Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DARVON vs ACTIQ
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Propoxyphene is a mu-opioid receptor agonist that inhibits ascending pain pathways by binding to opioid receptors in the CNS, altering pain perception. It also has weak local anesthetic effects.
Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.
Management of mild to moderate pain
Management of breakthrough pain in cancer patients aged 16 and older who are already receiving and tolerant to opioid therapy for their underlying persistent cancer pain
Propoxyphene hydrochloride (Darvon) for moderate to severe pain: 65 mg orally every 4 hours as needed; maximum 390 mg/day.
200 mcg transmucosally, titrated upward as needed; initial dose for opioid-tolerant patients is 200 mcg, with additional doses possible after 15 minutes if needed. Maximum 4 doses per episode. At least 4 hours between episodes.
6-12 hours (parent drug); norpropoxyphene half-life 30-36 hours, accumulates with repeated dosing, increasing risk of toxicity.
Terminal half-life 0.83–2 hours (mean 1.3 h) in adults; note that context: transmucosal absorption leads to rapid onset but short duration; half-life is not correlated with clinical effect due to oral transmucosal route and rapid redistribution.
Primarily hepatic via CYP3A4 isoenzyme, with major metabolite norpropoxyphene (which contributes to cardiotoxicity).
Primarily hepatic via CYP3A4 to inactive metabolites (norfentanyl, despropionylfentanyl, hydroxyfentanyl) and other metabolites; <7% excreted unchanged in urine.
Primarily hepatic metabolism to norpropoxyphene, then renal excretion of metabolites; <20% excreted unchanged in urine; minor biliary/fecal elimination.
Primarily renal as metabolites (about 75% as metabolites, <10% unchanged). Fecal excretion accounts for <9%. Biliary excretion is minor.
Approximately 80% bound primarily to albumin.
Fentanyl is 80–85% bound to plasma proteins (primarily albumin and α1-acid glycoprotein).
12-26 L/kg; high Vd indicates extensive tissue distribution.
Approximately 4 L/kg (range 3–6 L/kg); large Vd indicates extensive tissue distribution and redistribution contributing to short duration.
Oral: 30-70% due to first-pass metabolism; erratic and variable.
Oral transmucosal: 50% (range 47–54%) relative to IV; variable and enhanced by rapid absorption through buccal mucosa.
GFR 10-50 m L/min: administer 65 mg every 6 hours; GFR <10 m L/min: avoid or reduce dose to 65 mg every 8 hours due to accumulation of norpropoxyphene.
No specific GFR-based dose adjustment recommended; use with caution in severe renal impairment (Cr Cl < 30 m L/min) and consider dose reduction due to potential accumulation.
Child-Pugh class B or C: contraindicated; mild hepatic impairment: reduce dose to 65 mg every 6 hours and monitor closely.
Child-Pugh Class A/B: No adjustment. Child-Pugh Class C: Reduce initial dose to 100 mcg and titrate slowly; monitor closely for prolonged effects.
Not recommended for children under 12 years; for older children: 0.5-1 mg/kg/dose every 4 hours as needed, maximum 2 mg/kg/day.
Not approved for pediatric use; safety and efficacy not established in patients under 16 years.
Initiate at 65 mg every 6 hours; monitor for respiratory depression, dizziness, and constipation; avoid in elderly with renal or hepatic impairment.
Initiate at 100 mcg transmucosally; titrate slowly due to increased sensitivity and risk of respiratory depression. Monitor for adverse effects.
Propoxyphene is associated with fatal respiratory depression, especially when used in doses higher than recommended or in patients with respiratory compromise. Due to the risk of overdose and QT interval prolongation, propoxyphene was withdrawn from the U. S. market in 2010.
Risk of respiratory depression, addiction, abuse, and misuse; accidental ingestion can be fatal; concomitant use with benzodiazepines or CNS depressants may cause profound sedation, respiratory depression, coma, and death; not for use in opioid non-tolerant patients; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; serious, life-threatening, or fatal respiratory depression may occur even at recommended doses.
Risk of respiratory depression,Risk of QT prolongation and torsades de pointes,Risk of abuse, addiction, and diversion,Fatal overdose even at therapeutic doses,May cause CNS depression,Use caution in elderly, debilitated, or patients with renal/hepatic impairment
Risk of respiratory depression; addiction, abuse, and misuse; interactions with CNS depressants; serotonin syndrome; adrenal insufficiency; severe hypotension; seizures; withdrawal; use in patients with head injuries, increased intracranial pressure, biliary tract disease, pancreatitis; risk of choking with lozenge; oral mucosal irritation; dental caries; hypokalemia; hyponatremia; use in elderly, cachectic, or debilitated patients.
Hypersensitivity to propoxyphene,Significant respiratory depression,Acute or severe bronchial asthma,Suspected paralytic ileus,Concomitant use of MAO inhibitors or within 14 days,Concomitant use of CYP3A4 inhibitors (e.g., ketoconazole, erythromycin)
Significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment; known or suspected paralytic ileus; hypersensitivity to fentanyl or any component; opioid non-tolerant patients; management of acute or postoperative pain including headache/migraine, dental pain, or emergency department use.
