Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PROMETH W/ DEXTROMETHORPHAN vs CODOXY
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Promethazine is a phenothiazine derivative that acts as a central H1 receptor antagonist with anticholinergic, antiemetic, and sedative properties. Dextromethorphan is a non-competitive NMDA receptor antagonist and sigma-1 receptor agonist that suppresses cough by acting on the cough center in the medulla oblongata.
Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia. Oxycodone is combined with aspirin to provide additive analgesic effects.
Symptomatic relief of cough associated with upper respiratory tract infections,Allergic rhinitis,Motion sickness,Nausea and vomiting,Sedation
Management of moderate to moderately severe pain where the use of an opioid analgesic is appropriate
Adults: 10 m L (containing promethazine 6.25 mg and dextromethorphan 15 mg) orally every 4-6 hours, not to exceed 4 doses (40 m L) in 24 hours.
1-2 capsules orally every 4-6 hours as needed for pain, not to exceed 8 capsules per day. Each capsule contains 5 mg hydrocodone bitartrate and 325 mg acetaminophen.
Promethazine: terminal elimination half-life 10-14 hours (range 5-30 hours). Clinical context: prolonged half-life in elderly or hepatic impairment; requires dose adjustment in severe liver disease. Dextromethorphan: 3-6 hours for extensive CYP2D6 metabolizers; 24-48 hours in poor metabolizers.
Terminal half-life is 3.5 hours in patients with normal renal function; extends to 5-8 hours in moderate renal impairment.
Promethazine is extensively metabolized in the liver via sulfation (primary) and CYP2D6-mediated N-demethylation. Dextromethorphan is metabolized by CYP2D6 to dextrorphan, an active metabolite.
Oxycodone is metabolized by CYP3A4 and CYP2D6. N-demethylation to noroxycodone (via CYP3A4) is the primary metabolic pathway. CYP2D6-mediated O-demethylation to oxymorphone is a minor pathway but produces a more potent metabolite.
Promethazine is primarily excreted via renal elimination (70-80% as metabolites, <1% unchanged) and fecal/biliary elimination (20-30%). Dextromethorphan is extensively metabolized; renal excretion accounts for ~45% as dextrorphan and other metabolites, with minimal unchanged drug (<1%).
Renal excretion of unchanged drug accounts for approximately 70% of elimination; biliary/fecal excretion accounts for 30%.
Promethazine: 93% bound primarily to albumin. Dextromethorphan: 60-70% bound to albumin and alpha-1-acid glycoprotein.
Approximately 92% bound to albumin.
Promethazine: 7-9 L/kg, indicating extensive tissue distribution. Dextromethorphan: 5-7 L/kg, with high tissue binding. Clinical meaning: large Vd suggests poor dialyzability and prolonged washout.
2.4 L/kg; indicates extensive tissue distribution.
Promethazine: oral 25% (extensive first-pass metabolism), intramuscular 100%, rectal 70-80%. Dextromethorphan: oral 11-60% (dependent on CYP2D6 metabolism), intramuscular not available.
Oral: 60-70% due to first-pass metabolism.
GFR ≥ 30 m L/min: no adjustment. GFR < 30 m L/min: avoid use due to risk of CNS depression and accumulation of metabolites.
For GFR 30-50 m L/min: administer every 8 hours. For GFR 10-29 m L/min: administer every 12 hours. For GFR <10 m L/min: use not recommended.
Child-Pugh A (mild): no adjustment. Child-Pugh B (moderate): reduce dose by 50% or prolong dosing interval. Child-Pugh C (severe): avoid use.
Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% and extend interval to every 8 hours. Child-Pugh Class C: contraindicated.
Children 6-11 years: 5 m L (half the adult dose) every 4-6 hours, max 4 doses/24h. Children 2-5 years: 2.5 m L every 4-6 hours, max 4 doses/24h. Not recommended under 2 years due to risk of respiratory depression.
For children ≥2 years: 0.1-0.2 mg/kg hydrocodone component every 4-6 hours as needed, maximum 6 doses per day. Use weight-based dosing; do not exceed acetaminophen 75 mg/kg/day.
