Current Drug Safety - Volume 12, Issue 1, 2017

Background: It is known that calcium channel blockers are associated with a risk of gingival hyperplasia. These drugs are widely used in the management of gestational hypertensive disorders. Case: A 27-year-old G1 woman presented with gingival hyperplasia at 27 weeks gestation during a hospitalisation for preeclampsia. She had been on nifedipine for hypertension for the last 9 weeks. Nifedipine was discontinued and replaced by methyldopa and already after 48 hours the gingival hyperplasia improved. She delivered two weeks later and the gingival hyperplasia resolved completely without surgical intervention. The Naranjo’s score was used to prove the nifedipine’s imputability. Conclusion: This first case report of gingival hyperplasia induced by nifedipine in pregnancy could be used as a reference for clinicians in the management of this adverse effect during the pregnancy.

Herein, we report a 70-year-old male patient, with recurrent multiple hepatic abscesses, that was admitted to the internal medicine department for treatment of Carbapenem Resistant Escherichia Coli (CRE) bacteremia. The patient was treated with Tigecycline; few days later, he developed "Disseminated Intravascular Coagulation (DIC)" like coagulation study abnormality that seemed to be related to Tigecycline treatment. Upon discontinuing it, the DIC-like condition was resolved. Tigecycline should be considered as a possible etiological factor in patients with DIC-like, and this therapy should be withdrawn immediately in suspected cases.

The fixed dose combination of sitagliptin 50 mg and metformin 850 mg (Janumet ^®), is indicated for the treatment of type 2 diabetes mellitus in addition to diet and exercise to improve glycemic control in patients treated with metformin alone. Methods: We report a 69-year-old man with type 2 diabetes that developed sudden loss of eyebrows and eyelashes about 4 months after the beginning of Janumet^®. Clinical and laboratory findings excluded the presence of systemic or skin diseases able to induce these manifestations, while the Naranjo probability scale documented a possible association between the drug and the adverse drug reaction.

Background: Rasburicase is commonly used in patients with hematologic malignancies for tumor lysis syndrome prophylaxis and management. Methemoglobinemia is a serious rare adverse effect of rasburicase, more common in patients with G6PD deficiency. Prompt diagnosis and appropriate management of this condition can make the difference between successful recovery and significant morbidity. Here we discuss the link of rasburicase with methemoglobinemia and the pathophysiology behind increased incidence of this side effect in G6PD deficient patients. Methods: We report the case of a 73-year-old African American man who developed methemoglobinemia on rasburicase treatment, who was later confirmed to be G6PD deficient. We reviewed the literature using Pubmed and Google Scholar using the following key words: “methemoglobinemia”, “rasburicase”, “urate oxidase”, tumor lysis syndrome”, G6PD deficiency”, “hemolytic anemia” and “hyperuricemia”. Results: Rasburicase-induced methemoglobinemia is more common in patients with G6PD deficiency, and rasburicase is therefore contraindicated in these patients. Clinical presentation includes cyanosis, pallor, methemoglobin levels of 8-12%, and oxygen saturation gap which is evident from ABG analysis, though pulse oximetry is normal. Treatment consists of oxygen supplementation, ascorbic acid and blood transfusion. Importantly, methylene blue is avoided as therapy in G6PD deficiency as it can worsen the methemoglobinemia. Conclusion: Rasburicase-induced methemoglobinemia is a serious concern, especially in African- American patients. It should be considered when clinical signs and symptoms are present. Knowledge of this side effect is important in early diagnosis and successful management of the condition.

