Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DELSYM vs HY-PHEN
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Dextromethorphan is a non-competitive NMDA receptor antagonist and sigma-1 receptor agonist, which suppresses cough by elevating the threshold for coughing in the medullary cough center.
HY-PHEN is a combination of hydrocodone (a mu-opioid receptor agonist) and acetaminophen (an analgesic and antipyretic). Hydrocodone binds to mu-opioid receptors in the CNS, altering pain perception and emotional response to pain. Acetaminophen inhibits cyclooxygenase (COX) enzymes, particularly in the CNS, reducing prostaglandin synthesis.
Symptomatic relief of cough caused by minor throat and bronchial irritation
Management of moderate to moderately severe pain,Off-label: Acute pain, postoperative pain, chronic pain (limited use due to acetaminophen toxicity risk)
60 mg orally every 12 hours (extended-release suspension).
1-2 tablets (acetaminophen 500 mg/hydrocodone 5-10 mg) orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
Terminal elimination half-life of dextromethorphan is approximately 11 hours (range 9-14 hours) in extensive metabolizers; in poor metabolizers (CYP2D6 deficiency), half-life can exceed 24 hours, leading to accumulation.
2-3 hours (terminal elimination half-life). Clinical context: Short half-life requires frequent dosing (every 4-6 hours) for sustained analgesic effect.
Metabolized primarily by CYP2D6 to dextrorphan, an active metabolite; also undergoes O-demethylation and N-demethylation.
Hydrocodone is metabolized via CYP3A4 to hydromorphone (active) and via CYP2D6 to norhydrocodone. Acetaminophen is primarily metabolized via glucuronidation and sulfation; a minor pathway via CYP2E1 produces a hepatotoxic metabolite (NAPQI) that is normally detoxified by glutathione.
Renal excretion of unchanged drug and metabolites, primarily dextrorphan glucuronide; <5% excreted unchanged in urine. Biliary/fecal elimination is negligible.
Renal (primarily as glucuronide conjugates and unchanged drug). Approximately 90-95% eliminated in urine within 24 hours; fecal excretion <5%.
~45-50% bound to plasma albumin; main binding protein is albumin.
25-35% bound to plasma proteins (mainly albumin).
5-6 L/kg, indicating extensive tissue distribution.
0.9-1.5 L/kg. Clinical meaning: Moderate Vd indicates distribution into total body water; does not extensively accumulate in tissues.
Oral: ~10-25% due to extensive first-pass metabolism (CYP2D6 and CYP3A4); bioavailability is higher in poor metabolizers.
Oral: 60-90% (first-pass metabolism reduces systemic availability); Rectal: 70-80%; IV/IM: 100%.
No dose adjustment recommended for mild-to-moderate renal impairment; safety in severe renal impairment not established.
GFR 30-50 m L/min: administer at 75% of usual dose every 6 hours; GFR <30 m L/min: administer at 50% of usual dose every 8 hours. Avoid in severe renal impairment.
No dose adjustment recommended for mild-to-moderate hepatic impairment; safety in severe hepatic impairment not established.
Child-Pugh Class A: no adjustment; Class B: reduce dose by 50% and extend interval to every 8 hours; Class C: contraindicated.
Children 6-11 years: 30 mg orally every 12 hours. Children 12 years and older: 60 mg orally every 12 hours. Do not exceed 60 mg in 24 hours for ages 6-11 or 120 mg for ages 12+.
Not recommended for children under 18 years due to risk of opioid-related adverse effects; alternative analgesics preferred.
Start at low end of dosing range; monitor for anticholinergic effects and sedation. No specific dose adjustment in elderly but caution due to increased sensitivity.
Initiate with lowest effective dose (e.g., acetaminophen 500 mg/hydrocodone 5 mg) every 6 hours; monitor for respiratory depression, constipation, and falls; may require dose reduction by 25-50% compared to younger adults.
None
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion of acetaminophen (especially in children) can cause hepatotoxicity; neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risks from concomitant use with benzodiazepines or other CNS depressants (additive respiratory depression).
Do not use in children under 4 years of age,Avoid use with MAO inhibitors or for 2 weeks after stopping,Chronic use may lead to dependence and abuse,Caution in patients with respiratory depression, asthma, or chronic obstructive pulmonary disease
Hepatotoxicity due to acetaminophen (dose-dependent); respiratory depression (especially in elderly, debilitated, or COPD); opioid-induced hyperalgesia; adrenal insufficiency; severe hypotension; seizures; serotonin syndrome with serotonergic drugs; urinary retention; bile duct spasm; use in patients with head injury or increased intracranial pressure (risk of masking neurological signs); neonatal withdrawal syndrome.
Hypersensitivity to dextromethorphan or any component,Use with or within 14 days of MAO inhibitors,Use in patients with respiratory depression or severe asthma
Significant respiratory depression; acute or severe bronchial asthma; known or suspected gastrointestinal obstruction (e.g., paralytic ileus); severe hepatic impairment; hypersensitivity to hydrocodone, acetaminophen, or any component; use of MAO inhibitors within 14 days (hypertensive crisis).
No significant food interactions. Avoid grapefruit juice as it may increase dextromethorphan levels. Take with or without food.
Avoid alcohol consumption due to increased risk of hepatotoxicity and CNS depression. Grapefruit juice may inhibit CYP2D6 metabolism of hydrocodone, potentially altering analgesic effect; avoid concurrent use. High-fat meals may increase absorption of hydrocodone; take consistently with or without food.
