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McNeil Products Ltd

Foundation Park, Roxborough Way, Maidenhead, Berks, SL6 3UG
Medical Information Direct Line: 01344 864042
Medical Information e-mail: crc@its.jnj.com

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Summary of Product Characteristics last updated on the eMC: 05/04/2012
SPC Migraleve


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1. Name of the medicinal product

Migraleve


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2. Qualitative and quantitative composition

Each Migraleve Pink tablet contains:

Paracetamol DC 96%
(equivalent to Paracetamol 500 mg)

520 mg

Codeine Phosphate

8 mg

Buclizine Hydrochloride

6.25 mg

Each Migraleve Yellow tablet contains:

Paracetamol DC 96%
(equivalent to Paracetamol 500 mg)

520 mg

Codeine Phosphate

8 mg

For full list of excipients, see section 6.1


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3. Pharmaceutical form

Film-coated Tablets.

Migraleve Pink Tablets

Pink, capsule-shaped, film-coated tablets marked MGE on one face.

Migraleve Yellow Tablets

Yellow, capsule-shaped, film-coated tablets marked MGE on one face.


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4. Clinical particulars

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4.1 Therapeutic indications

For the short term treatment of acute moderate pain which is not relieved by Paracetamol, ibuprofen or aspirin alone such as migraine attacks including the symptoms of migraine headache, nausea and vomiting.


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4.2 Posology and method of administration

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.


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4.3 Contraindications

Do not give to children under 10 years of age except under medical supervision. Hypersensitivity to any of the ingredients.


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4.4 Special warnings and precautions for use

Migraine should be medically diagnosed.

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 respiratory depression. Estimates indicate that up to 1 to 2% of the Caucasian population may be ultra-rapid metabolisers.

The prevalence of ultra rapid metabolisers in other ethnic groups has been estimated as 0.5 to 1% in Chinese, Japanese and Hispanics, 3% in African Americans and 16 to 28% in North Africans, Ethiopians and Arabs.

When physicians prescribe codeine-containing drugs, they should choose the lowest effective dose for the shortest period of time and inform their patients about these risks and the signs of morphine overdose (see section 4.6 Use during pregnancy and lactation).

Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.

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.

Buclizine has an antimuscarinic action and therefore should be used with caution in prostatic hypertrophy, urinary retention. Also where susceptibility to angle-closure glaucoma.

For products in packs of 32 tablets or fewer:

Front of pack

• Can cause addiction.

• For three days use only.

Back of Pack

• Migraleve is for use in acute moderate pain associated with migraine which has been previously diagnosed by a doctor and where other painkillers have not worked. Do not take less than four hours after taking other painkillers.

• List of indications as agreed in 4.1 of the SmPC.

• If you need to take this medicine for more than three days you must see your doctor or pharmacist.

• This medicine contains codeine which can cause addiction if you take it continuously for more than three days. If you take this medicine for headaches for more than three days it can make them worse.

For both POM and P products:

Patient Information Leaflet

Headlines (at the start of the PIL)

• For the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone such as migraine attacks including the symptoms of migraine headache, nausea and vomiting.

• You should only take this product for a maximum of three days at a time. If you need to take it for longer than three days you should see your doctor or pharmacist for advice.

• This medicine contains codeine which can cause addiction if you take it continuously for more than three days. This can give you withdrawal symptoms from the medicine when you stop taking it.

• If you take this medicine for headaches for more than three days it can make them worse.

Section 1: What this medicine is for

For the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone such as migraine attacks including the symptoms of migraine headache, nausea and vomiting.

Section 2: Before taking this medicine

• This medicine contains codeine which can cause addiction if you take it continuously for more than three days. This can give you withdrawal symptoms from the medicine when you stop taking it.

• If you take this painkiller for headaches for more than three days it can make them worse.

• Ask your doctor or pharmacist for advice before taking this medicine if you are pregnant or breast-feeding.

• Usually it is safe to take Migraleve while breast feeding as the levels of the active ingredients in 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 longer than normal, and shallow or slow breathing.

Section 3: How to take this medicine

Under the sub-heading 'Check the tables below to see how much medicine to take'

• Do not take less than four hours after taking other painkillers.

• Do not take for more than 3 days. If you need to use this medicine for more than three days you must speak to your doctor or pharmacist.

Under the sub-heading 'Special warnings about addiction'

• This medicine contains codeine which can cause addiction if you take it continuously for more than three days. When you stop taking it you may get withdrawal symptoms. You should talk to your doctor or pharmacist if you think you are suffering from withdrawal symptoms.

Section 4: Possible Side-effects

Some people may have side-effects when taking this medicine. If you have any unwanted side-effects you should seek advice from your doctor, pharmacist or other healthcare professional. Also you can help to make sure that medicines remain safe as possible by reporting any unwanted side-effects via the internet at www.yellowcard.gov.uk ; alternatively you can call Freephone 0808 100 3352 (available between 10am-2pm Monday – Friday) or fill in a paper form available from your local pharmacy.

Under the sub-heading 'How do I know if I am addicted?'

If you take the medicine according to the instructions on the pack it is unlikely that you will become addicted to the medicine. However, if the following apply to you it is important that you talk to your doctor:

• You need to take the medicine for longer periods of time.

• You need to take more than the recommended dose.

• When you stop taking the medicine you feel unwell but you feel better when you start taking the medicine again.

The following statements should also be included:

• Do not take with any other product paracetamol-containing products.

Immediate medical advice should be sought in the event of an overdose, even if you feel well. (carton)

• Contains Paracetamol. (carton)

• If you drink large amounts of alcohol, you may be more open to the side-effects of paracetamol. (leaflet)

• Do not exceed the stated dose.

