Exotic venomous snakebites in Switzerland reported to the National Poisons Information Centre over 22 years.

OBJECTIVE: The private keeping of exotic venomous snakes is legally permitted in Switzerland. The aim of the present study was to characterise the epidemiological and clinical features of bites by exotic venomous snakes over a period of 22 years in Switzerland. METHODS: We included all calls related to exotic snakebites recorded at the Swiss National Poisons Information Centre (Tox Info Suisse) from 1997 to 2018. Exclusion criteria comprised indigenous snakes, non-venomous exotic snakes such boas or pythons, clinical courses incompatible with a snakebite or calls from abroad. Follow-up information was graded according to the Poisoning Severity Score. RESULTS: Within the study period, 1,364 calls related to snakebites were recorded at Tox Info Suisse; 148 (11%) cases were attributed to exotic venomous snakes and fulfilled the study criteria. A total of 112 (98%) of 114 patients with medical follow-up information exhibited sufficient causality between exposure and clinical effects. Only adult patients were affected. The median age was 40 years (range 16-71) and the male gender was predominant (n = 136, 92%). Viperidae were involved in 87 (78%) and Elapidae in 25 (22%) patients. Overall, the main affected body part was the hand (89 patients, 79%). In the majority of the patients the clinical course was mild (46, 41%) or moderate (40, 36%), in a lower proportion asymptomatic (6, 5%) or with severe symptoms (20, 18%). No fatalities were reported in the study period. Severe symptoms were observed after elapid bites in six patients (24%) and after viper bites in 14 patients (16%). Besides local effects, neurological disorders after elapid bites and haematological disorders after viper bites were most frequently reported. Antivenom was administered in 24% (27 patients: 18 Viperidae, 21% and 9 Elapidae, 36%; 5 patients (4%) required multiple doses), overall, with good resolution of symptoms. CONCLUSION: Exotic snakebite is a rare occurrence in Switzerland but has led to medically relevant morbidity, sometimes requiring antivenom treatment. Over half of the envenomed patients required symptomatic or specific treatment. No fatalities or bites in children were reported.

Observational cross-sectional case study of toxicities of antifungal drugs.

OBJECTIVES: In this study, we examined the toxicities, including poisoning and overdoses, with polyene, azole, flucytosine and echinocandin antifungals reported to the Swiss National Poison Centre. METHODS: An observational cross-sectional study on antifungals was performed based on reports between 1995 and 2016 to Tox Info Suisse. Patient demographic and clinical characteristics were summarised among all reported calls, stratified by age group. In secondary analyses, we evaluated cases with clinical follow-up information. RESULTS: In total, 149 cases were reported to the National Poison Centre during the study period, of which 49 (32.9%) were male and 91 (61.1%) were female, and 95 (63.8%) were adults and 54 (36.2%) were children (age ≤16 years). The most frequently reported drug class was azoles (136; 91.3%). In 31 cases (20.8%) reported by treating physicians, further clinical follow-up information was available. Nearly one-half of these patients were asymptomatic (15/31; 48.4%). In 11 patients (35.5%) among those with symptoms, the symptoms of toxicity were categorised with a strong causality to the respective antifungal. Clinical findings caused by triazoles were effects in the gastrointestinal tract, hallucinations and predelirium state. Clinical findings caused by polyenes were mostly minor symptoms with infusion-related effects or hypokalaemia. The severity was categorised as minor in 6 (54.5%) of 11 cases and as moderate in 5 cases (45.5%). CONCLUSION: Despite high administered doses, no severe or fatal cases occurred within the study period. Although various toxicities can occur with antifungal administration and overdoses, they showed a favourable safety profile.

Indigenous venomous snakebites in Switzerland: analysis of reports to the National Poisons Information Centre over 22 years.

