Rocuronium bromide 100mg/10ml solution for injection vials

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

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Active ingredient:
Rocuronium bromide
Available from:
Pfizer Ltd
ATC code:
M03AC09
INN (International Name):
Rocuronium bromide
Dosage:
10mg/1ml
Pharmaceutical form:
Solution for injection
Administration route:
Intravenous
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 15010500; GTIN: 5015997107774
Authorization number:
PL 04515/0402

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Package leaflet: Information for the patient

Rocuronium Bromide 10 mg/ml Solution for Injection/Infusion.

Rocuronium bromide

Read all of this leaflet carefully before you start using 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 or anaesthetist.

If you get any side effects, talk to your doctor or anaesthetist. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

What Rocuronium Bromide is and what it is used for

What you need to know before you use Rocuronium Bromide

How to take Rocuronium Bromide

Possible side effects

How to store Rocuronium Bromide

Contents of the pack and other information

1.

What Rocuronium Bromide is and what it is used for

Rocuronium Bromide belongs to a group of medicines called muscle relaxants.

Under normal circumstances your nerves send messages to the muscles by impulses.

Rocuronium Bromide acts by blocking these impulses so that the muscles become relaxed.

When you have an operation your muscles must be completely relaxed. This makes it easier

for the surgeon to perform the operation.

adults and children,

if you are under general anaesthesia

,

Rocuronium Bromide may be

used to ease the insertion of a tube into your windpipe (trachea), to help with mechanical

assistance of breathing and to ensure that your muscles are relaxed during surgery.

If you are an

adult

your doctor may also use this medicine for a short time as an additional

medicine in the intensive care unit (ICU) (e.g. to ease the insertion of a tube into your

windpipe and whilst you are receiving mechanical breathing). You may also receive this

medicine whenever there is an emergency situation and you need to receive a tube into your

windpipe very quickly.

2.

What you need to know before you use Rocuronium Bromide

You should not receive Rocuronium Bromide:

if you are allergic to rocuronium, the bromide ion or any of the other ingredients of this

medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or anaesthetist before using Rocuronium Bromide:

if you are allergic to any muscle relaxants

if you have had kidney, heart, liver or gall bladder disease

if you have a heart disease or a disease affecting your blood circulation

if you have had diseases affecting nerves and muscles, for example poliomyelitis,

myasthenia gravis or Eaton-Lambert syndrome

if you have fluid retention (oedema)

if you have been told you have low levels of calcium (hypocalcaemia), potassium

(hypokalaemia) or protein (hypoproteinaemia) in your blood

if you have been told you have high levels of magnesium (hypermagnesaemia) or

carbon dioxide (hypercapnia) in your blood

if you have lost a lot of water from your body, for example by being sick, having

diarrhoea, sweating

if you are very overweight (obese)

if you are elderly

if you have a very low body temperature (hypothermia)

if you have burns

if you have an increased amount of acids

in the blood (acidosis)

if you suffer from an excessive loss of weight and poor physical condition

(cachexia)

Children and the elderly

Rocuronium bromide can be used in children (newborns and adolescents) and the elderly but

your anaesthetist should first assess your medical history.

Other medicines and Rocuronium Bromide

Your doctor or anaesthetist needs to know if you are taking, have recently taken or might take

any other medicines. This includes medicines or herbal products that you have bought

without a prescription. Rocuronium Bromide may affect other medicines or be affected by

them, in particular:

certain anti-inflammatory medicines (corticosteroids) when used for a long time with

Rocuronium Bromide, for example during intensive care

certain antibiotics

certain medicines for heart disease or high blood pressure (water tablets, calcium

channel blockers, beta-blockers, alpha-blockers) and quinidine) magnesium salts

which may be used as a laxative or in certain heart conditions eg pre-eclampsia

lithium used for manic depressive illness (bipolar disorder)

certain medicines for epilepsy

calcium chloride and potassium chloride (medicines to change the levels of potassium

or calcium in the blood)

certain protease inhibitors called gabexate and ulinastatin (may be used for treating

various viral infections or conditions such as pancreatitis)

azathioprine (used after transplants and for treating of auto-immune diseases)

theophylline (used for the treatment of asthma)

medicines used for the treatment of myasthenia gravis (neostigmine, edrophonium,

pyridostigmine)

Aminopyridine derivatives(medicines used to treat Eaton-Lambert syndrome)

quinine (used to treat malaria or night time leg cramps)

Please note in addition, you may be given other medicines before or during surgery which

can alter the effects of Rocuronium Bromide. These include certain anaesthetics, other

muscle relaxants, medicines such as phenytoin and medicines which reverse the effects of

Rocuronium Bromide. Rocuronium Bromide may make certain anaesthetics work more

quickly. Your anaesthetist will take this into account when deciding the correct dose of

Rocuronium Bromide for you.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a

baby, ask your doctor or anaesthetist for advice before being given this medicine.

There is very limited information on the use of Rocuronium Bromide during human

pregnancy or in breast-feeding women. Rocuronium Bromide should only be given to

pregnant and nursing women when the doctor decides that the benefits outweigh the risks.

Rocuronium Bromide may be given to you if you are having a Caesarean section.

There is no information available on the influence of this medicine on your fertility.

Driving and using machines

Rocuronium has a major influence on driving and using machines. Therefore, it is not

recommended to drive a car or use potentially dangerous machines during the first 24 hours

after full recovery from the effect of this medicine.

Your doctor should advise you when you can start driving and using machines again. You

should always be accompanied home by a responsible adult after your treatment.

Rocuronium Bromide contains sodium

Each millilitre (ml) of Rocuronium Bromide contains 1.56mg of sodium.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially

“sodium-free”.

3.

How to take Rocuronium Bromide

Dose

Your anaesthetist will work out the dose of Rocuronium Bromide you need based on:

the type of anaesthetic

the expected length of the operation

other medicines you are taking

your state of health.

The normal dose is 0.6 mg per kg body weight and the effect will last 30–40 minutes.

How Rocuronium Bromide is given

Rocuronium Bromide will be given to you by your anaesthetist. Rocuronium Bromide is

given intravenously (into a vein), either as single injections or as a continuous infusion (a

drip).

