Fatal cold medication poisoning in an adolescent.

BACKGROUND: Toxicity from the intentional misuse of over-the-counter (OTC) combination cold products has been widely recognized. Adolescents are most frequently involved and dextromethorphan containing products are the most popular. Desired symptoms include stimulatory effects, euphoria, hallucinations, and dissociation. Potential adverse effects include tachycardia, agitation, hyperthermia, acidosis, and coma. However, mortality is rare [ 1-3]. Co-formulated ingredients such as acetaminophen, pseudoephedrine, and antihistamines may also be present and potentiate dangerous effects. We report a case of an adolescent decedent with markedly elevated postmortem chlorpheniramine (CPA) and dextromethorphan (DXM) blood concentrations and no other identifiable cause of death.

Pediatric Fatalities Associated With Over-the-Counter Cough and Cold Medications.

BACKGROUND AND OBJECTIVES: In 2008, over-the-counter cough and cold medications (CCMs) underwent labeling changes in response to safety concerns, including fatalities, reported in children exposed to CCMs. The objective of this study is to describe fatalities associated with exposures to CCMs in children <12 years old that were detected by a safety surveillance system from 2008 to 2016. METHODS: Fatalities in children <12 years old that occurred between 2008 and 2016 associated with oral exposure to one or more CCMs were identified by the Pediatric Cough and Cold Safety Surveillance System. An expert panel reviewed all cases to determine the causal relationship between the exposure and death, if the intent of exposure was therapeutic, and if the dose was supratherapeutic. Other contributing factors related to the child's death were also identified as part of a root cause analysis. RESULTS: Of the 180 eligible fatalities captured during the study period, 40 were judged by the expert panel to be either related or potentially related to the CCM. Of these, the majority (n = 24; 60.0%) occurred in children <2 years old and involved nontherapeutic intent (n = 22; 55.0%). The most frequently involved index ingredient was diphenhydramine (n = 28; 70.0%). In 6 cases (n = 6; 15.0%), the CCM was administered to murder the child. In another 7 cases (n = 7; 17.5%), death followed the intentional use of the CCM to sedate the child. CONCLUSIONS: Pediatric fatalities associated with CCMs occurred primarily in young children after deliberate medication administration with nontherapeutic intent by a caregiver.

In vitro study of pharmacobezoar formation in simulated acetaminophen overdose.

Objectives: There have been few studies of pharmacobezoar formation, but they can be an important contributor to overdose toxicity. Pharmacobezoars may explain the delayed peak or "double hump" pharmacokinetics, which were noted in previous case reports with delayed toxicity of acetaminophen (APAP). We validated the presence of APAP bezoar formation in a controlled modified in vitro environment simulating acute APAP overdose.Methods: This study involved the APAP and control groups (ferrous sulfate and chlorpheniramine). The APAP study group contained three subgroups of APAP with different dosage, i.e., 25 g (50 tabs)/37.5 g (75 tabs)/50 g (100 tabs). The positive control group containing ferrous sulfate, i.e., 15 g (50 tabs), has been reported previously to form pharmacobezoars in overdose. The negative control group containing chlorpheniramine, i.e., 200 mg (50 tabs), has not been reported to form pharmacobezoars in previous case studies. Tablets from each study group were placed into a separate pig stomach. Each stomach contained 28 ml USP standard simulated gastric acid. The stomach was placed in a plastic box filled with water maintaining at 37 °C. Each test group was examined for 4 h in the stomach. The primary outcome was the presence of clump formation. Positive clump formation was defined as tablets sticking together and the ability to maintain shape upon dissecting the pig stomach and lifting with fingers. Tablet clumps would then undergo dissolution testing with subsequent analysis of dissolution profiles.Results: Formation of tablets clumps was confirmed in APAP overdose in the in vitro environment. Clumps were noted to be present in the 37.5 g and 50 g APAP groups, while 25 g APAP was unlikely to form clumps. The dissolution profile of clump demonstrated slower release without reaching plateau at 60 min, as compared to corresponding individual tabs of APAP. f1 and f2 analyses showed the dissolution profile of clump was different compared to that of referenced individual tab.Conclusions: APAP clump formation was confirmed in acute overdose of 37.5 g or more. Dissolution tests revealed delayed and steady release of tablet residue from the clumps, which could explain prolonged or delayed toxicity in large APAP overdose.

