Current Drug Safety - Volume 9, Issue 3, 2014

Clozapine is, and will remain in the coming years, an irreplaceable drug in psychiatry which has elective indication in treatment-resistant schizophrenia, suicide risk in schizophrenia spectrum disorders, aggressiveness or violence in psychiatric patients, psychosis in Parkinson’s disease, prevention and treatment of tardive dyskinesia. Unfortunately, the drug is largely underused for many and serious side effects. Only a good knowledge of these side effects and of the main strategies to prevent their occurrence or minimize their impact can allow overcoming the underutilization of this valuable therapy. The article describes the clinical and epidemiological features of the non-motor side effects of clozapine including blood dyscrasias, constipation, diabetes, enuresis, fever, hepatitis, hypersalivation, ileus, myocarditis, nephritis, priapism, seizures, serositis, weight gain and metabolic syndrome. The paper suggests several strategies, supported by scientific evidence, in the management of these side effects. The neuropsychiatric side effects of clozapine are not discussed in this review.

Intestinal microbiota is composed by a community of microorganisms, which regulate intestinal functions and affect the global health. It is presumable that the well-known intestinal damages induced by Non Steroidal Antiinflammatory Drugs (NSAIDs) mirror on the homeostasis of microbiota, as confirmed by studies investigating this aspect. This review reports the evolving knowledge in this field taking into account both intestinal damage and microbiota involvement. In addition, we analyze a recent study reporting how NSAIDs change intestinal bacterial composition and, on this basis, hypothesize further possible interactions. Indeed, NSAIDs are responsible for a marked reduction of Lactobacilli, which act in the maintenance of luminal pH, mucosal permeability, enterocyte adhesion, mucus production, and immune system modulation. Moreover, Bifidobacteria are involved in the modulation of intestinal motility and local immunity and the demonstrated dangerous effect of NSAIDs could operate through an interference with these functions. A participation of microbiota in mesalazine and salycilate prevention of intestinal cancer may be supposed through their ability to stimulate bacterial production of molecules interfering with cell cycle on the basis of scanty available data. Finally, a supplementation with probiotics in chronic users of NSAIDs may help microbiota remodeling in a damaged intestine, but the poor current knowledge does not allow setting a clear indication for their use despite few evidences of a beneficial effect. In conclusion, it is presumable that the multiple effects of NSAIDs on the lower gastro-intestinal tract may involve microbiota alterations and this consideration suggests further investigations.

Study Objectives: Sleep maintenance problems are common, hence treatments enabling patients to fall asleep more rapidly after middle-of-the-night (MOTN) awakenings, without impairing next morning alertness, are needed. This literature review compares the effects of MOTN administration of various hypnotics on morning driving ability, a potentially dangerous daily activity under conditions of impairment. Methods: A literature search was conducted identifying on-the-road driving studies examining the effects of MOTN administration of hypnotics on morning driving performance. In a standardized 100-km highway driving test in normal traffic, subjects were instructed to drive with a steady lateral position and constant speed of 95 km/h. The primary outcome measure of the driving test is the Standard Deviation of Lateral Position (SDLP, cm), i.e. weaving of the car. Results: Four driving studies were identified. Driving performance after MOTN administration of traditional benzodiazepine hypnotics was not examined. Zolpidem (10 mg and 20 mg, oral immediate release tablets) significantly impaired driving in a dose-dependent manner, when tested 4 hours after MOTN administration. Also, gaboxadol (15 mg) and zopiclone (7.5 mg) significantly impaired next-morning driving after MOTN administration. In contrast, sublingual zolpidem (3.5 mg) and zaleplon (10 mg and 20 mg) did not significantly affect driving 4 hours after MOTN administration. Conclusion: Driving was not affected 4 hours after MOTN administration of sublingual zolpidem (3.5 mg) or zaleplon (10 mg and 20 mg). Significant driving impairment was found after MOTN administration of zolpidem (10 and 20 mg), gaboxadol (15 mg), and zopiclone (7.5 mg).

Introduction: Over-consumption of antibiotics has led to increased bacterial resistance and higher prevalence of hospital -acquired infections, resulting in rising treatment costs and prolonged length of hospital stay. The purpose of the study was to correlate the use of restricted antibiotics with recommended diagnosis and cost. Materials and Methods: All restricted antibiotics that were administered in a 240-bed general hospital in a semi-urban area within a year were recorded. The reason for administering each such antibiotic during the first three months of the study was also recorded. PASW 18 (SPSS Inc.) was used for the statistical analysis; a variable was considered statistically significant when statistical significance was p= 0.05. Results: 1118 patients were registered, of which 35,05% were employees, insured with IKA, 33,05% were farmers and covered by OGA and 31,9% were insured in other Social Insurance Funds or uninsured. The most commonly administered antibiotic combination was that of piperacillin/tazobactam, which was mainly used in the Internal Medicine Dept. of the Hospital. The most commonly used restricted antibiotic, administered after an antibiogram, was the combination of piperacillin/tazobactam (n= 13), mainly prescribed for respiratory infection. One third of the recorded restricted antibiotics were administered before an antibiogram had been taken for fever of unknown origin (n= 128). Conclusion: Rational use of restricted antibiotics is an important component of public health policies aiming at reducing hospital-acquired infections. Hospitalization costs rise when restricted antibiotics are used, and the possibility for the development of resistant bacteria increases.