INTRODUCTION: Two venomous snakes, the asp viper (Vipera aspis) and the common adder (Vipera berus) are native to Switzerland. Bites by both vipers cause mainly local effects, but systemic envenomation is possible. METHODS: We analysed all calls concerning indigenous venomous snakebites recorded at the Swiss National Poisons Information Centre between 1997 and 2018, including all cases with identification by a herpetologist, and/or with compatible symptoms and circumstances of the exposure. RESULTS: During the study period, 1,364 cases concerned snakebites. One third (466; 34%) were attributed to indigenous vipers. In 243 (52%) patients, medical follow-up information was available, with good causality between exposure and symptoms in 219 (90%) patients. Vipera aspis was identified in 77 of the cases (35%), Vipera berus in 54 (25%), and not further specified vipers in 88 (40%). In over two thirds of the 219 cases (155, 71%) adult patients were affected (male 109, female 46; median age 43 years [range 16-90]). Sixty-four patients were children (male 47, female 16; median age 11 years [range 1.3-15.9]). The highest occurrence of bites was in the summer months. In the majority of patients, the clinical course was mild (94; 43%) or moderate (80; 36%); a lower proportion was either asymptomatic (17; 8%) or exhibited severe symptoms (28; 13%). There were no fatalities reported. The most frequent symptoms were local effects at the bite site with mild (100; 46%) to moderate (56; 25%) swelling, pain (65; 30%) and redness (51; 23%). Gastrointestinal symptoms including nausea (31; 14%), vomiting (47; 22%) and abdominal pain (25; 11%) were also common. Other systemic symptoms included cardiovascular effects (e.g., hypotension (20; 9%) or shock [6; 3%]), neurotoxicity (e.g., visual impairment [5; 2.3%]) and haematotoxicity (e.g., coagulopathy [11; 5%]). Seven (3.2%) patients developed anaphylactic reactions. Antivenom was administered in only 20% (24 with moderate and 19 with severe symptoms) with good resolution of symptoms. The mean duration of hospitalization was 2 days (0-12 days). CONCLUSION: Snakebites in Switzerland can result in severe symptoms, sometimes necessitating antivenom treatment.

Coadministration of tizanidine and ciprofloxacin: a retrospective analysis of the WHO pharmacovigilance database.

PURPOSE: Tizanidine, an alpha-adrenergic substance with antinociceptive and antihypertensive effects, is extensively metabolized via cytochrome P450 (CYP) 1A2. Therefore, coadministration with potent CYP1A2 inhibitors, such as ciprofloxacin, is contraindicated. However, both drugs are broadly utilized in various countries. Their concomitant use bears an inherent high risk for clinically significant symptoms, especially in multimorbid patients experiencing polypharmacy. This study aims to investigate the impact of coadministration of tizanidine and ciprofloxacin using real-world pharmacovigilance data and to raise awareness of this potentially underestimated safety issue. METHODS: We conducted a retrospective study including Individual Case Safety Reports (ICSR) registered until March 1, 2017, in the World Health Organization (WHO) global database. Demographic data, drug administration information, the course of the adverse drug reaction (ADR), its severity, and outcomes were analyzed for cases reporting ciprofloxacin comedication. RESULTS: In 91 (2.0%) of the identified 4192 worldwide ICSR on tizanidine, coadministration of ciprofloxacin was reported. Most of the patients were female (n = 59, 64.8%) with a median age of 54 years (range 13-85 years). The countries contributing most reports were the USA (n = 54, 59.3%) and Switzerland (n = 16, 17.6%). ADRs reported most often affected the nervous system and the cardiac function, especially with large tizanidine doses or drugs with CNS and cardiovascular depressant effects. In two cases, a fatal outcome was reported. CONCLUSION: Despite the existing formal contraindication, the concomitant use of tizanidine and ciprofloxacin can be observed in real-world clinical practice. Reactions mainly affected the central nervous and the cardiovascular system resulting in potentially severe adverse effects. The concomitant use of tizanidine and ciprofloxacin should absolutely be avoided.

Extracorporeal life support as bridge to recovery in yew poisoning: case reports and literature review.

