Data Sheet
Codeine phosphate tablets
Codeine phosphate as 15mg, 30mg and 60mg tablets.
Presentation
Codeine phosphate 15mg, 30mg and 60mg tablets are white, circular, film-coated tablets embossed with 'DP' on one side and '15', '30' and '60' respectively on the other.
Uses
Actions
Codeine phosphate is an opioid analgesic with uses similar to those of morphine, but is much less potent as an analgesic and has only mild sedative effects. Its primary site of action is at the mu opioid receptors distributed throughout the central nervous system.
Codeine phosphate reduces intestinal motility through both a local and possibly central mechanism of action. Codeine phosphate also suppresses the cough reflex by a direct central action, probably in the medulla or pons.
Codeine and its salts are absorbed from the gastro-intestinal tract and onset of analgesic action occurs 30 to 45 minutes after administration, when given orally.
Peak effect is reached within 1 to 2 hours and the duration of analgesic and antitussive action are 4 hours and 4 to 6 hours respectively.
Pharmacokinetics
Codeine is readily absorbed from the gastro-intestinal tract and metabolised by O- and N-demethylation in the liver to morphine and norcodeine which with codeine are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid.
Most of the excretion products appear in the urine within 6 hours and 40 to 60 per cent of the codeine is excreted free or conjugated, approximately 5 to 15 per cent as free and conjugated morphine and about 10 to 20 per cent as free and conjugated norcodeine.
Indications
Codeine phosphate is indicated for:
- the relief of mild to moderate pain (including pain associated with terminal illness, post-operative pain and headache),
- the relief of symptoms of diarrhoea (except diarrhoea caused by poisoning),
- as an antitussive in the control of non-productive cough.
Codeine is particularly valuable for pain associated with coughing.
Dosage and administration
Adults: Codeine phosphate may be given orally in doses of 15mg-60mg up to 6 times a day for the relief of pain. If these doses fail to relieve pain, larger doses rarely succeed and may give rise to restlessness and excitement. The maximum recommended daily dose is 300mg.
For non-productive cough the usual dose is 10mg-20mg every 4-6 hours to a maximum total of 120mg in 24 hours.
Paediatric: The usual paediatric dose for analgesia in infants and children is 0.5mg per kg of body weight or 15mg per square meter of body surface, every 4 to 6 hours as needed.
For cough children may be given up to 0.25mg per kg every 4 - 6 hours.
On the basis of available data, codeine and other opioid cough suppressants should rarely be administered to children less than 6 to 12 months old. They should not be given in productive cough. When indicated for the treatment of non-productive cough, which interferes with sleep or school attendance, codeine may be recommended in the form of single-ingredient preparations.
Contraindications
Codeine phosphate is generally contraindicated in respiratory depression especially in the presence of cyanosis and excessive bronchial secretion. It is also contraindicated in the presence of acute alcoholism, head injuries and conditions in which intracranial pressure is raised. It should not be given during an attack of bronchial asthma or in heart failure secondary to chronic lung disease. Codeine should also not be used when diarrhoea associated with pseudomembranous colitis or diarrhoea caused by poisoning exist.
Administration of codeine is contraindicated in patients taking monoamine oxidase inhibitors or within fourteen days of stopping such treatment.
Warnings and precautions
Codeine should be given with caution or in reduced doses to patients with hypothyroidism, adrenocortical insufficiency, impaired kidney or liver function, prostatic hypertrophy, or shock. It should be used with caution in patients with obstructive bowel disorders. Opioid analgesics should be used with caution in patients with myasthenia gravis.
Prolonged use of high doses of codeine has produced dependence of the morphine type in a very small proportion of users. Codeine produces less euphoria and sedation than morphine and is not a completely satisfactory substitute for morphine in morphine addicts.
Withdrawal symptoms develop more slowly than with morphine and are milder.
The administration of opioid analgesics during labour may cause respiratory depression in the newborn infant.
Use in Pregnancy:
Risk-benefit must be considered because opioid analgesics cross the placenta. Regular use during pregnancy may cause physical dependence in the foetus, leading to withdrawal symptoms (convulsions, irritability, excessive crying, tremors, hyperactive reflexes, fever, vomiting, diarrhoea, sneezing and yawning) in the neonate.
Although teratogenic effects in humans have not been done, studies in animals have not shown codeine to cause adverse effects on foetal development. Studies in animals have shown codeine (single dose of 100mg per kg) to cause delayed ossification in mice and (in doses of 120mg per kg) increased resorption in rats.
Use in Lactation: Codeine is excreted into breast milk. However with usual analgesic doses, concentrations are generally low.