Background: Hyperprolactinemia can be caused by medications, primarily antipsychotics, or by anterior pituitary tumors. The consequences of hyperprolactinemia including gynecomastia, galactorrhea, and sexual dysfunction are very disturbing for males and females. It is sometimes difficult to differentiate the etiology of hyperprolactinemia from a clinical perspective. Objective: Identification of the etiology of hyperprolactinemia requires a careful review of the causes and appropriate work-up. Methods: A 55-year-old African American male with extensive psychiatric history and non-adherence to treatment was admitted from nursing home for aggression and psychotic symptoms. The patient was noted to have mild bilateral breast enlargement about ten days after hospitalization. Prolactin level done on August 26, 2014 was 93.8 ng/mL, and on September 5, 2014 was 112 ng/mL. The patient’s medications included haloperidol decanoate 150 mg q28d, haloperidol 10 mg po bid and benztropine 0.5 mg po bid. He did not have any other clinical signs or symptoms of hyperprolactinemia. He was also seen by an endocrinologist. MRI of the pituitary gland done on September 3, 2014, showed a 2.4 mm pituitary microadenoma. Bromocriptine was started at 1.25 mg qhs and titrated to 2.5 mg bid. Results: Prolactin level dropped from 112 ng/mL on September 5, 2014 to 99 ng/mL on September 9, 2014, 61.2 ng/mLon September 23, 2014 and 3.0 ng/mL on February 9, 2015. Conclusion: Diagnosis and etiology of hyperprolactinemia were complicated by the minimal nature of clinical symptoms, the type of antipsychotic agent and the prolactin level. The MRI facilitated the diagnosis of pituitary microadenoma and further treatment option with bromocriptine. MRI of the pituitary is indicated for patients with hyperprolactinemia where the etiology is not clearly due to medication.

Introduction: Prescription opioid abuse may have adverse dental effects that are irreversible, leaving younger populations with substantially decayed dentitions. This article explores the damaging effects of three years of prescription opioid abuse to a twenty-six-year-old’s dentition and oral health. Case Presentation: A twenty-six-year-old Caucasian male presented to the University of Pennsylvania School of Dental Medicine with a past medical history of Percocet® abuse. He was consuming approximately twenty tablets per day for three years, and he had neglected to visit a dentist for over five years before arriving to the School of Dental Medicine. Management and Outcome: Intraoral examination revealed gross generalized decay along with generalized plaque accumulation. He was diagnosed with severe plaque induced gingivitis with localized chronic periodontitis and xerostomia. The dental treatment for this patient included periodontal maintenance and control, caries excavation, root canal therapy, extractions of non-restorable teeth, and continuous dental education. Discussion: Prescription opioids are addictive, have high abuse potential, and dentists contribute to this problem by overprescribing these drugs.

Background: Technoshere insulin (TI), Afrezza, is a form of short-acting human insulin taken by oral inhalation with meals. Methods: literature search (English, French, Spanish) of all human studies and pertinent animal and in-vitro studies related to technosphere insulin until September 2016 with special emphasis on its safety. Results: Compared to subcutaneous insulin aspart, TI is slightly less effective, the difference in hemoglobin A1c (HbA1c) reduction being 0.19%. Use of TI is associated with lower risk of hypoglycemia and weight gain compared with insulin aspart. Apart from hypoglycemia, cough is the most common adverse effect of TI reported by 24-33% of patients. Cough induced by TI is mostly dry, occurs within 10 minutes after inhalation and usually subsides after few weeks of use. TI is contraindicated in patients with asthma and chronic obstructive lung disease in whom it causes acute bronchospasm. TI is also not recommended in smokers. All patients starting TI need to check their pulmonary function at baseline then after 6 months, and annually thereafter. Conclusions: Overall, while TI is an attractive form of prandial insulin, its use is limited by high incidence of cough, requirement of frequent monitoring of respiratory function, and lack of long-term safety data.

Objective: To determine the extent of QTc prolongation following administration of an atypical antipsychotic in critically ill patients diagnosed with delirium and to conduct an assessment of risk factors to identify the presence of specific risk factors associated with QTc prolongation in this patient population. Methods: Patients were included if they were at least 18 years of age, admitted to an Intensive Care Unit (ICU) at the study institution from July 1, 2013 through January 30, 2014, had a documented diagnosis of delirium within their electronic medical record, and received an atypical antipsychotic for delirium during their hospital admission. Excluded patients were those who received an atypical antipsychotic for an indication other than delirium, received fewer than two doses of the atypical antipsychotic, had an atypical antipsychotic documented as a home medication, or demonstrated a lack of EKG data at baseline or post administration of their atypical antipsychotic dose. Results: Of the 360 patient charts screened, 118 subjects met inclusion criteria. For the study’s primary outcome, the proportion of change from baseline EKG to the first EKG following atypical antipsychotic administration, 72 (61.0%) patients had a decrease in their QTc interval, 1 (0.85%) patient stayed the same, and 45 (38.1%) patients had an increase in their QTc interval. The median change in QTc interval was a decrease of 12.5 msec. Of the 45 (38%) subjects who had an increase in their QTc interval, the mean change from baseline to the first EKG post atypical antipsychotic administration was an increase of 30 msec. Sixty-six (56%) subjects reached steady state while on their first atypical antipsychotic. With respect to the secondary outcome, 40 of 66 (60.1%) had a decrease in their QTc interval, while 26 (39.4%) subjects had an increase in their QTc interval. The median change in QTc interval was a decrease of 10.5 msec. Receipt of a pro-arrhthymic medication was used concomitantly among 25 (21.2%) of patients at baseline. Antibiotics were the most commonly observed class used concomitantly in 39 (21.7%) of the 180 observed total instances of concomitant QTc prolonging agent use, followed by antidepressants (18.9%). Amiodarone was the single most commonly observed agent utilized (10%). Conclusion: This retrospective analysis of a mixed ICU population demonstrates that following initiation of an atypical antipsychotic, QTc interval increase occurred less frequently then a QTc interval decrease from baseline. Providers should correct modifiable risk factors and minimize concomitant QTc prolonging medications as much as possible.

