New Zealand - English - Medsafe (Medicines Safety Authority)
New Zealand Data Sheet
1 PRODUCT NAME CODALGIN TABLETS
Paracetamol 500 mg, Codeine Phosphate 8 mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Codalgin tablets contain the following Active ingredients –
Paracetamol 500 mg, codeine phosphate hemihydrate 8 mg.
It also contains the following Inactives - gelatin, magnesium stearate, microcrystalline
cellulose, purified talc, wheat starch
3 PHARMACEUTICAL FORM
Tablet - 12.7mm round, flat bevelled edge, white, with a break-bar on one side
4 CLINICAL PARTICULARS
4.1 Therapeutic Indications
For the temporary relief of pain and discomfort associated with migraine,
earache, period pain and rheumatic pain. Reduces fever.
4.2 Dose and method of administration
Adults and children over 12 years:
One to two tablets to be taken every
four to six hours as necessary. The maximum dosage of tablets in 24 hours is
Children 7 - 12 years: Half to one tablet to be taken every four to six hours
as necessary. The maximum dosage of tablets in 24 hours is 4 doses.
Codalgin should not be given to children under 7 years of age.
Paracetamol should not be used in patients with active alcoholism as
intolerance to the drug.
Codeine should not be used in cases of acute respiratory depression
pulmonary disease) since codeine may exacerbate the condition.
Codalgin should not be used in patients with a past history of allergic
reactions to codeine.
Hypersensitivity to any of the tablet excipients.
Due to codeine’s structural similarity to morphine and oxycodone,
patients experiencing systemic allergy (generalised rash, shortness of
breath) to these drugs should not receive codeine.
Codeine is contraindicated in patients with diarrhoea caused by
poisoning, until the toxic substance has been eliminated from the
pseudomembranous colitis caused by antibiotic administration since
codeine may slow the elimination of the toxic material or antibiotic.
4.4 Special warnings and precautions for use
Warnings and Precautions
Profound sedation, respiratory depression, coma, and death may result from
the concomitant use of CODALGIN with benzodiazepines or other CNS
depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics,
tranquilizers, muscle relaxants, general anaesthetics, medicines with
antihistamine-sedating actions such as antipsychotics, other opioids, alcohol).
Because of these risks, reserve concomitant prescribing of these drugs for
use in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid
analgesics and benzodiazepines increases the risk of medicine-related
mortality compared to use of opioid analgesics alone. Because of similar
pharmacological properties, it is reasonable to expect similar risk with the
concomitant use of other CNS depressant drugs with opioid analgesics [see
Section 4.5 Interactions with other medicines and other forms of interaction].
If the decision is made to prescribe a benzodiazepine or other CNS
depressant concomitantly with an opioid analgesic, prescribe the lowest
effective dosages and minimum durations of concomitant use. In patients
already receiving an opioid analgesic, prescribe a lower initial dose of the
benzodiazepine or other CNS depressant than indicated in the absence of an
opioid, and titrate based on clinical response. If an opioid analgesic is initiated
in a patient already taking a benzodiazepine or other CNS depressant,
prescribe a lower initial dose of the opioid analgesic, and titrate based on
clinical response. Follow patients closely for signs and symptoms of
respiratory depression and sedation.
Advise both patients and caregivers about the risks of respiratory depression
and sedation when
CODALGIN is used with benzodiazepines or other CNS depressants
(including alcohol and illicit drugs). Advise patients not to drive or
operate heavy machinery until the effects of concomitant use of the
benzodiazepine or other CNS depressant have been determined. Screen
patients for risk of substance use disorders, including opioid abuse and
misuse, and warn them of the risk for overdose and death associated
with the use of additional CNS depressants including alcohol and illicit
drugs [see Section 4.5 Interactions with other medicines and other
forms of interaction].
