Overdose : מינון יתר

4.9     Overdose

In the post-marketing experience, some cases of intentional overdose requiring hospitalization were reported with administration of enalapril/lercanidipine at doses from 100 up to 1000 mg each. The reported symptoms (blood pressure systolic decreased, bradycardia, restlessness, somnolence and flank pain) could also be due to the concomitant administration of high doses of other drugs (e.g. beta-blockers).

Symptoms of overdose with enalapril and lercanidipine alone:
The most prominent features of overdose reported with enalapril to date are marked hypotension (beginning some six hours after ingestion of the tablets), concomitant with blockade of the renin-angiotensin system, and stupor. Symptoms associated with overdose of ACE-inhibitors may include circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough. Serum enalaprilat levels 100- and 200-fold higher than usually seen after therapeutic doses have been reported after ingestion of 300 mg and 440 mg of enalapril respectively.

As with other dihydropyridines, lercanidipine overdosage results in excessive peripheral vasodilation with marked hypotension and reflex tachycardia. However, at very high doses, the peripheral selectivity may be lost, causing bradycardia and a negative inotropic effect.
The most common ADRs associated to cases of overdose have been hypotension, dizziness, headache and palpitations.

Treatment of cases of overdose with enalapril and lercanidipine alone: The recommended treatment of overdosage with enalapril is intravenous infusion of saline solution. If hypotension occurs, the patients should be placed in the shock position. If available, treatment with angiotensin II infusion and/or intravenous catecholamines may also be considered. If the tablets were ingested recently, measures to eliminate enalapril maleate should be taken (e.g. vomiting, gastric lavage, administration of absorbents or sodium sulfate). Enalaprilat can be removed from the circulation by haemodialysis (see section 4.4).
Pacemaker therapy is indicated for therapy-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be continuously monitored.

With lercanidipine, clinically significant hypotension requires active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities and attention to circulating fluid volume and urine output. In view of the prolonged pharmacological effect of lercanidipine, it is essential that the cardiovascular status of the patient is monitored for 24 hours at least. Since the product has a high protein binding, dialysis is not likely to be effective. Patients in whom a moderate to severe intoxication is anticipated should be observed in a high-care setting.