Overdose in young children treated with anti-reflux medications: Poisons enquiry evidence of excess 10-fold dosing errors with ranitidine.

BACKGROUND: Accidental drug overdose is a common problem in young children. We examined the influence of formulation and dose in enquiries for different gastro-oesophageal reflux disease treatments in children under 5 years to the UK's National Poisons Information Service. METHODS: Overdose characteristics with ranitidine, omeprazole or domperidone were compared with those of metoclopramide and the H-1 antagonist chlorphenamine, for the period 1 July 2007 to 30 June 2015. RESULTS: There were a total of 1092 ranitidine, 618 domperidone and 1193 omeprazole cases; 669, 281 and 424, respectively, were single agent enquiries; of these 77% (517) of ranitidine, 52% (145) domperidone and 32% (135) omeprazole cases occurred in children <5 years. In comparison, 17% (34/424) of metoclopramide and 53% (533/1013) of chlorphenamine were <5 years; 79% (410/517) of ranitidine overdose enquiries in children <5 years were under 6 months of age, higher than domperidone (68/145, 47%; p < 0.05), omeprazole (8/135, 6%), chlorphenamine (13/553, 2%) or metoclopramide (1/34, 3%) (all p < 0.01). In children aged <6 months, 101 were 10-fold overdoses, 86 with ranitidine. CONCLUSIONS: Tenfold overdoses in children (<5 years) were a feature of ranitidine enquiries, likely due to the high concentration of the syrup. This has relevance to other liquid formulations used for non-licenced indications in young children. Such therapeutic errors cause significant carer anxiety and healthcare utilization. Assistance is needed from manufacturers and legislators in modifying formulation so that drugs can be safely used in young children. Education of prescribers and carers is also needed to reduce the incidence of such errors that cause significant carer anxiety and healthcare utilization.

Accidental death of elderly persons under the influence of chlorpheniramine.

Older individuals are susceptible to accident, such as falls, some of which are fatal. In such cases, autopsies and toxicological analysis may be deemed unnecessary, especially if the critical injuries and manner of death can be determined conclusively based on information at the scene and an external investigation. Here, we report the results of two autopsies performed on elderly individuals who died accidentally under the influence of chlorpheniramine. These autopsies revealed valuable additional information. Case 1: A woman in her 70s, who was living alone, was found dead under the stairs in her house. She had no history of a condition that could have led to sudden death. The autopsy revealed a neck fracture, multiple rib fractures, and a coccyx fracture. The histopathological findings showed fat embolisms in numerous small vessels of the interalveolar septum. Toxicological analysis of blood samples revealed the presence of chlorpheniramine (0.41µg/ml). Case 2: A woman in her 70s, who was living alone, was found dead in the bathtub in her house. There was no past medical history other than diabetes mellitus and vertigo. The autopsy revealed hyper-inflated lungs and brown-red fluids in the trachea, but there was no evidence of a pathology or injury that could have induced a loss of consciousness. Toxicological analysis of the fluids in the right thoracic cavity revealed the presence of chlorpheniramine (0.57µg/ml). In both cases, re-examination of the scene after the autopsy revealed the presence of common cold medicine containing chlorpheniramine. The victim may have accidentally overdosed on common cold medicine. This overdose would have been compounded by anti-histamine-induced drowsiness. The present cases suggest that forensic pathologists should always notify physicians/pharmacists of findings pertaining to unexpected drug side effects. Such intervention would prevent many accidental deaths. In addition, each autopsy must be performed in conjunction with a detailed postmortem investigation. Such efforts would also increase the accuracy of the public health record's mortality statistics.

A fatal case due to cough syrup abuse.

