CODEINE PHOSPHATE 60 MG TABLETS - summary of medicine characteristics

Codeine Phosphate 60mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Codeine Phosphate 60mg

Oral – tablet

4.1 Therapeutic indications

Codeine is indicated in patients older than 12 years of age for the treatment of acute moderate pain which is not considered to be relieved by other analgesics such as paracetamol or ibuprofen (alone).

Dry or painful cough

Diarrhoea

4.2 Posology and method of administration

Prior to starting treatment with opioids, a discussion should be held with patients to put in place a strategy for ending treatment with codeine phosphate in order to minimise the risk of addiction and drug withdrawal syndrome (see section 4.4.).

Oral route

For Mild to Moderate Pain

Adults:

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 240 mg.

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.

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 240 mg daily. The dose is based on the body weight (0.5–1mg/kg).

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).

Dosage should be reduced in elderly patients.

15–30mg, 3–4 times daily

Not recommended

Dosage should be reduced in elderly patients

30mg three to four times daily (range 15–60mg)

Not recommended

Elderly:

Dosage should be reduced in elderly patients

4.3 Contraindications

Acute respiratory depression, hypersensitivity to codeine or other opioid analgesics or to any of the excipients, obstructive airways disease, liver disease, severe hepatic dysfunction, acute alcoholism.

Use should be avoided in patients with raised intracranial pressure or head injury (in addition to the risk of respiratory depression and increased intracranial pressure, may affect pupillary and other responses vital for neurological assessment).

Codeine should not be given to comatose patients.

Codeine is also contraindicated in conditions where inhibition of peristalsis is to be avoided, where there is a risk of paralytic ileus, where abdominal distension develops, or in acute diarrhoeal conditions such as acute ulcerative colitis or antibiotic associated colitis (e.g. pseudomembranous colitis) or diarrhoea caused by poisoning.

Codeine is also contraindicated in the following:

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 lifethreatening 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

4.4 Special warnings and precautions for use

4.5 Interaction with other medicinal products and other forms of interaction

Alcohol: the hypotensive, sedative and respiratory depressive effects of alcohol may be enhanced.

Anaesthetics: concomitant administration of codeine and anaesthetics may cause increased CNS depression and/or respiratory depression and/or hypotension.

Anti-arrhythmics: codeine delays the absorption of mexiletine. The analgesic activity of codeine is likely to be significantly impaired by quinidine which impairs codeine metabolism.

Antidepressants: The depressant effects of opioid analgesics may be enhanced by tricyclic antidepressants.

MAOIs taken with pethidine have been associated with severe CNS excitation or depression (including hypertension or hypotension). Although this has not been documented with codeine, it is possible that a similar interaction may occur and therefore the use of codeine should be avoided while the patient is taking MAOIs and for 2 weeks after MAOI discontinuation.

Antihistamines: concomitant administration of codeine and antihistamines with sedative properties may cause increased CNS depression and/or respiratory depression and/or hypotension.

Antipsychotics: enhanced sedative and hypotensive effect.

Anxiolytics and hypnotics: enhanced sedative effect.

Domperidone and metoclopramide: codeine antagonises the effect of cisapride, metoclopramide and domperidone on gastrointestinal activity.

Ulcer-healing drugs: Cimetidine may inhibit the metabolism of codeine resulting in increased plasma concentrations.

Sodium oxybate: concomitant administration of codeine and sodium oxybate may cause increased CNS depression and/or respiratory depression and/or hypotension.

Opioids may interfere with gastric emptying studies as they delay gastric emptying and with hepatobiliary imaging using technetium Tc 99m disofenin as opioid treatment may cause constriction of the sphincter of Oddi and increase biliary tract pressure.

4.6 Fertility, pregnancy and lactation

As with all medications caution should be exercised during pregnancy, especially in the first trimester. A possible association with respiratory and cardiac malformations has been reported following first trimester exposure to codeine.

Regular use during pregnancy may cause drug dependence in the foetus, leading to withdrawal symptom in the neonate.

If opioid use is required for a prolonged period in a pregnancy woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Administration during labour may depress respiration in the neonate and an antidote for the child should be readily available.

Opioid analgesics may cause gastric stasis during labour, increasing the risk of inhalation pneumonia in the mother.

Breast feeding

Administration to nursing women is not recommended as codeine phosphate be secreted in breast milk and may cause respiratory depression in the infant.

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 produces sedation and may also cause changes in vision, including blurred or double vision. If affected, patients should not drive or operate machinery. The effects of alcohol are enhanced by opioid analgesics.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road of Traffic Act 1988. When prescribing this medicine, patients should be told:

The medicine is likely to affect your ability to drive

Do not drive until you know how the medicine affects you

It is an offence to drive while under the influence of this medicine.