Codalgin should be given with care to patients with impaired renal or hepatic
function, viral hepatitis, and to patients taking other drugs which affect the
liver. In view of the increased risk of hepatotoxicity, the benefit should be
weighed against the risk when administering Codalgin to patients with viral
hepatitis or pre existing hepatic disease. In such patients, hepatic function
determinations may be required at periodic intervals during high dose or long-
Codeine should be used with caution in patients with a history of drug abuse
or with recent gastrointestinal tract surgery.
Codalgin may cause drowsiness. Those affected should not drive or operate
administration of codeine. Tolerance may also result following repeated
Codeine should be administered with great caution in patients with head
injury, brain tumour or increased intracranial pressure since codeine may
increase the risk of respiratory depression and further elevate intracranial
pressure. In addition codeine can produce side effects such as confusion,
miosis and vomiting which are important signs in following the clinical course
of patients with head injuries.
Codeine should be administered with great caution in patients with decreased
respiratory reserve (e.g. in emphysema, kyphoscoliosis, hypoxia, hypercapnia
or even severe obesity) or cor pulmonale, or chronic obstructive pulmonary
disease since codeine may exacerbate respiratory impairment.
Codeine should be administered with great caution if at all in patients with
CNS depression, since codeine may exacerbate the condition.
Codeine should be used with caution in elderly or debilitated patients because
of the danger of respiratory or cardiac depression.
Codeine should be administered with caution in patients with acute abdominal
conditions since codeine may obscure the diagnosis or the course of the
inflammatory bowel disease (risk of toxic megacolon may be increased,
especially with repeated dosing).
Codeine should be administered with caution in patients with hypothyroidism,
adrenocortical insufficiency (eg Addison’s disease), shock, myxedema, acute
alcohol intoxication or delerium tremens since codeine may exacerbate the
symptoms or increase the risk of respiratory and/or CNS depression.
Codeine should be administered with caution in patients taking Monoamine
Oxidase Inhibitors (MAOI’s) – see Interactions with Other Drugs.
Codeine should be administered with caution in patients with a history of
hypertrophy, urethral stricture or recent urinary tract surgery since codeine
may cause urinary retention.
Use in Children:
Codalgin can be given in reduced doses to children 7 years and over (see
Dosage and Administration). This medication is not suitable for children under
7 years of age.
Use in the Elderly:
The elderly are more likely to have age-related renal impairment and may be
reduction may be required.
4.5 Interaction with other medicines and other forms of
Benzodiazepines and other Central Nervous System (CNS) Depressants
Due to additive pharmacologic effect, the concomitant use
of benzodiazepines or other CNS depressants including
alcohol, increases the risk of respiratory depression,
profound sedation, coma, and death.
Reserve concomitant prescribing of these drugs for use in
patients for whom alternative treatment options are
inadequate. Limit dosages and durations to the minimum
required. Follow patients closely for signs of respiratory
depression and sedation [see Section 4.4 Warnings and
Benzodiazepines and other sedatives/hypnotics,
anxiolytics, tranquilizers, muscle relaxants, general
anaesthetics, drugs with antihistamine-sedating actions
such as antipsychotics, other opioids, alcohol.
Salicylates and NSAIDs:
Prolonged concurrent use of paracetamol and salicylates or non-steroidal
anti-inflammatory drugs may increase the risk of adverse renal effects.
Diflunisal may increase the plasma concentrations of paracetamol by 50%.
Codeine may potentiate the effects of general anaesthetics.
Tranquillisers, sedatives and hypnotics:
Codeine may potentiate the effects of these drugs.
Codeine may potentiate the effects of CNS depressants.
Codeine may potentiate the effects of alcohol and the likelihood of toxicity
may be increased by its concomitant use. The likelihood of toxicity may also
be increased by the concomitant use of alcohol with paracetamol.
Concurrent use of codeine and other opioid agonists is usually inappropriate
as additive CNS depression, respiratory depressant and hypotensive effects
may occur. Opioid agonists that decrease gastric emptying will decrease the
absorption of paracetamol.