AIMS: This short communication aims to review the treatment of cardiogenic shock in patients with yew poisoning based on two case reports from our institution, focusing on the use of extracorporeal life support (ECLS). METHODS AND RESULTS: We report two cases of Taxus baccata poisoning treated with ECLS at our institution and review the literature based on a search in PubMed and Google Scholar on the topic of yew poisoning and ECLS. All cases were combined for analysis of demographics, ECLS therapy, and outcome. Case 1: A 35-year-old woman developed polymorphic ventricular tachycardia followed by cardiovascular arrest 5 h after orally ingesting a handful of yew needles. Successful resuscitation required ECLS for 72 h due to ongoing cardiac arrhythmias and cardiogenic shock. The patient left the hospital without neurological sequelae after 10 days. Case 2: A 30-year-old woman developed refractory cardiac arrhythmias and circulatory arrest. Resuscitation included ECLS for 71 h. T. baccata needles found by gastroscopy confirmed the diagnosis. The patient had no neurologic deficits and was transferred to psychiatry after 11 days. REVIEW OF THE LITERATURE: Nine case reports were found and analysed along with our two cases. Five out of the 11 (45%) patients were female. Median (range) age was 28 (19-46) years. T. baccata needles were ingested with a suicidal intention in all patients. Median (range) duration of ECLS was 70 h (24-120 h). Eight (73%) patients had full neurological recovery. CONCLUSIONS: Yew poisoning is a differential diagnosis in young psychiatric patients presenting with polymorphic ventricular tachycardia and cardiogenic shock. A characteristic cardiac contraction pattern in echocardiography may present a diagnostic clue. The early use of ECLS is a valuable bridge to recovery in most of these patients.

National Poison Center Calls Before vs After Availability of High-Dose Acetaminophen (Paracetamol) Tablets in Switzerland.

Importance: Acetaminophen (paracetamol) is among the most widely used pain medications worldwide; while safe within the therapeutic range, intake exceeding 4000 mg/d can lead to hepatotoxicity. Prior evidence suggests that limiting the availability of large quantities of acetaminophen is associated with decreased acetaminophen-related poisonings and mortality; in Switzerland, 500-mg tablets are available over-the-counter (OTC) and, as of October 2003, 1000-mg tablets are available with prescription. Objective: To evaluate the association of adding 1000-mg acetaminophen tablets to the Swiss market with utilization and poisonings. Design, Setting, and Participants: This cross-sectional study used a quasi-experimental interrupted time series analysis to evaluate 15 790 acetaminophen poison records from January 1, 2000, to December 31, 2018. All calls for acetaminophen-related poisonings identified from the National Swiss Poisons Centre and all sales for oral acetaminophen tablets (prescription and OTC) dispensed between January 2000 and December 2018 were included. Exposure: October 3, 2003 (Q4 2003), was defined as the intervention date, corresponding to the date of market entry for 1000-mg acetaminophen tablets in Switzerland. Main Outcomes and Measures: The primary outcome was the number of quarterly acetaminophen-related poison calls to the National Poison Centre. Additional outcomes included quarterly sales for acetaminophen and change in poisoning circumstances, stratified by preintervention and postintervention periods and by formulation (ie, 500-mg and 1000-mg tablets). Results: Between 2000 and 2018, 15 790 acetaminophen-related poisoning calls were identified, of which 10 628 (67.3%) were regarding women, and the mean (SD) age of patients was 25.2 (18.2) years. The interrupted time series analysis identified a significant increase in the slope for the number of reported poisonings following the intervention point, particularly for accidental circumstances (z score, -3.62; P < .001). In the preintervention period, 120 of 961 poisonings (15.3%) involved a dose greater than 10 000 mg, while for the postintervention period, 1140 of 5696 (30.6%) had a dose larger than 10 000 mg (P < .001). There was a rapid uptake in 1000-mg acetaminophen sales, while sales of the 500-mg tablet decreased slightly. Since 2012, a mean (SD) of 20.7 million (1.4 million) 1000-mg tablets were dispensed quarterly compared with 2.7 million (0.5 million) 500-mg tablets. Conclusions and Relevance: This study found a significant increase in acetaminophen dispensing and acetaminophen-related poisonings in Switzerland following the approval of 1000-mg tablets in 2003. The availability of 1000-mg acetaminophen should be re-evaluated to minimize the potential for accidental poisonings.

Characteristics of emergency department presentations requiring consultation of the national Poisons Information Centre.