However, infants of nursing mothers taking codeine may have an increased risk of morphine overdose if the mother is an ultra-rapid metaboliser of codeine. When codeine enters the body and is metabolised, it changes to morphine. Nursing mothers taking codeine, who are ultra-rapid metabolisers of codeine, may have higher morphine levels in their breast milk. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies.
When prescribing codeine for a nursing mother, the lowest dose for the shortest amount of time to relieve pain should be prescribed. Nursing patients should be told how to recognize signs of high morphine levels in themselves and their babies.
Signs of high morphine levels in a mother are extreme sleepiness and trouble caring for the baby.
Breastfed babies usually nurse every two to three hours and should not sleep more than four hours at a time. If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, the mother should immediately seek medical advice.
Use in Children: (see under Dosage and Administration) Children up to 2 years of age may be more susceptible to the effects, especially the respiratory depressant effects of opioid analgesics. Paradoxical excitation is especially likely to occur in paediatric patients receiving these drugs.
Use in the Elderly: Geriatric patients may be more susceptible to the effects, especially the respiratory depressant effects, of these medications. Also geriatric patients are more likely to have prostatic hypertrophy or obstruction and age-related renal function impairment, and are therefore more likely to be adversely affected by opioid-induced urinary retention. The risk of constipation and faecal impaction is also greater in the elderly.
Geriatric patients may metabolise or eliminate opioid analgesics more slowly than younger adults. Lower doses or longer dosing intervals than those usually recommended for adults may be required, and are usually therapeutically effective for these patients.
Adverse effects
In normal doses the commonest side effects of codeine and other opioid analgesics are nausea, vomiting, constipation (especially during chronic therapy), drowsiness and confusion. Micturition may become difficult and there may be ureteric or biliary spasm; there is also an antidiuretic effect. Dry mouth, sweating, facial flushing, vertigo, bradycardia, palpitations, orthostatic hypotension, hypothermia, restlessness, changes of mood, and miosis also occur. These effects occur more commonly in ambient patients than in those at rest in bed. Raised intracranial pressure occurs in some patients.
Codeine has a lower dependence liability than other opioid agonists because of its comparatively lower potency with usual doses.
Withdrawal symptoms are also less severe than those produced by stronger opioid agonist analgesics.
Interactions
As serious and sometimes fatal reactions have occurred following administration of pethidine to patients receiving monoamine oxidase inhibitors, codeine and other opioid analgesics should be given with extreme caution. The depressant effects of codeine are enhanced by depressants of the central nervous system such as alcohol, anaesthetics, hypnotics and sedatives, tricyclic antidepressants, and phenothiazines. The actions of opioids may in turn affect the activities of other compounds. For instance, their gastro-intestinal effects may delay absorption as with mexilitine or may be counteractive as with metoclopramide.
Overdosage
Symptoms: Poisoning with codeine produces central stimulation and exhilaration and, in children, convulsions, followed by vomiting, drowsiness, respiratory depression and cyanosis, and coma. Death may occur from respiratory failure.
Toxic doses vary considerably with the individual and regular users may tolerate larger doses.
Treatment: The stomach should be emptied by aspiration or lavage. A laxative may be given to aid peristalsis. Intensive supportive therapy may be required to correct respiratory failure and shocks. In addition, the specific antagonist naloxone hydrochoride is used to counteract very rapidly the severe respiratory depression and coma produced by excessive doses of opioid analgesics. A dose of 0.4mg to 2mg is given intravenously, intramuscularly or subcutaneously, repeated at intervals of 2 to 3 minutes if necessary, up to 10mg. The effect of naloxone may be of shorter duration than that of the opioid analgesic and additional doses may be required to prevent relapses.
The use of opioid antagonists such as naloxone, nalorphine and levallorphan in persons physically dependant on opioid agonists may induce withdrawal symptoms.
Pharmaceutical precautions
Protect from light and moisture. Store below 30°C Keep out of reach of children.
Medicine classification
Controlled Drug C2.
Package quantities
Codeine 15mg: 100's
Codeine 30mg: 100's
Codeine 60mg: 100's
Further information
Codeine is obtained from opium or made by methylating morphine. It occurs as odourless colourless crystals or white crystalline powder. Codeine phosphate has a molecular formula and weight of C18H21NO3, H3PO4, ½H2O and 406.37 respectively.
Codeine phosphate tablets distributed by Douglas Pharmaceuticals Ltd are not substitutable with any other brands of codeine phosphate tablets.
Other ingredients of the tablets are: Lactose, Maize Cornflour, microcrystalline cellulose, Sodium Starch Glycolate, Magnesium Stearate, Polyvinylpyrrolidinone K30 and Opadry White Y-1-7000B.
Name and address
Douglas Pharmaceuticals Ltd
P.O. Box 45-027
AUCKLAND 0651
Ph: (09) 835-0660
Fax: (09) 835-0665
Date of preparation
28 August 2007