Current Drug Safety - Volume 9, Issue 1, 2014

Electrolyte and acid-base disorders are commonly encountered adverse effects of various diuretic agents, which are associated with considerable morbidity and mortality especially in elderly patients. Diuretic use is associated with hyponatraemia, hypernatraemia, hypokalaemia, hyperkalaemia, hyperuricaemia and alterations in magnesium, calcium, phosphate and acid-base homeostasis. Clinical studies have provided important data on the relative frequency and risk factors for these diuretic-associated electrolyte and acid-base disorders. Old age is one of the most recognized risk factors for diuretic-associated electrolyte and acid-base disorders. Hyponatraemia and hypokalaemia are the most common electrolyte abnormalities found among the elderly population taking diuretics. Both conditions are associated with short and long-term morbidity as well as mortality. This article presents an overview of the literature on diuretic-associated electrolyte disorders and suggested risk factors for their development especially in elderly patients when evidence is available. The impact of these electrolyte disorders on patients will be discussed. Strategies to prevent adverse outcomes related to these disorders should involve careful consideration of risk factors as well as ongoing clinical and laboratory evaluations in the course of using these diuretics.

Background: The requirements and methods for research and evaluation of the safety and efficacy of herbal medicines are more complex than those for conventional pharmaceuticals. In addition to the aforementioned and contrary to the general belief that herbal medicines are safe and despite the profound therapeutic advantages possessed by medicinal plants, some of their constituents have been shown to be potentially toxic, carcinogenic, mutagenic, and teratogenic. Thus, traditional medicine policy and regulation have been made an integral part of the WHO proposed critical determinants of herbal medicine safety. Objective: Therefore, this study is designed to assess the policy and regulation guiding herbal medicine in Nigeria as this information may form a safety index of herbal medicine use in Nigeria. Methodology: Structured questionnaire adopted from WHO was used to obtain the opinions of relevant stakeholders in the field of herbal medicine on the policy and regulation of herbal medicine in Nigeria. Results: The results show that 68.8% of respondents agreed that there is a national policy on TM with 31.2% disagreeing on this issue. 75% of respondents agreed that implementation of the manufacturing requirements of herbal medicines is ensured by control mechanisms while 25% disagreed. Only 25% said herbal medicines are sold by licensed practitioners, with 75% believing that herbal medicines are sold by non-licensed practitioners. 87.5% said support from the WHO is needed and should be in the form of workshops on national capacity building on safety monitoring of herbal medicines. Conclusion: There is need for the Federal Ministry of Health to harmonize the varying opinions on traditional medicine and policy as documented in this study through collaboration and workshops on traditional medicine. These proposed approaches may guarantee the safety and regulation of herbal medicine use in Nigeria.

We conducted a cohort study of acute, noninfectious liver injury among oral antimicrobial users. Potential cases were identified in the HealthCore Integrated Research Database (HIRDSM) population between July 1, 2001, and March 31, 2009, using ICD-9-CM codes primarily for acute and subacute necrosis of the liver, hepatic coma, and unspecified hepatitis. Liver test results were used to confirm case status according to published criteria. Two physician reviewers experienced in studying acute liver injury (blinded to study drug exposures) evaluated data abstracted from hospital and emergency department records to validate potential cases. Of 715 potential cases having claims associated with any of the primary screening codes, 312 (44%) were valid cases, 108 (15%) were not cases, and 295 (41%) were of uncertain status (records inadequate for validation). Among potential cases with adequate medical records, the PPV for presence of any of the primary codes was 74% (95% CI, 70%-78%). The highest PPV for a single code was for acute and subacute necrosis of the liver (84%; 95% CI, 77%-90%). Evaluation of cases of noninfectious liver injury using hospital and emergency department medical records continues to represent the preferred approach in studies using insurance claims data.

