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Drugs List
Therapeutic Indications
Dosage
Administration
Contraindications
Precautions and Warnings
Pregnancy and Lactation
Side Effects
Monograph

Dosage

Adults
Children
Patients with Renal Impairment
Patients with Hepatic Impairment
Additional Dosage Information

Initial: At onset of migraine, 2 initial treatment tablets containing paracetamol, codeine and buclizine (pink tablets). Maximum dose 2 initial treatment tablets (pink tablets) in 24 hours.

Maintenance: For further migraine relief, 2 continuation treatment tablets containing paracetamol and codeine (yellow tablets) starting at least 4 hours after initial treatment (pink tablets) and repeated every 4 hours if required. Maximum dose 6 continuation treatment tablets (yellow tablets) in 24 hours.

Maximum treatment duration 3 days.

Note that this product contains 500 mg paracetamol per tablet. The maximum total adult daily dose for paracetamol of 4g should not be exceeded if additional paracetamol containing analgesics are used.

Precautions and Warnings

Pregnancy (see Pregnancy)
Breastfeeding (see Lactation)
Hepatic impairment - (see Hepatic Impairment)
Renal impairment - (see Renal Impairment)

Migraine should be medically diagnosed by a doctor before this medicine is commenced.

Ultra-rapid metabolisers (CYP2D6*2x2 genotype), convert codeine into its active metabolite, morphine, more rapidly and completely than other people, resulting in higher than expected serum morphine levels. Even at labelled dosage regimens, overdose symptoms such as extreme sleepiness, confusion or shallow breathing can occur.

Care should be observed in administering the product to any patient whose condition may be exacerbated by opioids.
Therefore caution should be used in patients with:
Reduced or impaired respiratory function (including asthma)
Hypotension
Inflammatory bowel disease
Bowel obstruction
Biliary tract disorders
Addison's disease
Prostatic hypertrophy
Shock
Myasthenia gravis
Convulsive disorders
Cardiac arrhythmias
Gallstones
Urethral stricture.

Regular prolonged use of codeine is known to lead to addiction and tolerance.

Patients should be advised to consult their doctor if the medicine is needed for longer periods in higher doses than recommended, and if stopping the medicine makes them feel unwell but they feel better when they start taking it again.

The effects of CNS depressants (including alcohol) may be potentiated by codeine. Chronic heavy alcohol abusers may be at increased risk of liver toxicity from excessive paracetamol use, although reports of this event are rare. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease. Advise patient to avoid alcohol during treatment with this medication.

Caution is advised if prescribing for patients with a history of drug dependence.

For three days use only. Patients to consult their doctor if symptoms persist.

May cause drowsiness, and so patients should be advised not to drive or operate machinery if affected. Alcohol should be avoided as this will worsen the effects of drowsiness.

Frequent and prolonged use of opioid and non-opioid analgesics for migraine is associated with analgesic induced headache.

Note that this product contains 500mg paracetamol per tablet and the maximum total adult daily dose for paracetamol of 4g should not be exceeded if additional paracetamol containing analgesics are used.

Other paracetamol and codeine products have the following precautions:

A reduced dose is recommended, due to increased sensitivity to side effects in elderly or debilitated patients, in hypothyroidism, and in adrenocortical insufficiency.

Caution should be used in patients with phaeochromocytoma as opioids may stimulate catecholamine release by inducing the release of endogenous histamine.

Patients should seek urgent medical advice in the event of an overdose, even if they feel well. Serious delayed liver damage is possible in adults who have taken 10g or more of paracetamol. Patients on long term treatment with drugs which induce liver enzymes, such as St. John's Wort, are at risk of liver damage from paracetamol doses of 5 grams or more.

Opioids may interfere with the results of plasma amylase, lipase, bilirubin, ALP, LDH, AST and ALT results. The effects of codeine on the gut may interfere with diagnostic tests of gastro intestinal functions.

The use of codeine is not recommended in children under 18 years of age as it has been associated with rare but serious adverse reactions. Younger children may be more susceptible and codeine should not be used in children under 12 years of age.

Codeine should not be used in children under 18 years who are undergoing the removal of tonsils due to an increased risk of severe breathing difficulties.

Pregnancy and Lactation

Pregnancy

There are no contraindications to use in pregnancy, however, best practice indicates caution is advised in pregnancy.

Buclizine
Animal experiments have shown foetal abnormalities and maternal deaths following the administration of buclizine, however, these were at doses 120 times the human daily dose.

