Home | About the eMC | Help | Mobile
eMC - trusted, up to date and comprehensive information about medicines
Link to eMC medicine guides website
eMC homepage
Advanced search
Get Medicines Compendium UK app here

GlaxoSmithKline UK
Stockley Park West, Uxbridge, Middlesex, UB11 1BT
Telephone: +44 (0)800 221 441
Fax: +44 (0)208 990 4328
Medical Information e-mail: customercontactuk@gsk.com

Before you contact this company: often several companies will market medicines with the same active ingredient. Please check that this is the correct company before contacting them. Why?
Summary of Product Characteristics last updated on the eMC: 05/07/2011
SPC Tracrium Injection

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC. For each version, we show the dates it was published on the eMC and the reasons for change.

Updated on 05/07/2011 and displayed until Current
Reasons for adding or updating:
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text
Date of revision of text on the SPC:   01-Jul-2011
Legal Category:   POM
Black Triangle (CHM):   NO

Free-text change information supplied by the pharmaceutical company


Section

Summary of change

4.4

-       Update to Section 4.4 of the SmPC – addition of warning regarding bronchospasm in patients with a history of asthma. (to align with CSP).

-       Update to Section 4.4 of the SmPC – text regarding “Teratogenicity” and “Fertility” has been deleted from this section and moved to Section 4.6. (to align with CSP).

4.5

-       Correction to Section 4.5 of the SmPC - lidocaine has been corrected to lignocaine. (to align with CSP).

4.6

-       Update to Section 4.6 of the SmPC – inclusion of text regarding “Teratogenicity” and “Fertility” which has been moved from Section 4.4 to 4.6. (to align with CSP).

4.8

-       Update to Section 4.8 of the SmPC – addition of the introductory text regarding the most commonly reported adverse reactions. (to align with CSP).

-       Update to Section 4.8 of the SmPC – addition of “shock, circulatory failure and cardiac arrest” to very rare Immune System Disorders in association with “anaphylactic and anaphylactoid reactions”. (to align with CSP).

10

-       Updated date

Updated on 26/04/2011 and displayed until 05/07/2011
Reasons for adding or updating:
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text
Date of revision of text on the SPC:   16-Apr-2011
Legal Category:   POM
Black Triangle (CHM):   NO

Free-text change information supplied by the pharmaceutical company
Update section 4.8 of the SPC with the undesirable effect urticaria, with a frequency of rare
Reformat 4.8 to include MedDRA frequencies
Update section 10, date of revision
Updated on 20/07/2009 and displayed until 26/04/2011
Reasons for adding or updating:
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 10 date of revision of the text
Date of revision of text on the SPC:   15-Jul-2009
Legal Category:   POM
Black Triangle (CHM):   NO

Free-text change information supplied by the pharmaceutical company
Section 4.3 - 4.3       Contra-indications

 

Atracurium is contraindicated in patients known to be hypersensitive to atracurium, cisatracurium or benzenesulfonic acid (see section 4.4, Special Warnings and Precautions for Use).


Section 4.4 - 4.4       Special Warnings and Precautions for Use

 

Precautions: In common with all the other neuromuscular blocking agents, Tracrium paralyses the respiratory muscles as well as other skeletal muscles but has no effect on consciousness. Tracrium should be administered only with adequate general anaesthesia and only by or under the close supervision of an experienced anaesthetist with adequate facilities for endotracheal intubation and artificial ventilation.

 

The potential for histamine release exists in susceptible patients during Tracrium administration. Caution should be exercised in administering Tracrium to patients with a history suggestive of an increased sensitivity to the effects of histamine.

 

High rates of cross-sensitivity (greater than 50%) between neuromuscular blocking agents have been reported.  Therefore, where possible, before administering atracurium, hypersensitivity to other neuromuscular blocking agents should be excluded (see section 4.3, Contra-indications).  Atracurium should only be used when absolutely essential in susceptible patients.  Patients who experience a hypersensitivity reaction under general anaesthesia should be tested subsequently for hypersensitivity to other neuromuscular blockers.