AIMS OF THE STUDY: To describe the characteristics of cases presenting at the emergency department due to (suspected) poisoning for which consultation on patient management with the national Poisons Information Centre was required. METHODS: Retrospective study at the emergency department of Bern University Hospital, Switzerland, from May 2012 to December 2017. Cases were identified in the electronic patient database using appropriate full-text search terms. Cases were excluded if the contact with the National Poisons Information Centre was through an external hospital or directly by the patient. Cases in which the poison centre was not contacted and cases without the patient’s general consent to use their medical data for research purposes were also excluded. RESULTS: Overall, 667 cases from the study period were included. The median age was 32 years (range 16–94); 405 patients (61%) were female and 262 (39%) male. In most cases, the poisoning was acute (n = 631, 95%) and intentional (n = 505, 76%). The most common route of exposure was ingestion (n = 587, 88%) and the most commonly involved substances were sedatives (n = 185, 28%), antidepressants (n = 162, 24%) and non-opioid analgesics (n = 161, 24%). Impaired consciousness was documented in 299 cases (45%). Approximately half of the cases (n = 359, 54%) were of minor severity as assessed using the Poisoning Severity Score, 142 (21%) were of moderate severity, 110 (16%) were asymptomatic and 56 (8%) were severe. There were no fatalities. In most cases (n = 599, 90%), immediate therapeutic or diagnostic measures were undertaken prior to contact with the poison centre. Decontamination measures and specific antidotes undertaken or administered only after contacting the poison centre included whole bowel irrigation, haemodialysis, fomepizole, biperiden, silibinin, deferoxamine, leucovorin, dimercaptopropanesulfonic acid and hydroxocobalamin. Administration of a specific antidote/therapeutic agent was recommended in 87 cases (13%). In 70 of these 87 cases (80%), the specific agents were administered as recommended by the poison centre. In 17 cases (20%), the specific antidotes were not administered as recommended because of either clinical improvement (n = 11), termination of therapy based on laboratory results (n = 3), therapy refused by the patient (n = 2), or identification of a mushroom as non-poisonous (n = 1). In 109 cases (16%), there was no change in patient management after contacting the poison centre. CONCLUSIONS: For patients presenting at the emergency department with severe poisoning, contact with the poison information centre can help to implement specific treatment and avoid fatalities. In less severe cases involving more common agents (e.g. paracetamol, benzodiazepines), contact can help to avoid unnecessary treatment and serve as a source of information and/or confirmation.

Mushroom Poisoning-A 17 Year Retrospective Study at a Level I University Emergency Department in Switzerland.

The consequences of mushroom poisoning range from mild, mostly gastrointestinal, disturbances to organ failure or even death. This retrospective study describes presentations related to mushroom poisoning at an emergency department in Bern (Switzerland) from January 2001 to October 2017. Gastrointestinal disturbances were reported in 86% of the 51 cases. The National Poisons Information Centre and mycologists were involved in 69% and 61% of the cases, respectively. Identification of the mushroom type/family was possible in 43% of the cases. The most common mushroom family was Boletaceae (n = 21) and the most common mushrooms Xerocomus chrysenteron (n = 7; four being part of a cluster), Clitocybe nebularis, Lepista nuda and Lactarius semisanguifluus (n = 5 each, four being part of a cluster). Poisonous mushrooms included Amanita phalloides (n = 3, all analytically confirmed), Boletus satanas (n = 3), Amanita muscaria (n = 2) and Amanita pantherina (n = 2). There were no fatalities and 80% of the patients were discharged within 24 h. Mushroom poisoning does not appear to be a common reason for emergency consultation and most presentations were of minor severity and related to edible species (e.g., due to incorrect processing). Nevertheless, poisonous mushrooms and severe complications were also recorded. Collaboration with a poison centre and/or mycologists is of great importance, especially in high risk cases.

Acute Toxicity Associated With the Recreational Use of the Novel Psychoactive Benzofuran N-methyl-5-(2 aminopropyl)benzofuran.

N-methyl-5-(2 aminopropyl)benzofuran (5-MAPB) is a novel psychoactive benzofuran, created by N-methylation of 5-(2-aminopropyl)benzofuran (5-APB), which shares structural features with methylenedioxymethamphetamine (MDMA). To our knowledge, no case of 5-MAPB-related toxicity has been published in the scientific literature. We report a case of oral 5-MAPB exposure confirmed by liquid chromatography-tandem mass spectrometry in a 24-year-old previously healthy white man. Observed symptoms and signs such as paleness, cold and clammy skin, hypertension, elevated high-sensitive troponin T level, tachycardia, ECG change, diaphoresis, mild hyperthermia, mydriasis, tremor, hyperreflexia, clonus, agitation, disorientation, hallucinations, convulsions, reduced level of consciousness, and creatine kinase level elevation (305 IU/L) were compatible with undesired effects related to 5-APB or MDMA exposure. Signs and symptoms resolved substantially within 14 hours with aggressive symptomatic treatment, including sedation with benzodiazepines, external cooling, analgesia and sedation with fentanyl-propofol, and treatment with urapidil, an α-receptor-blocking agent. 5-MAPB showed first-order elimination kinetics with a half-life of 6.5 hours, comparable to the half-life of MDMA. According to the chemical structure, this case report, and users' Web reports, 5-MAPB appears to have an acute toxicity profile similar to that of 5-APB and MDMA, with marked vasoconstrictor effect.