If you are given more Rocuronium Bromide than you need

As your anaesthetist will be monitoring your condition carefully it is unlikely that you will be

given too much Rocuronium Bromide. However, if this happens, your anaesthetist will keep

you breathing artificially (on a ventilator) until you can breathe on your own. You will be

kept asleep while this takes place.

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

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If

these side effects occur while you are under anaesthetic, they will be seen and treated by your

anaesthetist.

If any of the side effects get serious, talk to your doctor or anaesthetist.

The following side-effects have been reported at the approximate frequencies shown:

uncommon (≥1/1,000 to <1/100);

very rare (<1/10,000);

Uncommon side effects

(up to 1 in 100 users are affected)

the medicine is too effective, or not effective enough

the medicine works for longer than expected

lowering of blood pressure

increase in heart rate

pain near the site of injection.

Very rare side effects

(less than 1 in 10,000 users are affected)

allergic reactions (such as difficulty in breathing, collapse of the circulation and

shock)

wheezing of the chest

muscle weakness

swelling, a rash or redness of the skin

problems with your airway

If you get any side effects, talk to your doctor or anaesthetist

.

This includes any possible side

effects not listed in this leaflet. You can also report side effects directly via

the national

reporting system for

United Kingdom

Yellow Card Scheme at:

www.mhra.gov.uk/yellowcard

Ireland

HPRA Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

e-mail: medsafety@hpra.ie

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

medicine.

5.

How to store Rocuronium Bromide

Keep this medicine out of the sight and reach of children.

After first opening: Since Rocuronium Hospira does not contain a preservative, the solution

should be used immediately after opening the vial.

After dilution with infusion fluids, chemical and physical in-use stability has been

demonstrated for 72 hours at 30°C.

From a microbiological point of view, the diluted 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°C to 8°C.

Store in a refrigerator (2

C – 8

C). Rocuronium Bromide can be stored outside of the

refrigerator at a temperature of up to 30

C for a maximum of 12 weeks. The product should

not be placed back into the refrigerator, once it has been kept outside. The storage period

must not exceed the shelf-life.

Do not use this medicine after the expiry date which is stated on the vial label and carton after

EXP:.

Do not use Rocuronium Bromide if you notice that the solution is not clear and not free from

particles.

Rocuronium Bromide should not be disposed of via wastewater or household waste. These

measures will help to protect the environment.

6.

Contents of the pack and other information

What Rocuronium Bromide contains

The active substance is rocuronium bromide.

Each millilitre (ml) contains 10 mg of rocuronium bromide

Each 5ml vial contains 50 mg rocuronium bromide.

Each 10ml vial contains 100 mg rocuronium bromide.

The other ingredients are sodium acetate anhydrous, sodium chloride, acetic acid glacial,

sodium hydroxide and water for injections.

Each 5 ml of Rocuronium Bromide contains 7.8 mg of sodium.

Each 10 ml of Rocuronium Bromide contains 15.6 mg of sodium.

What Rocuronium Bromide looks like and contents of the pack

Rocuronium Bromide is a colourless to yellow-orange solution for injection. It is available in

vials containing 50 mg (10 vials per pack) or 100 mg (10 vials per pack) of rocuronium

bromide.

Marketing Authorisation Holder and Manufacturer

Hospira UK Limited

Horizon,

Honey Lane,

Hurley

Maidenhead

SL6 6RJ

United Kingdom

Alternate Batch release site:

Hospira Enterprises B.V.

Randstad 2211,

1316 BN ALMERE

The Netherlands

This leaflet was last revised in

12/2016

Ref gx RB 1-0

<------------------------------------------------------------------------------------------------------------->

The following information is intended for healthcare professionals only

Rocuronium Bromide 10 mg/ml Solution for Injection/Infusion

Please refer to the Summary of Product Characteristics for full prescribing information.

Like other neuromuscular blocking agents, rocuronium bromide should only be administered

by, or under supervision of, experienced clinicians who are familiar with the action and use

of these drugs.

Each vial of the 50 mg presentation contains 5ml of solution.

Each vial of the 100 mg presentation contains 10ml of solution.

Special precautions for storage

Unopened product:

Store in a refrigerator (2-8

Rocuronium Bromide can be stored outside of the refrigerator at a temperature of up to 30

for a maximum of 12 weeks. The product should not be placed back into the refrigerator once

it has been kept outside. The storage period must not exceed the shelf-life.

After first opening:

Since Rocuronium Bromide does not contain preservative, the solution

should be used immediately after opening the vial.

Diluted product:

After dilution with Infusion fluids (‘Special precautions for disposal and

other handling’), chemical and physical in-use stability of the diluted product has been

demonstrated for 72 hours at 30

From a microbiological point of view, the product should be used immediately after dilution.

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

Special precautions for disposal and other handling

The solution is to be visually inspected prior to use. Only clear solutions practically free from

particles should be used.

Rocuronium bromide is administered intravenously as a bolus injection or continuous

infusion.

Compatibility studies have been conducted with the following infusion fluids listed below.

Rocuronium Bromide in nominal concentrations of 0.5 mg/ml and 2.0 mg/ml is compatible

with:

0.9% NaCl, 5% dextrose, 5% dextrose in 0.9% NaCl, sterile water for injection and lactated

Ringer’s solution.

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

local requirements.

Incompatibilities

Rocuronium bromide is physically incompatible with solutions of the following drugs:

amphotericin, amoxicillin, azathioprine, cefazolin, cloxacillin, dexamethasone, diazepam,

enoximone, erythromycin, famotidine, furosemide, hydrocortisone sodium succinate, insulin,

methohexital, methylprednisolone, prednislone sodium succinate, thiopental, trimethoprim

and vancomycin. Furthermore rocuronium bromide is incompatible with Intralipid.

Rocuronium bromide should not be mixed with other drugs, except those listed in ‘

Special

precautions for disposal and other handling’

If rocuronium bromide is administered via the same infusion line that is used for other drugs,

it is important that this infusion line is adequately flushed (e.g. with 0.9% NaCl) between

administration of rocuronium bromide and drugs for which incompatibility with rocuronium

bromide has been demonstrated of for which compatibility with rocuronium bromide is not

established.