 

Monitoring of serial creatinine phosphate (cpk) values should be considered in asthmatic patients receiving high dose corticosteroids and neuromuscular blocking agents in ICU.

 

Tracrium does not have significant vagal or ganglionic blocking properties in the recommended dosage range. Consequently, Tracrium has no clinically significant effects on heart rate in the recommended dosage range and it will not counteract the bradycardia produced by many anaesthetic agents or by vagal stimulation during surgery.

 

In common with other non-depolarising neuromuscular blocking agents, increased sensitivity to atracurium may be expected in patients with myasthenia gravis and other forms of neuromuscular disease.

 

As with other neuromuscular blocking agents severe acid-base and/or serum electrolyte abnormalities may increase or decrease the sensitivity of patients to atracrium.

 

As with other non-depolarising neuromuscular blockers hypophosphataemia may prolong recovery. Recovery may be hastened by correcting this condition.

 

Tracrium should be administered over a period of 60 seconds to patients who may be unusually sensitive to falls in arterial blood pressure, for example those who are hypovolaemic.

 

Tracrium is inactivated by high pH and so must not be mixed in the same syringe with thiopental or any alkaline agent.

 

When a small vein is selected as the injection site, Tracrium should be flushed through the vein with physiological saline after injection. When other anaesthetic drugs are administered through the same in-dwelling needle or cannula as Tracrium it is important that each drug is flushed through with an adequate volume of physiological saline. Atracurium besilate is hypotonic and must not be administered into the infusion line of a blood transfusion.

 

Studies in malignant hyperthermia in susceptible animals (swine), and clinical studies in patients susceptible to malignant hypothermia indicate that Tracrium does not trigger this syndrome.

 

In common with other non-depolarising neuromuscular blocking agents, resistance may develop in patients suffering from burns. Such patients may require increased doses, dependent on the time elapsed since the burn injury and the extent of the burn.

 

Intensive Care Unit (ICU) patients: When administered to laboratory animals in high doses, Laudanosine, a metabolite of atracrium has been associated with transient hypotension and, in some species, cerebral excitatory effects. Although seizures have been seen in ICU patients receiving atracurium, a causal relationship to laudanosine has not been established (see Undesirable Effects).

 

Carcinogenicity: Carcinogenicity studies have not been performed.

 

Teratogenicity: Animal studies have indicated that Tracrium has no significant effects on foetal development.

 

Fertility: Fertility studies have not been performed.


Section 10 - 15/07/2009
Updated on 16/12/2008 and displayed until 20/07/2009
Reasons for adding or updating:
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.7 - Effects on Ability to Drive and Use Machines
  • Change to section 5.2 - Pharmacokinetic Properties
  • Change to section 10 date of revision of the text
Date of revision of text on the SPC:   05-Dec-2008
Legal Category:   POM
Black Triangle (CHM):   NO

Free-text change information supplied by the pharmaceutical company
Section 4.5 - Interactions with other Medicaments and other forms of Interaction

The neuromuscular block produced by Tracrium may be increased by the concomitant use of inhalational anaesthetics such as halothane, isoflurane and enflurane.

In common with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with: antibiotics, including the aminoglycosides, polymyxins, spectinomycin, tetracyclines, lincomycin and clindamycin; antiarrhythmic drugs, propranolol, calcium channel blockers, lidocaine, procainamide and quinidine; diuretics: furosemide and possibly mannitol, thiazide diuretics and acetazolamide; magnesium sulphate, ketamine, lithium salts, ganglion blocking agents, trimetaphan, hexamethonium.

Rarely certain drugs may aggravate or unmask latent myasthenia gravis or actually induce a myasthenic syndrome; increased sensitivity to Tracrium would be consequent on such a development. Such drugs include various antibiotics, ß-blockers (propranolol, oxprenolol), antiarrhythmic drugs (procainamide, quinidine), antirheumatic drugs (chloroquine, D-penicillamine), trimetaphan, chlorpromazine, steroids, phenytoin and lithium.

The onset of non-depolarising neuromuscular block is likely to be lengthened and the duration of block shortened in patients receiving chronic anticonvulsant therapy.

