Codeine

Chemical formula: C₁₈H₂₁NO₃  Molecular mass: 299.364 g/mol  PubChem compound: 5284371

Interactions

Codeine interacts in the following cases:

Central nervous system depressants

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.

Renal impairment

Codeine phosphate should be used in caution in renal impairment.

Tricyclic antidepressants

Enhanced sedative effect.

Opioid antagonists

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

Antidiarrhoeal drugs

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

Antihypertensive drugs

Enhanced hypotensive effect.

Anaesthetics

Enhanced sedative and hypotensive effect.

Antipsychotics

Antipsychotics, including phenothiazines – enhanced sedative and hypotensive effect.

Hypnotics, anxiolytics

Enhanced sedative effect, increased risk of respiratory depression.

Anticholinergics

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

Cimetidine

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

Ciprofloxacin

Avoid premedication with opioids as they reduce plasma ciprofloxacin concentration.

Metoclopramide, domperidone

Antagonistic effect on GI activity.

Mexiletine

Delayed absorption of mexiletine.

Quinidine

Quinidine reduces the analgesic effect of codeine.

Ritonavir

Ritonavir may increase plasma levels of opioid analgesics.

Terbinafine

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

Gallbladder disease, gall stones

Opioids may cause biliary obstructions. Avoid in biliary disorders.

Drug abuse or dependence

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

Prostatic hypertrophy

Codeine should be used in caution in prostatic hypertrophy.

Phaeochromocytoma

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

Impaired respiratory function, asthma

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

Adrenocortical insufficiency

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

Gastrointestinal surgery

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

Urinary tract surgery

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.

Hypothyroidism

Codeine should be used in caution in hypothyroidism.

Hypotension, shock

Codeine should be used in caution in hypotension and shock.

Convulsive disorders

Convulsions – may be induced or exacerbated.

Myasthenia gravis

Codeine should be used in caution in myasthenia gravis.

Cross-check medications

Review your medication to ensure that there are no potentially harmful drug interactions or contraindications.

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