Introducing Mushroom Fruiting Patterns from the Swiss National Poisons Information Centre.

Changes in the ecology of macrofungi are poorly understood, not only because much of their life cycle is hidden belowground, but also because experiments often miss real-world complexity and most fruitbody inventories are limited in space and time. The National Poisons Information Centre 'Tox Info Suisse' provides countrywide 24hours/7days medical advice in case of poisonings since 1966. Here, we introduce a total of 12,126 mushroom-related phone calls that were received by Tox Info Suisse between 1966 and 2014. This indirect source of mycological information is dominated by the families of Boletaceae (11%), Agaricaceae (10%) and Amanitaceae (8%), which account for ~30% of all cases. Mushroom fruiting patterns revealed by the Poisons Centre inventory statistically resemble changes in fungal phenology, productivity and diversity as reflected by the Swiss National Data Centre 'SwissFungi'. Although the newly developed Tox Info Suisse dataset provides an innovative basis for timely environmental research, caution is advised when interpreting some of the observed long-term changes and autumnal extremes. Uncertainty of the new record relates to possible data incompleteness, imprecise species description and/or identification, as well as the inclusion of cultivated and non-indigenous mushrooms. Nevertheless, we hope that the Tox Info Suisse inventory will stimulate and enable a variety of ecological-oriented follow-up studies.

[Bites of venomous snakes in Switzerland]. / CME: Giftschlangenbisse in der Schweiz.

Although snake bites are rare in Europe, there are a constant number of snake bites in Switzerland. There are two domestic venomous snakes in Switzerland: the aspic viper (Vipera aspis) and the common European adder (Vipera berus). Bites from venomous snakes are caused either by one of the two domestic venomous snakes or by an exotic venomous snake kept in a terrarium. Snake- bites can cause both a local and/or a systemic envenoming. Potentially fatal systemic complications are related to disturbances of the hemostatic- and cardiovascular system as well as the central or peripheral nervous system. Beside a symptomatic therapy the administration of antivenom is the only causal therapy to neutralize the venomous toxins.

Adverse Effects of Plant Food Supplements and Plants Consumed as Food: Results from the Poisons Centres-Based PlantLIBRA Study.

Plant food supplements (PFS) are products of increasing popularity and wide-spread distribution. Nevertheless, information about their risks is limited. To fill this gap, a poisons centres-based study was performed as part of the EU project PlantLIBRA. Multicentre retrospective review of data from selected European and Brazilian poisons centres, involving human cases of adverse effects due to plants consumed as food or as ingredients of food supplements recorded between 2006 and 2010. Ten poisons centres provided a total of 75 cases. In 57 cases (76%) a PFS was involved; in 18 (24%) a plant was ingested as food. The 10 most frequently reported plants were Valeriana officinalis, Camellia sinensis, Paullinia cupana, Melissa officinalis, Passiflora incarnata, Mentha piperita, Glycyrrhiza glabra, Ilex paraguariensis, Panax ginseng, and Citrus aurantium. The most frequently observed clinical effects were neurotoxicity and gastro-intestinal symptoms. Most cases showed a benign clinical course; however, five cases were severe. PFS-related adverse effects seem to be relatively infrequent issues for poisons centres. Most cases showed mild symptoms. Nevertheless, the occurrence of some severe adverse effects and the increasing popularity of PFS require continuous active surveillance, and further research is warranted. Copyright © 2016 John Wiley & Sons, Ltd.

Risk of Seizures Associated with Antidepressant Use in Patients with Depressive Disorder: Follow-up Study with a Nested Case-Control Analysis Using the Clinical Practice Research Datalink.