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Object 1

Rocuronium Bromide Hospira 10 mg/ml solution

for injection/infusion

Summary of Product Characteristics Updated 11-Jun-2018 | Hospira UK Ltd

1. Name of the medicinal product

Rocuronium Bromide Hospira 10 mg/ml Solution for Injection/Infusion.

2. Qualitative and quantitative composition

Each ml of Rocuronium Bromide contains 10mg of rocuronium bromide .

Each 5ml vial contains 50 mg rocuronium bromide .

Each 10ml vial contains 100 mg rocuronium bromide .

Excipient(s) with known effect:

Each 5 ml of Rocuronium Bromide contains 7.8 mg of sodium.

Each 10 ml of Rocuronium Bromide contains 15.6 mg of sodium.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Solution for Injection/Infusion.

Clear, colourless to yellow-orange solution

pH of the solution: 3.8 to 4.2

Osmolality: 256-312 mOsmol/kg

4. Clinical particulars

4.1 Therapeutic indications

Rocuronium Bromide is indicated in adult and paediatric patients (from term neonates to adolescents

[aged 0 to 18 years]) as an adjunct to general anaesthesia to facilitate tracheal intubation during routine

induction and to provide skeletal muscle relaxation during surgery.

In adults Rocuronium Bromide is also indicated to facilitate tracheal intubation during rapid sequence

induction and as an adjunct in the intensive care unit (ICU) to facilitate tracheal intubation and

mechanical ventilation for short term use (See also sections 4.2 and 5.1).

4.2 Posology and method of administration

Posology

Like other neuromuscular blocking agents, Rocuronium Bromide should only be administered by, or

under supervision of, experienced clinicians who are familiar with the action and use of these drugs.

Like other neuromuscular blocking agents, the dosage of Rocuronium Bromide should be individualized

for each patient. The method of anaesthesia and the expected duration of surgery, the method of sedation

and the expected duration of mechanical ventilation, the possible interaction with other drugs that are

administered concomitantly, and the condition of the patient should be taken into account when

determining the dose.

The use of an appropriate neuromuscular monitoring technique is recommended for the evaluation of

neuromuscular block and recovery.

Surgical procedures

Inhalational anaesthetics do potentiate the neuromuscular blocking effects of Rocuronium Bromide . This

potentiation becomes clinically relevant during the course of anaesthesia when the volatile agents have

reached the tissue concentrations required for this interaction. Therefore, during surgery under inhalation

anaesthesia lasting longer than 1 hour, lower maintenance doses of Rocuronium Bromide at less frequent

intervals should be given or the infusion rate should be reduced (see section 4.5).

Adults

In adults, the following dosage schedule may serve as a general guideline for tracheal intubation and

muscle relaxation for short to long lasting surgical procedures and for use in the ICU.

Tracheal intubation

The standard intubation dose during routine induction of anaesthesia is 0.6 mg/kg Rocuronium Bromide,

after which adequate intubation conditions are established within 60 seconds in nearly all patients. A dose

of 1.0 mg/kg Rocuronium Bromide is recommended for facilitating tracheal intubation conditions during

rapid sequence induction of anaesthesia, after which adequate intubation conditions are established within

60 seconds in nearly all patients. When a dose of 0.6 mg/kg of Rocuronium Bromide is used for rapid

sequence induction of anaesthesia, it is recommended to intubate the patient 90 seconds after

administration of Rocuronium Bromide .

For use of Rocuronium Bromide during rapid sequence induction of anaesthesia in patients undergoing

Caesarean section reference is made to section 4.6.

Maintenance dosing

The recommended maintenance dose is 0.15 mg/kg Rocuronium Bromide; in the case of long-term

inhalational anaesthesia this should be reduced to 0.075-0.1 mg/kg Rocuronium Bromide. The

maintenance doses should best be administered when the twitch height has recovered to 25% of the

control twitch height, or when 2 to 3 responses to 'train of four '(TOF)-stimulation are present.

Continuous infusion

If Rocuronium Bromide is administered by continuous infusion, it is recommended to give a loading dose

of 0.6 mg/kg Rocuronium Bromide and, when neuromuscular block starts to recover, to start

administration by infusion. The infusion rate should be adjusted to maintain twitch response at 10% of the

control twitch height or to maintain 1 to 2 responses to TOF stimulation. In adults under intravenous

anaesthesia, the infusion rate required to maintain neuromuscular block at this level ranges from 0.3 to 0.6

mg/kg/h and under inhalation anaesthesia the infusion rate ranges from 0.3-0.4 mg/kg/h. Continuous

monitoring of neuromuscular block is essential since infusion rate requirements vary from patient to

patient and with the anaesthetic method used.

The dose is individual and monitoring is therefore essential. The above mentioned doses are to be seen as

guidance.

Paediatric population

For neonates (0-27 days), infants (28 days-2 months), toddlers (3-23 months), children (2-11 years) and

adolescents (12-17 years) the recommended intubation dose during routine anaesthesia and maintenance

dose are similar to those in adults.

However, the duration of action of the single intubating dose will be longer in neonates and infants than

in children (see section 5.1).

For continuous infusion in paediatric patients, the infusion rate, with the exception of children (2-11

years), is the same as for adults. For children aged 2-11 years higher infusion rates might be necessary.

For children (2-11 years) the same initial infusion rates as for adults are recommended and this should be

adjusted to maintain twitch response at 10% of control twitch height or to maintain 1 to 2 twitches to train

of four (TOF) stimulation during the procedure.

The experience with rocuronium during rapid sequence induction in paediatric patients is limited.

Rocuronium Bromide is therefore not recommended for facilitating tracheal intubation during rapid

sequence induction in paediatric patients.

Geriatric patients and patients with hepatic and /or biliary tract disease and /or renal insufficiency

The standard intubation dose for geriatric patients and patients with hepatic and /or biliary tract disease

and /or renal failure during routine induction of anaesthesia is 0.6 mg/kg Rocuronium Bromide. A dose of

0.6 mg/kg should be considered for rapid sequence induction of anaesthesia in patients in which a

prolonged duration of action is expected.