UNLABELLED: We describe here a fatal abused case of cough syrup, containing chlorpheniramine and dihydrocodeine. Postmortem blood concentration of chlorpheniramine was above fatal levels, but dihydrocodeine concentration was within a therapeutic ranges, and those drug levels in blood were discussed from the viewpoint of forensic pharmacokinetics. We concluded that the cause death was due to the chlorpheniramine poisoning. KEYWORDS: cough syrup abuse - chlorpheniramine - dihydrocodeine.

Dextromethorphan, chlorphenamine and serotonin toxicity: case report and systematic literature review.

The aim of this review was to describe a patient with serotonin toxicity after an overdose of dextromethorphan and chlorphenamine and to perform a systematic literature review exploring whether dextromethorphan and chlorphenamine may be equally contributory in the development of serotonin toxicity in overdose. A Medline literature review was undertaken to identify cases of serotonin toxicity due to dextromethorphan and/or chlorphenamine. Case reports were included if they included information on the ingested dose or plasma concentrations of dextromethorphan and/or chlorphenamine, information about co-ingestions and detailed clinical information to evaluate for serotonin toxicity. Cases were reviewed by two toxicologists and serotonin toxicity, defined by the Hunter criteria, was diagnosed when appropriate. The literature was then reviewed to evaluate whether chlorphenamine may be a serotonergic agent. One hundred and fifty-five articles of dextromethorphan or chlorphenamine poisoning were identified. There were 23 case reports of dextromethorphan, of which 18 were excluded for lack of serotonin toxicity. No cases were identified in which serotonin toxicity could be solely attributed to chlorphenamine. This left six cases of dextrometorphane and/or chlorphenamine overdose, including our own, in which serotonin toxicity could be diagnosed based on the presented clinical information. In three of the six eligible cases dextromethorphan and chlorphenamine were the only overdosed drugs. There is substantial evidence from the literature that chlorphenamine is a similarly potent serotonin re-uptake inhibitor when compared with dextrometorphan. Chlorphenamine is a serotonergic medication and combinations of chlorphenamine and dextromethorphan may be dangerous in overdose due to an increased risk of serotonin toxicity.

Life-threatening overdose with lamotrigine, citalopram, and chlorpheniramine.

Lamotrigine is a commonly used agent for seizure control in epilepsy. There are limited data on the adverse effects of lamotrigine in overdose. We report a number of serious side-effects associated with a large overdose of lamotrigine. A 23-year-old female presented to the emergency department after taking an intentional overdose of 9.2 g of lamotrigine, 56 mg of chlorpheniramine, and 220 mg of citalopram. On admission, she had a reduced level of consciousness and electrocardiographic abnormalities; a widened QRS and a prolonged corrected QT (QTc) interval. Prompt treatment with early intubation, along with the use of magnesium for cardioprotection and administration of sodium bicarbonate may have aided in a quick recovery with a short intensive care stay and good outcome.

Coricidin HBP abuse: patient characteristics and psychiatric manifestations as recorded in an inpatient psychiatric unit.

Coricidin HBP, a cold medication containing dextromethorphan, has become a popular agent abused among adolescents. This retrospective chart review examines the potential psychiatric manifestations of Coricidin HBP misuse and patterns of use among patients treated in an inpatient child and adolescent psychiatric unit. Coricidin HBP use was documented in 47 patient. The data revealed that Coricidin HBP use was associated with: (a) predominantly depressive symptomatology; (b) transient substance-induced psychosis; (c) cardiac toxicity; and (d) greater quantities used per episode by Caucasians. Clinicians treating adolescents need to be aware of the abuse potential and psychiatric manifestations of this dextromethorphan-containing product.

Acute intoxication of lidocaine and chlorpheniramine: report of one case.

A case of acute intoxication involving lidocaine and chlorpheniramine (an antihistamine) in a 13-month-old child after ingestion of a commercial topical agent is presented. The major toxic reaction consisted of convulsion, coma, tachycardia, fever, and fatigue. This report shows that parents and physicians should be made aware of the hazards of lidocaine and overdose of other topical agents in infants and children.

Severe manifestations of coricidin intoxication.

CoricidinHBP (Schering-Plough Health Care Products, Inc, Memphis, TN) is a popular over-the-counter product abused by teenagers for its potent euphoric properties. Clinically significant signs and symptoms after ingestion are usually short-lived and commonly include tachycardia, hypertension, somnolence, and agitation. We report 2 cases of severe toxicity from CoricidinHBP in adolescents that required prolonged hospitalization. The first case demonstrates prolonged anticholinergic complications from a suicidal attempt with CoricidinHBP. The second case demonstrates significant acetaminophen-induced hepatotoxicty from recreational use of CoricidinHBP Maximum Strength Flu. Adolescent abuse of these products is encouraged because of the easily accessible medium of the Internet. The significant morbidity seen in our cases clearly demonstrates the need for vigilance by health care professionals regarding the abuse of over-the-counter products.

Polydrug fatality involving metaxalone.

A 29-year old female with a history of depression was found dead in a hotel room. The death scene investigation found empty pill bottles and an empty liter bottle of wine. Metaxalone, a centrally acting muscle relaxant, along with citalopram, ethanol, and chlorpheniramine were identified in the postmortem samples and quantitated by gas chromatography-mass spectrometry. The concentration of metaxalone in femoral vein blood was 39 mg/L. The heart blood concentration was 54 mg/L. Femoral vein blood concentrations of citalopram and chlorpheniramine were 0.77 mg/L and 0.04 mg/L, respectively. Ethanol levels were 0.13 g/dL in vitreous and 0.08 g/dL in heart blood. Other tissue samples were also analyzed. The authors consider the metaxalone concentrations toxic and potentially fatal. The citalopram concentrations were lower than those reported in fatal cases for this drug alone. Death was ascribed to polydrug abuse/overdose with metaxalone a major contributor. This represents the first reported case to our knowledge in which a metaxalone overdose significantly contributed to death.

A possible trend suggesting increased abuse from Coricidin exposures reported to the Texas Poison Network: comparing 1998 to 1999.

Coricidin products seemed to be one of the over-the-counter medications being reportedly abused by adolescents, as observed from the Texas Poison Center Network data. This retrospective chart review investigated the occurrence of abuse, developed a patient profile, and defined the clinical effects resulting from the abuse of Coricidin products. Data collected from the Texas Poison Center Network Toxic Exposure Surveillance System database included human exposures between 1998 and 1999, patients > or = 10y old, intentional use or abuse, and single substance ingestion of I of the tablet formulations of Coricidin. Thirty-three cases from 1998 and 59 cases from 1999 were reviewed. Of these cases, 85% met the inclusion criteria. Of the 7 medications searched, only 4 substances were coded for: Coricidin D, Coricidin D (long acting), Coricidin D (cold, flu & sinus) and Coriciding HBP. These contain a combination of dextromethorphan hydrobromide, chlorpheniramine maleate, phenylpropanolamine hydrochloride, and acetaminophen. Of the 78 cases, 63% were male and 38% were female. The mean age was 14.67 years, 77% being between 13 to 17 years old. Eighteen different symptoms were reported: tachycardia 50%, somnolence 24.4%, mydriasis and hypertension 16.7%, agitation 12.8%, disorientation 10.3%, slurred speech 9%, ataxia 6.4%, vomiting 5.1%, dry mouth and hallucinations 3.9%, tremor 2.6%, and headache, dizziness, syncope, seizure, chest pain, and nystagmus each 1.3%; 12.8% of the calls originated from the school nurse. The incidence of abuse reported increased 60% from 1998 to 1999. This worrisome trend suggests increased abuse of these products.

Abuse of Coricidin HBP cough & cold tablets: episodes recorded by a poison center.