• Migraleve Pink Tablets only: May cause drowsiness. If affected, do not drive or operate machinery. Avoid alcoholic drink.

• If symptoms persist, consult your doctor.

• Keep out of the reach and sight of children.


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4.5 Interaction with other medicinal products and other forms of interaction

Codeine

Codeine may antagonise the effects of metoclopramide and domperidone on gastrointestinal motility.

Codeine may enhance the effects of other CNS depressants such as alcohol, hypnotics, sedatives, tranquilisers and other opioid analgesics. Codeine should be given with care to patients receiving monoamine oxidase inhibitors (MAOIs) or who have used MAOIs in the previous two weeks.

Paracetamol

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.

Buclizine

Sedating antihistamines, such as buclizine, have an additive sedative effect with alcohol and other CNS depressants. Sedating antihistamines have an additive antimuscarinic action with other antimuscarinic drugs such atropine and some antidepressants (both tricyclics and MAOIs)


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4.6 Fertility, pregnancy and lactation

There is inadequate evidence for the safety of codeine in human pregnancy.

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use.

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 Migraleve is not absolutely contraindicated during pregnancy, it should only be used when the physician has considered the potential benefit outweighs the potential risk.

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. Mothers using codeine should be informed about how to identify the signs and symptoms of opioid toxicity, such as drowsiness or sedation, difficulty breast-feeding, breathing difficulties, and decreased tone, in their baby. Nursing mothers should be instructed to talk to the baby's doctor immediately or seek emergency medical care.

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.

Nursing mothers who rapidly metabolise codeine may also experience overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. Prescribers should closely monitor mother-infant pairs and notify treating paediatricians about the use of codeine during breast-feeding.

Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

There is no data available relating to the safety of buclizine in breast-feeding mothers.

Migraleve should only be used in breast-feeding when the physician has considered that the potential benefit outweighs the potential risk.


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4.7 Effects on ability to drive and use machines

Migraleve Pink Tablets only: May cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink.


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4.8 Undesirable effects

Codeine may cause constipation, drowsiness, dizziness, nausea, vomiting, dyspepsia, dry mouth, acute pancreatitis in patients with a history of cholecystectomy, difficulty with micturition, pruritus and sweating according to dosage and individual susceptibility.

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.

Adverse effects of paracetamol are rare. Very rarely hypersensitivity and anaphylactic reactions including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocystosis but these were not necessarily causality related to paracetamol.

Buclizine hydrochloride may cause drowsiness. In addition, sedating antihistamines such as buclizine may cause headache, psychomotor impairment, dizziness, gastrointestinal disturbance, dry mouth, thickened respiratory tract secretions, difficulty in micturition or blurred vision. Hypersensitivity reactions have also been reported, in particular, skin rashes, erythema, urticaria and angioedema.


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4.9 Overdose

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

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) Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol, however the maximum protective effect is obtained up to 8 hours post-ingestion. 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. Management of patients who present with serious hepatic dysfunction beyond 24h from ingestion should be discussed with the NPIS or a liver unit.

Buclizine

Overdose with sedating antihistamines is associated with antimuscarinic, extrapyramidal, and CNS effects. When CNS stimulation predominates over CNS depression, which is more likely in children or the elderly, it causes ataxia, excitement, tremors, psychoses, hallucinations and convulsions; hyperpyrexia may also occur. Deepening coma and cardiorespiratory collapse may follow. In adults, CNS depression is more common with drowsiness, coma, and convulsions, progressing to respiratory failure and cardiovascular collapse.


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5. Pharmacological properties

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5.1 Pharmacodynamic properties

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.


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5.2 Pharmacokinetic 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 (Tmax 3 hours). The elimination half-life is approximately 15 hours.


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5.3 Preclinical safety data

No data presented.


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6. Pharmaceutical particulars

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6.1 List of excipients

Migraleve Pink Tablets

Gelatin

Magnesium Stearate

Colloidal Anhydrous Silica

Stearic Acid

Pregelatinised Maize Starch

Erythrosine (E127)

Hypromellose

Titanium Dioxide (E171)

Macrogol 400

Aluminium Oxide

Migraleve Yellow Tablets

Gelatin

Magnesium Stearate

Colloidal Anhydrous Silica

Stearic Acid

Pregelatinised Maize Starch

Hypromellose

Titanium Dioxide (E171)

Macrogol 400

Iron Oxide Yellow (E172)

Quinoline Yellow (E104)

Aluminium Oxide


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6.2 Incompatibilities

None known.


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6.3 Shelf life

36 months


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6.4 Special precautions for storage

None.


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6.5 Nature and contents of container

Packs of: 12 tablets (8 Migraleve Pink and 4 Migraleve Yellow)

Packs of: 24 tablets (16 Migraleve Pink and 8 Migraleve Yellow)

Packs of: 48 tablets (32 Migraleve Pink and 16 Migraleve Yellow)

Blister strips consist of clear amber PVC blister film and paper/aluminium foil child-resistant blister lidding.


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6.6 Special precautions for disposal and other handling

None.


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Administrative data

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7. Marketing authorisation holder

McNeil Products Limited

Foundation Park

Roxborough Way

Maidenhead

Berkshire SL6 3UG

United Kingdom


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8. Marketing authorisation number(s)

PL 15513/0105


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9. Date of first authorisation/renewal of the authorisation

23 April 2001/ 28 Jan 2009


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10. Date of revision of the text

22nd March 2012


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Legal category

Packs of 12 and 24 tablets: P

Packs of 48 tablets: POM



More information about this product

Link to this document from your website: http://www.medicines.org.uk/emc/medicine/1453/SPC/


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