Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about DBL™ Cisatracurium Injection Concentrate (cisatracurium besilate).

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given this medicine against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What DBL™ Cisatracurium Injection Concentrate is used for

This medicine is used to relax the body’s muscles during surgery or other medical procedures.

The medicine contains cisatracurium besilate, which belongs to a family of medicines called neuromuscular blockers.

The medicine works by blocking the effects of one of the body’s chemical messengers called acetylcholine. Acetycholine is involved in muscle contraction.

By relaxing your body’s muscles cisatracurium besilate makes it easier for you to be kept asleep (under anaesthesia) or sedation.

Cisatracurium besilate is only used in conjunction with an anaesthetic, so you will be asleep during the procedure.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is not addictive.

It is only available with a doctor’s prescription.

Before you are given DBL™ Cisatracurium Injection Concentrate

When you must not be given it

Do not have the medicine if you have an allergy to:

• any medicine containing cisatracurium besilate or atracurium
• any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

• shortness of breath
• wheezing or difficulty breathing
• swelling of the face, lips, tongue or other parts of the body
• rash, itching or hives on the skin.

Do not take cisatracurium besilate if the packaging is torn or shows signs of tampering.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

• you are allergic to any other muscle relaxants
• you suffer from myasthenia gravis, or any other form of neuromuscular disease
• you, or a relative have had previous difficulties with anaesthetics
• severe acid-base and/or serum electrolyte abnormalities

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you start using the medicine.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some other medicines and cisatracurium besilate may interfere with each other. These include:

• antibiotics
• anti-arrhythmics, which are used to control irregular heart or rapid heart beat
• diuretics, used to increase your volume of urine
• magnesium or lithium salts
• phenytoin or carbamazepine (for fits)

These medicines may be affected by cisatracurium besilate or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Talk to your doctor if you are not sure whether you should be given this medicine.

How DBL™ Cisatracurium Injection Concentrate is given

How much is given

Your doctor will decide what dose of cisatracurium besilate you will receive and how long you will receive it for. This depends on your condition and other factors, such as body weight and the duration of the procedure.

How it is given

DBL™ Cisatracurium Injection Concentrate is given by injection into your vein. This medicine will be administered by an anaesthetist or other highly trained doctor, usually during surgery or other medical procedures.

If you have any questions about the dose that you will receive ask your doctor.

If you have too much (overdose)

Overdoses of DBL™ Cisatracurium Injection Concentrate lead to prolonged relaxation of the body’s muscles. This can be readily treated. This situation is unlikely to occur because it is given to you under the supervision of your doctor, so it is very unlikely that you will receive too much. However, if you experience any severe side effects after being given this medicine, tell your doctor or nurse immediately, or, if you are not in hospital, go to the Accident and Emergency department at your nearest hospital. You may need urgent medical attention.

Please contact the Poisons Information Centre in Australia on 131 126 for advice on overdose management.

While you are being given DBL™ Cisatracurium Injection Concentrate

Things you must do

Tell your doctor or pharmacists if you are taking any other medicines.

Tell any other doctors, dentists, or pharmacists who treat you that you are having this medicine.

If you are about to be started on any new medicine, remind your doctor, dentist or pharmacist that you are having this medicine.

If you are going to have surgery, tell the surgeon, anaesthetist or dentist that you are using this medicine. It may affect other medicines used during surgery.

Things you must not do

Do not start to take any other medicine before talking to your doctor or pharmacist.

Things to be careful of

Be careful driving or operating machinery until you know how the medicine affects you.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are given this medicine. This medicine may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

• flushing of the face and upper body
• skin rashes
• slow heart beat
• dizziness or light headedness
• difficulty breathing
• muscle weakness

Tell your doctor immediately if you notice any of the side effects even after you have finished your treatment.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may occur in some people.

After using DBL™ Cisatracurium Injection Concentrate

Storage

DBL™ Cisatracurium Injection Concentrate should be stored between 2°C to 8°C. Protect from light. Do not freeze.

DBL™ Cisatracurium Injection Concentrate does not contain any antimicrobial preservative. To reduce microbiological hazard, use as soon as practicable after dilution. If storage is necessary, hold at 2°C to 8°C for not more than 24 hours.

Product description

What it looks like

DBL™ Cisatracurium Injection Concentrate is a colourless to pale yellow or greenish solution.

Ingredients

DBL™ Cisatracurium Injection Concentrate contains:

• 5 mg per 2.5mL or
• 10 mg per 5 mL of cisatracurium (as the besilate salt) as the active ingredient.