Concomitant use of codeine and anticholinergic agents may increase the risk
of severe constipation and/or urinary retention. Anticholinergics that decrease
the gastric emptying such as propantheline, will decrease the absorption of
Monoamine Oxidase Inhibitors:
Non-selective MAOI’s intensify the effects of opioid drugs which can cause
sometimes fatal reactions have occurred in patients concurrently administered
MAO inhibitors and pethidine. Codeine should not be given to patients taking
non-selective MAOI’s or within 14 days of stopping such treatment. As it is
(Reversible Inhibitors of Monoamine Oxidase A) and codeine, caution is
decreased by MAO inhibitors that decrease gastric emptying.
Barbiturates and antiepileptic medications:
The likelihood of toxicity may be increased by the concomitant use of enzyme
inducing agents such as alcohol, barbiturates or anti epileptic drugs.
Repeated high doses of paracetamol increase the anti coagulant response to
Paracetamol may also increase chloramphenicol concentrations.
Hypotensive effects of antihypertensive agents may be potentiated when used
concurrently with codeine and lead to orthostatic hypotension.
Antiperistaltic antidiarrhoeals (including kaolin, pectin, loperamide):
Concurrent use of these agents with codeine may increase the risk of severe
effects of metoclopramide on gastrointestinal motility.
Neuromuscular blocking agents:
Codeine may enhance the effects of neuromuscular blocking agents resulting
in increased respiratory depression.
Cholestyramine reduces the absorption of paracetamol if given within one
hour of paracetamol administration.
Effects on Laboratory Tests
Plasma amylase and lipase activity:
Codeine may cause increased biliary tract pressure, thus increasing plasma
amylase and/or lipase concentrations.
Gastric emptying studies:
Gastric emptying is delayed by codeine, so gastric emptying studies will not
4.6 Fertility, pregnancy and laction
Carcinogenicity, Mutagenicity, Impairment of Fertility:
Clinical toxicity studies in animals have shown that high doses of paracetamol
cause testicular atrophy and inhibition of spermatogenesis; the relevance of
this finding to use in humans is not known.
Use in Pregnancy: Category A
Paracetamol crosses the placenta, however problems in humans have not
Opioid analgesics cross the placenta. Regular use during pregnancy may
cause physical dependence in the foetus, leading to withdrawal symptoms in
the neonate. Administration of codeine during labour may cause respiratory
depression in the newborn infant.
Use in Lactation:
metabolites were detected in the urine of nursing infants after 650 mg
Codeine does pass into breast milk so it should be avoided in breastfeeding
Codalgin tablets should not be administered while breast-feeding.
4.7 Effects on ability to drive and use machines
Codalgin may cause drowsiness. Those affected should not drive or operate
4.8 Undesirable effects
Adverse effects of Codalgin tablets are generally infrequent and include:
Less frequent to rare
Less frequent to rare
Urinary retention or hesitancy
Less frequent to rare
Skin rashes and other allergic reactions
Histamine release (hypotension, flushing of the face,
Less frequent to rare
Overdosage with Codalgin tablets involves treatment of both paracetamol and
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
proceed to encephalopathy, coma and death. Acute renal failure with acute
tubular necrosis may develop in the absence of severe liver damage. Cardiac
arrhythmias have been reported. Liver damage is likely in adults who have
taken 10 g or more of paracetamol, due to excess quantities of a toxic
metabolite becoming irreversibly bound to liver tissue.
Symptoms of codeine overdosage include vomiting, hypotension, sweating,
central stimulation with exhilaration and convulsions in children, drowsiness,
respiratory depression, cyanosis, miosis and coma.
Contact the Poisons Information Centre on 0800 764 766 immediately.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Paracetamol has analgesic and antipyretic activity similar to aspirin. The
prostaglandin synthesis in the central nervous system and in the periphery,
and, to a lesser extent, by blocking pain impulse generation in the periphery.
