McNeil Healthcare (Ireland) Ltd

Section 4.2:
Addition of:

Do not take for more than 3 days continuously without medical review. If prescribed do not take for longer than directed.

Section 4.4:
Addition of:

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. Howver, if the patient is an ultra-rapid 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 repiratory depression. Estimates indicate that up to 1 to 2% of the Caucasian population may be ultra-rapid metabolisers. 

Section 4.5:
Addition of:

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.

The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

Section 4.6:
Text on breastfeeding changed to:

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

However if the patient is an ultra rapid metaboliser of CYP2D6, higher levels of teh active metabolite may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in teh 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 4.8:
Addtion of:

Regular prolonged use of codeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is stopped.

Prolonged use of a painkiller for headaches can make them worse.

Section 4.9:
Information on overdose changed to:

Paracetamol

Liver damage is possible in adults who have taken 10g or more of paracetamol.  Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk Factors:

If the patient

Is on long term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

Or

Regularly consumes ethanol in excess of recommended amounts.

Or

Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain.  Liver damage may become apparent 12 to 48 hours after ingestion.  Abnormalities of glucose metabolism and metabolic acidosis may occur.  In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death.  Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage.  Cardiac arrhythmias and pancreatitis have been reported.

Immediate treatment is essential in the management of paracetamol overdose.  Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention.  Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage.  Management should be in accordance with established treatment guidelines, see BNF overdose section.  Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour.  Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable) but results should not delay initiation of treatment beyond 8 hours after ingestion, as the effectiveness of the antidote declines sharply after this time.  If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule.  If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital.

Codeine

The effects in codeine overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Codeine overdose associated with central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been co-ingested, including alcohol, or the overdose is very large.  The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely.

Management of codeine overdose includes general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable.  Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg.

Give naloxone if coma or respiratory depression is present.  Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient.  Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

Section 1

Full name is now:

Migraleve Pink Film-coated Tablets

Paracetamol 500mg

Codeine phosphate 8mg

Buclizine hydrochloride 6.25mg

Section 2

The following statement added:

For a full list of excipients, see section 6.1.

Section 3

(Tablets) added to end of description of pharmaceutical form.

Section 4.6

Statement "Migraleve Pink is not contraindicated in breastfeeding mothers" has been removed.

Section 6.5

Statement "Not all packs sizes may be marketed" added

Section 10

Changed to November 2008