Only a few cases of human overdose with amlodipine have been reported. One patient was asymptomatic after a 250-mg ingestion; another, who combined 70 mg of amlodipine with an unknown large quantity of a benzodiazepine, developed refractory shock and died.
Human overdoses with any combination of amlodipine and benazepril have not been reported. In scattered reports of human overdoses with benazepril and other ACE inhibitors, there are no reports of death.
When mice were given single oral doses of benazepril/amlodipine, mortality was 20% at 50:25 mg/kg, 10% at 100:50 mg/kg, and 100% at 500:250 mg/kg. In rats, mortality was 25% (pooling two studies) at 500:250 mg/kg and 100% at 900:450 mg/kg.
Treatment: To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison-Control Center. Telephone numbers of certified poison-control centers are listed in the Physicians’ Desk Reference** (PDR). In managing overdose, consider the possibilities of multiple-drug overdoses, drug-drug interactions, and unusual drug kinetics in your patient.
The most likely effect of overdose with Lotrel is vasodilation, with consequent hypotension and tachycardia. Simple repletion of central fluid volume (Trendelenburg positioning, infusion of crystalloids) may be sufficient therapy, but pressor agents (norepinephrine or high-dose dopamine) may be required. Overdoses of other dihydropyridine calcium channel blockers are reported to have been treated with calcium chloride and glucagon, but evidence of a dose-response relation has not been seen, and these interventions must be regarded as unproven. With abrupt return of peripheral vascular tone, overdoses of other dihydropyridine calcium channel blockers have sometimes progressed to pulmonary edema, and patients must be monitored for this complication.
Analyses of bodily fluids for concentrations of amlodipine, benazepril, or their metabolites are not widely available. Such analyses are, in any event, not known to be of value in therapy or prognosis.
No data are available to suggest physiologic maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of amlodipine, benazepril, or their metabolites. Benazeprilat is only slightly dialyzable; attempted clearance of amlodipine by hemodialysis or hemo-perfusion has not been reported, but amlodipine’s high protein binding makes it unlikely that these interventions will be of value.
Angiotensin II could presumably serve as a specific antagonist-antidote to benazepril, but angiotensin II is essentially unavailable outside of scattered research laboratories.