Paracetamol
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol. Paracetamol is commonly used during all stages of pregnancy. There does not appear to be a risk to the embryo or foetus from the maternal use of therapeutic doses. Paracetamol crosses the placenta easily and does not inhibit prostaglandin synthesis.

Codeine
There is inadequate evidence of the safety of codeine in human pregnancy. Various reports have described associations between 1st trimester exposure to codeine and congenital defects. However, there is no clear evidence that opiates cause structural anomalies. Schaefer 2007, states that codeine may be used for analgesia if paracetamol alone is not sufficiently effective. Potential for dependency must also be kept in mind when prolonged treatment is required. Long term use during pregnancy may cause withdrawal syndromes in neonates and use during labour may cause neonatal respiratory depression.

Paracetamol and codeine have been used for many years without apparent ill consequences and animal studies have not shown any hazard.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

There is no contraindication to use whilst breastfeeding. However, caution should be used as codeine and its active metabolite, morphine, are secreted into breast milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount is low. Potentially dangerous levels of serum morphine may occur in the breastfed infants of rapid codeine metabolisers.

Paracetamol
The amount of paracetamol excreted in human milk is much less than the doses usually given to infants and adverse effects in infants are rarely observed. Paracetamol as a single agent is the analgesic and antipyretic of choice during breastfeeding.

Codeine
Can cause infant drowsiness and a physician must be contacted immediately if any of the following symptoms are observed in the infant, such as more than usual sleepiness, limpness, difficulty feeding or breathing. The amount of codeine (and morphine) in the breast milk can vary widely depending on the metabolism through CYP2D6 by the mother. Ultra rapid metabolisers of CY2D6 may produce larger amounts of the active metabolite morphine and put the infant, and particularly neonates, at increased risk from adverse effects. There is a report of an infant fatality due to exposure from breast milk from an ultra fast metabolising mother. Therefore long-term consumption of codeine-containing products should be avoided during breastfeeding. Regular use of any opioid beyond 1-2 days should be under close medical supervision.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Presentation

Initial treatment (pink) tablets containing
Paracetamol 500mg
Codeine Phosphate 8mg
Buclizine Hydrochloride 6.25mg

and

Continuation treatment (yellow) tablets containing
Paracetamol 500mg
Codeine Phosphate 8mg

Drugs List

MIGRALEVE COMPLETE MIGRAINE RELIEF tablets

Therapeutic Indications

Uses

Treatment of migraine attacks which can include the symptoms of migraine headache, nausea and vomiting.

The MHRA advises that these products should only be used for the short term treatment of acute, moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone.

Dosage

Adults

Initial: At onset of migraine, 2 initial treatment tablets containing paracetamol, codeine and buclizine (pink tablets). Maximum dose 2 initial treatment tablets (pink tablets) in 24 hours.

Maximum treatment duration 3 days.

Children

Children aged 16 to 18 years:
See Dosage; Adult.

Children aged 12 to 16 years:
Initial: At onset of migraine, 1 initial treatment tablet containing paracetamol, codeine and buclizine (pink tablets). Maximum dose 1 initial treatment tablets (pink tablets) in 24 hours.

Maintenance: For further migraine relief, 1 continuation treatment tablet containing paracetamol and codeine (yellow tablets) starting at least 4 hours after initial treatment (pink tablets) and repeated every 4 hours if required. Maximum dose 3 continuation treatment tablets (yellow tablets) in 24 hours.

Note that this product contains 500mg paracetamol per tablet. The maximum total daily dose for paracetamol should not be exceeded if additional paracetamol containing analgesics are used.

Patients with Renal Impairment

Use with caution in this population.
Codeine: Moderate to severe renal impairment: Reduce dose or avoid; opioid analgesics may have increased and prolonged effect and may increase cerebral sensitivity and increased risk of constipation.

Patients with Hepatic Impairment

Codeine: Avoid or reduce dose: Opioid analgesics may precipitate coma.
Paracetamol dose related hepatic toxicity when used in large amounts.

Additional Dosage Information

Tolerance to codeine can develop with continued use.

Administration

Oral administration

Contraindications

Not licensed for children under 10 years

Other paracetamol and codeine products have the following contraindications:

Respiratory depression

Predisposition to paralytic ileus

Raised intracranial pressure

Head injury

Obstructive airways disease

Acute alcoholism

Acute asthma

Diarrhoea caused by poisoning until the toxic material has been eliminated, or diarrhoea associated with pseudomembranous colitis.

Within 14 days of monoamine oxidase inhibitor therapy