The administration of combinations of non-depolarising neuromuscular blocking agents in conjunction with Tracrium may produce a degree of neuromuscular blockage in excess of that which might be expected were an equipotent total dose of Tracrium administered. Any synergistic effect may vary between different drug combinations.

A depolarising muscle relaxant such as suxamethonium chloride should not be administered to prolong the neuromuscular blocking effects of non-depolarising blocking agents such as atracurium, as this may result in a prolonged and complex block which can be difficult to reverse with anticholinesterase drugs.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 blockade with atracurium.

Section 4.7 - Effects on Ability to Drive and Use MachinesThis precaution is not relevant to the use of atracurium. Atracurium will always be used in combination with a general anaesthetic and therefore the usual precautions relating to performance of tasks following general anaesthesia apply.

Section 5.2 - Pharmacokinetic Properties

 

The pharmacokinetics of Atracurium in man are essentially linear with the 0.3-0.6 mg/kg dose range . The elimination half-life is approximately 20 minutes, and the volume of distribution is 0.16 L/kg. Atracurium is 82% bound to plasma proteins.

 

 

 

Atracurium is degraded spontaneously mainly by a non-enzymatic decomposition process (Hofmann elimination) which occurs at plasma pH and at body temperature and produces breakdown products which are inactive. Degradation also occurs by ester hydrolysis catalysed by non-specific esterases. Elimination of atracurium is not dependent on kidney or liver function.

The main breakdown products are laudanosine and a monoquaternary alcohol which have no neuromuscular blocking activity. The monoquaternary alcohol is degraded spontaneously by hofmann elimination and excreted by the kidney. Laudanosine is excreted by the kidney and metabolised by the liver. The half-life of laudanosine ranges from 3-6h in patients with normal kidney and liver function. It is about 15h in renal failure and is about 40h in renal and hepatic failure. Peak plasma levels of laudanosine are highest in patients without kidney or liver function and average 4 µg/ml with wide variation.

Concentration of metabolites are higher in ICU patients with abnormal renal and/or hepatic function (see Special Warnings and Special Precautions for Use). These metabolites do not contribute to neuromuscular block.

Section 10 - 5/12/08
Updated on 19/11/2007 and displayed until 16/12/2008
Reasons for adding or updating:
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text
Date of revision of text on the SPC:   10/2007
Legal Category:   POM
Black Triangle (CHM):   NO

Free-text change information supplied by the pharmaceutical company
Section 4.3:  Hypersensitivity wording updated
Section 4.4:  Updated to include wording regarding cross-sensitivity
Section 4.5:  Fruosemide updated to furosemide
Section 4.4:  Anaphylactic reaction added
Section 10:  Updated date
Updated on 07/11/2006 and displayed until 19/11/2007
Reasons for adding or updating:
  • Correction of spelling/typing errors
Updated on 26/09/2005 and displayed until 07/11/2006
Reasons for adding or updating:
  • Correction of spelling/typing errors
Updated on 26/01/2005 and displayed until 26/09/2005
Reasons for adding or updating:
  • Change from the BAN of the active substance to the rINN
Updated on 12/05/2003 and displayed until 26/01/2005
Reasons for adding or updating:
  • Improved Electronic Presentation
Updated on 22/04/2003 and displayed until 12/05/2003
Reasons for adding or updating:
  • Change to section 7 - Marketing Authorisation Holder
Updated on 17/03/2003 and displayed until 22/04/2003
Reasons for adding or updating:
  • Change to section 6. 4 - Special Precautions for Storage
  • Change to section 6. 5 - Nature and Contents of Container
  • Change to section 10 (date of (partial) revision of the text
Updated on 21/08/2001 and displayed until 17/03/2003
Reasons for adding or updating:
  • Transferred from eMC version 1
Updated on 07/08/2001 and displayed until 21/08/2001
Reasons for adding or updating:
  • Transferred from eMC version 1
Updated on 06/09/1999 and displayed until 07/08/2001
Reasons for adding or updating:
  • No reasons supplied

Active Ingredients/Generics

 
  atracurium besilate