Paracetamol with codeine and buclizine
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Initial treatment (pink) tablets containing
Codeine Phosphate 8mg
Buclizine Hydrochloride 6.25mg
Continuation treatment (yellow) tablets containing
Codeine Phosphate 8mg
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.
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.
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.
Not licensed for children under 10 years
Other paracetamol and codeine products have the following contraindications:
Predisposition to paralytic ileus
Raised intracranial pressure
Obstructive airways disease
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
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)
Inflammatory bowel disease
Biliary tract disorders
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
There are no contraindications to use in pregnancy, however, best practice indicates caution is advised in pregnancy.
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.
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.
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 ).
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.
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.
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
Effects on Ability to Drive and Operate Machinery
This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them.
Advise patients that their migraine should initially be diagnosed by a doctor.
Advise patients 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.
Advise patients to wait four hours before taking other painkillers.
Advise patients that regular use of codeine for a prolonged period of time can lead to addiction.
Advise patients 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.
Advise patients that dizziness or sedation may occur which may affect their ability to drive or operate machinery. Alcohol may worsen these effects.
Advise patients to consult their doctor if no relief from symptoms after 3 days.
Advise patients that prolonged use of a painkiller for headaches may make them worse.
Advise patients to seek urgent medical advice in the event of an overdose, even if they feel well due to the risk of delayed serious liver damage.
Advise patients not to take alcohol during treatment.
Advise patients not to take St. John's Wort concurrently with this medication.
Analgesic induced headache with frequent or prolonged use.
Regular, prolonged use may lead to codeine addiction with symptoms of restlessness and irritability on stopping treatment.
The following side effects have been reported with other combinations of paracetamol and codeine:
Diminution of potency
Difficulty in micturition
Shortness of breath
Raised intracranial pressure
Toxic epidermal necrolysis
Effects on Laboratory Tests
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.
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
The MHRA have produced 'generic' overdose sections for the top ten drugs for which the NPIS received the greatest number of queries about management of overdose in 2002. This information is represented below:
The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.
Liver damage is possible in patients who have taken 75mg/kg or more of paracetamol in less than an hour, and these patients should be referred to hospital. To avoid underestimating the potentially toxic paracetamol dose ingested by obese patients who weigh more than 110kg, a bodyweight of 110kg (rather than the actual bodyweight) should be used to calculate the total dose of paracetamol ingested in mg/kg.
Signs and Symptoms
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.
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.
This should include 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.
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.
Treatment with activated charcoal should be considered if the overdose in excess of 150mg/kg has been taken within 1 hour. Treatment with acetylcysteine is used up to, and possibly beyond, 24 hours of ingesting paracetamol. It is most effective if given within 8 hours of ingestion, after which effectiveness declines. If required, the patient should be given intravenous acetylcysteine, in line with the established dosage schedule. Giving acetylcysteine by mouth (unlicensed route) is an alternative if intravenous access is not possible. Acetylcysteine can be given irrespective of the plasma paracetamol concentration:
in circumstances where the overdose is staggered or there is doubt over the time of paracetamol ingestion; or
in overdose with a timed plasma paracetamol concentration on or above a single treatment line joining points of 100mg/L at 4 hours and 15mg/L at 15 hours nomogram (https://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con184396.pdf), regardless of risk factors of hepatotoxicity.
Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentration are unreliable). If vomiting is not a problem, and overdose has been taken within 10-12 hours, oral methionine may be a suitable alternative for remote areas outside hospital. Management of patients who present beyond 24 hours from ingestion or with serious hepatic dysfunction should be discussed with the NPIS (https://www.npis.org/) or a liver unit.
Shelf Life and Storage
No special requirements
Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 6 January 2015 New drug driving offence implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 6 January 2015
MHRA Drug Safety Update: Volume 3, Issue 2, September 2009. Over-the-counter painkillers containing codeine or dihydrocodeine.
Last accessed 06/01/2011
MHRA 2nd September 2009. Updated advice on non-prescription medicines containing codeine or dihydrocodeine (DHC).
Last accessed 06/01/2011
MHRA 16th October 2009. Guidance on the development of artwork in relation to medicines containing codeine and dihydrocodeine.
Last accessed 06/01/2011
MHRA 19th September 2005
Last accessed: September 20, 2012
MHRA 10th September 2012
Last accessed: September 20, 2012
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 19 May 2021
Summary of Product Characteristics: Migraleve. McNeil Products Ltd. Revised April 2014.
Already a member? Log in
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.