have not improved, she was started on lithium 300mg po bid and titrated up to 300 mg po bid and 450 mg po qhs over 7-8 days. Her lithium levels ranged from 0.4 mEq/L on 11/11/16 to 1.5 mEq/L on 11/22/16. Patient was observed to have aphasia symptoms intermittently at lithium level of 1.5 mEq/L. CT scan of head and neurology consultations were unremarkable. The Naranjo Adverse Drug Reaction Probability Scale score was 8 in the probable range for an adverse drug reaction. Patient's sodium was also found to be high at 148 mmol/L. Results: Lithium was discontinued and patient rehydrated with intravenous fluids. Patients aphasia resolved completely in 2-3 days. Conclusion: Clinicians should be aware of this rarely reported side effect of lithium particularly in patients at risk for volume depletion and closely monitor fluid intake, lithium level, and potential side effects.

Introduction: Incidence of antibiotic- associated diarrhoea is a common (10–30%) but pseudomembranous colitis (PMC) is less frequent (1-5%). Fluoroquinolones, clindamycin, penicillins, cephalosporins (mostly third generation) are commonly associated with PMC. The association between cephalosporins and PMC is now well established. Case Presentation: A 78 year old male patient developed pseudomembraneous colitis after administration of Ceftriaxone and Cefazoline for the treatment of pleural effusion. The reaction was confirmed by ultrasonography and CT scan. Causative agents were stopped and patient was managed by systemic therapy. Patient was expired due to respiratory complications as there was complexity in management of disease due to development of pseudomembraneous colitis. Conclusion: Increase awareness of prescribers for high-risk drugs, close monitoring, with immediate withdrawal of the culprit drug can reduce the complexity of management that occur due to development of such adverse drug reaction.

Background: Clomiphene is normally used in women with ovulatory dysfunction. In men, it is used off label in some cases of infertility. Psychological adverse effects are reported in women but very few in men. Case: A 34-year-old man treated with clomiphene for oligoteratospermia presented anxiety, decreased appetite, and mood change making him unable to function properly at work, five days after initiation of therapy. Symptoms required reduction followed by discontinuation of treatment four days later because of absence of improvement. Following cessation, the patient noted a gradual then a complete resolution approximately one week later. The patient did not have any psychiatric or other medical condition neither drug nor substance abuse that could explain this clinical presentation. The Naranjo's score was used to prove the clomiphene's imputability. Conclusion: Health care providers should advise patients of the risk of psychological adverse effects when initiating treatment with clomiphene and should provide a close monitoring of mood change, especially during the initial weeks.

Background: A 54-year-old man presented complaining of severe pain and blurred vision in his left eye. Slit-lamp biomicroscopy revealed a large epithelial defect with an underlying prominent ring infiltrate and severe anterior uveitis with fibrinous exudates and hypopyon. Patient admitted abuse of topical tetracaine, which was discontinued and topical treatment with a non-steroidal antiinflammatory agent, an antibiotic, a cycloplegic agent were instituted while a therapeutic contact lens was applied. Response to treatment was favorable with a rapid resolution of anterior uveitis within days while the epithelial defect fully healed within a month. Four months later the patient returned with a new subtotal epithelial defect with no previous history of trauma or topical anesthetic abuse. Conclusion: In conclusion, while a common complication of topical tetracaine abuse is toxic keratopathy, we describe a case where tetracaine abuse was also complicated with a severe fibrinous anterior uveitis. Interestingly, in our case, anaesthetic abuse was complicated in the mid-term with a spontaneous corneal epithelial defect attributed to possible anaesthetic-induced anatomical changes, such as poor adhesion between the stroma and the epithelium.