It also contains:

• benzenesulphonic acid
• water for injection

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

DBL™ Cisatracurium Injection Concentrate is supplied in Australia by:

Sponsor

Australian Sponsor:

Pfizer Australia Pty Ltd
ABN 50 008 422 348
38-42 Wharf Road
West Ryde NSW 2114
Australia
Toll Free Number: 1800 675 229

DBL™ Cisatracurium Injection Concentrate is available in two strengths:

• 5 mg/2.5 mL x 5 vials AUST R 170579
• 10 mg/5 mL x 5 vials AUST R 170580

This leaflet was prepared in May 2017.

Published by MIMS May 2019

Name of the medicine

Cisatracurium besilate.

Excipients.

Description

The active ingredient, cisatracurium besilate, is a white to off-white or yellowish powder.
DBL Cisatracurium Injection Concentrate is presented as a clear, colourless or faint yellow solution containing cisatracurium besilate, benzenesulfonic acid and water for injections, pH is 3.0 - 3.7. It contains no antimicrobial preservative.
DBL Cisatracurium Injection Concentrate is available in the following presentations:
Cisatracurium (as besilate salt), 5 mg per 2.5 mL;
Cisatracurium (as besilate salt), 10 mg per 5 mL.
Chemical name: (1R,1'R,2R,2'R)-2,2'- (3,11-dioxo-4,10-dioxatridecamethylene) -bis-(1,2,3,4-tetrahydro-6,7 -dimethoxy-2-methyl-1- veratry-lisoquinolinium) dibenzenesulfonate. Molecular formula: C₆₅H₈₂N₂O₁₈S₂. Molecular weight: 1,243.5. CAS number: 96946-42-8.
DBL Cisatracurium Injection Concentrate has pH 3.0-3.7. The active ingredient, cisatracurium besilate, is a white to off-white or yellowish powder.

Actions

Cisatracurium besilate, a stereoisomer of atracurium, is an intermediate duration, nondepolarising benzylisoquinolinium skeletal muscle relaxant.

Pharmacology

Pharmacodynamics.

Pharmacokinetics.

Pharmacokinetics in adult patients.

Pharmacokinetics during infusion.

Pharmacokinetics in intensive care unit patients.

Pharmacokinetics in elderly patients.

Pharmacokinetics in paediatric patients.

Pharmacokinetics in patients with renal impairment.

Pharmacokinetics in patients with hepatic impairment.

Clinical Trials

The cisatracurium besilate clinical development program was constructed to provide for systematic collection of efficacy and safety data and to ensure exposure to therapeutically relevant doses of cisatracurium besilate in various populations of patients undergoing a diversity of surgical procedures during opioid, propofol or inhalation anaesthesia as well as ICU patients who require neuromuscular blocking agents to facilitate mechanical ventilation. The result was 23 clinical trials conducted in 1,295 surgical and ICU patients administered cisatracurium besilate and 255 patients administered control neuromuscular blocking agents (atracurium or vecuronium). A total of 20 of these studies contributed efficacy data and included 1,206 patients administered cisatracurium. All studies contributed safety data.
The major population of patients were classified by the American Society of Anesthesiologists (ASA) classification or New York Heart Association (NYHA) classification as: healthy (ASA class 1 or 2) young adult (aged 18 to 50 years), elderly adult (aged 65 to 89 years) and paediatric patients (aged 1 month to 12 years); seriously ill (ASA class 3 or 4) elderly patients or patients with endstage renal or hepatic disease; seriously ill (NYHA class I to IV) adult patients with serious cardiovascular disease scheduled for coronary artery bypass graft (CABG) surgery; critically ill adult ICU patients requiring neuromuscular blocking agents to facilitate mechanical ventilation. The studies included 660 healthy adult patients, 236 paediatric patients (aged 2 to 12 years), 110 paediatric patients (aged 1 to 23 months), 15 patients with endstage liver disease (ESLD), 17 patients with endstage renal failure (ESRF), 182 patients with serious cardiovascular disease (undergoing CABG surgery) and 68 critically ill patients in the ICU. 48 elderly patients (greater than or equal to 65 years) were specifically studied in two studies. Overall, 172 (13%) of the patients administered cisatracurium were greater than or equal to 65 years.
The most common types of surgical procedures were urological (28% of cisatracurium besilate patients) and CABG (14% of cisatracurium besilate patients). Other types of procedures included general surgery (11%), gynaecological (7%), neurosurgical (5%), orthopaedic (8%), oral (3%), plastic (2%), ear, nose and throat (3%) and vascular (1%). ICU patients accounted for 5% of patients administered cisatracurium besilate. There were no obstetric studies.
The clinical development program acquired substantive data in regard to efficacy and safety of large bolus doses of cisatracurium besilate. The mean clinically effective dose of cisatracurium besilate (ED₉₅) estimated from two dose response studies of adult patients receiving opioid anaesthesia was 0.05 mg/kg. Of the 1,295 patients to whom cisatracurium was administered in clinical trials, 102 (8%) received initial bolus doses < ED₉₅, 649 (50%) received initial bolus doses in the ED₉₅ to two times the ED₉₅ range, and 515 (40%) received initial doses that exceeded two times the ED₉₅. ICU patients had neuromuscular block initiated with an infusion and/or bolus dose.
Following the initial dose of cisatracurium besilate, many patients received one or more additional bolus doses, continuous intravenous (IV) infusion, or both to maintain an adequate level of neuromuscular block. The use of cisatracurium besilate by continuous infusion during surgical procedures requiring extended neuromuscular block was investigated in healthy (ASA class 1 or 2) adult patients in seven studies. The majority of patients received cisatracurium besilate by infusion during opioid anaesthesia, the duration of infusion ranging from 11 to 261 minutes. Maintenance dose data for cisatracurium besilate were captured in six studies, a total of 154 adult surgical patients being administered 1 to 21 maintenance doses of 0.03 mg/kg.
The adequacy of intubation conditions following cisatracurium was assessed in five studies in a total of 480 patients (aged 1 month to 87 years) administered cisatracurium besilate.

