Codeine

Concomitant administration of codeine with MAOIs is not recommended. 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.

Concomitant use of opioids and benzodiazepines or other CNS depressants, including alcohol, may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of codeine with CNS depressant medicines, such as other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally active anti-emetics and other CNS depressants, should be reserved for patients for whom other treatment options are not possible. If a decision is made to prescribe codeine concomitantly with any of the medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible. Patients should be followed closely for signs and symptoms of respiratory depression and sedation. Patients and their caregivers should be made aware of these symptoms. Patients and their caregivers should also be informed of the potential harms of consuming alcohol while taking codeine.

Codeine phosphate should be used in caution in renal impairment.

Enhanced sedative effect.

Opioid antagonists e.g. buprenorphine, naltrexone, naloxone – may precipitate withdrawal symptoms.

Antidiarrhoeal drugs (e.g. loperamide, kaolin) - increased risk of severe constipation.

Enhanced hypotensive effect.

Enhanced sedative and hypotensive effect.

Antipsychotics, including phenothiazines – enhanced sedative and hypotensive effect.

Enhanced sedative effect, increased risk of respiratory depression.

Risk of severe constipation which may lead to paralytic ileus and/or urinary retention.

Cimetidine inhibits the metabolism of opioid analgesics causing increased plasma concentration of codeine.

Avoid premedication with opioids as they reduce plasma ciprofloxacin concentration.

Antagonistic effect on GI activity.

Delayed absorption of mexiletine.

Quinidine reduces the analgesic effect of codeine.

Ritonavir may increase plasma levels of opioid analgesics.

Terbinafine may reduce the activity of codeine by inhibiting the production of its active metabolite.

Opioids may cause biliary obstructions. Avoid in biliary disorders.

Codeine should be used in caution in drug abuse or dependence (including alcoholism).

Codeine should be used in caution in prostatic hypertrophy.

Opioids may stimulate catecholamine release by inducing the release of endogenous histamine.

Codeine should be used in caution in impaired respiratory function (avoid in chronic obstructive pulmonary disease) and asthma (avoid during an acute attack).

Codeine should be used in caution in adrenocortical insufficiency, e.g. Addison’s Disease.

Use with caution after recent GI surgery as codeine may alter GI mobility.

Following recent surgery patient will be more prone to urinary retention caused directly by spasm of the urethral sphincter, and via constipation caused by codeine.

Codeine should be used in caution in hypothyroidism.

Codeine should be used in caution in hypotension and shock.

Convulsions – may be induced or exacerbated.

Codeine should be used in caution in myasthenia gravis.

There is inadequate evidence of the safety of codeine in human pregnancy and administration of the drug during pregnancy should be considered only if the potential benefit justifies the potential risk to the foetus.

Opioid analgesics cross the placenta and newborn infants should be observed closely for signs of respiratory depression if the mother has received codeine during labour. Use of codeine during pregnancy may lead to withdrawal symptoms in neonates. Should such signs/symptoms be noted in mother or baby, the mother should immediately stop taking all codeine-containing medicines and seek medical advice.

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.

Codeine should not be used during breastfeeding.

At normal therapeutic doses codeine 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 metabolites 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.

Codeine may cause sedation and dizziness and patients should be advised not to drive or to operate machinery if affected.

Undesirable effects are especially likely to occur at treatment onset or at dose increase.

The undesirable effects are listed below by organ class and the following frequency convention:

Not known – cannot be estimated from the available data.

^* 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. Symptoms of restlessness and irritability may result when treatment is then stopped.

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