However, you would not be committing an offence (called ‘statutory defence’) if:

o The medicine has been prescribed to treat a medical or dental problem and

o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and o It was not affecting your ability to drive safely

4.8 Undesirable effects

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.

Tolerance and some of the most common side effects – drowsiness, nausea, and vomiting, and confusion – generally develops with long term use.

Immune system disorders: maculopapular rash has been seen as part of a hypersensitivity syndrome associated with oral codeine phosphate; fever, splenomegaly and lymphadenopathy also occurred.

Endocrine disorders: hyperglycaemia.

Metabolism and nutrition disorders: anorexia.

Psychiatric disorders: mental depression, hallucinations and nightmares, restlessness, confusion, mood changes, euphoria and dysphoria.

Frequency unknown: Drug dependence (see section 4.4)

General disorders and administration site conditions:

Uncommon: drug withdrawal syndrome

Nervous system disorders: convulsions (especially in infants and children), dizziness, drowsiness, headache (prolonged use of a painkiller for headaches can make them worse). Raised intracranial pressure may occur in some patients.

Eye disorders: blurred or double vision or other changes in vision. Miosis.

Ear and labyrinth disorders: vertigo

Cardiac disorders: tachycardia, palpitations and bradycardia.

Vascular disorders: postural hypotension, facial flushing. Large doses produce hypotension.

Respiratory, thoracic and mediastinal disorders: Dyspnoea. Large doses produce respiratory depression.

Gastrointestinal disorders: nausea, vomiting, constipation, dry mouth, stomach cramps, pancreatitis.

Hepatobiliary disorders: Biliary spasm (may be associated with altered liver enzyme values).

Skin and subcutaneous tissue disorders: allergic reactions such as skin rashes, urticaria, pruritus, sweating and facial oedema.

Musculoskeletal and connective tissue disorders: Uncontrolled muscle movements. Muscle rigidity may occur after high doses.

Renal and urinary disorders: difficulty with micturation, urinary retention, ureteric spasm, dysuria._An antidiuretic effect may also occur with codeine.

Reproductive system and breast disorders: sexual dysfunction, erectile dysfunction, decreased potency. Decreased libido.

General disorders and administration site conditions: malaise, tiredness, hypothermia.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

4.9 Overdose

Patients should be informed of the signs and symptoms of overdose to ensure that family and friends are also aware of these signs and to seek immediate medical help if they occur.

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 coingested, including alcohol, or the overdose is very large. The triad of coma, pinpoint pupils and respiratory depression is considered indicative of opioid overdosage with dilation of the pupils occurring as hypoxia develops. Nausea and vomiting are common Other opioid overdose symptoms include hypothermia, confusion, convulsions, severe dizziness, severe drowsiness, hypotension and tachycardia (possible but unlikely), nervousness or restlessness, excitement, hallucinations, bradycardia, circulatory failure, slow or troubled breathing, severe weakness, convulsions, especially in infants and children. Rhabdomyolysis, progressing to renal failure, has been reported in overdosage with opioids.

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. In acute overdosage with respiratory depression or coma, the specific opioid antagonist naloxone is indicated using one of the recommended dose regimens- repeated doses may be required in a seriously poisoned patient as naloxone is a competitive antagonist with a short half life. Patients should be observed closely for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Codeine has similar uses to morphine but is much less potent as an analgesic and has only mild sedative effects.

Codeine is a centrally acting weak analgesic. Codeine exerts its effect through p 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 well absorbed from the gastrointestinal tract following oral administration. It is metabolised in the liver to morphine and norcodeine which are both excreted in the urine partly as conjugates with glucuronic acid. Most of the excretion products appear in the urine within 6 hours and up to 86% 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. The plasma half life is between approximately 3 and 4 hours.

5.3 Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to those included in other sections

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose

Acacia spray dried

Maize starch

Magnesium stearate Stearic Acid

6.2 Incompatibilities

None.

6.3 Shelf life

36 months for polypropylene/po­lyethylene containers.

24 months for blister packaging.

6.4 Special precautions for storage

Do not store above 25°C.

Store in the original container.

6.5 Nature and contents of container

100 and 500 tablets in polypropylene/po­lyethylene containers.

28, 30, 56, 60, 84 and 90 tablets in polypropylene/po­lyethylene containers in cartons.

28, 30, 56, 60, 84, 90 and 100 tablets in blister pack strips of 20 micron, hard tempered aluminium foil, coated with PVC compatible heat seal lacquer on the reverse side, and PVC film, in cartons.

6.6 Special precautions for disposal

Not applicable.

Kensington Pharma Ltd., Unit A Newlands House, 60 Chain House Lane, Whitestake Preston, Lancashire, United Kingdom, PR4 4LG

8 MARKETING AUTHORISATION NUMBER(S)

PL 44853/0084

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION