Are one or two dangerous? Diphenoxylate-atropine exposure in toddlers.

Lomotil (Pfizer Inc., New York, NY) (diphenoxylate-atropine) is said to be potentially toxic to toddlers with exposure to as little as one to two tablets. A review of the data on diphenoxylate-atropine poisonings from the American Association of Poison Control Centers annual reports, review articles, and case series disputes this view. Fatalities associated with diphenoxylate-atropine have been reported in toddlers after repetitive or incorrect dosages. Fortunately, trends in pediatric diphenoxylate-atropine ingestions are decreasing. We review the management, trends, and current concepts regarding pediatric diphenoxylate-atropine ingestions.

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.

Diphenoxylate-atropine (Lomotil) overdose in children: an update (report of eight cases and review of the literature)

Eight pediatric accidental overdoses of diphenoxylate-atropine (Lomotil) are reported, and 28 literature cases are reviewed. This overdose is primarily an opioid intoxication, occasionally associated with atropine toxicity. Only 6 of 36 children showed signs of atropine overdose (central nervous system excitement, hypertension, fever, flushed dry skin). Contrary to popular belief, atropine effects occur before, during, or after opioid effects. Opioid overdose (central nervous system and respiratory depression with miosis) predominated or occurred without any signs of atropine toxicity in 33 cases (92%). Diphenoxylate-induced hypoxia was the major problem and was associated with slow or fast respirations, hypotonia or rigidity, cardiac arrest, and in 3 cases cerebral edema and death. Respiratory depression recurred 13 to 24 hours after the ingestion in 7 cases and was probably due to accumulation of difenoxine, an active metabolite of diphenoxylate. Recommended treatment is intravenous naloxone for depressed or inadequate respirations, followed by continuous intravenous naloxone infusion, prompt gastric lavage, repeated administration of activated charcoal, and close monitoring for 24 hours.

Deadly pediatric poisons: nine common agents that kill at low doses.

More than 97% of pediatric exposures reported to the AAPCC in 2001 had either no effect or mild clinical effects. Despite the large number of exposures, only 26 of the 1074 reported fatalities occurred in children younger than age 6. These findings reflect the fact that, in contrast to adolescent or adult ingestions, pediatric ingestions are unintentional events secondary to development of exploration behaviors and the tendency to place objects in the mouth. Ingested substances typically are nontoxic or ingested in such small quantities that toxicity would not be expected. As a result, it commonly is believed that ingestion of one or two tablets by a toddler is a benign act and not expected to produce any consequential toxicity. Select agents have the potential to produce profound toxicity and death, however, despite the ingestion of only one or two tablets or sips. Although proven antidotes are a valuable resource, their value is diminished if risk after ingestion is not adequately appreciated and assessed. Future research into low-dose, high-risk exposures should be directed toward further clarification of risk, improvements in overall management strategies,and, perhaps most importantly, prevention of toxic exposure through parental education and appropriate safety legislation.

Acute renal failure and intravascular hemolysis following henna ingestion.

The powder of henna plant (Lawsonia inermis Linn.) is extensively used as a decorative skin paint for nail coloring and as a hair dye. Most reports of henna toxicity have been attributed to adding a synthetic dye para-phenylenediamine (PPD). PPD is marketed as black henna added to natural henna to accentuate the dark color and shorten the application time. PPD toxicity is well known and extensively reported in medical literature. We report a case of a young Saudi male who presented with characteristic features of acute renal failure and intravascular hemolysis following ingestion of henna mixture. Management of PPD poisoning is only supportive and helpful only if instituted early. Diagnosis requires a high degree of clinical suspicion, as the clinical features are quite distinctive.

Small doses, big problems: a selected review of highly toxic common medications.

Many commonly used medications have serious toxicity in children when ingested in small doses. The toxicologic characteristics of methyl salicylate, camphor, topical imidazolines, benzocaine, and diphenoxylate-atropine are striking examples. All of these medications except Lomotil are over-the-counter and therefore, are often perceived as minimally harmful when ingested. For all of these substances, however, doses as little as 1/4 teaspoon or 1/2 tablet can have serious or fatal consequences. Thus, referral to an emergency department is prudent for ingestions involving these products. Options for initial gastrointestinal (GI) decontamination are variable, depending on the estimated amount and time of the ingestion. Induction of emesis is contraindicated for significant camphor, topical imidazoline, and Lomotil ingestions. Activated charcoal should be administered in all cases. Finally, the emergency physician must recognize the potential seriousness of these ingestions, as well as their clinical presentations to provide expeditious evaluation and treatment.