The antipyretic effect is due to a central action on the hypothalamic heat-
regulating centre to produce peripheral vasodilatation and subsequent heat
Codeine phosphate is an opioid analgesic that binds with stereospecific
receptors at many sites within the CNS to alter processes affecting both the
perceptions of pain and the emotional response to pain. There are multiple
sub-types of opioid receptors, each mediating various therapeutic and/or side
effects of drugs. Its analgesic effect is thought to be due to its partial
analgesic activity of morphine. Codeine can also cause other effects eg CNS
depression, nausea and vomiting, orthostatic hypotension and constipation.
It has been shown that the analgesic effects of paracetamol and codeine are
additive due to their different mechanisms of action.
5.2 Pharmacokinetic properties
Paracetamol is readily absorbed from the gastrointestinal tract with peak
plasma concentrations occurring some 30 minutes to 2 hours after ingestion.
The onset of therapeutic action is 30 minutes and the duration of effect is 4
Codeine is well absorbed from the gastrointestinal tract and peak plasma
concentrations are reached one hour after oral administration. Onset of action
occurs in 15-30 minutes and analgesia is maintained for 4-6 hours.
Paracetamol is rapidly and uniformly distributed into most body tissues. It
crosses the placenta and is present in breast milk.
gastrointestinal tract, lungs, spleen and brain. It crosses the placenta and is
distributed in low levels in breast milk.
Approximately 90-95% of the paracetamol dose is metabolised in the liver,
primarily by conjugation with glucuronic acid, sulphuric acid and cysteine. An
intermediate metabolite which may accumulate in overdosage is hepatotoxic
and possibly nephrotoxic.
Codeine is metabolised mainly in the liver. The major metabolic pathway
involves glucuronidation of codeine to codeine-6-glucuronide. Codeine can
also undergo O- and N-demethylation catalysed by CYP2D6 and CYP3A4
respectively. About 10% of an administered dose of codeine is converted by
O-demethylation to morphine which subsequently undergoes glucuronidation
to morphine-3 or morphine-6 glucuronide, or N-demethylation to normorphine.
Approximately 5-10% of the Caucasian population cannot convert codeine to
morphine as they are deficient in the CYP2D6 enzyme. Codeine is also
converted by N-demethylation to norcodeine which subsequently undergoes
Approximately 85% of a dose of paracetamol is recovered from the urine
consisting mainly of the glucuronide and sulfate conjugates. The elimination
half-life varies from 1 to 4 hours and may be prolonged in acute overdosage,
in liver disease, the elderly and the neonate.
Codeine is excreted mainly by the kidneys as its metabolite codeine-6-
excreted as unchanged or conjugated morphine. The plasma half-life of
codeine is 2-4 hours. Only traces of codeine and its metabolites are found in
5.3 Preclinical safety data
Codalgin contains the following excipients - gelatin, magnesium stearate,
microcrystalline cellulose, purified talc, wheat starch.
6.3 Shelf life
Store below 30°C in a dry place.
6.4 Special precautions for storage
Store away from heat and moisture
6.5 Nature and contents of container
Available in blister packs of 50 and 100 tablets
6.6 Special precautions for disposal
7 MEDICINE SCHEDULE
Pharmacy Retailing (NZ) Limited Trading as Healthcare Logistics
58 Richard Pearce Drive
Auckland, New Zealand
Ph (09) 918 5100 Fax (09) 901 5101
9 DATE OF FIRST APPROVAL
10 DATE OF REVISION OF THE TEXT
22 June 2017
SUMMARY TABLE OF CHANGES
Reformatted old data sheet (2014) into new style format.
Added in new Warnings/precautions text as per MEDSAFE letter of 12
Added in new interactions text as per MEDSAFE letter of 12 April 2017
concerning - Benzodiazepines and other Central Nervous System