McNeil Healthcare (Ireland) Ltd

Migraleve Yellow Film-coated Tablets

Paracetamol 500mg

Codeine phosphate 8mg

Each Migraleve Yellow tablet contains:

Paracetamol 500mg (as Paracetamol DC 96%)

Codeine Phosphate 8 mg

For a full list of excipients, see section 6.1

Film Coated Tablet (Tablet)

Yellow film-coated capsule-shaped tablets engraved 'MGE' on one face.

For the prevention and treatment of migraine attacks which can include the symptoms of migraine headache, nausea and vomiting. Route of administration: oral.

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

Adults and the elderly: Two Migraleve Pink tablets to be swallowed immediately it is known that a migraine attack has started or is imminent. If further treatment is required, two Migraleve Yellow tablets every 4 hours.

Maximum dose: 8 tablets (two Migraleve Pink and six Migraleve Yellow) in 24 hours.

Children 10 – 14 years: One Migraleve Pink tablet to be swallowed immediately it is known that a migraine attack has started or is imminent. If further treatment is required, one Migraleve Yellow tablet every 4 hours.

Maximum dose: 4 tablets (one Migraleve Pink and three Migraleve Yellow) in 24 hours.

Do not give to children under 10 years of age except under medical supervision.

Hypersensitivity to any of the ingredients.

Migraine should be medically diagnosed. Because some medicines do not combine, if you are already taking prescribed medicines please consult your doctor. If symptoms persist, consult your doctor. Migraleve Pink tablets contain potent medicaments and should not be taken continuously for extended periods without the advice of a doctor. Do not exceed the stated dose. May cause drowsiness. Avoid alcoholic drink. Should be used with caution in patients with severe renal disease or liver dysfunction.

Prolonged regular use, except under medical supervision, may lead to physical and psychological dependence (addiction) and result in withdrawal symptoms, such as restlessness and irritability once the drug is stopped.

Patients should be advised not to take other paracetamol-containing products concurrently.

Immediate medical advice should be sought in the event of an overdose, even if the patient feels well, because of the risk of irreversible liver damage.

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 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.

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.

Although experiments in some animal species gave rise to adverse effects following the administration of buclizine to pregnant animals e.g. foetal abnormalities and maternal deaths, these occurred at doses in excess of 120 times the human daily dose. Whilst there are no specific reasons for contra-indicating Migraleve during pregnancy, as with all drugs it is recommended that Migraleve be used in pregnancy only when the physician has considered the need in respect of the patients' welfare.

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.

May cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink.

Rare allergic reactions to paracetamol, such as skin rashes, hives or itching. Codeine may cause constipation.

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.

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.

Paracetamol has analgesic, antipyretic and mild, acute anti-inflammatory properties. Paracetamol inhibits prostaglandin synthesis, especially in the CNS. Paracetamol does not inhibit chronic inflammatory reactions.

Codeine is an opioid analgesic. Codeine also has anti-tussive properties.

Paracetamol is rapidly absorbed from the upper G.I. tract after oral administration, with the small intestine being an important site of absorption. Peak blood levels of 15-20 mcg/ml after normal 1 g oral doses of paracetamol occur within 30 – 90 minutes. Depending upon dosage form, it is rapidly distributed throughout the body and is primarily metabolised in the liver with excretion via the kidney. Elimination half-life is about 2 hours after reaching a peak following a 1 g oral dose. Paracetamol crosses the placental barrier and is present in breast milk.

Codeine is absorbed from the gastro-intestinal tract and peak plasma concentrations occur after one hour. Codeine is metabolised by O- and N- demethylation in the liver to morphine, norcodeine and other metabolites. Codeine and its metabolites are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid. Codeine is not extensively bound to plasma proteins. The plasma half-life has been reported to be between 3 and 4 hours.

No data presented.

Gelatin

Magnesium Stearate

Colloidal Anhydrous Silica.

Stearic Acid

Pregelatinised Maize Starch

Opadry Yellow OY-6126 *

* Opadry Yellow OY-6126 contains :

Hypromellose.

Titanium Dioxide (E171)

Macrogol 400

Yellow Iron Oxide (E172)

Quinoline Yellow Aluminium Lake (E104) consisting of Quinoline Yellow (E104) and Aluminium Oxide.

Not applicable

3 years.

Do not store above 30°C.

Clear amber PVC/aluminium foil blister strips.

Or

Clear amber PVC/laminated paper and aluminium foil child resistant blisters

Packs of 12, 24 and 48 tablets.

Not all pack sizes may be marketed.

No special requirements.

McNeil Healthcare (Ireland) Limited

Airton Road

Tallaght

Dublin 24

Ireland

PA 823/36/2.

Date of first authorisation: 01 April 1978

Date of last renewal: 01 April 2008

May 2011