- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- Administrative data
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
- Legal category
|Each Migraleve Pink tablet contains:|
|Paracetamol DC 96%||520 mg|
|(equivalent to Paracetamol 500 mg)|
|Codeine Phosphate||8 mg|
|Buclizine Hydrochloride||6.25 mg|
|Each Migraleve Yellow tablet contains:|
|Paracetamol DC 96%||520 mg|
|(equivalent to Paracetamol 500 mg)|
|Codeine Phosphate||8 mg|
Migraleve Pink TabletsPink, capsule-shaped, film-coated tablets marked MGE on one face.
Migraleve Yellow TabletsYellow, capsule-shaped, film-coated tablets marked MGE on one face.
CYP2D6 metabolismCodeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained. Estimates indicate that up to 7% of the caucasian population may have this deficiency. However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses. These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels.General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe cases this may include symptoms of circulatory and respiratory depression which may be life-threatening and very rarely fatal.Estimates of prevalence of ultra-rapid metabolisers in different populations are summarized below:
|African American||3.4% to 6.5%|
|Asian||1.2% to 2%|
|Caucasian||3.6% to 6.5%|
Post-operative use in childrenThere have been reports in the published literature that codeine given post-operatively in children after tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, led to rare, but life-threatening adverse events including death (see also section 4.3). All children received doses of codeine that were within the appropriate dose range; however there was evidence that these children were either ultra-rapid or extensive metabolisers in their ability to metabolise codeine to morphine.
Children with compromised respiratory functionCodeine is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures. These factors may worsen symptoms of morphine toxicity.
For products in packs of 32 tablets or fewer:
Front of pack• Can cause addiction.• For three days use only.
Back of Pack• This medicine can make you feel sleepy. Do not drive while taking this medicine until you know how it makes you feel. See the leaflet inside for more information. • 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 forFor 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.Codeine can be used in children over 12 years of age for the short-term relief of moderate pain that is not relieved by other painkillers such as paracetamol or ibuprofen alone.This product contains codeine. Codeine belongs to a group of medicines called opioid analgesics which act to relieve pain. It can be used on its own or in combination with other pain killers such as paracetamol.
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.
Do not use this medicine:• For pain relief in children and adolescents (0-18 years of age) after removal of their tonsils or adenoids due to obstructive sleep apnoea syndrome• If you know that you metabolise very rapidly codeine into morphine• If you are breastfeeding
Warnings and precautionsCodeine is transformed to morphine in the liver by an enzyme. Morphine is the substance that produces pain relief. Some people have a variation of this enzyme and this can affect people in different ways. In some people, morphine is not produced or produced in very small quantities, and it will not provide enough pain relief. Other people are more likely to get serious side effects because a very high amount of morphine is produced. If you notice any of the following side effects, you must stop taking this medicine and seek immediate medical advice: slow or shallow breathing, confusion, sleepiness, small pupils, feeling or being sick, constipation, lack of appetite.
Children and adolescents
Use in children and adolescents after surgeryCodeine should not be used for pain relief in children and adolescents after removal of their tonsils or adenoids due to Obstructive Sleep Apnoea Syndrome.
Use in children with breathing problemsCodeine is not recommended in children with breathing problems, since the symptoms of morphine toxicity may be worse in these children.
Pregnancy and breastfeedingDo not take codeine while you are breastfeeding. Codeine and morphine passes into breast milk.Special warnings about drowsinessThese tablets may cause drowsiness. If affected do not operate machinery.This medicine can affect your ability to drive. Do not drive whilst taking this medicine until you know how this medicine affects you. It may be an offence to drive when taking this medicine if your ability to drive safely is affected. Talk to your doctor or pharmacist if you are not sure whether it is safe for you to drive while taking this medicine. There is further information for patients who are intending to drive in the UK - go to https://www.gov.uk/drug-driving-law. Avoid alcoholic drink. 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.• Children aged 12 years or above should take one Migraleve Pink tablet to be swallowed immediately if it is known that a migraine attack has started or is imminent. If further treatment is required, one Migraleve Yellow tablet every 4 hours. Do not take more than 4 tablets (one Migraleve Pink and three Migraleve Yellow) in 24 hours.This medicine should not be taken for more than 3 days. If the pain does not improve after 3 days, talk to your doctor for advice.• This medicine should not be taken by children below the age of 12 years, due to the risk of severe breathing problems.
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-effectsSome 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.
CodeineCodeine 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.
ParacetamolThe 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.
BuclizineSedating 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)
CodeineThe 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.
ParacetamolLiver 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.
BuclizineOverdose 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.
Migraleve Pink TabletsGelatinMagnesium Stearate Colloidal Anhydrous SilicaStearic Acid Pregelatinised Maize StarchErythrosine (E127)Hypromellose Titanium Dioxide (E171)Macrogol 400Aluminium Oxide
Migraleve Yellow TabletsGelatinMagnesium Stearate Colloidal Anhydrous SilicaStearic Acid Pregelatinised Maize StarchHypromellose Titanium Dioxide (E171)Macrogol 400 Iron Oxide Yellow (E172)Quinoline Yellow (E104)Aluminium Oxide
McNeil Products Ltd
Foundation Park, Roxborough Way, Maidenhead, Berks, SL6 3UG