This descriptive study used the Japanese spontaneous reporting data to investigate the time taken (TTILD) to development of interstitial lung disease (ILD) after initiation of chemotherapy and the death rates attributed in part to post-chemotherapy ILD (i.e., DR) for anticancer drugs. We evaluated TTILD and DR endpoints for 36 anticancer drugs, which are widely used for treating 11 solid and 3 hematological cancers, and are suspected of causing ILD, by using 8- year spontaneous reporting data recording for 2,553 patients in the reporting system of the relevant Japanese regulatory agency. The median TTILD and overall DR attributable to post-chemotherapy ILD for the drugs were 1.8 months and 29%, respectively. For most drugs, the median TTILDs were between 1 to 4 months, and the DRs attributable to postchemotherapy ILD were <40%; however, TTILDs were as long as 4 to 6 months and DRs attributable to postchemotherapy ILD were ≥40% for several other drugs. Of the 36 drugs, we identified those that may trigger postchemotherapy late-onset ILDs or result in high DRs. The anticancer drugs that may have triggered late-onset ILDs were defined as those that caused ILD development after approximately 4 months from the initial drug administration.

Background: Atypical antipsychotics (AA) differ from one another in their adverse event (AE) profiles. Patient-specific pre-existing risk factors for AEs, including comorbidities and concomitant medications, may render the use of certain AAs potentially inappropriate, and others relatively safer or more tolerable. Objective: To quantify the prevalence of pre-existing risk factors for AEs and potential drug-drug interactions (DDIs) associated with AA treatment among patients with schizophrenia (SCZ), bipolar disorder (BD), or major depressive disorder (MDD) newly-initiating AA treatment. Methods: Retrospective, observational study using US claims databases. Patients identified had newly-initiated on a single AA (1/1/2010-11/30/2011; index date), were aged 18–64 years, had insurance enrolment for 12 months pre- (baseline) and 1 month post-index, and had ≥1 medical claim with an ICD-9-CM diagnosis of SCZ, BD, or MDD during baseline. A comprehensive list of AE risk factors, including potential DDIs, was developed based on AA package inserts. Administrative claims-based identification algorithms flagged the presence of each medical risk factor during baseline and identified concomitant prescribing of medications (90 days pre- to 30 days post-index) potentially causing DDIs with AAs. Results: Of 97,010 patients identified, mean age was 41.2 years and 66.7% were female. Among patients initiating AA treatment, prevalence of pre-existing AE risk factors were aripiprazole 32.2%; olanzapine 51.6%; ziprasidone 75.6%; quetiapine 77.4%; risperidone 82.5%. Conclusion: Despite the availability of several AAs to treat psychiatric conditions, pre-existing AE risk factors can limit patient treatment options. Given inter-AA variability in risk factors, open access to AA may help to optimize appropriate prescribing.

Migraine is a potentially debilitating neurologic disorder affecting approximately 12% of the United States population. Sumatriptan manufacturer-provided drug information states that life threatening arrhythmias, including ventricular tachycardia and ventricular fibrillation (VF), have been reported. A literature search revealed only seven reported cases of ventricular arrhythmias immediately after sumatriptan administration. Twenty minutes after a 42 year old female received sumatriptan, her femoral pulses were not palpable and the electrocardiograph (EKG) showed torsades de pointes followed by VF. After defibrillation and one round of cardiopulmonary resuscitation (CPR), the patient regained spontaneous circulation. The patient was eventually discharged home. Despite studies concluding that sumatriptan has minimal effects on coronary arteries, several cases of sumatriptan-associated myocardial infarction have been documented. In addition, a small number of documented cases have reported life threatening arrhythmias and cardiorespiratory arrest after sumatriptan administration.

Rituximab, a chimeric anti-CD20 monoclonal antibody, is used to treat rheumatologic and hematologic diseases. Serum sickness, a Type III delayed hypersensitivity reaction, has been reported with rituximab treatment. Traditionally, drug desensitization has been used to treat Type I IgE-mediated hypersensitivity reactions. We report the first case of successful drug desensitization to rituximab in a patient with medication-induced serum sickness. In our case, a 37-year-old woman with Sjogren’s syndrome and papillary thyroid carcinoma developed serum sickness 72 hours following rituximab infusion for gastric mucosal associated lymphoma tissue (MALT). Her MALT progressed after stopping rituximab. She underwent a rapid 12-step intravenous rituximab desensitization without recurrence of serum sickness. Following the completion of 4 rituximab desensitizations, she had gastric MALT remission. She received 25 maintenance rituximab doses using this desensitization protocol quarterly without complications. This is the first report documenting rituximab desensitization for the treatment of delayed drug reactions like serum sickness.