NIMBEX FORTE 5 MG / ML SOLUTION FOR INJECTION/INFUSION - patient leaflet, side effects, dosage

cisatracurium

cisatracurium

Nimbex 2 mg/ml solution for injection/infusion

Nimbex Forte 5 mg/ml solution for injection/ infusion

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor.
• If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

• 1 What Nimbex is and what it is used for

• 2 What you need to know before you are given Nimbex

• 3 How Nimbex is given

• 4 Possible side effects

• 5 How to store Nimbex

• 6 Contents of the pack and other information

1 What Nimbex is and what it is used for

Nimbex contains a medicine called cisatracurium. This belongs to a group of medicines called muscle relaxants.

Nimbex is used:

• to relax muscles during operations on adults and children over 1 month of age, including heart surgery
• to help insert a tube into the windpipe (tracheal intubation), if a person needs help to breathe
• to relax the muscles of adults in intensive care. Ask your doctor if you would like more explanation about this medicine.

2 What you need to know before you are given Nimbex

Do not use Nimbex:

• if you are allergic to cisatracurium, any other muscle relaxant or any of the other ingredients in Nimbex (listed in section 6)
• you have reacted badly to an anaesthetic before. Do not have Nimbex if any of the above apply to you. If you are not sure, talk to your doctor, nurse or pharmacist before you have Nimbex.

Take special care with Nimbex

Talk to your doctor, nurse or pharmacist before having this medicine:

• if you have muscle weakness, tiredness or difficulty in co-ordinating your movements (myasthenia gravis)
• you have a neuromuscular disease, such as a muscle wasting disease, paralysis, motor neurone disease or cerebral palsy
• if you have a burn which requires medical treatment.
• you have ever had an allergic reaction to any muscle relaxant which was given as part of an operation

If you are not sure if any of the above apply to you, talk to your doctor, nurse or pharmacist before you are given Nimbex.

Other medicines and Nimbex

Tell your doctor if you are taking or have recently taken any other medicines. This includes any herbal products or medicines bought without a prescription.

In particular tell your doctor if you are taking any of the following:

• anaesthetics (used to reduce sensation and pain during surgical procedures)
• antibiotics (used to treat infections)
• medicines for uneven heart beats (anti-arrhythmics)
• medicines for high blood pressure
• water tablets (diuretics), such as furosemide
• medicines for inflammation of the joints, such as chloroquine or d-penicillamine
• steroids
• medicines for fits (epilepsy), such as phenytoin or carbamazepine
• medicines for mental illness, such as lithium or chlorpromazine (which can also be used for sickness)
• medicines containing magnesium
• drugs for Alzheimer’s disease (anticholines­terases e.g. donepezil).

Pregnancy and breast-feeding

Do not breast feed for at least 3 hours after your last dose when the effects of cisatracurium have worn off.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Driving and using machines

If you are only staying in hospital for the day, your doctor will tell you how long to wait before leaving the hospital or driving a car. It can be dangerous to drive too soon after having an operation.

3 How Nimbex is given

How your injection is given

You will never be expected to give yourself this medicine. It will always be given to you by a person who is qualified to do so.

Nimbex can be given:

• as a single injection into your vein (intravenous bolus injection)
• as a continuous infusion into your vein. This is where the drug is slowly given to you over a long period of time.

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Following discontinuation of infusion of Nimbex, spontaneous .

recovery from neuromuscular block proceeds at a rate comparable.. to that following administration of a single bolus.

Dosage in neonates (aged less than 1 month)

The use of Nimbex in neonates is not recommended as it has not been studied in this patient population.

Dosage in elderly patients

No dosing alterations are required in elderly patients. In these patients Nimbex has a similar pharmacodynamic profile to that observed in young adult patients but, as with other neuromuscular blocking agents, it may have a slightly slower onset.

Dosage in patients with renal impairment

No dosing alterations are required in patients with renal failure.

In these patients Nimbex has a similar pharmacodynamic profile to that observed in patients with normal renal function but it may have a slightly slower onset.

Dosage in patients with hepatic impairment

No dosing alterations are required in patients with end-stage liver disease. In these patients Nimbex has a similar pharmacodynamic profile to that observed in patients with normal hepatic function but it may have a slightly faster onset.

Dosage in patients with cardiovascular disease

When administered by rapid bolus injection (over 5 to 10 seconds) to adult patients with serious cardiovascular disease (New York Heart Association Class I-III) undergoing coronary artery bypass graft (CABG) surgery, Nimbex has not been associated with clinically significant cardiovascular effects at any dose studied (up to and including 0.4 mg/kg (8 x ED95)). However, there are limited data for doses above 0.3 mg/kg in this patient population.

Nimbex has not been studied in children undergoing cardiac surgery.

Dosage in Intensive Care Unit (ICU) patients

Nimbex may be administered by bolus dose and/or infusion to adult patients in the ICU.

