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CODEINE PHOSPHATE TABLETS 60MG BP

Active substance: CODEINE PHOSPHATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Codeine Phosphate Tablets BP 60mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 60 mg of codeine phosphate.
Excipient:
Each tablet contains 76.92 mg of lactose.
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Tablet.
White circular normal biconvex tablets, embossed with R117.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Codeine is indicated in adults as an analgesic, an anti-tussive, and for the
symptomatic treatment of chronic diarrhoea.
Codeine is indicated in patients older than 12 years for the treatment of acute
moderate pain which is not considered to be relieved by other analgesics such
as paracetamol or ibuprofen alone.

4.2

Posology and method of administration
For oral administration.
As an analgesic:
Adults and children over 12 years: 30-60mg every four hours, when necessary
to a maximum 240mg daily.
Elderly: Dosage should be reduced in the elderly where there is impairment of
hepatic or renal function.
Children under 12 years: Not recommended.

As an anti-tussive:
Adults and children over 12 years: 15-30mg three or four times daily.
Elderly: Dosage should be reduced in the elderly where there is impairment of
hepatic or renal function.
Children under 12 years: Not recommended.
For the symptomatic treatment of chronic diarrhoea.:
Adults and children over 12 years: 15-60mg every four to six hours.
Elderly: Dosage should be reduced in the elderly where there is impairment of
hepatic or renal function.
Children under 12 years: Not recommended.
In general dosage should be reduced in elderly patients.
Codeine should be used at the lowest effective dose for the shortest period of
time. This dose may be taken up to 4 times a day at intervals of not less than 6
hours. Maximum daily dose of codeine should not exceed 240mg.
The duration of treatment should be limited to 3 days and if no effective pain
relief is achieved the patients/carers should be advised to seek the views of a
physician.
Paediatric population
Children aged 12 years to 18 years:
The recommended codeine dose for children 12 years and older should be 3060mg every 6 hours when necessary up to a maximum dose of codeine of
240mg daily. The dose is based on the body weight (0.5-1mg/kg).
Children aged less than 12 years:
Codeine should not be used in children below the age of 12 years because of
the risk of opioid toxicity due to the variable and unpredictable metabolism of
codeine to morphine (see sections 4.3 and 4.4).
4.3

Contraindications
Patients with:
• Known hypersensitivity to codeine phosphate, other opioid analgesics or any
other of the excipients in the tablets.
• Acute respiratory depression
• Obstructive airways disease e.g. emphysema;
• Asthma – Opioids should not be administered during an asthma attack,
hepatic failure;
• Head injuries or conditions where intracranial pressure is raised;
• Acute alcoholism;
• Diarrhoea associated with either pseudomembranous colitis or poisoning;



Risk of paralytic ileus.

This product is also contraindicated:




4.4

In all paediatric patients (0-18 years of age) who undergo tonsillectomy and/or
adenoidectomy for obstructive sleep apnoea syndrome due to an increased risk of
developing serious and life-threatening adverse reactions (see section 4.4).
In women during breastfeeding (see section 4.6)
In patients for whom it is known they are CYP2D6 ultra-rapid metabolisers.

Special warnings and precautions for use
CYP2D6 metabolism
Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active
metabolite. If a patient has a deficiency or is completely lacking this enzyme
an adequate analgesic effect will not be obtained. Estimates indicate that up
to 7% of the Caucasian population may have this deficiency. However, if the
patient is an extensive ultra-rapid metaboliser there is an increased risk of
developing side effects of opioid toxicity even at commonly prescribed doses.
These patients convert codeine into morphine rapidly resulting in higher than
expected serum morphine levels.
General symptoms of opioid toxicity include confusion, somnolence, shallow
breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In
severe cases this may include symptoms of circulatory and respiratory
depression, which may be life-threatening and very rarely fatal. Estimates of
prevalence of ultra-rapid metabolisers in different populations are
summarized below:
Population
African/Ethiopian
African American
Asian
Caucasian
Greek
Hungarian
Northern European

Prevalence %
29%
3.4% to 6.5%
1.2% to 2%
3.6% to 6.5%
6.0%
1.9%
1% to 2%

Post-operative use in children
There have been reports in the published literature that codeine given postoperatively in children after tonsillectomy and/or adenoidectomy for
obstructive sleep apnoea, led to rare, but life-threatening adverse events
including death (see also section 4.3). All children received doses of codeine
that were within the appropriate dose range; however there was evidence that
these children were either ultra-rapid or extensive metabolisers in their ability
to metabolise codeine to morphine.