Grapefruit and grapefruit juice may increase propoxyphene levels; avoid concurrent consumption. Alcohol consumption is contraindicated due to additive CNS depression and increased risk of hepatotoxicity.
No significant food interactions. Grapefruit juice may increase fentanyl levels, but specific studies with ACTIQ are lacking. Avoid alcohol, as it may increase sedation and respiratory depression risk.
FDA Pregnancy Category C. First trimester: Limited data, but no clear evidence of major malformations. Second and third trimesters: Risk of neonatal respiratory depression and withdrawal if used near term or in high doses. Chronic use may lead to neonatal opioid withdrawal syndrome.
FDA Pregnancy Category C. First trimester: limited human data; animal studies show increased resorptions and fetal growth restriction. Second/third trimester: chronic use may cause neonatal opioid withdrawal syndrome; avoid use during labor due to risk of neonatal respiratory depression.
Enters breast milk. M/P ratio approximately 1.0. Use caution; monitor infant for drowsiness, respiratory depression, and poor feeding. American Academy of Pediatrics considers use compatible with breastfeeding with careful monitoring.
Excreted in breast milk; M/P ratio not established. Limited data suggest low levels, but risk of infant sedation and respiratory depression. Avoid use while breastfeeding unless potential benefit outweighs risk.
Pharmacokinetic changes: increased clearance and volume of distribution, potentially requiring dose increases to maintain analgesia. Taper slowly to avoid withdrawal; use lowest effective dose for shortest duration.
Due to increased plasma volume and hepatic metabolism in pregnancy, dose requirements may increase; adjust based on clinical response and tolerance. Avoid use during labor and delivery due to risk of neonatal respiratory depression; short-term use preferred.
Darvon (propoxyphene) is a weak opioid analgesic; due to risk of QT prolongation and cardiac arrhythmias, it was withdrawn from the US market in 2010. Consider monitoring ECG in patients with cardiac history or concurrent use of QT-prolonging agents. Propoxyphene has a narrow therapeutic index; overdose can cause seizures, respiratory depression, and cardiac toxicity. Combination with alcohol or CNS depressants increases risk of fatal respiratory depression.
ACTIQ is a transmucosal immediate-release fentanyl formulation indicated for breakthrough cancer pain in opioid-tolerant patients. Initiate with the lowest strength (200 mcg) and titrate upward. Avoid use in opioid-naive patients due to risk of fatal respiratory depression. Place the unit between cheek and lower gum, not sublingually. Instruct patient not to bite or suck the unit. Monitor for sedation and respiratory depression. Multiple units may be used per episode if needed, but wait at least 4 hours before next episode. Dispose of partially used units by flushing down toilet.
Do not exceed prescribed dose as overdose can be life-threatening.,Avoid alcohol and other CNS depressants while taking this medication.,May cause dizziness or drowsiness; avoid driving or operating machinery until effects are known.,Take exactly as prescribed; do not share with others.,Seek emergency care for signs of overdose: slow breathing, severe drowsiness, or fainting.
Only use ACTIQ if you are already taking regular around-the-clock opioid pain medicine and are tolerant to opioids.,Do not use ACTIQ for short-term pain like after surgery, headache, or dental pain.,Place the unit in your cheek pouch, not under your tongue. Do not chew or suck it.,If you need more than 4 units per day, contact your doctor as your dose may need adjustment.,Store ACTIQ in a safe place away from children, as accidental ingestion can be fatal.,Dispose of unused or partially used units by flushing them down the toilet.
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 DARVON vs ACTIQ, answered by our medical review team.
DARVON is a Opioid Analgesic that works by Propoxyphene is a mu-opioid receptor agonist that inhibits ascending pain pathways by binding to opioid receptors in the CNS, altering pain perception. It also has weak local anesthetic effects.. ACTIQ is a Opioid Analgesic that works by Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between DARVON and ACTIQ depend on the specific clinical indication. These are both Opioid Analgesic agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of DARVON is: Propoxyphene hydrochloride (Darvon) for moderate to severe pain: 65 mg orally every 4 hours as needed; maximum 390 mg/day.. The standard adult dose of ACTIQ is: 200 mcg transmucosally, titrated upward as needed; initial dose for opioid-tolerant patients is 200 mcg, with additional doses possible after 15 minutes if needed. Maximum 4 doses per episode. At least 4 hours between episodes.. 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 DARVON and ACTIQ 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. DARVON is classified as Category C. FDA Pregnancy Category C. First trimester: Limited data, but no clear evidence of major malformations. Second and third trimesters: Risk of neonatal respiratory depression and with. ACTIQ is classified as Category C. FDA Pregnancy Category C. First trimester: limited human data; animal studies show increased resorptions and fetal growth restriction. Second/third trimester: chronic use may cause. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.