Acute verapamil toxicity in a patient with chronic toxicity: possible interaction with ceftriaxone and clindamycin

OBJECTIVE: To report a case of acute toxicity in a patient with chronic verapamil toxicity, possibly precipitated by intravenous administration of the highly protein-bound drugs ceftriaxone and clindamycin. DATA SOURCES: Case reports, review articles, and relevant laboratory and clinical studies identified by MEDLINE (1984-forward), and relevant cross references from those articles. DATA EXTRACTION: Data were abstracted from pertinent sources by one author and reviewed by the remaining authors. CASE SUMMARY: A 59-year-old man who had been receiving sustained-release verapamil 240 mg q12h for more than two years for hypertension, and phenytoin 300 mg/d for many years for prophylaxis against seizures, was noted to be in junctional rhythm when he presented to the emergency room with bilateral pneumonia. Administration of intravenous ceftriaxone 1 g and clindamycin 900 mg precipitated symptoms of acute verapamil toxicity in this patient. The toxicity led to complete heart block requiring cardiopulmonary resuscitation and insertion of a temporary pacemaker. He spontaneously reverted to normal sinus rhythm after 16 hours. Subsequent cardiac evaluation, including echocardiogram, 48-hour dynamic electrocardiographic recording (Holter), and exercise stress test were normal. The patient has remained in sinus rhythm for more than one year after this episode. CONCLUSIONS: We believe that junctional rhythm on admission was a result of chronic verapamil toxicity. This may have been because of increased bioavailability of the drug or increased sensitivity of the receptors. Administration of ceftriaxone, clindamycin, or both agents might have precipitated acute verapamil toxicity by displacing verapamil from its protein-binding sites. Extreme caution is necessary when a highly protein-bound drug is given to a patient already receiving verapamil.