Children with compromised respiratory function
Codeine is not recommended for use in children in whom respiratory function
might be compromised including neuromuscular disorders, severe cardiac or
respiratory conditions, upper respiratory or lung infections, multiple trauma or
extensive surgical procedures. These factors may worsen symptoms of
morphine toxicity.
Codeine phosphate should be used with caution in the following conditions:
• Codeine Phosphate Tablets contain lactose. Patients with rare
hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption should not take this
medicinal product.
• Convulsions – they may be induced or exacerbated
• Drug abuse or dependence (including alcoholism). Prolonged use of
high doses has produced drug dependence of the Morphine type.
Codeine should be used with caution in patients with a history of drug
dependence
• There is a possible risk of CNS excitation or depression with
concomitant use of opioids with MAOIs and use is not recommended
(see section 4.5).
• Myasthenia gravis
• Phaeochromocytoma – opiods may stimulate catecholamine release by
inducing the release of endogenous histamine
• Adrenocortical insufficiency e.g. Addison’s Disease
• Hypothyroidism
• Hypotension and shock; , history of cardiac arrhythmias.
• Reduced respiratory function or history of asthma
• Inflammatory bowel disease – codeine reduces peristalsis, increases
tone and segmentation in the bowel and can raise colonic pressure,
therefore should be used with caution in diverticulitis, acute colitis,
diarrhoea associated with pseudomembranous colitis or after bowel
surgery.
• Gastro-intestinal surgery – use with caution after recent GI surgery as
opioids may alter GI motility.
• Gall bladder disease or gall stones – opioids may cause biliary
contraction. Avoid in biliary disorders.
• Hepatic impairment – avoid if severe. Codeine may precipitate coma
• Renal impairment
• Urinary tract surgery – following recent surgery patients will be more
prone to urinary retention caused directly by spasm of the urethral
sphincter, and via constipation caused by codeine
• Prostatic hypertrophy
• Pregnancy and breast feeding (see section 4.6)
• Elderly patients may metabolise and eliminate opioid analgesics more
slowly than younger patients (see section 4.2)
• The risk-benefit of continued use should be assessed regularly by the
prescriber.

The leaflet will state in a prominent position in the “before taking” section:




Do not take for longer than directed by your prescriber.
Taking codeine regularly for a long time can lead to addiction, which
might cause you to feel restless and irritable when you stop the tablets.
Taking a painkiller for headaches too often or for too long can make
them worse.

The leaflet will also state in the “Pregnancy and breast-feeding” subsection of
“Before taking your medicine”:
Usually it is safe to take Codeine Phosphate Tablets BP 15mg, 30mg & 60mg
while breast feeding as the level of the active ingredients of this medicine in
breast milk are too low to cause your baby any problems. However, some
women who are at increased risk of developing side effects at any dose may
have higher levels in their breast milk. If any of the following side effects
develop in you or your baby stop taking this medicine and seek immediate
medical advice; feeling sick, vomiting, constipation, decreased or lack of
appetite, feeling tired or sleeping for longer than normal, and shallow or slow
breathing.
The label will state (To be displayed prominently on outer pack – not boxed):
Do not take for longer than directed by your prescriber as taking codeine
regularly for a long time can lead to addiction.
4.5

Interaction with other medicinal products and other forms of interaction
Concomitant combinations not recommended (see section 4.4):
MAOIs (e.g. linezolid, moclobemide, selegiline) due to the possible risk of excitation
or depression – avoid concomitant use and for 2 weeks after discontinuation of
MAOI.
Combinations to be used with caution:
Respiratory related
• Alcohol – enhanced sedative and hypotensive effect, increased risk of
respiratory depression
• Sedative antihistamines – enhanced sedative and hypotensive effect and
increased risk of respiratory depression
• Hypnotics and anxiolytics – enhanced sedative effect, increased risk of
respiratory depression
Gastrointestinal related
• Anticholinergics (e.g. atropine) – risk of severe constipation which may lead
to paralytic ileus and/or urinary retention
• Metoclopramide and domperidone – antagonise effect on GI activity
• Antidiarrhoeal drugs (e.g. loperamide, kaolin) – increased risk of severe
constipation.
CNS related








Anaesthetics – enhanced sedative and hypotensive effect
Tricyclic antidepressants – enhanced sedative effect
Antipsychotics – enhanced sedative and hypotensive effect
Opioid antagonists e.g. buprenorphine, naltrexone, naloxone – may
precipitate withdrawal symptoms
Quinidine – reduced analgesic effect
Antihypertenstive drugs – enhanced hypotensive effect

PHARMACOKINETIC INTERACTIONS
• Ciprofloxacin – avoid premedication with opioids as they reduce plasma
ciprofloxacin concentration.
• Ritonavir may increase plasma levels of opioid analgesics such as codeine
• Mexiletine – delayed absorption of mexiletine
• Cimetidine inhibits the metabolism of opioid analgesics causing increased
plasma concentration of codeine
Forms codeine-phenobarbital complex with phenobarbital sodium and crystals of
codeine periodide with potassium iodide.
Codeine also interferes with some laboratory tests e.g. plasma amylase, lipase,
bilirubin.

