CODEINE PHOSPHATE 15 MG TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Codeine Phosphate 15mg Tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Codeine Phosphate BP 15 mg

3. PHARMACEUTICAL FORM

Tablets

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).

As an anti-tussive.

For the symptomatic treatment of chronic diarrhoea.

4.2. Posology and Method of Administration

Dosage:

The recommended dosage range is 30 to 60 mg.

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.

Children aged 12 years to 18 years:

The recommended codeine dose for children 12 years and older should be 30 to 60 mg 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).

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).

15–30mg three or four times daily.

Not suitable for children.

15–60 mg three to four times daily.

Not suitable for children.

There is no evidence that the dose differs in the elderly.

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.

Method of Administration:

To be taken by mouth.

4.3. Contraindications

Hypersensitivity to codeine or any of the tablet excipients.

Acute respiratory depression and acute alcoholism where there is a risk of paralytic ileus, raised intracranial pressure and head injury.

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 who are known to be CYP2D6 ultra-rapid metabolisers.

4.4. Special Warnings and Precautions for Use

Tolerance and dependence may occur with prolonged use.

Avoid when there is a history of asthma, hepatic or renal impairment, or of drug abuse.

The use of cough suppressants containing codeine or similar opioid analgesics is not generally recommended in children and should be avoided altogether in those under 1 year of age.

Care should be taken if the patient has hypotension, hypothyroidism, adrenocortical insufficiency, prostatic hypertrophy, acute abdominal conditions, recent GI surgery, gallstones, myasthenia gravis, history of cardiac arrhythmias or convulsions.

Patients with rare hereditary problems of glucose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medication.

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 or 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:

Post-operative use in children

There have been reports in the published literature that codeine given post-operatively 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.

The risk-benefit of continued use should be assessed regularly by the prescriber.

4.5 Interaction with Other Medicaments and other Forms of Interaction

With phenobarbital sodium it forms codeine-phenobarbital complex. With potassium iodine it forms crystals of codeine periodide. Delayed absorption of mexiletine therefore reduced anti-arrhythmic effect. Codeine interacts with CNS depressants (e.g. alcohol, anaesthetics, hypnotics, sedatives, tricyclic antidepressants and phenothiazide), other antidiarrhoeal agents, neuromuscular blocking agents, antihypertensives, cimetidine and monoamine oxidase inhibitors (also within two weeks of stopping treatment with MAOI). Codeine also interferes with some laboratory tests e.g. plasma amylase, lipase, bilirubin.

4.6. Pregnancy and Lactation

Use of codeine phosphate is not recommended during pregnancy.

Codeine should not be used during breast-feeding (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 breastfed 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

In combination with alcohol it has deleterious effects on driving.

4.8 Undesirable effects

Nausea and vomiting (particularly in the initial stages), constipation, tolerance, sedation, dizziness and drowsiness may occur: may enhance the effects of alcohol. Other side effects are; difficulty with micturition, ureteric or biliary spasm, dry mouth, sweating, headache and facial flushing, vertigo, bradycardia, tachycardia, palpitations, postural hypotension, hypothermia, hallucinations, dysphoria, mood changes, dependence, miosis, decreased libido or potency, reports of hypersensitivity reactions, including urticaria, rash, pruritus. Bronchospasm and angioedema are very rare. A few cases of acute pancreatitis occurring shortly after ingestion of single doses of codeine containing preparations have been reported. Larger doses produce respiratory depression, hypotension and muscle rigidity.

Regular prolonged use of codeine is known to lead to addiction and tolerance. Symptoms of restlessness and irritability may result when treatment is stopped.

Prolonged use of a painkiller for headaches can make them worse.

4.9 Overdose

The effects in overdose will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Central nervous depression, including respiratory depression, may develop but is unlikely be severe unless other sedative agents, including alcohol, have been co-ingested, 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.

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 350 mg or a child more than 5 mg/kg.

Give naloxone if coma or respiratory depression are 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 four hours after ingestion, or eight hours if a sustained release preparation has been taken.

5.1. Pharmacodynamic Properties

Codeine is a centrally-acting weak analgesic. Codeine exerts its effect through li 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 (~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

There is no preclinical data of relevance to a prescriber which is additional to that already included in other sections of the SmPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose

Maize Starch

Sodium Starch Glycollate

Magnesium Stearate

6.2 Incompatibilities

None known

6.3 Shelf life

36 months

6.4 Special precautions for storage

Store below 25°C.

6.5 Nature and contents of container

The tablets are available in packs of 50, 100 and 500 in securitainers.

The securitainers are made up of High Density Polypropylene with Low Density Polyethylene caps.

6.6 Instructions for use, handling and disposal

None.

7 MARKETING AUTHORISATION HOLDER

Waymade Plc

t/a Sovereign Medical

Sovereign House

Miles Gray Road

Basildon

Essex

SS14 3FR

8. MARKETING AUTHORISATION NUMBER

PL 06464/0187

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

11/11/2005