FDA

Cisatracurium Besylate

Approved 24 Apr 2019InjectionInjectable

The FDA lists this product in 30 strengths and forms.

Indications

Cisatracurium besylate injection, USP is indicated: as an adjunct to general anesthesia to facilitate tracheal intubation in adults and in pediatric patients 1 month to 12 years of age to provide skeletal muscle relaxation in adults during surgical procedures or during mechanical ventilation in the ICU to provide skeletal muscle relaxation during surgical procedures via infusion in pediatric patients 2 years and older Limitations of Use Cisatracurium besylate injection, USP is not recommended for rapid sequence endotracheal intubation due to the time required for its onset of action.

Cisatracurium besylate injection is a nondepolarizing neuromuscular blocker indicated: as an adjunct to general anesthesia to facilitate tracheal intubation in adults and in pediatric patients 1 month to 12 years of age (1) to provide skeletal muscle relaxation during surgery in adults and in pediatric patients 2 to 12 years of age as a bolus or infusion maintenance (1) for mechanical ventilation in the ICU in adults (1) Limitations of Use: Cisatracurium besylate injection is not recommended for rapid sequence endotracheal intubation due to the time required for its onset of action

Contraindications

Cisatracurium besylate injection is contraindicated in patients with known hypersensitivity to cisatracurium. Severe anaphylactic reactions to cisatracurium besylate injection have been reported [see Warnings and Precautions (5.4)] . The use of 10 mL cisatracurium besylate injection multiple-dose vials is contraindicated for use in pediatric patients less than 1 month of age and low birth-weight infants because the formulation contains benzyl alcohol [see Warnings and Precautions (5.2) and Use in Specific Populations (8.4)] .

Known hypersensitivity to cisatracurium (4)

Warnings and precautions

Residual Paralysis: Patients with neuromuscular diseases are at higher risk. Use a lower initial bolus dose and consider using a reversal agent in these patients. (2.2, 5.1) Benzyl Alcohol: Consider combined daily load of benzyl alcohol from all sources when the 10 mL multiple dose vials are used in infants (4, 5.2) Risk of Seizure: Monitor level of neuromuscular blockade during long-term administration to limit exposure to toxic metabolites (5.3) Hypersensitivity Reactions and Anaphylaxis: Severe hypersensitivity reactions including anaphylactic reactions have been reported.

Consider cross-reactivity among neuromuscular blocking agents, both depolarizing and non-depolarizing. (4, 5.4) Risk of Death due to Medication Errors: Accidental administration can cause death. (5.5) Inadequate Anesthesia: Use cisatracurium besylate injection in the presence of appropriate sedation or general anesthesia and monitor patients to ensure level of anesthesia is adequate (5.6)

At a glance

Brand name: Cisatracurium Besylate
Route: Injection
Dosage form: Injectable
Applicant: Somerset
Status: Prescription
FDA approval: 24 Apr 2019
Application: ANDA209132-001

Indications

Contraindications

Known hypersensitivity to cisatracurium (4)

Warnings and precautions

Interactions

Succinylcholine: May decrease time to onset of maximum neuromuscular blockade (7.1) Inhalational anesthetics, antibiotics, local anesthetics, magnesium salts, procainamide, lithium, quinidine: May potentiate or prolong neuromuscular blockade action of cisatracurium besylate injection. Use peripheral nerve stimulator and monitor clinical signs of neuromuscular blockade. (5.8, 7.1) Phenytoin and Carbamazepine: May shorten duration of neuromuscular blockade.

Use peripheral nerve stimulator and monitor clinical signs of neuromuscular blockade. (5.9, 7.1)

7.1Clinically Significant Drug Interactions Table

4 displays clinically significant drug interactions with cisatracurium besylate injection Table 4 Clinically Significant Drug Interactions with Cisatracurium Besylate Injection Drug or Drug Class Clinical Implications* Succinylcholine The use of succinylcholine prior to cisatracurium besylate injection administration may decrease the time to onset of maximum neuromuscular blockade but has no effect on the duration of neuromuscular blockade.

Inhalational Anesthetics Administration of inhalational anesthetics with nitrous oxide/oxygen for greater than 30 minutes to achieve

1.25Minimum Alveolar Concentration

(MAC) may prolong the duration of action of initial and maintenance doses of cisatracurium besylate injection. This may potentiate the neuromuscular blockade. Antibiotics† Local anesthetics Magnesium salts Procainamide Lithium Quinidine May prolong the neuromuscular blockade action of cisatracurium besylate injection. Phenytoin, Carbamazepine May increase resistance to the neuromuscular blockade action of cisatracurium besylate injection resulting in shorter durations of neuromuscular blockade and infusion rate requirements may be higher. * The use of peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of cisatracurium besylate injection, and to determine whether adjustments need to be made to the dose with subsequent administration. † Examples: aminoglycosides, tetracyclines, bacitracin, polymyxins, lincomycin, clindamycin, colistin, sodium colistimethate

7.2Drugs Without Clinically Significant Drug Interactions with Cisatracurium Besylate Injection

In clinical studies, propofol had no effect on the duration of action or dosing requirements for cisatracurium besylate injection. Cisatracurium besylate injection is not compatible with propofol for Y-site administration.