Regardless of the anaesthetic technique, the recommended maintenance dose for these patients is 0.075 to

0.1 mg/kg Rocuronium Bromide, and the recommended infusion rate is 0.3 to 0.4 mg/kg/h (see

'Continuous infusion').

Overweight and obese patients

When used in overweight and obese patients (defined as patients with a body weight of 30% or more

above the ideal body weight), doses should be reduced taking into account the lean body mass.

Intensive Care Procedures

Tracheal intubation

For tracheal intubation, the same doses should be used as described above under surgical procedures.

Maintenance dosing

The use of an initial loading dose of 0.6 mg/kg Rocuronium Bromide is recommended, followed by a

continuous infusion as soon as the twitch height has recovered to 10% or upon reappearance of 1 to 2

twitches to train of four stimulation. The dosage should always be titrated to effect in the individual

patient. The recommended initial infusion rate for the maintenance of a neuromuscular block of 80-90%

(1 to 2 twitches to TOF stimulation) is 0.3 to 0.6 mg/kg/h during the first hour of administration which

will need to be decreased over the following 6 to 12 hours, depending on the individual response.

Thereafter, individual dose requirements remain relatively constant.

A large variability in infusion rates were seen in clinical trials. The average infusion rates ranging from

0.2 to 0.5 mg/kg/h, depending on the nature and extent of organ failure(s), concomitant medication, and

individual patient characteristics. To provide optimal individual patient control, monitoring of

neuromuscular transmission is strongly recommended. Administration for up to 7 days has been

investigated.

Special Populations

Rocuronium Bromide is not recommended for the facilitation of mechanical ventilation in paediatric and

geriatric patients due to a lack of data on safety and efficacy.

Method of administration

Rocuronium Bromide is administered intravenously as a bolus injection or continuous infusion (see

section 6.6).

4.3 Contraindications

Hypersensitivity to rocuronium or to the bromide ion or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Since Rocuronium Bromide causes paralysis of the respiratory muscles, ventilatory support is mandatory

for patients treated with this drug until adequate spontaneous respiration is restored. As with all

neuromuscular blocking agents, it is important to anticipate intubation difficulties, particularly when used

as part of a rapid sequence induction technique. In case of intubation difficulties resulting in a clinical

need for immediate reversal of a rocuronium induced neuromuscular block, the use of sugammadex

should be considered.

As with other neuromuscular blocking agents, residual neuromuscular blockade has been reported for

Rocuronium Bromide. In order to prevent complications resulting from residual neuromuscular blockade,

it is recommended to extubate only after the patient has recovered sufficiently from neuromuscular block.

Elderly patients (65 years or older) may be at increased risk of residual neuromuscular blockade. Other

factors which could cause residual neuromuscular blockade after extubation in the post-operative phase

(such as drug interactions or patient condition) should also be considered. If not used as part of standard

clinical practice, the use of a reversal agent should be considered (such as sugammadex or

acetylcholinesterase inhibitors), especially in those cases where residual neuromuscular blockade is more

likely to occur.

It is essential to ensure that the patient is breathing spontaneously, deeply and regularly before leaving the

theatre after anaesthesia. Anaphylactic reactions may occur after administration of neuromuscular

blocking agents. Precautions for treating such reactions should always be taken. Particularly in the case of

previous anaphylactic reactions to neuromuscular blocking agents, special precautions should be taken

since allergic cross-reactivity to blocking agents has been reported.

In general, following long term use of neuromuscular blocking agents in the ICU, prolonged paralysis

and/or skeletal muscle weakness has been noted. In order to help preclude possible prolongation of

neuromuscular block and/or overdosage it is strongly recommended that neuromuscular transmission is

monitored throughout the use of neuromuscular blocking agents. In addition, patients should receive

adequate analgesia and sedation. Furthermore, neuromuscular blocking agents should be titrated to effect

in the individual patients by or under supervision of experienced clinicians who are familiar with their

actions and with appropriate neuromuscular monitoring techniques.

Myopathy after long term administration of other non-depolarising neuromuscular blocking agents in the

ICU in combination with corticosteroid therapy has been reported regularly. Therefore, for patients

receiving both neuromuscular blocking agents and corticosteroids, the period of use of the neuromuscular

blocking agent should be limited as much as possible.

If suxamethonium is used for intubation, the administration of Rocuronium Bromide should be delayed

until the patient has clinically recovered from the neuromuscular block induced by suxamethonium.

The following conditions may influence the pharmacokinetics and/or pharmacodynamics of

rocuronium bromide:

Hepatic and / or biliary tract disease and renal failure

Because rocuronium is excreted in the urine and bile, it should be used with caution in patients with

clinically significant hepatic and/or biliary disorders and/or renal failure. In these patient groups

prolongation of the duration of action has been observed with doses of 0.6 mg/kg Rocuronium Bromide.

Prolonged circulation time

Conditions associated with prolonged circulation time such as cardiovascular disease, advanced age and

oedematous state resulting in an increased volume of distribution, may contribute to a slower onset of

action. The duration of action may also be prolonged due to a reduced plasma clearance.

Neuromuscular disorders

Like other neuromuscular blocking agents, Rocuronium Bromide should be used with extreme caution in

patients with neuromuscular disease or after poliomyelitis since the response to neuromuscular blocking

agents may be considerably altered in these cases. The magnitude and direction of this alteration may

vary widely. In patients with myasthenia gravis or with the myasthenic (Eaton-Lambert) syndrome, small

doses of rocuronium bromide may have profound effects and rocuronium bromide should be titrated to

the response.

Hypothermia

In surgery under hypothermic conditions, the neuromuscular blocking effect of Rocuronium bromide is

increased and the duration prolonged.

Obesity

Like other neuromuscular blocking agents, Rocuronium Bromide may exhibit a prolonged duration and a

prolonged spontaneous recovery in obese patients when the administered doses are calculated on actual

body weight.