Objective: The aim of the present study was to investigate safety and efficacy of billinaster drop and glycerin suppository in hyperbilirubinemia of healthy term newborns who had passage of first meconium. Methods: In a randomized clinical trial, 90 neonates with total plasma bilirubin(TPB) level of 15–20mg/dL, were randomly assigned to be treated with alone phototherapy (control) or 5drop/kg of bilinaster drop every eight hours and phototherapy(B) or half of glycerin suppository every twelve hours and phototherapy(G). The primary outcomes were safety of drugs and efficacy in obtaining TPB of less than 14 mg/dL as measured at the beginning, 12, 24 and 48 hours after intervention. Secondary endpoint was hospitalization days. Results: After 48 hours of intervention, achieving TPB of less than 14 mg/dL was seen in 50 %( N=15) in control group, 73.3 %( N=22) in B group and 86.7 %( N=26 neonates) in G group (P= 0.01). Watery stool was seen in two neonates of glycerin group and safety of the treatments was not significantly different. Mean of TPB 12 hours after beginning of phototherapy(mean±SD:14.38±2.27mg/dL in G, 15.97±1.96mg/dL in B and 16.67±1.77mg/dL in control), 24 hours after intervention(mean±SD:12.56 ±1.59mg/dL in G, 12.57±2.05mg/dL in B and 14.36±2.26mg/dL in control), 48 hours after intervention (mean±SD: 9.34 ± 1.6mg/dL in G, 9.96 ± 2.95mg/dL in B and 12.27 ± 2.4mg/dL in control) and mean of hospitalization days (mean± SD: 1.5 ± 0.4days in G, 1.7 ± 0.4days in B and 2.9 ± 1.1days in control) were significantly lower in glycerin and billinaster groups. Conclusion: Bilinaster drop and glycerin suppository can be used as hazardless, efficient and cost effective drugs in treatment of neonatal hyperbilirubinemia.

Introduction and Objectives: Inappropriate abbreviations used in prescriptions have led to medication errors. We investigated the use of error-prone and other unapproved abbreviations in prescriptions, and assessed the attitudes of pharmacists on this issue. Methods: A reference list of error-prone abbreviations was developed. Prescriptions of outpatients and specialty clinic patients in a teaching hospital in Sri Lanka were reviewed during one month. An interviewer administered questionnaire was used to assess attitudes of pharmacists. Results: 3370 drug items (989 prescriptions) were reviewed. The mean (standard deviation) number of abbreviations per prescription was 5.9 (3.5). The error-prone abbreviations used in the hospital were, μg (microgram), mcg (microgram), u (units), cc (cubic centimeter), OD (once a day), @ sign, d (days/daily), m (morning) and n (night), and among all prescriptions reviewed, they were used at a rate of 17.4%, 0.1%, 1.9%, 0.2%, 0.2%, 4.9%, 23.5%, 4.4% and 15.8% respectively. Among the 103 types of abbreviations observed, 71 were not standard acceptable abbreviations. Multiple abbreviations were used to indicate a single drug item/ instruction (N = 7). The abbreviation ‘d’ was used to denote ‘daily’ as well as ‘days’. All pharmacists believed that using error-prone abbreviations will always (5.3%) or sometimes (94.7%) lead to medication errors. Conclusions: Error-prone abbreviations and many other unapproved abbreviations are frequently used in hospitals. There is a need to educating health care professionals on this issue and introduce an in-house error-prone abbreviation list for their guidance.

Nearly all atypical antipsychotic drugs (AAPDs) of second- generation are associated with body weight gain in adults with prolonged exposure; but reports on third-generation AAPDs like Aripiprazole (ARI) and weight gain are scanty and ambiguous. This may be attributed to some unknown mechanism of action, the study of which is essential to investigate gestational exposure of equivalent therapeutic doses of ARI on maternal and fetal weight gain and its longlasting impact on postnatal development and growth of offspring in rodent model. 30 pregnant Wistar rats were exposed to selected doses (2mg, 3mg and 5mg/kg BW) of ARI from GD3-21 orally, with control subjects. Half of the pregnant subjects of each group were sacrificed at GD22 and rest dams were allowed to deliver normally and pups were reared postnatally up to 10 weeks of age. In ARI treated groups, there was no substantial alteration of body weight gain and food intake in pregnant subjects while significant reduction was found in fetal and postnatal (pre-and post weaning) body weight gain. ARI was found neutral for substantial weight gain in pregnant rats but may induce significant weight loss in fetuses, creating long-lasting negative impact on offspring growth (in weight) till PND70. Therefore, ARI could be a good alternative of second- generation AAPDs for adult females but may not be safe for developing fetuses and offspring.