Pregnancy and breastfeeding

8.1 Pregnancy Risk Summary The 10 mL cisatracurium besylate injection multiple-dose vials contain the preservative benzyl alcohol. Therefore, if cisatracurium besylate injection is needed during pregnancy, consider using a benzyl alcohol-free formulation (i.e., 5 mL and 20 mL cisatracurium besylate injection single-dose vials). Because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely.

However, adverse reactions have occurred in premature neonates and low birth weight infants who received intravenously administered benzyl alcohol-containing drugs [see Contraindications (4), Warnings and Precautions (5.2), and Use in Specific Populations (8.4)] . There are no available clinical trial data on cisatracurium use in pregnancy to evaluate a drug- associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Animal studies conducted in rats administered cisatracurium besylate during organogenesis (Gestational Day 6 to 15) found no evidence of fetal harm at 0.8 times (ventilated rats) the exposure from a human starting IV bolus dose of 0.2 mg/kg (see Data). The estimated background risk for major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Labor or Delivery The action of neuromuscular blocking agents may be enhanced by magnesium salts administered for the management of preeclampsia or eclampsia of pregnancy. Data Animal Data Two embryofetal developmental reproductive toxicity studies were conducted in rats.

In a non-ventilated rat study, pregnant animals were treated with cisatracurium besylate subcutaneously twice per day from Gestational Day 6 to 15 using subparalyzing doses (2 and 4 mg/kg daily; equivalent to 6- and 12-times, respectively, the AUC exposure in humans following a bolus dose of 0.2 mg/kg IV). In the ventilated rat study, pregnant animals were treated with cisatracurium besylate intravenously once a day between Gestational Day 6 to 15 using paralyzing doses (0.5 and 1 mg/kg; equivalent to 0.4- and 0.8-times, respectively, the exposure in humans following a bolus dose of 0.2 mg/kg IV based on mg/m2 comparison).

Neither of these studies revealed maternal or fetal toxicity or malformations.

Adverse reactions

The most common adverse reactions (0.1% to 0.4%) were bradycardia, hypotension, flushing, bronchospasm, and rash. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Somerset Therapeutics, LLC at 1-800-417-9175 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Adverse Reactions in Clinical Trials of Cisatracurium Besylate Injection in Surgical Patients The data presented below are based on studies involving 945 surgical patients who received cisatracurium besylate injection in conjunction with other drugs in US and European clinical studies in a variety of procedures [see Clinical Studies (14.1)] .

Table 3 displays adverse reactions that occurred at a rate of less than 1%. Table 3. Adverse Reactions in Clinical Trials of Cisatracurium Besylate Injection in Surgical Patients Adverse Reaction Incidence Bradycardia 0.4% Hypotension 0.2% Flushing 0.2% Bronchospasm 0.2% Rash 0.1% Adverse Reactions in Clinical Trials of Cisatracurium Besylate Injection in Intensive Care Unit Patients The adverse reactions presented below were from studies involving 68 adult ICU patients who received cisatracurium besylate injection in conjunction with other drugs in US and European clinical studies [see Clinical Studies (14.3)] .

One patient experienced bronchospasm. In one of the two ICU studies, a randomized and double-blind study of ICU patients using TOF neuromuscular monitoring, there were two reports of prolonged recovery (range: 167 and 270 minutes) among 28 patients administered cisatracurium besylate injection and 13 reports of prolonged recovery (range: 90 minutes to 33 hours) among 30 patients administered vecuronium.

6.2Postmarketing Experience

The following events have been identified during post-approval use of cisatracurium besylate injection in conjunction with one or more anesthetic agents in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to cisatracurium besylate injection: anaphylaxis, histamine release, prolonged neuromuscular block, muscle weakness, myopathy.

Cisatracurium Besylate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Cisatracurium Besylate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Residual Paralysis

5.3Risk of Seizure Laudanosine,

5.4Hypersensitivity Reactions Including Anaphylaxis

5.5Risk of Death Due to Medication Errors Administration

5.6Risks Due to Inadequate Anesthesia

5.8Potentiation of Neuromuscular Blockade

5.9Resistance to Neuromuscular Blockade with Certain Drugs

5.10Malignant Hyperthermia (MH)

Interactions

7.1Clinically Significant Drug Interactions Table

1.25Minimum Alveolar Concentration

7.2Drugs Without Clinically Significant Drug Interactions with Cisatracurium Besylate Injection

Pregnancy and breastfeeding

Adverse reactions

6.1Clinical Studies Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information