| Migraine should be medically diagnosed. |
CYP2D6 metabolism Codeine 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:
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.
|Population ||Prevalence %
||3.4% to 6.5%
||1.2% to 2%
||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 function Codeine 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• 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.
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-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.