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 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.

- Patients 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 should be used at the lowest dose in the shortest time.

Use in pregnancy and lactation

- Cozeter should not be used during pregnancy and breastfeeding.

- 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.

Effects on ability to drive and use machines

Patients should be advised not to drive, operate machinery if affected drowsiness.

Interactions

- The CNS depressant effects of codeine may be enhanced by alcohol, barbiturate hypnotics, and tricyclic antidepressants.

- Risk of respiratory failure may be reported by concurrent use with morphine.

- Avoid use in combination with atropine containing preparations, which may lead to decreased excretion and dryness of the respiratory tract.

Dosage & administration

- Adults: 2 capsules 3 times daily.

- Children aged 12 years to 18 years: 1 capsule 3 times daily.

For treatment of cough symptoms, Cozeter is not recommended in children with respiratory dysfunction (See Special warnings and precautions for use).

Children less than 12 years of age: Cozeter should not be used in children below the age of 12 years to treat cough symptoms (see Contraindications).

Cozeter is for oral administration.

Cozeter should be taken with a lot of water.

Undesirable effects

Cozeter is generally well tolerated. Constipation, drowsiness, dizziness, nausea, vomiting, bronchospasm, rash, respiratory depression may occur, but in rare cases.

Overdose

Symptoms of codeine overdose: respiratory impairment (lower respiratory rate, respiratory Cheyne - Stokes, cyanosis), somnolence leading to glassy state or coma, tender muscle, cold and clammy skin, slow pulse and hypotension. Severe cases: apnea, pulse collapse, cardiac arrest, death.

Management: Respiratory restoration must be done by providing oxygen and giving respiratory aid under control. In severe cases, naloxone should be indicated immediately via intravenous injection.

Inform your doctor about any side effects that may occur during the treatment.

Shelf-life: 36 months from the manufacturing date.

Storage: Store in cool dry places, below 30^oC, protect from direct light.