Promethazine + Codeine

Oral
Cough, Upper respiratory tract symptoms associated with allergy, Upper respiratory tract symptoms associated with common cold

Cachectic or debilitated patients: Reduce initial dose.

Reduce initial dose.

Reduce initial dose.

Lower respiratory tract symptoms (e.g. asthma, comatose states), acute febrile illness associated with productive cough or in chronic respiratory disease where interference with the ability to clear the tracheobronchial tree of secretions may have a deleterious effect to patient. Children <12 years, children <18 years who have undergone adenoidectomy or tonsillectomy. Concomitant use with benzodiazepines and other CNS depressants.

Patient with severe respiratory disease (e.g. COPD, sleep apnoea), benign prostatic hyperplasia, urinary retention, acute abdominal conditions, decreased gastrointestinal motility, pyloroduodenal obstruction, inflammatory bowel disease, xerostomia, bone marrow suppression, adrenal insufficiency, myasthenia gravis, Parkinson’s disease, toxic psychosis, biliary tract dysfunction, acute pancreatitis, delirium tremens, fever, visual problems (e.g. narrow-angle glaucoma), head injury, intracranial lesions, elevated intracranial pressure, hypovolaemia, thyroid dysfunction, CV disease (e.g. unstable angina, MI or history of MI), circulatory shock, risk factors or history of seizures, recent gastrointestinal or urinary tract surgery, history of drug abuse or acute alcoholism. Strenuous exercise, heat exposure, dehydration. Hepatic and renal impairment. Cachectic or debilitated patients. Children and elderly. Pregnancy and lactation.

Significant: Constipation, urinary retention, xerostomia, blurred vision, CNS depression, convulsions, pseudoparkinsonism, acute dystonic reactions, akathisia, tardive dyskinesia, severe hypotension, orthostatic hypotension, syncope, agranulocytosis, leucopenia, cholestatic jaundice, photosensitivity, impaired core body temperature regulation.
Cardiac disorders: Tachycardia, bradycardia, faintness, palpitation.
Ear and labyrinth disorders: Tinnitus.
Eye disorders: Diplopia.
Gastrointestinal disorders: Nausea, vomiting, biliary tract spasm, laryngeal oedema, dry mouth.
General disorders and administration site conditions: Fatigue.
Immune system disorders: Angioedema.
Nervous system disorders: Dizziness, drowsiness, headache, lightheadedness, sedation, extrapyramidal symptoms (e.g. torticollis, oculogyric crisis, tongue protrusion).
Psychiatric disorders: Confusion, disorientation, dysphoria, euphoria, insomnia, disorientation, excitation, hallucination, hysteria.
Renal and urinary disorders: Oliguria, urinary retention.
Respiratory, thoracic and mediastinal disorders: Asthma, nasal stuffiness.
Skin and subcutaneous tissue disorders: Pruritus, urticaria, sweating, dermatitis.
Vascular disorders: Increased or decreased blood pressure, facial flushing.
Potentially Fatal: Respiratory depression, apnoea, neuroleptic malignant syndrome, arrhythmias.

PO: C

This drug may cause CNS depression (e.g. drowsiness), if affected, do not drive or operate machinery. Avoid prolonged exposure to sunlight.

Monitor blood pressure, heart rate, respiratory and mental status; signs of misuse, abuse, and addiction.

Promethazine: May reverse the vasopressor effect of epinephrine. Increased incidence of extrapyramidal effects with MAOIs.
Potentially Fatal: Concomitant use of codeine with benzodiazepines and other CNS depressants may lead to profound sedation, respiratory depression and coma.

Alcohol may cause profound sedation, respiratory depression and coma.

Promethazine: May cause false-positive pregnancy test results. May interfere with glucose tolerance test.
Codeine: May interfere with results in the determination of amylase or lipase levels.

Description:
Mechanism of Action: Promethazine is a phenothiazine derivative that blocks postsynaptic mesolimbic dopaminergic receptors in the brain. It exhibits a strong α-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones and competes with histamine for the H₁-receptor. In addition, it also reduces stimuli to the brainstem reticular system and exhibits antiemetic effect.
Codeine, a narcotic analgesic, binds to opioid receptors in the CNS, causing inhibition of ascending pain pathways thereby altering perception and response to pain. It also causes cough suppression through its direct central action in the medulla.
Onset: Promethazine: Within 20 minutes.
Codeine: Cough suppression: 15 minutes.
Duration: Promethazine: 4-6 hours, may last up to 12 hours.
Codeine: ≤3 hours.
Pharmacokinetics:
Absorption: Promethazine: Well absorbed from the gastrointestinal tract. Time to peak plasma concentration: 2-3 hours.
Codeine: Well absorbed. Time to peak plasma concentration: Approx 1 hour.
Distribution: Promethazine: Crosses the blood-brain barrier and placenta and enters breast milk. Plasma protein binding: 76-93%.
Codeine: Crosses the placenta and enters breast milk.
Metabolism: Promethazine: Metabolised in the liver to a variety of compound including promethazine sulfoxide and N-demethylpromethazine.
Codeine: Metabolised mainly in the liver via O- and N-demethylation to morphine, norcodeine, and other metabolites including normorphine and hydrocodone, and partial conjugation with glucuronic acid.
Excretion: Promethazine: Via urine, as metabolites. Elimination half-life: 5-14 hours.
Codeine: Via urine (primarily as inactive metabolites; conjugated morphine in small amount). Plasma elimination half-life: 3-4 hours.

Source: National Center for Biotechnology Information. PubChem Database. Promethazine, CID=4927, https://pubchem.ncbi.nlm.nih.gov/compound/Promethazine (accessed on Jan. 21, 2020)

Source: National Center for Biotechnology Information. PubChem Database. Codeine, CID=5284371, https://pubchem.ncbi.nlm.nih.gov/compound/Codeine (accessed on Jan. 23, 2020)

Store between 20-25°C. Protect from light.

Other Drugs Acting on the Respiratory System

R06AD52 - promethazine, combinations ; Belongs to the class of phenothiazine derivatives used as systemic antihistamines.

Anon. Promethazine and Codeine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/06/2018.

Buckingham R (ed). Codeine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/06/2018.

Buckingham R (ed). Promethazine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/06/2018.

Promethazine Hydrochloride and Codeine Phosphate Syrup (Amneal Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/06/2018.