Burns

Patients with burns are known to develop resistance to non-depolarising neuromuscular blocking agents.

It is recommended that the dose is titrated to response.

Treatment with magnesium salts for toxaemia

Reversal of neuromuscular block induced by neuromuscular blocking agents may be inhibited or

unsatisfactory in patients receiving magnesium salts for toxaemia of pregnancy because magnesium salts

enhance neuromuscular blockade. Therefore, in these patients the dosage of Rocuronium Bromide should

be reduced and be titrated to twitch response.

Conditions which may increase the effects of Rocuronium Bromide

Hypokalaemia (e.g. after severe vomiting, diarrhoea and diuretic therapy), hypermagnesaemia,

hypocalcaemia (after massive transfusions), hypoproteinemia, dehydration, acidosis, hypercapnia,

cachexia.

Severe electrolyte disturbances, altered blood pH or dehydration should therefore be corrected when

possible.

Each ml contains 1.56 mg sodium. This medicinal product contains less than 1 mmol sodium (23 mg) per

dose, i.e. essentially “sodium- free”.

4.5 Interaction with other medicinal products and other forms of interaction

The following drugs have been shown to influence the magnitude and/or duration of action of non-

depolarising neuromuscular blocking agents.

Effect of other medicinal products on Rocuronium Bromide

Increased effect

Halogenated volatile anaesthetics (eg, halothane, enflurane and methoxyflurane) potentiate the

neuromuscular block of Rocuronium Bromide. The effect only becomes apparent with maintenance

dosing (see section 4.2). Reversal of the block with acetylcholinesterase inhibitors could also be inhibited.

After intubation with suxamethonium (see section 4.4).

High doses of thiopental, methohexital, ketamine, fentanyl, gammahydroxybutyrate, etomidate,

propofol.

Other non-depolarising neuromuscular blocking agents.

Long-term concomitant use of corticosteroids and Rocuronium Bromide in the ICU may result in

prolonged duration of neuromuscular block or myopathy (see section 4.4 and 4.8).

Other medicinal products

antibiotics: aminoglycoside, lincosamide (e.g. lincomycin and clindamycin), polypeptide antibiotics,

acylamino-penicillin antibiotics , tetracyclines, high doses metronidazole.

diuretics, quinidine and its isomer quinine, magnesium salts, calcium channel blocking agents, lithium

salts, local anaesthetics (lidocaine i.v, bupivacaine epidural) and acute administration of phenytoin or ß-

blocking agents.

Recurarisation has been reported after post-operative administration of: aminoglycoside, lincosamide,

polypeptide and acylamino-penicillin antibiotics, quinidine, quinine and magnesium salts (see section

4.4).

Decreased effect

Prior chronic administration of phenytoin or carbamazepine.

Protease inhibitors (gabexate, ulinastatin).

Calcium chloride, potassium chloride

Noradrenaline, azathioprine (only transient and limited effect), theophylline

Neostigmine, edrophonium, pyridostigmine, aminopyridine derivatives

Variable effect

Administration of other non-depolarising neuromuscular blocking agents in combination with

Rocuronium Bromide may produce attenuation or potentiation of the neuromuscular block, depending on

the order of administration and the neuromuscular blocking agent used.

Suxamethonium given after the administration of Rocuronium Bromide may produce potentiation or

attenuation of the neuromuscular blocking effect of Rocuronium Bromide.

Effect of Rocuronium Bromide on other drugs

Combined use with lidocaine may result in a faster onset of action of lidocaine.

Paediatric patients

No formal interaction studies have been performed. The above mentioned interactions for adults and their

special warnings and precautions for use (see section 4.4) should also be taken into account for paediatric

patients.

4.6 Fertility, pregnancy and lactation

Pregnancy

For rocuronium bromide, no clinical data on exposed pregnancies are available. Animal studies do not

indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development,

parturition or postnatal development. Caution should be exercised when prescribing rocuronium bromide

to pregnant women.

Caesarean section

In patients undergoing Caesarean section, Rocuronium Bromide can be used as part of a rapid sequence

induction technique, provided no intubation difficulties are anticipated and a sufficient dose of anaesthetic

agent is administered or following suxamethonium facilitated intubation.Rocuronium Bromide,

administered in doses of 0.6 mg/kg-1, has been shown to be safe in parturients undergoing Caesarean

section. Rocuronium Bromide does not affect Apgar score, foetal muscle tone or cardio respiratory

adaptation. From umbilical cord blood sampling it is apparent that only limited placental transfer of

Rocuronium Bromide occurs which does not lead to the observation of clinical adverse effects in the

newborn.

Note:

1 - doses of 1.0 mg/kg have been investigated during rapid sequence induction of anaesthesia, but not in

Caesarean section patients. Therefore, only a dose of 0.6 mg/kg is recommended in this patient group.

2 - reversal of neuromuscular block induced by neuromuscular blocking agents may be inhibited or

unsatisfactory in patients receiving magnesium salts for toxaemia of pregnancy because magnesium salts

enhance neuromuscular blockade. Therefore, in these patients the dosage of rocuronium bromide should

be reduced and be titrated to twitch response.

Lactation

It is unknown whether Rocuronium Bromide is excreted in human breast milk. Other medicines in this

class show limited milk excretion, as well as low absorption by the infant. Insignificant amounts of

rocuronium bromide are found in the milk of lactating rats. Rocuronium Bromide should be given to

lactating women only when the attending physician decides that the benefits outweigh the risks.

Fertility

There are no data with regard to effects of Rocuronium Bromide on fertility.

4.7 Effects on ability to drive and use machines

Rocuronium bromide has major influence on the ability to drive and use machines. It is not recommended

to use potentially dangerous machinery or to drive a car during the first 24 hours after the full recovery

from the neuromuscular blocking action of rocuronium bromide.

Since Rocuronium Bromide is used as an adjunct to general anaesthesia, the usual precautionary measures

after a general anaesthesia should be taken for ambulatory patients.

4.8 Undesirable effects

The frequency of undesirable effects is classified into the following categories:

uncommon/rare (≥1/10,000 to <1/100); very rare (<1/10,000); not known (cannot be estimated from the

available data).

