McNeil Healthcare (Ireland) Ltd

Migraleve Film-coated Tablets

Migraleve combines two dosage forms, Migraleve Pink and Migraleve Yellow film-coated tablets.

Each Migraleve Pink film-coated tablet contains:

Paracetamol 500mg (as Paracetamol DC 96%)

Codeine Phosphate 8 mg

Buclizine Hydrochloride 6.25 mg

Each Migraleve Yellow film-coated tablet contains:

Paracetamol 500mg (as Paracetamol DC 96%)

Codeine Phosphate 8 mg

For a full list of excipients, see section 6.1

Film coated Tablets (Tablets).

Migraleve Pink: Pink film-coated capsule-shaped tablets engraved 'MGE' on one face.

Migraleve Yellow: 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.

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.

Use of codeine containing products is contraindicated in mothers who are breastfeeding unless prescribed by a doctor.

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 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. If affected, do not drive or operate machinery. 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.

None known.

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.

In nursing mothers, who are ultra-rapid metabolisers of codeine, higher than expected serum and breast milk morphine levels can occur. Morphine toxicity in babies can cause excessive somnolence, hypotonia, miosis and difficulty breastfeeding or breathing. In severe cases respiratory depression and death can occur. In severe cases, naloxone may be appropriate to reverse the effects. The lowest effective dose should be used, for the shortest possible time.

Nursing mothers should be informed about carefully monitoring the infant during treatments for any signs and/or symptoms of morphine toxicity such as increased drowsiness or sedation, difficulty breastfeeding , breathing difficulties, miosis and decreased tone, and seeking immediate medical care if such symptoms or signs are noticed. The nursing mother should be informed about monitoring for signs and symptoms of maternal opoid toxicity as well. Should such signs be noted in mother or baby, the mother should immediately stop taking all codeine-containing medicines and seek medical advice.

Codeine-containing products must not be used while breastfeeding unless prescribed by a doctor.

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. Buclizine hydrochloride may cause drowsiness.

Symptoms of paracetamol overdosage are often delayed for at least 24 hours, but to prevent damage, treatment should be given as soon as possible and within 10 hours of ingestion. Treatment is by the administration of i.v. acetylcysteine. Oral methionine may also be used, but is less certain in its effect because of its need for G.I. absorption. Once hepatic failure has developed, standard measures of management should be employed.

Patients on enzyme-inducing agents (such as barbiturates) and chronic non-cirrhotic alcoholics may be more susceptible to the toxicity of a paracetamol overdosage.

Symptoms of codeine overdosage include nausea and vomiting, and circulatory and respiratory depression. Initial treatment includes gastric lavage. If CNS depression is severe, artificial respiration, oxygen and parenteral naloxone may be required.

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.

The combination of paracetamol and codeine has been shown to have hyperadditive analgesic effects in animals.

Buclizine is a piperazine derivative with the actions and uses of H₁-receptor antagonists. It has anti-muscarinic and central sedative properties. It is used mainly for its anti-emetic 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.

Buclizine hydrochloride is more slowly absorbed from the G.I. tract (T_max 3 hours). The elimination half-life is approximately 15 hours.

No data presented.

Migraleve Pink Tablets

Gelatin

Magnesium Stearate.

Colloidal Anhydrous Silica

Stearic Acid

Pregelatinised Maize Starch

Erythrosine Aluminium Lake(E127)

Opadry Pink OY-1367 *

*Opadry Pink OY-1367 contains :

Hypromellose.

Titanium Dioxide (E171)

Macrogol 400

Erythrosine Aluminium Lake (E127) consisting of Erythrosine (E127) and Aluminium Oxide

Migraleve Yellow Tablets

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 30ºC.

Clear amber PVC/aluminium foil blister strips.

Or clear amber PVC/laminated paper and aluminium foil child resistant blisters

Packs of,

12 tablets (8 Migraleve Pink and 4 Migraleve Yellow).

24 tablets (16 Migraleve Pink and 8 Migraleve Yellow).

48 tablets (32 Migraleve Pink and 16 Migraleve Yellow).

Not all pack sizes may be marketed,

McNeil Healthcare (Ireland) Limited

Airton Road

Tallaght

Dublin 24

Ireland

PA 823/36/3.

Date of first authorisation: 01 April 1978

Date of last renewal: 01 April 2008

November 2008