Brevibloc (Esmolol Hydrochloride) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Catecholamine-depleting drugs, e.g., reserpine, may have an additive effect when given with beta blocking agents. Patients treated concurrently with BREVIBLOC (Esmolol Hydrochloride) and a catecholamine depletor should therefore be closely observed for evidence of hypotension or marked bradycardia, which may result in vertigo, syncope, or postural hypotension.

A study of interaction between BREVIBLOC and warfarin showed that concomitant administration of BREVIBLOC and warfarin does not alter warfarin plasma levels. BREVIBLOC concentrations were equivocally higher when given with warfarin, but this is not likely to be clinically important.

When digoxin and BREVIBLOC were concomitantly administered intravenously to normal volunteers, there was a 10-20% increase in digoxin blood levels at some time points. Digoxin did not affect BREVIBLOC pharmacokinetics. When intravenous morphine and BREVIBLOC were concomitantly administered in normal subjects, no effect on morphine blood levels was seen, but BREVIBLOC steady-state blood levels were increased by 46% in the presence of morphine. No other pharmacokinetic parameters were changed.

The effect of BREVIBLOC on the duration of succinylcholine-induced neuromuscular blockade was studied in patients undergoing surgery. The onset of neuromuscular blockade by succinylcholine was unaffected by BREVIBLOC, but the duration of neuromuscular blockade was prolonged from 5 minutes to 8 minutes.

Although the interactions observed in these studies do not appear to be of major clinical importance, BREVIBLOC should be titrated with caution in patients being treated concurrently with digoxin, morphine, succinylcholine or warfarin.

While taking beta blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Caution should be exercised when considering the use of BREVIBLOC and verapamil in patients with depressed myocardial function. Fatal cardiac arrests have occurred in patients receiving both drugs. Additionally, BREVIBLOC should not be used to control supraventricular tachycardia in the presence of agents which are vasoconstrictive and inotropic such as dopamine, epinephrine, and norepinephrine because of the danger of blocking cardiac contractility when systemic vascular resistance is high.

OVERDOSAGE

ACUTE TOXICITY

Overdoses of BREVIBLOC (Esmolol Hydrochloride) can cause cardiac arrest. In addition, overdoses can produce bradycardia, hypotension, electromechanical dissociation and loss of consciousness. Cases of massive accidental overdoses of BREVIBLOC have occurred due to dilution errors. Use of BREVIBLOC PREMIXED INJECTION and BREVIBLOC DOUBLE STRENGTH PREMIXED INJECTION may reduce the potential for dilution errors. Some of these overdoses have been fatal while others resulted in permanent disability. Bolus doses in the range of 625 mg to 2.5 g (12.5-50 mg/kg) have been fatal. Patients have recovered completely from overdoses as high as 1.75 g given over one minute or doses of 7.5 g given over one hour for cardiovascular surgery. The patients who survived appear to be those whose circulation could be supported until the effects of BREVIBLOC resolved.

Because of its approximately 9-minute elimination half-life, the first step in the management of toxicity should be to discontinue the BREVIBLOC infusion. Then, based on the observed clinical effects, the following general measures should also be considered.

Bradycardia:    Intravenous administration of atropine or another anticholinergic drug.

Bronchospasm:    Intravenous administration of a beta₂ stimulating agent and/or a theophylline derivative.

Cardiac Failure:    Intravenous administration of a diuretic and/or digitalis glycoside. In shock resulting from inadequate cardiac contractility, intravenous administration of dopamine, dobutamine, isoproterenol, or amrinone may be considered.

Symptomatic Hypotension:    Intravenous administration of fluids and/or pressor agents.

CONTRAINDICATIONS

BREVIBLOC (Esmolol Hydrochloride) is contraindicated in patients with sinus bradycardia, heart block greater than first degree, cardiogenic shock or overt heart failure (see WARNINGS).