Introduction: Pharmacosurveillance during the administration of antibiotics is of extreme importance in paediatric patients given their different physiology and adverse drug reaction (ADR) profile compared to the adult population. Systematic reviews show that one in ten hospitalised children will experience ADRs. Administration of antibiotics is among the leading causes of such ADRs. The aim of this study was to assess ADRs reporting related to the administration of antibiotics in hospitalized paediatric patients in Greece. Methods: A cross-sectional study was conducted over a seven month period (January to July 2012) in paediatric departments in Greece. A self-administered questionnaire was distributed to a total of 750 health professionals providing paediatric care in 3 specialized paediatric hospitals and 33 paediatric departments in general and university hospitals. Descriptive and multivariate statistical analyses were performed. Levels of significance were two-tailed and statistical significance was set at P =0.05 Results: Overall, 576 out of 750 questionnaires were returned completed, at a response rate of 76.8%. ADRs related to antibiotics were reported by 44.8% of nurses and 23.7% of doctors as occurring often/very often during their practice. 45% of doctors reported amoxicillin/clavulanic acid as the drug with the most frequent ADRs. Overall, 63% of nurses and 32.7% of doctors stated they had never reported ADRs. Doctors used yellow cards more often than nurses (65.2% vs 33.9%). Only 48.4% of doctors and 35.9% of nurses knew that ADR reporting constitutes part of their professional duties. Conclusions: ADRs following antibiotic administration are common in paediatric practice in Greece; however, underreporting remains a significant problem.

Although cases of Selective Serotonin Reuptake Inhibitor (SSRI) induced akathisia have often been reported in literature, this adverse effect has not adequately been mentioned in major pharmacology textbooks. As a result, SSRIinduced akathisia is very frequently under-recognized. A review of literature showed that almost all frequently used SSRIs such as Fluvoxamine, Fluoxetine, Sertraline, Citalopram have been reported to be causing akathisia. SSRI-induced restless legs syndrome and movement disorders have also been reported. However, Escitalopram-induced akathisia is rare. In our review of literature, we could find only one single case of Escitalopram-induced severe akathisia. And this specific SSRI drug has rarely been implicated with occurrence of restless legs syndrome and extra-pyramidal side-effects like dytonia etc. Here, we present a case of Escitalopram-induced severe akathisia - a 53year old female, who had developed severe akathisia after taking Escitalopram for a few days. According to the Barnes Akathisia Rating Scale (BARS), her Global Clinical Assessment of Akathisia Score was 5 i.e. severe akathisia. As per Naronjo Adverse Drug Reaction Scale the probability of association of this adverse reaction with Escitalopram was 7 (i.e. probable). Her symptoms continued in spite of prompt discontinuation of the drug. But, she improved rapidly with the use of Propranolol and Clonazepam. On the last follow-up, she was free from any symptoms. As new generation antidepressants are rarely associated with extra-pyramidal symptoms, the recognition of such adverse effects requires a high index of suspicion. Early recognition of the symptoms and discontinuation of the offending agent along with supportive therapy like a short course of benzodiazepines, beta-adrenergic antagonists or anticholinergics may rapidly relieve the patient from this distressing symptom.

The association of extrapyramidal side effects (EPS) with the use of conventional antipsychotics is well established, however, EPS can occur during treatment with anticonvulsant medications as well. We will present the case of a patient who developed an acute dystonic reaction during treatment with lamotrigine and again during re-challenge with the same agent. We will review common side effects of this medication and the previous reports of lamotrigineassociated dystonias. We will also discuss a possible underlying mechanism.

Case Description: We report a patient with growth hormone deficiency that developed cholestatic hepatitis during treatment with recombinant human growth hormone (HGH). The patient developed jaundice and pruritus during treatment with growth hormone. She did not use any other medications. Her jaundice and pruritus were disappeared and liver enzyme disturbances were normalized after HGH discontinuation. Conclusion: Clinician should be aware of this potential adverse drug reaction and frequent checking of liver enzymes is recommended in patients treating with HGH.

Purpose: To report a possible association between human papilloma virus (HPV) vaccination and uveitis. Methods: Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization and Food and Drug Administration were collected on uveitis associated with human papilloma virus vaccination. A MEDLINE search was performed using keywords “uveitis,” “iritis,” “iridocyclitis,” “human papilloma virus,” “Cervarix”, and “Gardasil.” Main Outcome Measures: Data garnered from spontaneous reports included the age, gender, adverse drug reaction (ADR), date of administration, concomitant administration of other vaccinations, time until onset of ADR, other systemic reactions, and dechallenge and rechallenge data. Results: A total of 24 case reports of uveitis associated with human papilloma virus vaccination were identified, all cases were female, and the median age was 17. Median time from HPV vaccination to reported ADR was 30 days (range 0-476 days). Discussion: According to World Health Organization criteria, the relationship between human papilloma virus vaccination and uveitis is “possible.” Causality assessments are based on the time relationship of drug administration, uveitis development and re-challenge data. Conclusions: Clinicians should be aware of a possible bilateral uveitis and papillitis following HPV vaccination.