The most commonly occurring adverse drug reactions include injection site pain/reaction, changes in vital

signs and prolonged neuromuscular block. The most frequently reported serious adverse drug reactions

during post-marketing surveillance is 'anaphylactic and anaphylactoid reactions' and associated

symptoms.

See also the explanations below the table.

MedDRA System Organ Class

MedDRA Preferred Term

1

Uncommon/ Rare

2

(≥1/10,000 to <1/100)

Very rare

(<1/10,000)

Immune system disorders

Hypersensitivity

Anaphylactic reaction

Anaphylactoid reaction

Anaphylactic shock

Anaphylactoid shock

Nervous system disorders

Flaccid paralysis

Cardiac disorders

Tachycardia

Vascular disorders

Hypotension

Circulatory collapse and

shock

Flushing

Respiratory, thoracic and mediastinal

disorders

Bronchospasm

Skin and subcutaneous tissue

disorders

Angioneurotic oedema

Urticaria

Rash

Erythematous skin rash

Musculoskeletal and connective

tissue disorders

Muscular weakness

Steroid myopathy

General disorders and administration

site conditions

Drug ineffective

Drug effect/ therapeutic response

decreased

Drug effect/ therapeutic response

increased

Injection site reaction

Injection site pain

Face oedema

Injury, poisoning and procedural

complications

Prolonged neuromuscular block

Delayed recovery from anaesthesia

Airway complication of

anaesthesia

Frequencies are estimates derived from post-marketing surveillance reports and data from the general

literature.

Post-marketing surveillance data cannot give precise incidence figures. For that reason, the reporting

frequency was divided over two rather than five categories.

after long-term use in the ICU

Myopathy

Myopathy has been reported after use of various neuromuscular blocking agents in combination with

corticosteroids in the ICU (see also sections 4.4 and 4.5).

Local injection site reactions

During rapid sequence induction of anaesthesia, pain on injection has been reported, especially when the

patient has not yet completely lost consciousness and particularly when propofol is used as an induction

agent. In clinical studies, pain on injection was observed in 16% of patients who underwent rapid

sequence induction of anaesthesia with propofol and in less than 0.5% of patients who underwent rapid

sequence induction of anaesthesia with fentanyl and thiopental.

Class effects

Anaphylactic reactions

Although very rare, severe anaphylactic/anaphylactoid reactions to neuromuscular blocking agents,

including Rocuronium Bromide were reported. The anaphylactic /anaphylactoid reactions are:

bronchospasm, alteration at cardiovascular level (e.g., hypotension, tachycardia, circulatory collapse,

shock), and cutaneous disorders (e.g., angioedema, urticaria). These reactions, in some cases, are fatal.

Due to the potential severity of these reactions, one should always take into account the necessary

precautions (see section 4.4).

Increased histamine level

Since neuromuscular blocking agents are known to be capable of inducing histamine release both locally

and systemically, the possible occurrence of itching and erythematous reaction at the site of injection

and/or generalised histaminoid (anaphylactoid) reactions such as bronchospasm and cardiovascular

changes e.g. hypotension and tachycardia should always be taken into consideration when administering

these drugs. Rash, exanthema, urticaria, bronchospasm and hypotension have been reported very rarely in

patients given Rocuronium Bromide.

In clinical studies only a slight increase in mean plasma histamine level has been observed following

rapid bolus administration of 0.3 - 0.9 mg Rocuronium Bromide per kg body weight.

Prolonged neuromuscular block

The most frequent adverse reaction to non depolarising blocking agents as a class consists of an extension

of the drug's pharmacological action beyond the time period needed. This may vary from skeletal muscle

weakness to profound and prolonged skeletal muscle paralysis resulting in respiratory insufficiency or

apnea.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are

asked to report any suspected adverse reactions via:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

Paediatric patients

A meta-analysis of 11 clinical studies in paediatric patients (n=704) with rocuronium bromide (up to 1

mg/kg) showed that tachycardia was identified as adverse drug reaction with a frequency of 1.4%.

4.9 Overdose

In the event of overdosage and prolonged neuromuscular block, the patient should continue to receive

ventilatory support and sedation. There are two options for the reversal of neuromuscular block:

(1) In adults, sugammadex can be used for reversal of intense (profound) and deep block. A dosage of 16

mg/kg is recommended. After administration of sugammadex, the patient should be carefully monitored

for sustained return of neuromuscular function.

(2) An acetylcholinesterase inhibitor (e.g. neostigmine, edrophonium, pyridostigmine) can be used once

spontaneous recovery starts and should be administered in adequate doses. When administration of an

acetylcholinesterase inhibiting agent fails to reverse the neuromuscular effects of Rocuronium Bromide

ventilation must be continued until spontaneous breathing is restored. Repeated dosage of an

acetylcholinesterase inhibitor can be dangerous.

In animal studies, severe depression of cardiovascular function, ultimately leading to cardiac collapse did

not occur until a cumulative dose of 750 x ED

(135 mg/kg rocuronium bromide) was administered.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group (ATC code): muscle relaxants, peripherally acting agents,

ATC code: M03AC09

Mechanism of action

Rocuronium Bromide is a fast onset, intermediate acting non-depolarising neuromuscular blocking agent.

It has all the pharmacological properties characteristic to this class of drugs (curariform). It acts by

competing for nicotinic cholinoceptors at the motor end-plate. This action is antagonized by

acetylcholinesterase inhibitors such as neostigmine, edrophonium and pyridostigmine.

Pharmacodynamic effects

The ED

(the dose required to produce 90% suppression of twitch response of the thumb to stimulation

of the ulnar nerve) during intravenous anaesthesia is approximately 0.3 mg/kg rocuronium bromide. The

in infants is lower than in adults and children (0.25, 0.35 and 0.40 mg/kg respectively).

The clinical duration (the duration until spontaneous recovery to 25% of control twitch height) at a dose

of 0.6 mg/kg rocuronium bromide is 30-40 minutes. The total duration (time until spontaneous recovery

of twitch to 90% of control value) is 50 minutes. The mean time to spontaneous recovery of twitch

response from 25% to 75% of control after a bolus dose of 0.6 mg/kg rocuronium bromide is 14 minutes.

