Tipepidine hibenzate is a centrally acting cough suppressant in the opioid family. It was developed in Japan in 1959 and is used in citrate and hibenzate salts. The drug comes in tablet, fine granule, and syrup forms. It is commonly believed that tipepidine hibenzate is very safe and easy to use. As such, it is frequently used by Japanese pediatricians in outpatient clinics. It is not well known that the side-effects of tipepidine hibenzate include drowsiness, vertigo, delirium, disorientation, disturbance of consciousness, and confusion. In severe cases, barbiturate administration is required. 1 Herein, we describe a pediatric case of intoxication due to tipepidine hibenzate overdose. We also present a review of the literature.
Case reportA 3-year-old boy with a history of good health developed a cough and nasal discharge and was diagnosed as having an upper respiratory tract infection. He was prescribed a syrup consisting of carbocysteine in a daily dose of 400 mg, mequitazine in a daily dose of 1.5 mg, and tipepidine hibenzate in a daily dose of 40 mg in three divided portions. The patient weighed 14 kg and was well developed; the prescription dosage was thus appropriate for his bodyweight. The prescription was filled at a local pharmacy. He was given a 6-day course of medicine in one bottle. This mixed syrup was administered for 6 days. One hour after his last dose of medication, he suddenly grew agitated. Because of his persistent excitement, his family brought him to the emergency room at Nihon University Itabashi Hospital 3 h after the onset of symptoms.At this point the boy was delirious, crying loudly, and unable to answer simple questions regarding his name or age. On physi-cal examination his pulse rate was a regular 90 beats/min. The systolic blood pressure was 108 mmHg and the diastolic was 66 mmHg, and his temperature was 36.9°C. The pupils were equal but dilated to 5 mm and were sluggish to light. Other cranial nerves were normal, and there was no sign of meningeal irritation. He could stand but his gait was unsteady. There was no muscle weakness or limitation of movement in any joint. Deep tendon reflexes could be elicited. Heart and lungs auscultation was normal, and the abdomen was flat and soft without any signs of hepatosplenomegaly. Results of laboratory tests, including complete blood count, liver and renal function tests, blood sugar, serum electrolytes, and blood gas analysis, were within normal limits. Computed tomography of the brain was normal. Electroencephalogram results 12 h after the onset of symptoms showed nearly normal slow alpha waves merging with theta waves without any paroxysmal discharge.After admission, additional history was provided by his mother. At this point it was found that the patient's last dose had included a thick precipitate at the bottom of the bottle. We suspected medication overdose on the basis of the symptoms and the history; we then measured the serum concentration of tipepidine hibenzate and mequitazine 5 h after the last dose of medication, using high-pe...