Indications

During surgical and other procedures and in intensive care to relax skeletal muscles, and to facilitate tracheal intubation and mechanical ventilation. An adjunct to general anaesthesia, or sedation in intensive care units.

Contraindications

Known hypersensitivity to cisatracurium besilate, atracurium or benzenesulfonic acid.

Precautions

Cisatracurium besilate paralyses the respiratory muscles as well as other skeletal muscles but has no effect on consciousness or pain threshold. Cisatracurium besilate should only be administered by, or under the supervision of, anaesthetists or other clinicians who are familiar with the use and action of neuromuscular blocking agents. Facilities for tracheal intubation and maintenance of pulmonary ventilation and adequate arterial oxygenation should be available.
Little information is available of the plasma levels and clinical consequences of cisatracurium metabolites that may accumulate during days to weeks of cisatracurium administration in ICU patients. Laudanosine, a major biologically active metabolite of atracurium and cisatracurium without neuromusclular blocking activity, produces transient hypotension and, in higher doses, cerebral excitatory effects (generalised muscle twitching and seizures) when administered to several species of animals. Consistent with the decreased infusion rate requirements of cisatracurium, plasma laudanosine concentrations are approximately one-third those following atracurium infusion. There have been rare spontaneous reports of seizures in ICU patients who have received atracurium and other agents. These patients usually had predisposing causes (e.g. cranial trauma, cerebral oedema, hypoxic encephalopathy, viral encephalitis, uraemia). There is insufficient data to determine whether or not laudanosine contributes to seizures in ICU patients.
Caution should be exercised when administering cisatracurium besilate to patients who have shown allergic hypersensitivity to other neuromuscular blocking agents since a high rate of cross sensitivity (> 50%) between neuromuscular agents has been reported.
Cisatracurium besilate does not have significant vagolytic or ganglion blocking properties. Consequently, cisatracurium besilate has no clinically significant effect on heart rate and will not counteract the bradycardia produced by many anaesthetic agents or by vagal stimulation during surgery.
Patients with myasthenia gravis and other forms of neuromuscular disease have shown greatly increased sensitivity to nondepolarising blocking agents. An initial dose of not more than 0.02 mg/kg bodyweight of cisatracurium besilate is recommended in these patients.
Rarely, certain drugs may aggravate or unmask latent myasthenia gravis or actually induce a myasthenic syndrome. Increased sensitivity to nondepolarising neuromuscular blocking agents might result (see Interactions with Other Medicines).
Severe acid-base and/or serum electrolyte abnormalities may increase or decrease the sensitivity of patients to neuromuscular blocking agents.
Cisatracurium besilate has not been studied in patients with a history of malignant hyperthermia. Studies in malignant hyperthermia susceptible pigs indicated that cisatracurium besilate does not trigger this syndrome.
Patients with burns have been shown to develop resistance to nondepolarising neuromuscular blocking agents, including atracurium. The extent of altered response depends upon the size of the burn and the time elapsed since the burn injury. Cisatracurium besilate has not been studied in patients with burns, however, based on its structural similarity to atracurium, the possibility of increased dosing requirements and shortened duration of action must be considered if cisatracurium besilate is administered to burn patients.
As with other neuromuscular blocking agents, monitoring of neuromuscular function is recommended during the use of DBL Cisatracurium Injection Concentrate in order to individualise dosage requirements.
As with other drugs administered intravenously, when a small vein is selected as the injection site, DBL Cisatracurium Injection Concentrate should be flushed through the vein with a suitable intravenous fluid (e.g. sodium chloride intravenous solution 0.9% w/v).
DBL Cisatracurium Injection Concentrate does not contain an antimicrobial preservative. Dilution should therefore be carried out immediately prior to use. Administration should commence as soon as possible thereafter and any remaining solution should be discarded (see Dosage and Administration, Stability).
DBL Cisatracurium Injection Concentrate is hypotonic and must not be administered into the infusion line of a blood transfusion.
Enflurane or isoflurane anaesthesia may extend the clinically effective duration of an initial dose of cisatracurium besilate by as much as 15% in adults. In children, halothane may be expected to extend the clinically effective duration of a dose of cisatracurium besilate by up to 20%. No information is available on the use of cisatracurium besilate in children during isoflurane or enflurane anaesthesia but these agents may also be expected to extend the clinically effective duration of a dose of cisatracurium besilate by up to 20%.

