Abbott Laboratories Limited

4.4    Special warnings and precautions for use

During epidural administration of levobupivacaine, concentrated solutions (0.5-0.75%) should be administered in incremental doses of 3 to 5 ml with sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection. Cases of severe bradycardia, hypotension and respiratory compromise with cardiac arrest (some of them fatal), have been reported in conjunction with local anesthetics, including levobupivacaine. When a large dose is to be injected, e.g. in epidural block, a test dose of 3-5 ml lidocaine with adrenaline is recommended.  An inadvertent intravascular injection may then be recognised by a temporary increase in heart rate and accidental intrathecal injection by signs of a spinal block.  Syringe aspirations should also be performed before and during each supplemental injection in continuous (intermittent) catheter techniques.  An intravascular injection is still possible even if aspirations for blood are negative.  During the administration of epidural anesthesia, it is recommended that a test dose be administered initially and the effects monitored before the full dose is given.

4.8     Undesirable effects

There have been reports of prolonged weakness or sensory disturbance, some of which may have been permanent, in association with levobupivacaine therapy. It is difficult to determine whether the long-term effects where the result of medication toxicity or unrecognized trauma during surgery or other mechanical factors, such as catheter insertion and manipulation.

Rare reports have been received of cauda equina syndrome or signs and symptoms of potential injury to the base of the spinal cord or spinal nerve roots (including lower extremity weakness or paralysis, loss of bowel control and/or bladder control and priapism) associated with bupivacaine or Llevobupivacaine therapy. However, it cannot be determined whether these events are due to an effect of levobupivacaine, mechanical trauma to the spinal cord or spinal nerve roots, or blood collection at the base of the spine.

There have also been rare reports of transient Horner’s syndrome (ptosis, miosis, enophtalmus enophthalmos, unilateral sweating and/or flushing) in association with use of regional anaesthetics, including levobupivacaine. This event resolves with discontinuation of therapy.

5.1     Pharmacodynamic properties

• Section 4.8 - updated to add awarning that levobupivacaine can cause acute allergic reactions, cardiovascular affects and neurological damage, with reference to section 4.8.
• Section 4.8 - updated to include preffered terms in the table that were originally found in a paragraph underneath the table.

• Section 7 - The address of the MAH has been updated from Queenborough, Kent, ME5 9EL to Abbott House, Vanwall Business Park, Vanwall Road, Maidenhead, Berks, SL6 4XE.
• Section 10 - Updated to reflect the date of approval of Section 7 above.

• In Section 2 (Qualitative and Quantitative Composition), the statement 'Full a full list of excipients, see section 6.1' has been placed after 'Excipients: 3.6mg/ml of sodium per bag'.
• In Section 4.4 (Special wanrings and precautions for use), A warning regarding patients on a sodium controlled diet has been added.
• Section 4.8 (Undesirable effects), has been completely reformatted to MedDRA terminology and frequency.
• In Section 6.3 (Shelf life), the paragraphs have been clarified to show the difference between using the product immediately and dilutions in 0.9% sodium chloride solution.
• In Section 6.4 (Special precautions for storage), a statement regarding the storage of reconstituted product has been added.