With a lower dose of 0.3 to 0.45 mg/kg rocuronium bromide (1-1.5 x ED

), there is a later onset and

shorter duration of action. With a higher dose of 2 mg/kg the duration of action is 110 minutes.

Intubation during routine anaesthesia

Within 60 seconds after intravenous administration of a dose of 0.6 mg/kg rocuronium (2 x ED

intravenous anaesthesia), adequate intubation conditions can be achieved in nearly all patients of which in

80% intubation conditions are rated excellent. General muscle paralysis adequate for any type of

procedure is established within 2 minutes. After administration of 0.45 mg/kg rocuronium bromide,

acceptable intubation conditions are present after 90 seconds.

Rapid Sequence Induction

During rapid sequence induction of anaesthesia under propofol or fentanyl/thiopental anaesthesia,

adequate intubation conditions are achieved within 60 seconds in 93% and 96% of the patients

respectively after administration of a dose of 1.0 mg/kg rocuronium bromide . Within these groups, 70%

of the cases were rated as excellent. The clinical duration with this dose approaches 1 hour, at which time

the neuromuscular block can be safely reversed. Following a dose of 0.6 mg/kg rocuronium bromide,

adequate intubation conditions are achieved within 60 seconds in 81% and 75% of the patients during a

rapid sequence induction technique with propofol or fentanyl/thiopental, respectively.

Paediatric patient

Mean onset time in infants, toddlers and children at an intubating dose of 0.6 mg/kg is slightly shorter

than in adults. Comparison between the paediatric age groups showed that the average onset in neonates

and adolescents (1.0 minute) is slightly longer than in infants, toddlers and children (0.4, 0.6 and 0.8

minutes, respectively). The duration of action and time to recovery are usually shorter in children than in

infants and adults. Comparison between the paediatric age groups showed that the average time to return

of T

was prolonged in neonates and infants (56.7 and 60.7 minutes, respectively) compared with toddlers

, children and adolescents (45.5, 37.6 and 42.9 minutes, respectively).

Mean (SD) time to onset and clinical duration following 0.6 mg/kg rocuronium initial intubating

dose* during sevoflurane/nitrous oxide and isoflurane/nitrous oxide (maintenance) anaesthesia

(Paediatric patients)

Time to maximum block**

(min)

Time to reappearance of T

(min)

Neonates (0-27 days)

n=10

0.98 (0.62)

56.69 (37.04)

Infants (28 days-2 months)

n=11

0.44 (0.19)

n=10

60.71 (16.52)

Toddlers (3-23 months)

n=28

0.59 (0.27)

45.46 (12.94)

n=27

Children (2-11 years)

n=34

0.84 (0.29)

37.58 (11.82)

Adolescents (12-17 years)

n=31

0.98 (0.38)

42.90 (15.83)

n=30

*Dose of rocuronium administered with 5 seconds.

** Calculated from the end of administration of the rocuronium intubating dose.

Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal insufficiency

The duration of the effect of maintenance doses of 0.15 mg/kg of Rocuronium Bromide might be

somewhat longer under enflurane and isoflurane anaesthesia in geriatric patients and in patients with

hepatic or renal disease (approximately 20 minutes) than in patients without impairment of excretory

organ functions under intravenous anaesthesia (approximately 13 minutes) (see section 4.2). No

cumulation of effect (progressive increase in duration of action) with repetitive maintenance doses at the

recommended level has been observed.

Intensive Care

Following continuous infusion in the ICU, the time of recovery of the train of four ratio to 0.7 is not

significantly correlated to the total duration of rocuronium infusion. After a continuous infusion for 20

hours or more the median (range) time between return of T

to TOF-stimulation and recovery of the TOF-

ratio to 0.7 is 1.5 (1-5) hours in patients without failure of multiple organs (multiple organ failure) and 4

(1-25) hours in patients with multiple organ failure.

Cardiovascular surgery

In patients scheduled for cardiovascular surgery the most common cardiovascular changes during the

onset of maximum blockage after receiving a dose of 0.6 to 0.9 mg/kg rocuronium bromide are a slight

and clinically insignificant increase in heart rate up to 9% and an increase in mean arterial blood pressure

up to 16% from the control values.

Reversal of the muscle relaxant effect

The action of rocuronium can be reversed by either sugammadex or by acetylcholinesterase inhibitors

(neostigmine, pyridostigmine or edrophonium). Sugammadex can be given for routine reversal (at 1-2

post-tetanic counts (PTC) for the return of T

), or for immediate termination (3 minutes after

administration of Rocuronium Bromide). Acetylcholinesterase inhibitors can be administered at

reappearance of T

or the first signs of clinical recovery.

5.2 Pharmacokinetic properties

Distribution and elimination

After intravenous administration of a single bolus dose of Rocuronium Bromide, the time course of the

plasma concentration runs in three exponential phases. In normal adults, the mean (95% Confidence

Interval) elimination half-life is 73 (66-80) minutes, the (apparent) volume of distribution at steady state

conditions is 203 (193-214) ml/kg and the plasma clearance is 3.7 (3.5-3.9) ml/kg/min.

When administered as a continuous infusion to facilitate mechanical ventilation for a time period of 20

hours or more, the mean elimination half-life and the mean (apparent) volume of distribution at steady

state are increased. A high variability between patients was found in controlled clinical studies, related to

the nature and extent of (multiple) organ failure and individual patient characteristics. In patients with

multiple organ failure a mean (±SD) elimination half-life of 21.5 (±3.3) hours, an (apparent) volume of

distribution at steady state of 1.5 (±0.8) l/kg and a plasma clearance of 2.1 (±0.8) ml/kg/min were found.

Rocuronium is excreted via urine and bile. Excretion in urine approaches 40% within 12-24 hours. After

administration of a radio-labelled dose of Rocuronium Bromide, the excretion of the radio-label after 9

days is on average 47% in urine and 43% in faeces. Approximately 50% is recovered as the parent

compound.

Biotransformation

No metabolites are detected in the plasma.

