Toxic side effects from antiretroviral overdose in children have not been widely reported. Antiretroviral drugs are widely used as oral medications throughout sub-Saharan Africa.
We describe the clinical presentation and management of a 3-year-old male in rural Kenya, who accidentally overdosed on abacavir/lamivudine combination pills. The number of pills taken was approximately 250 tablets, that is 15 g of abacavir and 7.5 g of lamivudine. He presented 24 hours later to Homabay County Referral Hospital, with unresponsiveness, inability to feed and absence of playfulness. Physical examination revealed a sick-looking, ‘unconscious’ child, responding only to voice, with tachycardia, hypertension and moderate dehydration.
He was managed conservatively with rehydration, namely intravenous 1125 mL of 5% dextrose in 0.9% saline, and the monitoring of his neurologic status, urine output and all vital signs. He regained normal neurological function after 24 hours, and recovered uneventfully, but was lost to follow-up.
In an area endemic for HIV and where antiretroviral drug use is commonplace, there is a need for health education to ensure that parents keep drugs out of the reach of children. In the case of a suspected overdose, parents need to be reminded to seek medical attention immediately. Physician awareness of the clinical presentation, management and challenges with an antiretroviral drug overdose is also important.
Antiretroviral therapy has changed infection with HIV from a fatal illness to one that is manageable.
Despite the widespread use of antiretroviral drugs (ARVs), paediatric overdose-related toxicity remains unreported in resource-poor settings. In 2018, Van Dam et al. described an adult parasuicide with dolutegravir/abacavir/lamivudine that resulted in lactic acidosis and hypokalemia. This was managed with intravenous fluids, potassium supplementation, the monitoring of drug levels and blood chemistries.
Abacavir and lamivudine are ARVs that are well absorbed orally.
We report a case of suspected abacavir/lamivudine toxicity managed conservatively in a resource-poor setting. We highlight the scarcity of information and the challenges faced.
A 3-year-old male from rural Kenya, weighing 12.5 kg, was admitted to the paediatric ward of the Homabay County Referral Hospital. This was 24 hours after ingesting four and a half bottles of abacavir 600 mg/lamivudine 300 mg combination pills prescribed for his stepbrother. Each bottle contained 60 tablets, that is, a total of 250 tablets or 15 g of abacavir and 7.5 g of lamivudine. He had been playing unattended when he ingested the tablets and afterwards appeared well and as playful as usual. He did not have a fever, rash, diarrhoea, vomiting or difficulty with breathing that would have suggested an abacavir hypersensitivity reaction. There was no report of confusion, drowsiness or seizures. He ate and slept well but the next morning was drowsy, unable to walk and feed.
He arrived looking sick, lethargic and responding only to voice commands. His airway was intact and breathing and circulation were normal. There was no pallor, jaundice, cyanosis or oedema. The eyes were sunken and the skin turgor was reduced suggesting moderate dehydration. He had a tachycardia of 156/min, a respiratory rate of 27/min, SPaO2 of 99% – 100%, an elevated blood pressure of 131/78 mmHg. His temperature was 37.1°C. Physical examination was unremarkable and all systems were normal. Blood glucose and full hemogram were normal. His HIV test was negative. Serum drug levels, renal and other metabolic tests were unavailable.
The child was admitted to the acute room and re-hydrated as per the Holliday-Segar method, with 1125 mL of dextrose 5% in 0.9% sodium chloride over 24 h. Vital signs and urine output were monitored hourly. Activated charcoal and gastric lavage were omitted because of the late presentation. There was improvement within 24 h. He became ambulant, fed orally and his urine output normalised. He was discharged after 24 hours of observation.
The child’s mother was counselled and advised on the safe handling of household poisons.The stepbrother’s prescription was refilled. She was single, uneducated and unemployed. She avoided discussions around paternity, marital status and HIV status. She provided no reliable contacts and never returned for follow-up.
This article followed all ethical standards for research without direct contact with human or animal subjects.
Abacavir and lamivudine are commonly used in treating children with HIV. They are well absorbed orally with short half-lives of about 2 hours. While abacavir is metabolised in the liver, lamivudine is excreted unchanged in the urine. Nausea, vomiting, diarrhoea, cough, fever and fatigue are side effects of both drugs.
Therapeutic daily paediatric doses of abacavir and lamivudine are 16 mg/kg and 10 mg/kg, not exceeding 600 mg and 300 mg per day.
There is no known antidote for overdose. Management is supportive, and ideally the patient should be admitted to a high dependency unit for continuous monitoring of urine output, neurologic status and vital signs. Liver and renal function tests, with abacavir/lamivudine levels would immediately be useful to assess excretion.
Fatal overdoses have reduced since the introduction of child-resistant containers.
There is limited awareness of ARV overdose toxicity in children, its social factors, and management options in resource-poor settings. Antiretroviral drugs are supplied orally for prolonged periods, reducing mortality and HIV transmission. The potential for accidental overdosing remains and parental education must include the safe storage and handling of ARVs in the home.
The authors wish to thank Dr Antony Gatheru and Prof. Otieno C.F. of the University of Nairobi for taking their time to review and intellectually critique the article prior to submission.
The authors declare that they have no financial or personal relationships that might have inappropriately influenced them in writing this article.
All authors contributed equally to this work.
The authors did not receive financial support for the research, authorship, or publication of this article.
Data sharing is not applicable to this article, as no new data were created or analysed in this study.
The authors declare that the views expressed in the submitted article are their own and not an official position of the their affiliate institutions.