Sustained-Release Diltiazem Overdose

Home , Diltiazem

S Morimoto, S Sasaki, M Kiyama, T Hatta, J Moriguchi, S Miki, T Kawa, K Nakamura, H Itoh, T Nakata, K Takeda and M Nakagawa Second Department of Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

Keywords: sustained-release diltiazem; overdose; hypertension; gastrointestinal decontamination

Introduction in water and 2 litres of polyethylene glycol solution. Blood pressure and heart rate decreased progress- Diltiazem, a calcium channel blocker, is now com- ively. After 14 h, the lowest levels of 120/62 mm Hg monly used in the treatment of various cardiovascu- in blood pressure and a 40 bpm in heart rate were lar diseases, such as hypertension, ischaemic heart observed. Both of these haemodynamic changes disease, and supraventricular arrhythmias. This gradually recovered without additional treatment drug produces toxicity such as hypotension and bra- (ie, using atropine, catecholamines, and cardiac dyarrhythmias in the case of excessive adminis- pacing). No heart block or junctional escape was tration. Case reports of its overdose are increasing observed. Serum diltiazem concentration 10 h after in number, but to-date, only one case with an over- the ingestion (329 ng/ml) was about six times higher dose of newer sustained-release preparation has than that necessary to lower blood pressure in been reported. Here, a rare case of sustained-release Japanese hypertensive patients.1 By contrast, serum diltiazem overdose which showed excellent efficacy levels of enalapril (51.5 ng/ml) or trichlormethiazide of gastrointestinal decontamination is described. (6.9 ng/ml) 10 h after the ingestion were not elevated probably due to their fast clearance. Although enala- Case report pril and trichlormethiazide were also taken in excess, their haemodynamic effects were considered A 52-year-old Japanese woman with essential hyper- to be minimal because of the small change in blood tension was admitted to our hospital. Physical pressure as compared with the change in heart rate, examination showed that she was 135 cm in height and because of their low serum concentration 10 h and weighed 43 kg. Blood pressure was 156/100 after ingestion. mm Hg and heart rate was 80 bpm under treatment with 100 mg of sustained-release diltiazem, 5 mg of enalapril, and 2 mg of trichlormethiazide. On the Discussion second day of hospitalisation, she complained of 2–4 nausea, with vacant press-through packages of a 7- For the treatment of diltiazem overdose, gastrointestinal decontamination and calcium injection day supply of all these drugs beside her. An anam- 4 nesis confirmed that she had erroneously taken have been recommended. Most cases, however, them all at once 30 min before. Considering her with hypotension or bradycardia require inotropic 2–4 body size, these drug doses were extremely high. supports or cardiac pacing. It is assumed that Hypotension and bradycardia were not initially appearance of haemodynamic changes due to sus- apparent (Figure 1) and thus the patient’s nausea tained-release diltiazem might be delayed and that was likely to be a gastrointestinal symptom. Intra- gastrointestinal decontamination might be quite venous infusion of crystalloid was started immedi- effective shortly after its ingestion. However, these ately and 0.85 g of calcium gluconate was intra- presumptions had not been proved because the only 5 venously injected. Upon subsequent gastric lavage reported case with sustained-release diltiazem with a nasogastric tube for approximately 1 h, mass- overdose, who arrived at the hospital 6 to 7 h after ive pill fragments were found in the effluent. The the ingestion, required inotropic supports and car- patient was lavaged with 50 g of activated charcoal diac pacing. By contrast, the subject of the present study took an overdose of sustained-release diltiazem while in the hospital and intensive gastrointestinal decontamination was performed shortly after Correspondence: Dr Satoshi Morimoto, Second Department of its ingestion, and thus the haemodynamic changes Medicine, Kyoto Prefectural University of Medicine, Kawarama- chi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan without intensive cardiac supports could be fol- Received 22 December 1998; revised 15 March 1999; accepted 18 lowed up. Accordingly, this is the first report that March 1999 really indicates the delayed appearance of toxicity Sustained-release diltiazem overdose S Morimoto et al 644

Figure 1 Patient’s clinical course. (sBP, systolic blood pressure; HR, heart rate).

of sustained-release diltiazem: maximal haemody- References namic changes appeared 14 h after ingestion. The present case also demonstrated the excellent efﬁcacy 1 Oyama Y. Hemodynamics and electrophysiological of gastrointestinal decontamination. Therefore, this evaluations of diltiazem hydrochloride: a clinical study. case report teaches us a fundamental lesson that in In: Bing RJ (ed). New drug therapy with a calcium patients with sustained-release diltiazem, blood antagonist. Excerpta Medica: Amsterdam, 1978, pp pressure and heart rate levels should be followed up 169–189. carefully after an intensive gastrointestinal decon- 2 Ferner RE et al. Pharmacokinetics and toxic effects of tamination since severe hypotension and bradycar- diltiazem in massive overdose. Human Toxicol 1989; 8: dia might appear later. It should be noted that the 497–499. newer preparation of sustained-release diltiazem 3 Roberts D, Honcharik N, Sitar DS, Tenenbein M. Diltia- should be followed up somewhat differently than zem overdose: pharmacokinetics of diltiazem and its metabolites and effect of multiple dose charcoal ther- the older preparation. apy. Clin Toxicol 1991; 29: 45–52. 4 Howarth DM et al. Calcium channel blocking drug over- Acknowledgement dose: an Australian series. Human Exp Toxicol 1994; 13: 161–166. We are indebted to Dr Ruben D Bunag for his assist- 5 Proano L, Chiang WK, Wang RY. Calcium channel ance in revising the manuscript. blocker overdose. Am J Emerg Med 1995; 13: 444–450.