Category D (positive evidence of human fetal risk): First trimester exposure associated with rare reports of congenital malformations including cardiac defects and oral clefts based on observational studies. Second and third trimester use may cause fetal respiratory depression, bradycardia, and neonatal adaptation syndrome with prolonged use near term. Risks increase with higher doses and chronic use.
Pregnancy Category C. First trimester: No well-controlled studies; potential for fetal harm based on animal studies (cleft palate, skeletal anomalies). Second and third trimesters: Prolonged use may cause neonatal withdrawal syndrome (irritability, hypertonia, respiratory depression) if used near term. Avoid use in pregnancy unless benefit outweighs risk.
Excreted into breast milk in low concentrations (M/P ratio 0.1–0.4). Considered compatible with breastfeeding by American Academy of Pediatrics; however, monitor infant for drowsiness, respiratory depression, and poor feeding. Avoid if infant is premature or has respiratory compromise. Use shortest duration possible.
HY-PHEN (hydrocodone/acetaminophen) is excreted into breast milk in low concentrations. M/P ratio for hydrocodone is approximately 2.0, for acetaminophen ~1.0. Use caution; monitor infant for sedation, respiratory depression, and poor feeding. Consider risk of neonatal withdrawal if maternal use is chronic.
No pharmacokinetic studies show significant changes in dextromethorphan clearance during pregnancy. Therefore, no empiric dose adjustment is recommended. However, because of increased plasma volume and renal blood flow in pregnancy, the duration of action may be shorter, requiring more frequent dosing if clinically indicated. Use lowest effective dose for shortest duration.
No specific dose adjustments established for pregnancy. Increased plasma volume and enhanced hepatic metabolism in pregnancy may reduce drug concentrations, potentially requiring higher doses to achieve analgesic effect. However, avoid high doses due to risk of acetaminophen hepatotoxicity and fetal opioid exposure. Use lowest effective dose for shortest duration.
DELSYM (dextromethorphan polistirex) is a sustained-release formulation providing up to 12 hours of cough suppression. Do not crush or chew capsules; swallow whole. Avoid use in patients with asthma, COPD, or respiratory insufficiency due to risk of respiratory depression. Contraindicated with MAOIs and within 14 days of MAOI use due to serotonin syndrome risk. Not recommended for chronic cough or cough associated with excessive secretions. Use caution in patients with G6PD deficiency (rare hemolysis risk).
HY-PHEN is a combination of hydrocodone and acetaminophen. Monitor for acetaminophen hepatotoxicity; maximum daily acetaminophen dose should not exceed 4 g from all sources. Hydrocodone is a prodrug metabolized by CYP2D6 to hydromorphone; poor metabolizers may have reduced analgesia while ultra-rapid metabolizers risk toxicity. Avoid concurrent use with other CNS depressants including alcohol due to additive respiratory depression. Taper dose when discontinuing after prolonged use to prevent withdrawal.
Take DELSYM only as directed for temporary cough relief.,Swallow capsules whole; do not crush, chew, or dissolve.,Do not exceed recommended dose or use for more than 7 days unless directed by a doctor.,Avoid alcohol while taking this medication.,Do not use if you are taking or have taken a monoamine oxidase inhibitor (MAOI) within the last 14 days.,Seek medical attention if cough persists, comes with fever, rash, or headache, or if you experience signs of serotonin syndrome (agitation, hallucinations, rapid heart rate, fever, muscle stiffness).,Keep out of reach of children; accidental overdose may cause death.
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.,Do not take other products containing acetaminophen (e.g., Tylenol, cold medicines) while using this medication to avoid liver damage.,Avoid alcohol completely while taking this drug; it increases the risk of liver damage and severe drowsiness.,Do not drive or operate heavy machinery until you know how this medication affects you; it may cause dizziness or drowsiness.,Store securely away from children and others; misuse can cause addiction, overdose, or death.,Do not stop taking suddenly after long-term use; your doctor will help you taper off to prevent withdrawal symptoms.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about DELSYM vs HY-PHEN, answered by our medical review team.
DELSYM is a Antitussive that works by Dextromethorphan is a non-competitive NMDA receptor antagonist and sigma-1 receptor agonist, which suppresses cough by elevating the threshold for coughing in the medullary cough center.. HY-PHEN is a Opioid Antitussive Combination that works by HY-PHEN is a combination of hydrocodone (a mu-opioid receptor agonist) and acetaminophen (an analgesic and antipyretic). Hydrocodone binds to mu-opioid receptors in the CNS, altering pain perception and emotional response to pain. Acetaminophen inhibits cyclooxygenase (COX) enzymes, particularly in the CNS, reducing prostaglandin synthesis.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between DELSYM and HY-PHEN 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 DELSYM is: 60 mg orally every 12 hours (extended-release suspension).. The standard adult dose of HY-PHEN is: 1-2 tablets (acetaminophen 500 mg/hydrocodone 5-10 mg) orally every 4-6 hours as needed for pain; maximum 8 tablets per day.. 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 DELSYM and HY-PHEN 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. DELSYM is classified as Category C. Category D (positive evidence of human fetal risk): First trimester exposure associated with rare reports of congenital malformations including cardiac defects and oral clefts base. HY-PHEN is classified as Category C. Pregnancy Category C. First trimester: No well-controlled studies; potential for fetal harm based on animal studies (cleft palate, skeletal anomalies). Second and third trimesters:. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.