Brevibloc

Warnings and Precautions, Hypoglycemia (

BREVIBLOC injection is a beta adrenergic blocker indicated for the short-term treatment of:

• •Control of ventricular rate in supraventricular tachycardia including atrial fibrillation and atrial flutter and control of heart rate in noncompensatory sinus tachycardia (
  1.1 Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia

  BREVIBLOC (Esmolol Hydrochloride) injection is indicated for the rapid control of ventricular rate in patients with atrial fibrillation or atrial flutter in perioperative, postoperative, or other emergent circumstances where short term control of ventricular rate with a short-acting agent is desirable. BREVIBLOC injection is also indicated in noncompensatory sinus tachycardia where, in the physician’s judgment, the rapid heart rate requires specific intervention. BREVIBLOC injection is intended for short-term use.
  )
• •Control of perioperative tachycardia and hypertension (
  1.2 Intraoperative and Postoperative Tachycardia and/or Hypertension

  BREVIBLOC (Esmolol Hydrochloride) injection is indicated for the short-term treatment of tachycardia and hypertension that occur during induction and tracheal intubation, during surgery, on emergence from anesthesia and in the postoperative period, when in the physician’s judgment such specific intervention is considered indicated.

  Use of BREVIBLOC injection to prevent such events is not recommended.
  )

• •Administer intravenously (
  2.1 Dosing for the Treatment of Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia

  BREVIBLOC injection is administered by continuous intravenous infusion with or without a loading dose. Additional loading doses and/or titration of the maintenance infusion (step-wise dosing) may be necessary based on desired ventricular response.

  Table 1 Step-Wise Dosing

  Step	Action
  1	Optional loading dose (500 mcg per kg over 1 minute), then 50 mcg per kg per min for 4 min
  2	Optional loading dose if necessary, then 100 mcg per kg per min for 4 min
  3	Optional loading dose if necessary, then 150 mcg per kg per min for 4 min
  4	If necessary, increase dose to 200 mcg per kg per min

  In the absence of loading doses, continuous infusion of a single concentration of esmolol reaches pharmacokinetic and pharmacodynamic steady-state in about 30 minutes.

  The effective maintenance dose for continuous and step-wise dosing is 50 to 200 mcg per kg per minute, although doses as low as 25 mcg per kg per minute have been adequate. Dosages greater than 200 mcg per kg per minute provide little added heart rate lowering effect, and the rate of adverse reactions increases.

  Maintenance infusions may be continued for up to 48 hours.
  ,
  2.2 Intraoperative and Postoperative Tachycardia and Hypertension

  In this setting it is not always advisable to slowly titrate to a therapeutic effect. Therefore two dosing options are presented: immediate control and gradual control.

  Immediate Control

  • •Administer 1 mg per kg as a bolus dose over 30 seconds followed by an infusion of 150 mcg per kg per min if necessary.
  • •Adjust the infusion rate as required to maintain desired heart rate and blood pressure. Refer to Maximum Recommended Doses below.

  Gradual Control

  • •Administer 500 mcg per kg as a bolus dose over 1 minute followed by a maintenance infusion of 50 mcg per kg per min for 4 minutes.
  • •Depending on the response obtained, continue dosing as outlined for supraventricular tachycardia. Refer to Maximum Recommended Doses below.

  Maximum Recommended Doses

  • •For the treatment of tachycardia, maintenance infusion dosages greater than 200 mcg per kg per min are not recommended; dosages greater than 200 mcg per kg per min provide little additional heart rate-lowering effect, and the rate of adverse reactions increases.
  • •For the treatment of hypertension, higher maintenance infusion dosages (250-300 mcg per kg per min) may be required. The safety of doses above 300 mcg per kg per minute has not been studied.
  )
• •Titrate using ventricular rate or blood pressure at ≥4-minute intervals. (
  2.1 Dosing for the Treatment of Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia

  BREVIBLOC injection is administered by continuous intravenous infusion with or without a loading dose. Additional loading doses and/or titration of the maintenance infusion (step-wise dosing) may be necessary based on desired ventricular response.

  Table 1 Step-Wise Dosing

  Step	Action
  1	Optional loading dose (500 mcg per kg over 1 minute), then 50 mcg per kg per min for 4 min
  2	Optional loading dose if necessary, then 100 mcg per kg per min for 4 min
  3	Optional loading dose if necessary, then 150 mcg per kg per min for 4 min
  4	If necessary, increase dose to 200 mcg per kg per min

  In the absence of loading doses, continuous infusion of a single concentration of esmolol reaches pharmacokinetic and pharmacodynamic steady-state in about 30 minutes.

  The effective maintenance dose for continuous and step-wise dosing is 50 to 200 mcg per kg per minute, although doses as low as 25 mcg per kg per minute have been adequate. Dosages greater than 200 mcg per kg per minute provide little added heart rate lowering effect, and the rate of adverse reactions increases.

  Maintenance infusions may be continued for up to 48 hours.
  ,
  2.2 Intraoperative and Postoperative Tachycardia and Hypertension

  In this setting it is not always advisable to slowly titrate to a therapeutic effect. Therefore two dosing options are presented: immediate control and gradual control.