INTRODUCTION: Antidepressant use has been associated with an increased risk of seizures. Evidence on the association between antidepressant use at therapeutic doses and seizures mainly comes from clinical trials that were not designed to investigate this potential relationship. OBJECTIVE: The objective of this study was to assess the risk of first-time seizures in association with exposure to antidepressants in patients with depressive disorders. METHODS: We conducted a retrospective follow-up study with a nested case-control analysis between 1998 and 2012, using data from the UK-based Clinical Practice Research Datalink (CPRD). We estimated crude incidence rates with 95 % confidence intervals (CIs) of seizures in depressed patients who used selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), 'other antidepressants', no antidepressants, or who had used antidepressants in the past. To adjust for potential confounding, we estimated odds ratios of antidepressant drug use among cases with seizures and matched controls in a nested case-control analysis. RESULTS: Of 151,005 depressed patients, 619 had an incident seizure during follow-up. Incidence rates per 10,000 person-years were 12.44 (95 % CI 10.67-14.21) in SSRI users, 15.44 (95 % CI 8.99-21.89) in SNRI users, 8.33 (95 % CI 4.68-11.98) in TCA users, 9.33 (95 % CI 6.19-12.46) in non-users of antidepressants, and 5.05 (95 % CI 4.49-5.62) in past users of antidepressants. In the case-control analysis, relative risk estimates for seizures were increased in current users of SSRIs (adjusted odds ratio 1.98, 95 % CI 1.48-2.66) and SNRIs (adjusted odds ratio 1.99, 95 % CI 1.20-3.29), but not TCAs (adjusted odds ratio 0.99, 95 % CI 0.63-1.53), compared with non-users. CONCLUSION: Current use of SSRIs or SNRIs was associated with a twofold increased risk of first-time seizures compared with non-use, while current use of TCAs (mostly low dose) was not associated with seizures. Treatment initiation in SSRI and SNRI users was associated with a higher risk of seizures than longer-term treatment.

Incidence and causative agents of chemical eye injuries in Switzerland.

CONTEXT: Chemical eye injuries are ophthalmological emergencies with a high risk of secondary complications and severe visual loss. Only limited epidemiological data for such injuries are available for many countries. PATIENTS AND METHODS: We performed two independent studies. The cause of chemical eye injuries was assessed with a prospective questionnaire study. Questionnaires were sent to all ophthalmologists in Switzerland. A total of 163 patients (205 eyes) were included, between December 2012 and October 2014. Independent of the questionnaire study, the incidence of chemical eye injuries was assessed with a retrospective cohort study design using the database of the mandatory accident insurance. RESULTS: Ophthalmological questionnaires revealed that plaster/cement (20.5%), alkaline (12.2%) and acid (10.2%) solutions caused the highest number of chemical injuries. Only 2% of all injuries were classified as grade III and none as grade IV (Roper-Hall classification). The official toxicological information phone-hotline was contacted in 4.3% of cases. Using data from the accident insurance, an incidence of chemical eye injuries of about 50/100 000/year was found in the working population. CONCLUSION: Here, we present data on the involved agents of chemical eye injuries in Switzerland, and also the incidence of such injuries in the working population. This may also help to assess the need for further education programs and to improve and direct preventive measures.

[Nalmefene and Opioid Withdrawal Syndrome: Analysis of the Global Pharmacovigilance Database for Adverse Drug Reactions]. / Nalmefen und Opioid-Entzugssyndrom: systematische Analyse der globalen PharmacovigilanceDatenbank.

Nalmefene (Selincro®) is a selective opioid receptor antagonist, licensed in April 2014 in Switzerland for the reduction of alcohol consumption in adults with a high drinking risk level. 200 reports of adverse drug reactions of nalmefene have been documented worldwide in the WHO global pharmacovigilance database between 7th March 1997 to 1st March 2015. In 21 cases (10,5%) nalmefene and an opioid were administered concomitantly, causing withdrawal symptoms. Until now, the regional pharmacovigilance center in Zurich received four cases of nalmefene combined with opioids. This combination should be avoided.

Acute sirolimus overdose: a multicenter case series.