Paediatric patients

The apparent volume of distribution in infants (3–12 months) is higher compared to older children (1–8

years) and adults. In children aged 3-8 years, clearance is higher and the elimination half-life is

approximately 20 minutes shorter compared to adults and children < 3 years.

Pharmacokinetics of Rocuronium Bromide in paediatric patients (n=146) with ages ranging from 0 to 17

years were evaluated using a population analysis of the pooled pharmacokinetic datasets from two clinical

trials under sevoflurane (induction) and isoflurane/nitrous oxide (maintenance) anaesthesia. All

pharmacokinetic parameters were found to be linearly proportional to body weight illustrated by a similar

clearance (l/hr/kg). The volume of distribution (l/kg) and elimination half-life (h) decrease with age

(years). The pharmacokinetic parameters of the typical paediatric patient with each age group are

summarized below:

Estimated pharmacokinetic (PK) parameters (mean [SD]) characteristic of Rocuronium Bromide in

paediatric patients during sevoflurane and nitrous oxide (induction), and isoflurane/nitrous oxide

(maintenance) anaesthesia.

PK parameters

Age of patients

Term newborns (0-

27 days)

Infants (28

days-2 months)

Infants (3-23

months)

Children (2-11

years)

Adolescents (12-

17 years)

Cl (l/kg/hr)

0.31 (0.07)

0.30 (0.08)

0.33 (0.10)

0.35 (0.09)

0.29 (0.14)

Distribution

volume (l/kg)

0.42 (0.06)

0.31 (0.03)

0.23 (0.03)

0.18 (0.02)

0.18 (0.01)

β (hr)

1.1 (0.2)

0.9 (0.3)

0.8 (0.2)

0.7 (0.2)

0.8 (0.3)

Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal insufficiency

In controlled studies the plasma clearance in geriatric patients and in patients with renal failure was

lowered, but in most studies without reaching the limit of statistical significance. In patients with liver

failure, the mean elimination half-life extended by 30 minutes and the average plasma clearance is

reduced by 1 ml/kg

min. (See section 4.2.)

5.3 Preclinical safety data

Effects in animal studies were observed only at exposures sufficiently in excess of the maximum human

exposure levels. These effects are therefore of little relevance to clinical practice.

There is no proper animal model to mimic the usually extremely complex clinical situation of the

Intensive Care Unit patient. Therefore the safety of Rocuronium Bromide when used to facilitate

mechanical ventilation in the Intensive Care Unit is mainly based on results obtained in clinical studies.

6. Pharmaceutical particulars

6.1 List of excipients

sodium acetate anhydrous (E262)

sodium chloride

Acetic acid, glacial (for pH adjustment) (E260)

sodium hydroxide (for pH adjustment) (E524)

water for injections

6.2 Incompatibilities

Rocuronium Bromide is physically incompatible with solutions of the following drugs: amphotericin,

amoxicillin, azathioprine, cefazolin, cloxacillin, dexamethasone, diazepam, enoximone, erythromycin,

famotidine, furosemide, hydrocortisone sodium succinate, insulin, methohexital, methylprednisolone,

prednislone sodium succinate, thiopental, trimethoprim and vancomycin. Furthermore Rocuronium

Bromide is incompatible with Intralipid.

Rocuronium Bromide should not be mixed with other drugs, except those listed in Section 6.6.

If Rocuronium Bromide is administered via the same infusion line that is used for other drugs, it is

important that this infusion line is adequately flushed (e.g. with 0.9% NaCl) between administration of

Rocuronium Bromide and drugs for which incompatibility with Rocuronium Bromide has been

demonstrated of for which compatibility with Rocuronium Bromide is not established.

6.3 Shelf life

Unopened bottle: 3 years

After first opening: Since Rocuronium Bromide does not contain preservative, the solution should be used

immediately after opening the vial.

Diluted product: After dilution with infusion fluids (see section 6.6), chemical and physical in-use

stability of the diluted product (see section 6.6) has been demonstrated for 72 hours at 30°C.

From a microbiological point of view, the diluted 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 dilution has taken place in controlled and

validated aseptic conditions.

6.4 Special precautions for storage

Store in a refrigerator (2-8°C).

Rocuronium Bromide can be stored outside of the refrigerator at a temperature of up to 30°C for a

maximum of 12 weeks. The product should not be placed back into the refrigerator, once it has been kept

outside. The storage period must not exceed the shelf-life.

6.5 Nature and contents of container

Rocuronium Bromide 50mg/5ml presentation (10mg/ml)

5 ml glass vial (type I), bromobutyl rubber stopper and aluminium flip-off seal. The rubber stopper of the

vial does not contain latex.

Each vial of the 50mg presentation contains 5ml of solution.

Rocuronium Bromide 100mg/10ml presentation (10mg/ml)

10 ml glass vial (type I), bromobutyl rubber stopper and aluminium flip-off seal. The rubber stopper of

the vial does not contain latex.

Each vial of the 100mg presentation contains 10ml of solution.

Each carton contains 10 vials.

6.6 Special precautions for disposal and other handling

The solution is to be visually inspected prior to use. Only clear solutions practically free from particles

should be used.

Compatibility studies have been conducted with the following infusion fluids listed below.

Rocuronium Bromide in nominal concentrations of 0.5 mg/ml and 2.0 mg/ml is compatible with:

0.9% NaCl, 5% dextrose, 5% dextrose in 0.9% NaCl, sterile water for injection and lactated Ringer's

solution.

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

requirements.

7. Marketing authorisation holder

Hospira UK Limited

Horizon

Honey Lane

Hurley

Maidenhead

SL6 6RJ

United Kingdom

8. Marketing authorisation number(s)

PL 04515/0402

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 24/1/2014

10. Date of revision of the text

12/2016

Ref gx RB 1-0

Company Contact Details

Hospira UK Ltd

Address

Horizon, Honey Lane, Hurley, Maidenhead, SL6 6RJ, UK

+44 (0)800 098 8653

Medical Information Fax

+44 (0)1304 656221

http://www.hospira.com

Medical Information Direct Line

+44 (0)1304 616161

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