An initial infusion rate of Nimbex of 3 pg/kg (body weight)/min (0.18 mg/kg/hr) is recommended for adult ICU patients. There may be wide interpatient variation in dosage requirements and these may increase or decrease with time. In clinical studies the average infusion rate was 3 pg/kg/min [range 0.5 to 10.2 pg/kg (body weight)/min (0.03 to 0.6 mg/kg/hr )]. Table 6 provides guidelines for delivery of undiluted Nimbex Forte (5 mg/ml) injection.

The median time to full spontaneous recovery following long-term (up to 6 days) infusion of Nimbex in ICU patients was approximately 50 minutes.

The recovery profile after infusions of Nimbex to ICU patients is independent of duration of infusion.

Contraindications

Nimbex is contraindicated in patients known to be hypersensitive to cisatracurium, atracurium, or benzene sulfonic acid.

Special warnings and special precautions for use

Cisatracurium paralyses the respiratory muscles as well as other skeletal muscles but has no known effect on consciousness or pain threshold. Nimbex should be only 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 have to be available.

Great caution should be exercised when administering Nimbex to patients who have shown hypersensitivity to other neuromuscular blocking agents since a high rate of cross-sensitivity (greater than 50%) between neuromuscular blocking agents has been reported.

Cisatracurium does not have significant vagolytic or ganglion- blocking properties. Consequently, Nimbex 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 non-depolarising blocking agents. An initial dose of not more than 0.02 mg/kg Nimbex is recommended in these patients.

Severe acid-base and/or serum electrolyte abnormalities may increase or decrease the sensitivity of patients to neuromuscular blocking agents.

There is no information on the use of Nimbex in neonates aged less than one month since it has not been studied in this patient population.

Cisatracurium has not been studied in patients with a history of malignant hyperthermia. Studies in malignant hyperthermia-susceptible pigs indicated that cisatracurium does not trigger this syndrome.

There have been no studies of cisatracurium in patients undergoing surgery with induced hypothermia (25 to 28°C). As with other neuromuscular blocking agents the rate of infusion required to maintain adequate surgical relaxation under these conditions may be expected to be significantly reduced.

Cisatracurium has not been studied in patients with burns; however, as with other non-depolarising neuromuscular blocking agents, the possibility of increased dosing requirements and shortened duration of action must be considered if Nimbex injection is administered to these patients.

Nimbex is hypotonic and must not be applied into the infusion line of a blood transfusion.

Intensive Care Unit (ICU) Patients

When administered to laboratory animals in high doses, laudanosine, a metabolite of cisatracurium and atracurium, has been associated with transient hypotension and in some species, cerebral excitatory effects. In the most sensitive animal species, these effects occurred at laudanosine plasma concentrations similar to those that have been observed in some ICU patients following prolonged infusion of atracurium.

Consistent with the decreased infusion rate requirements of cisatracurium, plasma laudanosine concentrations are approximately one third those following atracurium infusion.

There have been rare reports of seizures in ICU patients who have received atracurium and other agents. These patients usually had one or more medical conditions predisposing to seizures (e.g. cranial trauma, hypoxic encephalopathy, cerebral oedema, viral encephalitis, uraemia). A causal relationship to laudanosine has not been established.

Pharmaceutical particulars

Benzene sulfonic acid solution 32% w/v, Water for Injections.

Shelf life

Shelf life before dilution: 2 years.

Chemical and physical in-use stability has been demonstrated for at least 24 hours at 5°C and 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

Special precautions for storage

Store in a refrigerator (2 to 8°C). Do not freeze.

Store in the original package in order to protect from light.

For storage conditions of the diluted medicinal product, see section 5 of the Package Leaflet.

Instructions for use/handling

This product is for single use only. Use only clear and almost colourless up to slightly yellow/greenish yellow coloured solutions. The product should be visually inspected before use, and if the visual appearance has changed or if the container is damaged, the product must be discarded.

Diluted Nimbex is physically and chemically stable for at least 24 hours at 5°C and 25°C at concentrations between 0.1 and 2 mg/ml in the following infusion fluids, in either polyvinyl chloride or polypropylene containers.

Sodium Chloride (0.9% w/v) Intravenous Infusion.

Glucose (5% w/v) Intravenous Infusion.

Sodium Chloride (0.18% w/v) and Glucose (4% w/v) Intravenous Infusion. Sodium Chloride (0.45% w/v) and Glucose (2.5% w/v) Intravenous Infusion.

However, since the product contains no antimicrobial preservative, dilution should be carried out immediately prior to use, or failing this be stored as directed under section 5 of the Package Leaflet.