Background: Fatal intoxications are a topic of great relevance in today’s society. They typically occur by accidental or voluntary ingestion, but its characterization by a forensic perspective was not fully explored. Objective: This study retrospectively reviews fatal intoxication cases autopsied at the northern forensic medicine services of Portugal, between 2001 and 2013. Method: For this purpose, we analyzed postmortem forensic medical reports with positive qualitative analysis for xenobiotics. Results: A total of 27,778 autopsy reports were analyzed, of which 1,269 cases fulfilled the selection criteria, representing 4.6% of total number of individuals autopsied during the period under analysis. Men were involved in most of the cases (73.8%) and most individuals were adults with ages between 36 and 65 years old (57.0%). The highest incidences were medicines (22.9%) and alcohol (15.8%), followed by their association. Cases of fatal intoxications involving opioids come on fifth place (5.8%) namely due to accidental overdoses. Moreover, intoxications appeared as the leading cause of death in reports concerning accidental etiology, with drugs and alcohol associations having a great expression. Conclusion: Due to morbidity and relevant number of fatal cases, risk prevention measures, such as public health policies should be implemented to reduce the number of intoxications.

Objectives: Find possible causative agents causing cutaneous adverse reactions; clinical patterns, causality and severity of Drug induced cutaneous adverse reactions (CADR) and treatment outcome. Methods: Retrospective study was undertaken including cases of CADR. Causality, preventability and severity of Drug Induced cutaneous reactions were judged with the use of Naranjo's algorithm, WHO causality scale, modified Schumock and Thorton scale, and Hartwig’s scale respectively. Results: Among 275 total cADRs reported, Antimicrobials (46.55%) were the main drugs involved followed by Non steroidal anti-inflammatory drugs (NSAIDs) (25.09%) and Antifungal (9.82%). Urticaria (63.64%) followed by Erythema multiform(12.36%) was most frequently observed CDRs. Amongst all cADRs 50.18% were certain according to Naranjo’s scale, none of them were preventable according to modified Schumock and Thorton scale. All reactions were moderate according to Hartwig’s severity scale. Conclusion: It was observed that antibiotics and NSAIDs cause maximum number of CADRs. Therefore strict vigilance is required while using them.

Abstract: Background: The Pharmacovigilance Program of India recently initiated a process for direct patient reporting of Adverse Drug Reactions (ADRs) with a designated form. Patients and Methods: A survey of 200 patients reporting ADRs filling the form. Forms were analysed for patient data, the suspected medication(s), ADRs and possible causality. Results: 54.3% of respondents provided their contact information; the implicated medicine was mentioned in 60% and the description of ADRs in 80% although 46.2% were not interpretable. The severity of ADRs was mentioned in 73.5%. No responder filled the expiry date component of the implicated modification and a causality assessment from most forms was unclassifiable (57%) or unclassified (26%). Details of concomitant drugs were missing. Conclusion: Missing information was a deterrent in analysing the consumer ADR reports for signal detection. It is recommended that the following fields are highlighted in the form: consumer’s initials, address, date suspected reaction started, description of event, name, dose, and the reason for the use the medication as well as its expiry date. These should be mandatory in the existing form and new fields added for weight and height, batch number for vaccines and biological products, de challenge and rechallenge results to the suspected medicine and concomitantly used medicines. To improve the quality of information in the consumer reporting form an awareness campaign is also suggested.