  Immediate Control

  • •Administer 1 mg per kg as a bolus dose over 30 seconds followed by an infusion of 150 mcg per kg per min if necessary.
  • •Adjust the infusion rate as required to maintain desired heart rate and blood pressure. Refer to Maximum Recommended Doses below.

  Gradual Control

  • •Administer 500 mcg per kg as a bolus dose over 1 minute followed by a maintenance infusion of 50 mcg per kg per min for 4 minutes.
  • •Depending on the response obtained, continue dosing as outlined for supraventricular tachycardia. Refer to Maximum Recommended Doses below.

  Maximum Recommended Doses

  • •For the treatment of tachycardia, maintenance infusion dosages greater than 200 mcg per kg per min are not recommended; dosages greater than 200 mcg per kg per min provide little additional heart rate-lowering effect, and the rate of adverse reactions increases.
  • •For the treatment of hypertension, higher maintenance infusion dosages (250-300 mcg per kg per min) may be required. The safety of doses above 300 mcg per kg per minute has not been studied.
  )
• •Supraventricular tachycardia (SVT) or noncompensatory sinus tachycardia (
  2.1 Dosing for the Treatment of Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia

  BREVIBLOC injection is administered by continuous intravenous infusion with or without a loading dose. Additional loading doses and/or titration of the maintenance infusion (step-wise dosing) may be necessary based on desired ventricular response.

  Table 1 Step-Wise Dosing

  Step	Action
  1	Optional loading dose (500 mcg per kg over 1 minute), then 50 mcg per kg per min for 4 min
  2	Optional loading dose if necessary, then 100 mcg per kg per min for 4 min
  3	Optional loading dose if necessary, then 150 mcg per kg per min for 4 min
  4	If necessary, increase dose to 200 mcg per kg per min

  In the absence of loading doses, continuous infusion of a single concentration of esmolol reaches pharmacokinetic and pharmacodynamic steady-state in about 30 minutes.

  The effective maintenance dose for continuous and step-wise dosing is 50 to 200 mcg per kg per minute, although doses as low as 25 mcg per kg per minute have been adequate. Dosages greater than 200 mcg per kg per minute provide little added heart rate lowering effect, and the rate of adverse reactions increases.

  Maintenance infusions may be continued for up to 48 hours.
  )
  • •Optional loading dose: 500 mcg per kg infused over one minute
  • •Then 50 mcg per kg per minute for the next 4 minutes
  • •Adjust dose as needed to a maximum of 200 mcg per kg per minute.
  • •Additional loading doses may be administered
• •Perioperative tachycardia and hypertension (
  2.2 Intraoperative and Postoperative Tachycardia and Hypertension

  In this setting it is not always advisable to slowly titrate to a therapeutic effect. Therefore two dosing options are presented: immediate control and gradual control.

  Immediate Control

  • •Administer 1 mg per kg as a bolus dose over 30 seconds followed by an infusion of 150 mcg per kg per min if necessary.
  • •Adjust the infusion rate as required to maintain desired heart rate and blood pressure. Refer to Maximum Recommended Doses below.

  Gradual Control

  • •Administer 500 mcg per kg as a bolus dose over 1 minute followed by a maintenance infusion of 50 mcg per kg per min for 4 minutes.
  • •Depending on the response obtained, continue dosing as outlined for supraventricular tachycardia. Refer to Maximum Recommended Doses below.

  Maximum Recommended Doses

  • •For the treatment of tachycardia, maintenance infusion dosages greater than 200 mcg per kg per min are not recommended; dosages greater than 200 mcg per kg per min provide little additional heart rate-lowering effect, and the rate of adverse reactions increases.
  • •For the treatment of hypertension, higher maintenance infusion dosages (250-300 mcg per kg per min) may be required. The safety of doses above 300 mcg per kg per minute has not been studied.
  )
  • •Loading dose: 500 mcg per kg over 1 minute for gradual control (1 mg per kg over 30 seconds for immediate control)
  • •Then 50 mcg per kg per min for gradual control (150 mcg per kg per minute for immediate control) adjusted to a maximum of 200 (tachycardia) or 300 (hypertension) mcg per kg per min

All BREVIBLOC injection dosage forms are iso-osmotic solutions of esmolol hydrochloride in sodium chloride.

Esmolol hydrochloride has been shown to produce increased fetal resorptions with minimal maternal toxicity in rabbits when given in doses approximately 8 times the maximum human maintenance dose (300 mcg/kg/min). There are no adequate and well-controlled studies in pregnant women. BREVIBLOC injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Teratogenicity studies in rats at intravenous dosages of esmolol hydrochloride up to 3000 mcg/kg/min (10 times the maximum human maintenance dosage) for 30 minutes daily produced no evidence of maternal toxicity, embryotoxicity or teratogenicity, while a dosage of 10,000 mcg/kg/min produced maternal toxicity and lethality. In rabbits, intravenous dosages up to 1000 mcg/kg/min for 30 minutes daily produced no evidence of maternal toxicity, embryotoxicity or teratogenicity, while 2500 mcg/kg/min produced minimal maternal toxicity and increased fetal resorptions.