Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: M & A Pharmachem Ltd, Allenby Laboratories Wigan, Road, Westhoughton, Bolton BL5, 2AL
Paracetamol has analgesic and antipyretic actions.
Codeine phosphate is an analgesic of the opioid class. Opioid analgesics bind with stereospecific receptors at many sites within the CNS to alter processes affecting both the perception of pain and the emotional response to it. It has been hypothesised that alterations in release of various neurotransmitters from afferent nerves sensitive to painful stimuli may be partially responsible for the analgesic effect.
Codeine is a centrally acting weak analgesic. Codeine exerts its effect through μ opioid receptors, although codeine has low affinity for these receptors, and its analgesic effect is due to its conversion to morphine. Codeine, particularly in combination with other analgesics such as paracetamol, has been shown to be effective in acute nociceptive pain.
The drugs are additive and some workers suggest there may be synergy between the constituents.
Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma levels occurring about 30 minutes to 2 hours after ingestion. It is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted unchanged.
The elimination half-life of paracetamol varies from about 1 to 4 hours. Plasma protein binding is negligible at usual therapeutic doses.
Codeine phosphate is absorbed from the gastrointestinal tract and peak plasma concentrations occur after about one hour. Codeine is metabolised by O-and N-demethylation in the liver to morphine, and norcodeine and other metabolites. Codeine and its metabolites are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid. Most of the excretion products appear in the urine within six hours and up to 80% of the dose is excreted in 24 hours. About 70% of the dose is excreted as free codeine, 10% as free and conjugated morphine and a further 10% as free or conjugated norcodeine. Only traces are found in the faeces.
Codeine is not extensively bound to plasma proteins. The plasma half-life varies from about 3 to 4 hours.
Both actives have been in clinical use separately and in combination products for many years. Preclinical data has therefore been superseded by clinical data.
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