Cases involving ingestion of a dextromethorphan-containing product recorded at a poison control center were studied. A retrospective review of all consultations involving the ingestion of Coricidin HBP Cough & Cold tablets recorded by the California Poison Control System was conducted for the period from January 1 to October 1, 2000. Computerized charts on the consultations were reviewed to obtain data on patient age and sex, number of tablets taken, reason for tablet ingestion, symptoms, treatment, disposition, and outcome. A total of 92 charts (for 92 patients) documenting Coricidin HBP Cough & Cold tablet ingestion were reviewed. The reason for tablet ingestion was classified as abuse in 65 patients (71%), a suicide attempt in 8 (9%), misuse in 1 (1%), malicious administration in 1 (1%), and normal use (but with an adverse drug reaction) in 1 (1%); 16 patients (17%) consumed the tablets for an unknown reason. The 92 patients comprised 42 males and 50 females. Among all patients, 78 (85%) were 13-17 years old, and among those classified as having abusive intent, 58 (89%) were in the same age range. The most commonly reported signs and symptoms associated with ingestion were tachycardia (50 patients), hypertension (29), lethargy (40), mydriasis (20), agitation (15), ataxia or dizziness (20), and vomiting (9). Sixty-one patients (66%) had some alteration in mental status. Fifty-six (61%) were treated in the emergency department; 11 (12%) were admitted. All patients recovered completely. Information on the ingestion of Coricidin HBP Cough & Cold tablets recorded at a poison control center indicated a high rate of abuse of the product among teenagers.

Acute intoxication with guaifenesin, diphenhydramine, and chlorpheniramine.

Mixed drug reactions are frequently encountered in emergency department overdose cases and also in fatal intoxications. Assessment of the relative contribution of each drug in producing adverse effects is often compounded by lack of case history and the paucity of cases reported in the literature. This report describes a fatal intoxication with three common over-the-counter medications: guaifenesin, diphenhydramine, and chlorpheniramine. A 48-year-old woman was found dead in the attic bedroom of her residence. Specimens obtained at autopsy for toxicologic analysis included heart blood, urine, bile, gastric contents, vitreous humor, and cerebrospinal fluid. The over-the-counter drugs were identified and quantitated by acid/neutral or basic liquid-liquid extraction followed by gas chromatographic analysis with nitrogen phosphorus detection. Concentrations of guaifenesin, diphenhydramine, and chlorpheniramine detected in the heart blood were 27.4, 8.8, and 0.2 mg/L, respectively. The cause of death was determined to be acute intoxication by the combined effects of guaifenesin, diphenhydramine, and chlorpheniramine, and the manner of death was determined to be suicide. To our knowledge, the blood guaifenesin concentration in this case is the highest reported concentration to date associated with an acute intoxication.

Delayed peak serum valproic acid in massive divalproex overdose--treatment with charcoal hemoperfusion.

BACKGROUND: Increased clearance and apparent clinical improvement in valproic acid overdose has been reported following in-series hemodialysis/hemoperfusion therapy. We report a case of divalproex sodium and chlorpheniramine overdose treated with charcoal hemoperfusion and multiple-dose activated charcoal. CASE REPORT: A 32-year-old female presented alert three hours postingestion of her own medication. Serum valproic acid was 105 micrograms/mL. No anticholinergic toxicity was seen. Despite three doses of activated charcoal over 14 hours, serum valproic acid continued to rise. Whole bowel irrigation and multiple-dose activated charcoal were commenced 17 h postingestion when serum valproic acid was 1380 micrograms/mL. Charcoal hemoperfusion was instituted three hours later when serum valproic acid had not fallen and the patient remained obtunded. RESULTS: Initial extraction ratio of the hemoperfusion cartridge was 0.54 with plasma clearance of 54.5 mL/min. Valproic acid elimination half-life was 3 h during the 190 min hemoperfusion cycle. Posthemoperfusion elimination half-life was 4.8 h with continued multiple-dose activated charcoal dosing. The clinical condition improved during hemoperfusion. CONCLUSION: Enteric coated valproic acid preparations may cause delayed toxicity in overdose, particularly with coingested anticholinergic medications. In our case, charcoal hemoperfusion appeared to increase valproic acid clearance.