Coma and seizure caused by an afloqualone overdose.

Afloqualone, an analogue of methaqualone developed in the 1980s in Japan,1, 2 is a centrally acting muscle relaxant that affects the spinal polysynaptic reflexes and is used by patients with cervico‐omobrachial syndrome, lumbar pain, and spastic paralysis. An important side‐effect of the drug is photosensitization, causing skin symptoms such as dermatitis.3 An overdose of afloqualone has been previously reported in one Japanese study,4 but never before in the English‐language literature. We report here the case of an infant who had a coma and seizure after accidentally ingesting a massive dose of afloqualone, and describe the serum concentration of the drug in the acute phase. Informed consent was obtained orally from the patient and her parents and described on a medical record for publication of this case report.

A 2‐year‐9‐month‐old girl with no past medical history ingested afloqualone, which her mother was taking for joint pain relief. The mother had placed the drug where she thought it would be out of the child's reach, but the patient was able to find the medicine, remove the tablets from the press‐through‐package sheets, and swallow 29 tablets (580 mg). The mother noticed that the patient was ingesting the medicine and tried to induce vomiting unsuccessfully. After the patient began to show a change in her behavior, her mother called the emergency services and the patient was brought to hospital.

On her arrival at the emergency room, the patient was agitated and showed signs of an altered mental state. Glasgow coma scale score was E2V3M5; blood pressure, 102/54 mmHg; pulse rate, 120 beats/min; respiratory rate, 36 breaths/min; O2 saturation, 98% on room air; and body temperature, 36.5°C. Because the dose of the medicine ingested far exceeded the standard dose for adults, she was transferred to the pediatric intensive care unit (PICU) for intensive monitoring. At the time, she showed no paralysis or irregular reflexes. Soon after arrival at PICU, she exhibited generalized tonic–clonic convulsion. The PICU staff rapidly gave midazolam to stop the seizures. She was intubated intratracheally and sedated. The seizures did not recur thereafter. Electroencephalography (EEG) showed low electrical activity with generalized slow waves. Although the anti‐epileptic drugs and sedatives were tapered, the slow waves on EEG continued until 24 h after the accidental ingestion, then gradually disappeared with the reappearance of normal background activity. Brain computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy on day 2 of hospitalization were normal. The initial laboratory data were normal except for a slight elevation of transaminases, which normalized on day 4. The patient received supportive therapy and was extubated on day 2. After extubation, she was able to speak normally and showed no neurological deficits. There were no sequelae after discharge. We asked Towa Pharmaceutical (Osaka, Japan) to measure the plasma concentration of afloqualone. The concentration of afloqualone at 1, 24, 37, and 62 h after ingestion was 5,060.0, 2,621.7, 293.0, and 43.5 ng/mL, respectively.

The girl accidentally ingested a massive dose of afloqualone and presented with coma and seizure. To date, there has been no study in the English‐language literature dealing with the symptoms, plasma concentrations of the drug, and the prognosis of afloqualone overdose. In the present case the dose was 48 mg/kg (580 mg; bodyweight, 12 kg). Given that adults take 20 mg afloqualone three times a day, the patient ingested almost 120‐fold the standard dose for an adult. Given that the afloqualone lethal dose required to kill 50% of rats (LD50) is 249 mg/kg,5 the dose this case ingested was one‐fifth of the LD50 in rats. The plasma concentration of afloqualone 1 h after ingestion was 5,060 ng/mL. Given that the time to peak blood concentration for afloqualone is approximately 1 h after intake, the concentration of 5,060 ng/mL is considered to be close to the maximum and was responsible for causing the coma and seizure.

According to the Japan Poison Information Center, the side‐effects of afloqualone overdose are dyspnea/tachypnea and brady/tachycardia in addition to central nervous system symptoms.4 The mechanism by which an overdose of afloqualone induces seizure is unknown, and there is no established treatment for an overdose of the drug. The present patient fully recovered on anticonvulsants and supportive therapy.

In conclusion, a patient who massively overdosed on afloqualone presented with coma and seizure. In the emergency setting, seizure control and the stabilization of the patient's general condition are crucial in managing afloqualone overdose.

Disclosure

The authors declare no conflict of interest.

Author contributions

Y.K., H.T. and Y.N. mainly saw this patient in the emergency room and PICU. K.F. and S.M. supported the examinations and decision making. Y.K., H.T., Y.N., K.F. and S.M. wrote the manuscript. All authors read and approved the final manuscript.