Carcinogenesis, mutagenesis, impairment of fertility.

Use in pregnancy.

Use in lactation.

Interactions

A number of drugs have been shown to influence the magnitude and/or duration of action of nondepolarising neuromuscular blocking agents.
The following drugs have been shown to increase the effects on nondepolarising neuromuscular blocking agents; volatile anaesthetics such as enflurane, isofluorane and halothane (see Precautions); ketamine; other nondepolarising neuromuscular blocking agents; antibiotics, including the aminoglycosides, polymyxins, spectinomycin; tetracyclines, lincomycin and clindamycin; antiarrhythmic drugs, including propranolol, calcium channel blockers, lignocaine, procainamide and quinidine; diuretics, including frusemide and possibly thiazides, mannitol and acetazolamide; magnesium salts; lithium salts; and ganglion blocking drugs (trimetaphan, hexamethonium).
Prior chronic administration of phenytoin or carbamazepine has been shown to decrease the effects of nondepolarising neuromuscular blocking agents.
Prior administration of suxamethonium has no effect on the duration of neuromuscular block following bolus doses of cisatracurium besilate or on infusion rate requirements.
Administration of suxamethonium to prolong the effects of nondepolarising neuromuscular blocking agents may result in a prolonged and complex block which can be difficult to reverse with anticholinesterases.
Rarely, certain drugs may aggravate or unmask latent myasthenia gravis or actually induce a myasthenic syndrome. Increased sensitivity to nondepolarising neuromuscular blocking agents might result. Such drugs include various antibiotics, β-blockers (propranolol, oxprenolol), antiarrhythmic drugs (procainamide, quinidine), antirheumatic drugs (chloroquine, penicillamine), trimetaphan, chlorpromazine, steroids, phenytoin and lithium.
Treatment with anticholinesterases, commonly used in the treatment of Alzheimer's disease e.g. donepezil, may shorten the duration and diminish the magnitude of neuromuscular blockage with cisatracurium.

Laboratory tests.

Adverse Effects

No adverse experiences considered to be reasonably attributable to cisatracurium besilate were reported amongst 937 surgical patients studied during the clinical development program. The following adverse experiences were judged by investigators during the clinical trials to have a possible causal relationship to administration of cisatracurium besilate:
Adverse effects are ranked under the headings of frequency, using the following convention: very common (> 10%), common (> 1% to < 10%), uncommon (> 0.1% to < 1%), rare (> 0.01% to < 0.1%), very rare (< 0.01%).

Cardiac disorders.

Vascular disorders.

Respiratory disorders.

Skin and subcutaneous disorders.

Clinical trials with intensive care unit patients.

Clinical practice.

Hypersensitivity.

Other reported reactions.

Dosage and Administration

DBL Cisatracurium Injection Concentrate contains no antimicrobial preservative and is intended for single patient use.

Intravenous bolus injection.

Adults.

Tracheal intubation.

Maintenance.

Spontaneous recovery.

Reversal.

Children 1 month to 12 years.

Tracheal intubation.

Intubation not required.

Maintenance.

Spontaneous recovery.

Reversal.

Intravenous infusion.

Adults, children 1 month to 12 years.

Use in neonates.

Intensive care unit patients.

Use in the elderly.

Impaired renal function.

Impaired hepatic function.

Cardiovascular disease.

Hypothermic cardiac surgery.

Monitoring.

Instructions for use.

Physical compatibilities.

Stability.

Physical compatibilities (other drugs).

Physical incompatibilities.

Overdosage

Symptoms.

Treatment.

Presentation

DBL Cisatracurium Injection Concentrate packs contain 5 vials (5 mg/2.5 mL and 10 mg/5 mL).

Storage

Store DBL Cisatracurium Injection Concentrate packs between 2°C to 8°C. Protect from light. Do not freeze.
See Instructions for use for storage of infusion solutions.

Poison Schedule

S4.