CODEINE LINCTUS B.P - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Codeine Linctus BP

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5 ml of Codeine Linctus BP contains 15 mg of Codeine Phosphate BP.

For the full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Clear orange syrup, with an orange odour and taste

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Recommended as an anti-tussive for a non productive cough by oral administration.

4.2 Posology and method of administration

The usual dosage for adults is 5 to 10 ml, 3 to 4 times daily. Dosage should be reduced in elderly or debilitated patients.

Paediatric population:

Children aged less than 12 years:

Codeine is contraindicated in children below the age of 12 years (see sections 4.3).

Children aged 12 years to 18 years:

Codeine is not recommended for use in children aged 12 years to 18 years with compromised respiratory function (see section 4.4).

4.3 Contraindications

Hypersensitivity to-the active substance or to any of the excipients listed in section 6.1

Liver disease: drug may accumulate.

Ventilatory failure condition may be exacerbated.

In children below the age of 12 years due to an increased risk of developing serious and life threatening adverse reactions.

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 use4.1 Special warnings and precautions for use

Geriatric patients should be supervised while on this medication, and consideration of reduced dosage should be based on response. Codeine should only be used with caution in patients with kidney or liver impairment. Care should be taken in patients with asthma, hypothyroidism, and in patients with a history of drug abuse. Tolerance and dependency may occur with prolonged 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 therapeutic 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:

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

4.5 Interaction with other medicinal products and other forms of interaction

CNS depressants, anticholinergics, hydroxyzine and methadone – concurrent use of these medicines may result in potentiation of effects and hypotensive effects and CNS depressant effects may be increased; levallorphan is a morphine antagonist; the respiratory effects of neuromuscular blocking agents may be addictive to the central respiratory effects of the opioid analgesics; metoclopramide and codeine have opposing effects on gastro – intestinal activity; codeine causes delayed absorption of mexiletine; the effects of hypnotics and sedatives may be potentiated by codeine; hypertensive crisis may be caused by concurrent use of codeine and monoamine – oxidase inhibitors.

4.6 Fertility, pregnancy and lactationPregnancy

Risk – benefit must be considered before using codeine during pregnancy. Codeine crosses the placenta and is excreted in small amounts in breast milk. Regular use during pregnancy may cause physical dependency in the foetus, depression of neonatal respiration, withdrawal effects in the neonate. Teratogenic effects in humans have not been documented but controlled studies have not been done. There is a risk of gastric stasis in the mother during labour which may lead to inhalation pneumonia.

Breastfeeding

Codeine is contraindicated in women 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 cause drowsiness. Patients receiving this medication should not drive or operate machinery unless it has been shown not to affect mental or physical ability.

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 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

Gastrointestinal side effects, constipation is not uncommon; loss of appetite; flushing of face might occasionally occur; respiratory depression may be experienced; sputum retention may occur particularly in patients with chronic bronchitis and bronchiectasis.

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

In cases of overdosage supportive therapy is recommended. Gastric lavage should be carried out and a saline purgative may then be given to reduce absorption from the gastro – intestinal tract. Symptomatic treatment of respiratory embarrassment should be given. If respiration is seriously depressed intravenous naloxone HCl may be required.

5.1 Pharmacodynamic properties

Morphine derivative. Antitussive – suppresses the cough reflex by a direct central action, probably in the medulla or pons.

Codeine is a centrally acting weak analgesic. Codeine exerts it’s effect through |i 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

Protein binding is very low.

Half life from 2.5 to 4 hours.

Duration of action approximately 4 hours.

Onset of action after oral administration is 30 to 45 minutes.

Excretion is primarily renal with 5 to 15% of the drug excreted unchanged.

5.3 Preclinical safety data

Not applicable

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium Benzoate (E211)

Citric Acid Monohydrate

Saccharin Sodium (E954)

Sunset Yellow (E110)

Sorbitol Solution 70% (E420)

Purified Water (to volume)

Orange Flavour

Carboxymethyl­cellulose 7H3SFX

Propylene Glycol

6.2 Incompatibilities

None known

6.3 Shelf life

High density polyethylene Bottles:           3 years

Amber glass Bottles:                       3 years

6.4 Special precautions for storage

Do not store above 25°C

Store in the original container

6.5 Nature and contents of container

Pharmaceutical Grade III Amber Glass Bottles with CRC caps:

100ml, 125ml and 200ml

High Density Polyethylene Bottles:

2000ml and 1000ml

6.6 Special precautions for disposal

As for all medicines – no special warnings

7 MARKETING AUTHORISATION HOLDER

Pinewood Laboratories Ltd

Ballymacarbry

Clonmel

Co. Tipperary Ireland

8 MARKETING AUTHORISATION NUMBER(S)

PL 04917/0001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

30/08/1988 / 20/11/2003