BACKGROUND: There are few data relating to sirolimus overdose in the medical literature. Our objectives were to describe all cases of overdose with sirolimus reported to Swiss, German and Austrian Poisons Centres between 2002-2013. METHODS: An observational case-series analysis was performed to determine circumstances, magnitude, management and outcome of sirolimus overdose. RESULTS: Five cases of acute sirolimus overdose were reported--three in young children and two in adults. Four were accidental and one was with suicidal intent. Two patients developed symptoms probably related to sirolimus overdose: mild elevation of alkaline phosphatase, fever and gastroenteritis in a 2.5-year-old male who ingested 3 mg, and mild changes in total cholesterol in an 18-year-old female after ingestion of 103 mg. None of these events were life-threatening. Serial blood concentration measurements were performed starting 24 h after ingestion of 103 mg in a single case, and these followed a similar pharmacokinetic time-course to measurements taken after dosing in the therapeutic range. CONCLUSIONS: Acute sirolimus overdose occurred accidentally in the majority of cases. Even large overdoses appeared to be well-tolerated, however children might be at greater risk of developing complications. Further study of sirolimus overdose is needed.

Acute toxicity profile of tolperisone in overdose: Observational poison centre-based study.

INTRODUCTION: Tolperisone is a centrally acting muscle relaxant that acts by blocking voltage-gated sodium and calcium channels. There is a lack of information on the clinical features of tolperisone poisoning in the literature. The aim of this study was to investigate the demographics, circumstances and clinical features of acute overdoses with tolperisone. METHODS: An observational study of acute overdoses of tolperisone, either alone or in combination with one non-steroidal anti-inflammatory drug in a dose range not expected to cause central nervous system effects, in adults and children (< 16 years), reported to our poison centre between 1995 and 2013. RESULTS: 75 cases were included: 51 females (68%) and 24 males (32%); 45 adults (60%) and 30 children (40%). Six adults (13%) and 17 children (57%) remained asymptomatic, and mild symptoms were seen in 25 adults (56%) and 10 children (33%). There were nine adults (20%) with moderate symptoms, and five adults (11%) and three children (10%) with severe symptoms. Signs and symptoms predominantly involved the central nervous system: somnolence, coma, seizures and agitation. Furthermore, some severe cardiovascular and respiratory signs and symptoms were reported. The minimal dose for seizures and severe symptoms in adults was 1500 mg. In 11 cases the latency between the ingestion and the onset of symptoms was known and was reported to be 0.5-1.5 h. CONCLUSIONS: The acute overdose of tolperisone may be life-threatening, with a rapid onset of severe neurological, respiratory and cardiovascular symptoms. With alternative muscle relaxants available, indications for tolperisone should be rigorously evaluated.

Adverse effects of plant food supplements and botanical preparations: a systematic review with critical evaluation of causality.

AIMS: The objective of this review was to collect available data on the following: (i) adverse effects observed in humans from the intake of plant food supplements or botanical preparations; (ii) the misidentification of poisonous plants; and (iii) interactions between plant food supplements/botanicals and conventional drugs or nutrients. METHODS: PubMed/MEDLINE and Embase were searched from database inception to June 2014, using the terms 'adverse effect/s', 'poisoning/s', 'plant food supplement/s', 'misidentification/s' and 'interaction/s' in combination with the relevant plant name. All papers were critically evaluated according to the World Health Organization Guidelines for causality assessment. RESULTS: Data were obtained for 66 plants that are common ingredients of plant food supplements; of the 492 papers selected, 402 (81.7%) dealt with adverse effects directly associated with the botanical and 89 (18.1%) concerned interactions with conventional drugs. Only one case was associated with misidentification. Adverse effects were reported for 39 of the 66 botanical substances searched. Of the total references, 86.6% were associated with 14 plants, including Glycine max/soybean (19.3%), Glycyrrhiza glabra/liquorice (12.2%), Camellia sinensis/green tea ( 8.7%) and Ginkgo biloba/gingko (8.5%). CONCLUSIONS: Considering the length of time examined and the number of plants included in the review, it is remarkable that: (i) the adverse effects due to botanical ingredients were relatively infrequent, if assessed for causality; and (ii) the number of severe clinical reactions was very limited, but some fatal cases have been described. Data presented in this review were assessed for quality in order to make the results maximally useful for clinicians in identifying or excluding deleterious effects of botanicals.