Promethazine + Codeine


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Temporary relief of cough and upper respiratory tract symptoms Each 5 mL syrup contains promethazine 6.25 mg and codeine 10 mg: 5 mL 4-6 hourly. Max: 30 mL/24 hours.
Dosage Details
Oral
Cough, Upper respiratory tract symptoms associated with allergy, Upper respiratory tract symptoms associated with common cold
Adult: Available preparations:
Promethazine 6.25 mg and codeine 10 mg per 5 mL syrup

For temporary relief: 5 mL 4-6 hourly. Max: 30 mL per 24 hours.
Child: ≥12 years Same as adult dose.
Elderly: Dose reduction may be needed.
Special Patient Group
Cachectic or debilitated patients: Reduce initial dose.
Renal Impairment
Reduce initial dose.
Hepatic Impairment
Reduce initial dose.
Contraindications
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.
Special Precautions
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.
Adverse Reactions
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.
Patient Counseling Information
This drug may cause CNS depression (e.g. drowsiness), if affected, do not drive or operate machinery. Avoid prolonged exposure to sunlight.
MonitoringParameters
Monitor blood pressure, heart rate, respiratory and mental status; signs of misuse, abuse, and addiction.
Drug Interactions
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.
Food Interaction
Alcohol may cause profound sedation, respiratory depression and coma.
Lab Interference
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.
Action
Description: 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.
Chemical Structure

Chemical Structure Image
Promethazine

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


Chemical Structure Image
Codeine

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

Storage
Store between 20-25°C. Protect from light.
ATC Classification
R06AD52 - promethazine, combinations ; Belongs to the class of phenothiazine derivatives used as systemic antihistamines.
References
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.

Disclaimer: This information is independently developed by MIMS based on Promethazine + Codeine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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