Initiate at lowest effective dose (e.g., 5 m L every 6-8 hours). Monitor for sedation, confusion, and anticholinergic effects. Avoid in elderly with dementia or high fall risk.
Initiate at lowest effective dose (e.g., 1 capsule every 6 hours) due to increased risk of respiratory depression and falls. Titrate cautiously. Maximum 6 capsules per day.
Promethazine should not be used in children younger than 2 years of age due to the risk of respiratory depression that can be fatal. Use with caution in children older than 2 years.
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; and interactions with drugs affecting cytochrome P450 isoenzymes.
Respiratory depression, especially in children and elderly,CNS depression and impaired alertness,Anticholinergic effects (e.g., dry mouth, urinary retention),Extrapyramidal symptoms with high doses,Neuroleptic malignant syndrome (rare),Photo-sensitivity,Seizure threshold lowering,Increased risk of hypotension,Hepatic impairment may require dose adjustment
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; severe hypotension; gastrointestinal obstruction; seizures; serotonin syndrome; adrenal insufficiency; and androgen deficiency.
Hypersensitivity to promethazine, dextromethorphan, or any component,Children younger than 2 years,Comatose states,Use of MAO inhibitors within 14 days,Lower respiratory tract symptoms including asthma,Severe CNS depression,Angle-closure glaucoma (relative),Prostatic hypertrophy (relative),Seizure disorders (caution)
Significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected gastrointestinal obstruction, including paralytic ileus; hypersensitivity to oxycodone, aspirin, or any component of the formulation.
Avoid grapefruit juice as it may increase dextromethorphan levels. No significant food interactions with promethazine.
Avoid alcohol and grapefruit juice. Alcohol potentiates CNS depression. Grapefruit juice may increase codeine metabolism via CYP3A4, leading to variable effects. No significant food restrictions otherwise; take with food if GI upset occurs.
First trimester: Limited human data; animal studies with promethazine show no consistent teratogenicity. Dextromethorphan is not teratogenic in animal studies. Second/third trimester: Use of promethazine near term may cause respiratory depression or extrapyramidal symptoms in neonates. Dextromethorphan has minimal fetal risk. Overall, FDA Pregnancy Category C for promethazine; dextromethorphan is Category A (no evidence of risk).
No human data; animal studies not available. Avoid during pregnancy, especially first trimester, due to potential oxycodone-induced neural tube defects.
Promethazine is excreted into breast milk in small amounts; M/P ratio not well established. Dextromethorphan is excreted in breast milk but levels are low. Use with caution; monitor infant for drowsiness or irritability.
Oxycodone is excreted into breast milk; M/P ratio ~3.6:1. Risk of infant sedation and respiratory depression. Contraindicated during breastfeeding.
No specific dosing adjustments required for pregnancy; however, use lowest effective dose and shortest duration. Consider increased renal clearance of dextromethorphan in pregnancy, but no dose adjustment is established.
No established dose adjustments; increased clearance in pregnancy may require higher doses for analgesia, but use is contraindicated.
Promethazine (a phenothiazine antiemetic/antihistamine) combined with dextromethorphan (an NMDA receptor antagonist/antitussive) is used for cough and cold symptoms. Promethazine can cause respiratory depression, especially in children, and is contraindicated under age 2. Dextromethorphan at high doses can cause dissociative effects; avoid concurrent use with MAOIs or serotonergic drugs. This combination has significant anticholinergic effects (dry mouth, urinary retention, constipation). Use cautiously in patients with asthma, COPD, or sleep apnea due to respiratory depression risk.
CODOXY is a fixed-dose combination of codeine (opioid) and doxylamine (antihistamine). Use lowest effective dose for shortest duration due to opioid dependence and respiratory depression risk. Avoid in children <12 years for post-tonsillectomy pain and in those <18 with respiratory compromise. Monitor for CNS depression, especially with alcohol. Doxylamine adds anticholinergic effects (constipation, dry mouth, urinary retention). Caution in elderly, renal impairment, and breastfeeding.
