1. Name Of The Medicinal Product
Migraleve
2. Qualitative And Quantitative Composition
Each Migraleve Pink tablet contains: | |
Paracetamol DC 96%
| 520 mg
|
Each Migraleve Yellow tablet contains: | |
Paracetamol DC 96%
| 520 mg
|
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.
4. Clinical Particulars
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.
4.2 Posology And Method Of Administration
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.
4.3 Contraindications
Do not give to children under 10 years of age except under medical supervision. Hypersensitivity to any of the ingredients.
4.4 Special Warnings And Precautions For Use
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.
Some individuals may be ultra-rapid metabolisers due to a specific CYP2D6*2x2 genotype. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labelled dosage regimens, individuals who are ultra-rapid metabolisers may experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing.
The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese, Japanese and Hispanics, 1 to 10% in Caucasians, 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).
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. Migraleve Pink Tablets only: 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.
Keep out of the reach and sight of children.
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.
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.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
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.
4.6 Pregnancy And Lactation
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.
Migraleve is not contra-indicated in breast-feeding mothers; however, codeine and its active metabolite, morphine, are secreted into human milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low. Some women rapidly metabolise codeine, which may result in higher serum levels of codeine's active metabolite, morphine, in breast milk and, therefore, potentially dangerous levels of serum morphine in their breastfed infants. This could lead to potentially serious adverse reactions, including death, in nursing infants. Mothers using codeine should be informed about how to identify the signs and symptoms of neonatal 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.
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.
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.
4.8 Undesirable Effects
Rare allergic reactions to paracetamol, such as skin rashes, hives or itching. Codeine may cause constipation. Buclizine hydrochloride may cause drowsiness.
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.
4.9 Overdose
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.
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.
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.
5.3 Preclinical Safety Data
No data presented.
6. Pharmaceutical Particulars
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
6.2 Incompatibilities
None known.
6.3 Shelf Life
36 months
6.4 Special Precautions For Storage
None.
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.
6.6 Special Precautions For Disposal And Other Handling
None.
Administrative data
7. Marketing Authorisation Holder
McNeil Products Limited
Foundation Park
Roxborough Way
Maidenhead
Berkshire SL6 3UG
United Kingdom
8. Marketing Authorisation Number(S)
PL 15513/0105
9. Date Of First Authorisation/Renewal Of The Authorisation
23 April 2001/ 28 Jan 2009
10. Date Of Revision Of The Text
12 April 2010
Legal Category
Packs of 12 and 24 tablets: P
Packs of 48 tablets: POM
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