Nimbex has been shown to be compatible with the following commonly used peri-operative drugs, when mixed in conditions simulating administration into a running intravenous infusion via a Y-site injection port: alfentanil hydrochloride, droperidol, fentanyl citrate, midazolam hydrochloride and sufentanil citrate. Where other drugs are administered through the same indwelling needle or cannula as Nimbex, it is recommended that each drug be flushed through with an adequate volume of a suitable intravenous fluid, e.g., Sodium Chloride Intravenous Infusion (0.9% w/v).

As with other drugs administered intravenously, when a small vein is selected as the injection site, Nimbex should be flushed through the vein with a suitable intravenous fluid, e.g., sodium chloride intravenous infusion (0.9% w/v).

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Nimbex 2 mg/ml solution for injection/infusion

Instructions to open the ampoule (only applicable to 2 mg/ml ampoule) Ampoules are equipped with the OPC (One Point Cut) opening system and must be opened following the below instructions:

• Hold the bottom part of the ampoule with the hand as indicated in picture 1
• Put the other hand on the top of the ampoule positioning the thumb above the coloured point and press as indicated in picture 2

Information for the physician leaflet date: September 2021

Nimbex is a trademark of the Aspen group. © 2021 Aspen group of companies.

All rights reserved.

Q aspen

Your doctor will decide the way you are given the drug and the dose you will receive. It will depend on:

• your body weight
• the amount and duration of muscle relaxation required
• your expected response to the medicine.

Children less than 1 month old should not have this medicine.

If you receive more Nimbex than you should Nimbex will always be given under carefully controlled conditions. However, if you think that you have been given more than you should tell your doctor or nurse immediately.

If you have any further questions on the use of this medicine, ask your doctor.

4 Possible side effects

Like all medicines, Nimbex can cause side effects, although not everybody gets them.

If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet.

Allergic reactions (affects less than 1 in 10,000 people)

• If you have an allergic reaction, tell your doctor or nurse straight away. The signs may include: sudden wheeziness, chest pain or chest tightness swelling of your eyelids, face, lips, mouth or tongue a lumpy skin rash or ‘hives’ anywhere on your body a collapse and shock.

Talk to your doctor, nurse or pharmacist if you notice any of the following:

Common (affects less than 1 in 10 people)

• decrease in heart rate
• decrease in blood pressure.

Uncommon (affects less than 1 in 100 people)

• a rash or redness of your skin
• wheezing or coughing.

Very rare (affects less than 1 in 10,000 people)

• weak or aching muscles.

Reporting of side effects

If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at:.

By reporting side effects you can help provide more information on the safety of this medicine.

5 How to store Nimbex

• Keep Nimbex out of the sight and reach of children.
• Do not use Nimbex after the expiry date shown on the pack after ‘Exp’. The expiry date refers to the last day of that month.
• Store in a refrigerator (2°C – 8°C). Do not freeze.
• Store in the original package in order to protect from light.
• If diluted, store the infusion solution between 2°C and 8°C and use within 24 hours. Any unused infusion solution should be discarded 24 hours after it was prepared.
• Do not throw away any medicines via wastewater or household waste. Your doctor or nurse will throw away any medicine that is no longer required. This will help protect the environment.

6 Contents of the pack and other information

What Nimbex contains

• The active substance is 2 mg/ml or 5 mg/ml cisatracurium (as besilate).
• The other ingredients are benzene sulfonic acid (32% w/v) and Water for Injections.

What Nimbex looks like and contents of the pack

Nimbex 2 mg/ml solution for injection/infusion comes:

• 2.5 ml clear glass ampoule in a box of 5 (each

• 2.5 ml ampoule contains 5 mg of cisatracurium)

• 5 ml clear glass ampoule in a box of 5 (each

5 ml ampoule contains 10 mg of cisatracurium)

• 10 ml clear glass ampoule in a box of 5 (each

10 ml ampoule contains 20 mg of cisatracurium)

• 25 ml clear glass ampoule in a box of 2 (each 25 ml ampoule contains 50 mg of cisatracurium)

Nimbex Forte 5 mg/ml solution for injection/infusion comes in a box containing one 30 ml clear glass vial. Each 30 ml vial contains 150 mg of cisatracurium.

Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Marketing Authorisation Holder:

Aspen Pharma Trading Limited, 3016 Lake Drive, City West Business Campus, Dublin 24, Ireland Service-Tel: 0800 008 7392 (+ 44 1748 828 391)

Manufacturer: Aspen Pharma Ireland Limited, One George’s Quay Plaza, Dublin 2, Ireland

Other formats

To listen to or request a copy of this leaflet in Braille, large print or audio please call, free of charge: 0800 198 5000 (UK only)

Please be ready to give the following information:

Product name Nimbex 2 mg/ml solution for injection

Nimbex Forte 5 mg/ml solution for injection

Reference number PL 39699/0092

This is a service provided by the Royal National Institute of Blind People.

Leaflet date: September 2021.

Nimbex is a trade mark of the Aspen group. © 2021 Aspen group of companies. All rights reserved.

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