• In Section 1 (Name of Medicinal Product), addition of 30 mg / 500 mg to the name, clarification of dosage strength.
• In Section 2 (Qualitative and Quantitative Composition), addition of the amount of sodium and aspartame contained in the product.
• In Section 3 (Pharmaceutical Form), an addition of a description for the tablets i.e. Round, white or off white tablets.
• In Section 4.4 (Contraindications) - minor formatting update TYLEX EFFERVESCENT to lower case.
• In Section 4.4 (Special warnings and precautions for use) - Addition of a warning for patients with CNS depression, inflammatory or obstructive bowel disorders and pre-existing respiratory depression or those with the potential to develop respiratory depression. Addition of information regarding patients with a sensitivity to aspirin.  Deletion of the warning for biliary tract disorders (including recent biliary tract surgery) and deletion of the statement regarding acute abdominal conditions. Re-wording of warning for potential liver damage with overdose or if Tylex is taken with large amounts of alcohol. 
• In Section 4.5 (Interaction with other medicinal products and other forms of interaction) - Addition of a statement that concurrent use with centrally acting muscle relaxants may increase the risk of respiratory depression. Addition of a statement regarding MAOIs and enzyme-inducing medicines.
• In Section 4.8 - (Undesirable effects) - The list of adverse events has been tabulated.  Addition of statements regarding deafness, pancreatitis, anaphylaxis, angiodema and toxic epidermal necrolysis.
• Section 4.9 (Overdose symptoms, emergency procedures, antidotes) - Addition of standard wording for paracetamol overdose.
• Section 6.1 (List of excipients) minor clarification, no change to actual excipients
• Section 6.2 (Incompatibilities) minor clarification
• Section 6.3 (Shelf Life) - Changed from 36 months to 3 years.
• Section 6.4 (Special Precautions for Storage) - Minor update to wording. Added protect from moisture.
• Section 6.6 (Special Precautions for Disposal) - Minor update to wording, no significant change.

Codeine is partially metabolised by CYP2D6. If a patient has a deficiency or is completely lacking this enzyme they will not obtain adequate analgesic effects. Estimates indicate that up to 7% of the Caucasian population may have this deficiency. However, if the patient is an ultrarapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at low doses. General symptoms of opioid toxicity include nausea, vomiting, constipation, lack of appetite and somnolence. In severe cases this may include symptoms of circulatory and respiratory depression. Estimates indicate that up to 1 to 2% of the Caucasian population may be ultra-rapid metabolisers.

The leaflet will state in the "Pregnancy and breast-feeding" subsection of Section 2 "Before taking your medicine":

Usually it is safe to take Tylex/Medocodene while breast feeding as the levels of the active ingredients of this medicine in breast milk are too low to cause your baby any problems. However, some women who are at increased risk of developing side effects at any dose may have higher levels in their breast milk. If any of the following side effects develop in you or your baby, stop taking this medicine and seek immediate medical advice; feeling sick, vomiting, constipation, decreased or lack of appetite, feeling tired or sleeping for longer than normal, and shallow or slow breathing.

At normal therapeutic doses codeine and its active metabolites may be present in breast milk at very low doses and is unlikely to adversely affect the breast fed infant.

However, if the patient is an ultra-rapid metaboliser of CYP2D6, higher levels of the active metabolites may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant.

If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be stopped and alternative non-opioid analgesics prescribed. In severe cases consideration should be given to prescribing naloxone to reverse these effects.

·         Section 7 MARKETING AUTHORISATION HOLDER

Change to UCB Pharma Limited, 208 Bath Road , Slough, Berkshire, SL1 3WE, United Kingdom

·         Section 8 MARKETING AUTHORISATION NUMBER(S)

Change PL number to PL 00039/0750

·         Section 9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

5 November 2009

10      Section 10 DATE OF REVISION OF THE TEXT now blank