Do not use in children younger than 2 years due to risk of serious breathing problems.,May cause drowsiness or dizziness; avoid driving or operating heavy machinery until you know how you react.,Avoid alcohol and other CNS depressants (e.g., benzodiazepines, opioids) as they increase sedation and respiratory depression risk.,Do not take with MAO inhibitors or within 14 days of stopping them.,Increase fluid intake to help loosen mucus.,Stop use and seek medical attention if cough persists > 1 week, is accompanied by fever or rash, or if excessive sedation occurs.
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.,This medication may cause drowsiness, dizziness, or blurred vision; avoid driving or operating machinery until you know how it affects you.,Avoid alcohol and other sedatives (e.g., benzodiazepines, sleep aids) as they increase risk of severe drowsiness and breathing problems.,Do not use with other products containing codeine or antihistamines (including cough/cold medicines).,Store securely away from children; misuse can cause addiction, overdose, or death.,If you are pregnant, plan to become pregnant, or are breastfeeding, inform your healthcare provider before use.,Common side effects: constipation, dry mouth, nausea. Increase fluid intake and fiber to prevent constipation.,Seek emergency help if you experience slow or shallow breathing, confusion, or fainting.
"The combination of dextromethorphan, a centrally acting antitussive with NMDA receptor antagonist and sigma-1 receptor agonist properties, and aceprometazine, a phenothiazine neuroleptic with strong antihistaminergic and moderate anticholinergic and antidopaminergic effects, can result in additive central nervous system depression. This interaction may lead to excessive sedation, respiratory depression, impaired psychomotor function, and an increased risk of falls or cognitive impairment, particularly in elderly or debilitated patients. Concurrent use may also lower the seizure threshold, especially in patients with predisposing factors."
"Dextromethorphan, a serotonergic agent metabolized by CYP2D6, when combined with cariprazine, a dopamine D3/D2 receptor partial agonist, may increase the risk of serotonin syndrome due to additive serotonergic effects. Cariprazine can inhibit CYP2D6, reducing dextromethorphan clearance and elevating its plasma concentration, leading to enhanced serotonin activity. Clinically, patients may present with altered mental status, autonomic instability, and neuromuscular abnormalities."
"Dextromethorphan inhibits CYP2B6 and CYP2C9, which are involved in valproic acid metabolism. This results in decreased valproic acid clearance, potentially elevating valproic acid serum concentrations and increasing the risk of dose-dependent adverse effects such as hepatotoxicity, thrombocytopenia, and sedation. Concurrent use requires dose adjustment and close monitoring for signs of valproate toxicity."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about PROMETH W/ DEXTROMETHORPHAN vs CODOXY, answered by our medical review team.
PROMETH W/ DEXTROMETHORPHAN is a Antihistamine-antitussive combination that works by Promethazine is a phenothiazine derivative that acts as a central H1 receptor antagonist with anticholinergic, antiemetic, and sedative properties. Dextromethorphan is a non-competitive NMDA receptor antagonist and sigma-1 receptor agonist that suppresses cough by acting on the cough center in the medulla oblongata.. CODOXY is a Antitussive Combination that works by Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia. Oxycodone is combined with aspirin to provide additive analgesic effects.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between PROMETH W/ DEXTROMETHORPHAN and CODOXY depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of PROMETH W/ DEXTROMETHORPHAN is: Adults: 10 m L (containing promethazine 6.25 mg and dextromethorphan 15 mg) orally every 4-6 hours, not to exceed 4 doses (40 m L) in 24 hours.. The standard adult dose of CODOXY is: 1-2 capsules orally every 4-6 hours as needed for pain, not to exceed 8 capsules per day. Each capsule contains 5 mg hydrocodone bitartrate and 325 mg acetaminophen.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between PROMETH W/ DEXTROMETHORPHAN and CODOXY in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. PROMETH W/ DEXTROMETHORPHAN is classified as Category C. First trimester: Limited human data; animal studies with promethazine show no consistent teratogenicity. Dextromethorphan is not teratogenic in animal studies. Second/third trimest. CODOXY is classified as Category C. No human data; animal studies not available. Avoid during pregnancy, especially first trimester, due to potential oxycodone-induced neural tube defects.. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.