4.6

Fertility, pregnancy and lactation
Pregnancy
Not recommended during pregnancy due to neonatal withdrawal symptoms
and impaired effect of foetus. Regular use during pregnancy may cause
physical dependence in the foetus, leading to withdrawal symptoms in the
neonate. During labour opioids enter the foetal circulation and may cause
respiratory depression in the neonates. Respiratory malformation in neonates
may be associated with exposure to codeine during pregnancy. Gastric stasis
and a risk of inhalation pneumonia could occur in the mother during labour.
Administration should be avoided during the late stages of labour and during
the delivery of a premature infant.
Breast-feeding
Codeine should not be used during breastfeeding (see section 4.3)
At normal therapeutic doses codeine and its active metabolite may be present
in breast milk at very low doses and is unlikely to adversely affect the breast
fed infant.
However, if the patient is an ultra-rapid metaboliser of CYP2D6, higher levels
of the active metabolite, morphine, may be present in breast milk and on very
rare occasions may result in symptoms of opioid toxicity in the infant, which
may be fatal.
If symptoms of opioid toxicity develop in either the mother or the infant, then
all codeine containing medicines should be stopped and alternative non-opioid
analgesics prescribed. In severe cases consideration should be given to
prescribing naloxone to reverse these effects.

4.7

Effects on ability to drive and use machines
Codeine may impair the mental and/or physical abilities required for the performance
of potentially hazardous tasks such as driving a car or operating machinery. Effects
such as confusion, drowsiness, dizziness, hallucinations, blurred or double vision or
convulsions may occur. The effects of alcohol are enhanced with this combination.
Driving and operating machinery is not recommended if affected.

4.8

Undesirable effects
Immune system disorders: (may be caused by histamine release) – including rash,
urticaria, pruritus, difficulty breathing, increased sweating, redness or flushed face.

Nervous system disorders: confusion, drowsiness, malaise, tiredness, vertigo,
dizziness, changes in mood, hallucinations, CNS excitation (restlessness/excitement),
convulsions, mental depression, headache or nightmare, raised intracranial pressure,
tolerance or dependence, dysphoria, hypothermia.
Eye disorders: - miosis, blurred or double vision.
Cardiac disorders: bradycardia, palpitations, hypotension, orthostatic hypotension,
tachycardia.
Respiratory, thoracic and mediastinal disorders: respiratory depression with larger
doses.
Gastrointestinal disorders: constipation (too constipating for long-term use), biliary
spasm, nausea, vomiting, dry mouth.
Muscoskeletal, connective tissue and bone density: muscle rigidity.
Renal and urinary disorders: ureteral spasm, antidiuretic effect, urinary retention.
Reproductive system and breast disorders: decrease in libido and potency
Withdrawal effects: abrupt withdrawal precipitates a withdrawal syndrome.
Symptoms may include tremor, insomnia, restlessness, irritability, anxiety,
depression, anorexia, nausea, vomiting, diarrhoea, sweating, lacrimation, rhinorrhoea,
sneezing, yawning, piloerection, mydriasis, weakness, pyrexia, muscle cramps,
dehydration, and increase in heart rate, respiratory rate and blood pressure.
NOTE – tolerance diminishes rapidly after withdrawal so a previously tolerated dose
may prove fatal.
• Regular prolonged use of codeine is known to lead to addiction and tolerance.
Symptoms of restlessness and irritability may result when treatment is then
stopped.
• Prolonged use of a painkiller for headaches can make them worse.

4.9

Overdose
The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and
psychotropic drugs.
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.
Management
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 350mg or a child more than
5mg/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 4 hours after ingestion, or 8 hours if a
sustained release preparation has been taken.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Opium alkaloids and derivatives, codeine
ATC code: R05DA04
The action of codeine is largely that of Morphine from which it is derived i.e.
it is a CNS suppressant.
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.

5.2.

Pharmacokinetic Properties
Codeine is metabolised in the liver and is excreted in the urine, largely in
inactive forms. A small fraction (approximately 10%) of administered Codeine
is demethylated to form Morphine; traces of free morphine can be found in the
urine after therapeutic doses of codeine.

5.3.

Preclinical Safety Data
Animal work suggested that the analgesic activity of Codeine was not affected
by Acetylation.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

6.2.

Lactose
Starch
Magnesium Stearate
Sodium Starch Glycolate
Incompatibilities
None stated.

6.3.

Shelf Life
36 months: Polypropylene tamper-evident containers.
24 months: Blister strips.

6.4

Special precautions for storage
Store below 25°C.

6.5

Nature and contents of container
Polypropylene tamper-evident containers: 1000, 500, 100, 90, 80, 70, 60, 50,
40, 30, 20 and 10 tablets
Blister strips: 100, 90, 80, 70, 60, 50, 40, 30, 20 and 10 tablets.
Not all pack types or sizes may be marketed.

6.6.
7.

Special precautions for disposal
No special requirements.
MARKETING AUTHORISATION HOLDER
Ranbaxy Ireland Ltd..
Spafield, Cork Road,
Cashel, Co. Tipperary,
Ireland.

8

MARKETING AUTHORISATION NUMBER(S)
PL 06809/0080

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
13th February 1990

10

DATE OF REVISION OF THE TEXT
29/11/2013

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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