Background: Dispensing patterns reflect drug usage trends. Benzodiazepines are known as drugs with potential for misuse, and frequent dispensing may be a surrogate marker of misuse. Objective: The primary aim of this study was to obtain a comparative snapshot of anxiolytic and sedative-hypnotic dispensing in a developing country and a developed country, to determine whether further research about benzodiazepines is warranted. Method: A cross-national, cross-sectional retrospective drug utilisation study was conducted on benzodiazepines and z-drugs. The South African database was obtained from a national medical insurance administrator and the Australian data were de-identified and extracted from pharmacies in the city of Brisbane in Queensland. Results: Diazepam was the most frequently dispensed anxiolytic in the Australian dataset (26.4%; n=1057/4010) while in the South African data, diazepam dispensing (17.2%; n=11597/67354) was superseded by alprazolam (17.8%; n=12009/67354) and followed by bromazepam (13.6%; n=9146/67354). The most frequently dispensed hypnotic in the South African data was zolpidem which accounted for 18.7% of records (n=12603/67354), while in the Australian data it was temazepam (24.9%; n=998/4010). Zolpidem was dispensed more frequently than zopiclone in both datasets. Conclusion: In South Africa there was relatively frequent use of alprazolam, bromazepam and zolpidem while in the Australian data diazepam, oxazepam and temazepam were most frequently dispensed. The use of alprazolam, identified as a drug of abuse in Australia, warrants further research in South Africa. The indicator described in this paper permitted a (qualitative) cross-sectional comparison of anxiolytics and sedative-hypnotics between a developed and a developing country (Australia and South Africa).

Background: Observational studies have suggested an increased risk of nephrotoxicity when piperacillin-tazobactam is added to vancomycin, although the data are confliciting. Objective: To perform a meta-analysis of identified studies to assess if adding piperacillin-tazobactam to vancomycin increases the incidence of nephrotoxicity. Method: A systematic review of PubMed, EMBASE, Cochrane Central, and Google Scholar was conducted to identify studies. Studies selected for meta-analysis were full length reports, retrospective or prospective, and designed specifically to assess if the combining piperacillin-tazobactam with vancomycin increases nephrotoxicity. Results: Six observational trials involving 963 patients were identified and analyzed. Five trials were retrospective and one was prospective. Vancomycin/piperacillin-tazobactam was compared to vancomycin alone in 2 trials, to vancomycin/cefepime in 3 trials, and vancomycin/cefepime or meropenem in one. Meta-analysis showed a statistical increase in the incidence of nephrotoxicity when piperacillin-tazobactam/vancomycin is compared to the control group (2.26 95% CI 1.41-3.63, p= 0.0007). No differences were noted between groups in patients requiring renal replacement. Conclusion: Adding piperacillin-tazobactam to vancomycin increases the risk of nephrotoxicity when compared to vancomycin alone or vancomycin with either cefepime or meropenem.

Background: Ketorolac use has significantly expanded for postoperative pain management since it first became available in the United States, primarily due to well established effects on patient pain scores and its ability to reduce perioperative opioid requirements. As an inhibitor of cyclooxygenase, ketorolac use has raised clinical concern including particular controversy regarding its potential effects on bone healing, postoperative kidney function and perioperative bleeding. Objective: To review the supporting data from clinical studies addressing the safety of ketorolac use for postoperative pain. Method: This review highlights the most up-to-date research from clinical trials as well as from retrospective studies and meta-analyses regarding the effects of perioperative use of ketorolac on bone healing, kidney function and blood loss. Results: Based on the most up-to-date literature, ketorolac in normal doses has been demonstrated to be safe with respect to bone healing. In patients with normal kidney function, numerous studies have established the safety of Ketorolac; however other studies have raised safety concerns in patients with comorbid kidney, heart and liver disease. While there is evidence that ketorolac may cause prolonged bleeding time and may be associated with increased postoperative blood loss after tonsillectomy, large scale prospective randomized controlled trials and subsequent meta-analyses have failed to establish an association of ketorolac use and perioperative blood loss. Conclusion: Perioperative administration of ketorolac has been demonstrated to be safe and effective in healthy patients and is particularly beneficial as an opioid-sparing agent in vulnerable patient groups. However, in certain surgical and medical contexts, proper patient selection based on the multidisciplinary collaboration between perioperative clinician specialists will optimize patient safety and pain management outcomes.