Rheumatoid arthritis (RA) is a chronic erosive inflammatory disease which can involve the locomotor system and cause systemic involvement. The efficacy and safety of anti-TNF-alpha drugs have been shown in active RA cases that are resistant to traditional disease-modifying antirheumatic drugs. However, it is well known that anti-TNF-alpha drugs may cause lymphomas and various solid malignancies. On the other hand, there are studies on the efficacy of anti- TNF-alpha drugs in the treatment of resistant renal cell cancer. This case report presents a 57-year-old female patient with hematuria who had been followed up with the diagnosis of RA for 20 years and had been using adalimumab for the last 4 years. A solid mass was found in the left kidney in the abdominal ultrasonography and computed tomography. Nephrectomy was performed by general surgery. Histopathological findings of the specimen were consistent with renal cell carcinoma.

This report presents the case of a 67-year-old woman affected by glioblastoma. After a few days of adjuvant therapy with temozolomide and prophylaxis with trimetrophin-sulfamethoxazolo to prevent Pneumocystis Jiroveci, she had progressive and rapid worsening of symptoms with weakness, dyspnea and orthopnea. She had peripheral edema and proximal hyposthenia of the lower limbs. Chest CT showed bilateral ground-glass opacities and laboratory exams revealed hypoxemia and hypocapnia, an initial reduction in platelet and white blood cells, and an elevation of LDH, AST, ALT, and active urinary sediment. Blood cultures, bronchoalveolar lavage (BAL) data and transbronchial biopsy showed no infections, and in particular no evidence of Pneumocystis Jiroveci pneumonia. Histological examination revealed a typical pattern of AIP. She was treated with broad-spectrum antibiotics and high-dose steroids. The symptoms worsened and respiratory failure required mechanical ventilation. The pneumonia was not responsive to medical or invasive care. She died after ten days of hospitalization. At present very little can be found in the literature about lung toxicity caused by temozolomide. This case can be added as a new report describing this risk. The combination therapy with temozolamide and trimetophin-sulfamethoxazolo could have a synergistic action inducing various forms of pulmonary toxicity. Established Facts: Acute interstitial pneumonia is a common manifestation of lung toxicity caused by drugs. The clinical course is favorable with a good response to corticosteroids. Novel Insight: This is the first fatal case of lung toxicity caused by Temozolomide. Clinicians must be aware that a combination therapy including trimetophin-sulfamethoxazolo could have a synergistic action in inducing pulmonary toxicity.

Many drugs may induce psoriatic lesions or exacerbate preexisting psoriasis. We report an exceptional case of psoriasis vulgaris probably induced by clarithromycin. A 37-year-old man was prescribed for pharyngitis clarithromycin 500mg twice a day. On the third day of treatment, he presented a non pruriginous erythemato-squamous eruption, of trunk and limbs. Skin biopsy showed a typical aspect of psoriasis vulgaris. The drug was interrupted and the patient was treated by topical corticoids with rapid improvement.

Trimethoprim (TMP) is a commonly prescribed antibiotic with few adverse effects. However on rare occasions, TMP is associated with electrolyte disturbances. As seen in our three patients, TMP can be associated with symptomatic hyponatraemia which required hospitalization. In one of these patients, hyperkalaemia and type 4 renal tubular acidosis were also present. These electrolyte and acid-base disorders were corrected after discontinuation of TMP. A small number of patients with TMP-induced electrolyte imbalances have been reported in the English-language medical literature to date but mostly with the use of TMP in combination with sulfamethoxazole. In association with TMP use, hyperkalaemia has been more commonly reported than hyponatraemia. These changes in sodium and potassium balance are thought to be related to TMP inhibiting sodium ion influx via the epithelial sodium channel in the cortical collecting duct. The association between symptomatic hyponatraemia and TMP emphasizes the need to evaluate electrolytes in patients presenting with clinical change after commencing on this drug.