Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DARVON-N 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 weak mu-opioid receptor agonist that produces analgesia by binding to opioid receptors in the central nervous system, altering the perception of and response to pain. Its metabolite norpropoxyphene has local anesthetic and sodium channel blocking effects, which may contribute to cardiac toxicity.
Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.
Mild to moderate pain,Off-label: None established
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
100 mg orally every 4 hours as needed for pain; maximum 600 mg per 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.
Propoxyphene: 6-12 hours; norpropoxyphene: 30-36 hours. Accumulation of norpropoxyphene on repeated dosing increases 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 and CYP2D6 to norpropoxyphene (active metabolite). Propoxyphene and norpropoxyphene undergo further metabolism and conjugation.
Primarily hepatic via CYP3A4 to inactive metabolites (norfentanyl, despropionylfentanyl, hydroxyfentanyl) and other metabolites; <7% excreted unchanged in urine.
Primarily renal (approximately 70% as unchanged drug and glucuronide conjugates); minor biliary/fecal elimination (25-30%).
Primarily renal as metabolites (about 75% as metabolites, <10% unchanged). Fecal excretion accounts for <9%. Biliary excretion is minor.
Propoxyphene: 70-80%; norpropoxyphene: 75-85%. Primarily bound to albumin.
Fentanyl is 80–85% bound to plasma proteins (primarily albumin and α1-acid glycoprotein).
Propoxyphene: 12-26 L/kg; widely distributed into tissues, including CNS.
Approximately 4 L/kg (range 3–6 L/kg); large Vd indicates extensive tissue distribution and redistribution contributing to short duration.
Oral: approximately 30-70% due to extensive first-pass metabolism; interindividual variability.
Oral transmucosal: 50% (range 47–54%) relative to IV; variable and enhanced by rapid absorption through buccal mucosa.
GFR 30-89 m L/min: no adjustment; GFR <30 m L/min: reduce dose by 50% or extend interval to every 8-12 hours; not recommended for GFR <15 m L/min.
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 A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use.
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 adolescents 12-17 years: 100 mg every 4 hours as needed, maximum 400 mg per day.
Not approved for pediatric use; safety and efficacy not established in patients under 16 years.
Initiate at 50 mg every 4 hours as needed; maximum 400 mg per day; monitor for CNS depression and constipation.
Initiate at 100 mcg transmucosally; titrate slowly due to increased sensitivity and risk of respiratory depression. Monitor for adverse effects.
DARVON-N (propoxyphene) is contraindicated in patients with a history of drug abuse, and its use should be monitored for signs of abuse, addiction, or misuse. It should not be used in patients with severe respiratory depression, acute or severe bronchial asthma, or known hypersensitivity to propoxyphene. Additionally, because of the risk of QT prolongation and cardiac arrhythmias, propoxyphene-containing products were withdrawn from the US 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.
Addiction, abuse, and misuse,Respiratory depression,Accidental ingestion (especially in children) can be fatal,Neonatal opioid withdrawal syndrome,Interactions with CNS depressants (e.g., alcohol, benzodiazepines),Elderly or debilitated patients: increased risk of respiratory depression,Hepatic or renal impairment,QT prolongation and risk of torsade de pointes
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 or any component,Significant respiratory depression,Acute or severe bronchial asthma in an unmonitored setting,Known or suspected gastrointestinal obstruction (e.g., paralytic ileus),Concurrent use of alcohol, sedatives, or other CNS depressants,History of substance abuse,Concurrent MAOIs or within 14 days
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.
Avoid alcohol; may enhance CNS depression. No specific food interactions known, but high-fat meals may delay absorption.
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.
First trimester: Limited data; potential for neural tube defects with first-trimester exposure. Second and third trimesters: Risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal withdrawal syndrome. Use only if clearly needed.
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.
Propoxyphene is excreted into breast milk with a milk-to-plasma ratio of approximately 1.0. Theoretical risk of neonatal respiratory depression and withdrawal. Not recommended; consider alternative analgesics.
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.
Increased clearance in pregnancy may necessitate higher doses; however, due to risks, avoid use or limit to lowest effective dose for shortest duration. No established dose adjustment guidelines.
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-N (propoxyphene napsylate) is a weak opioid analgesic with efficacy similar to codeine; its use is limited by narrow therapeutic index and risk of QT prolongation. It is metabolized by CYP2D6 to norpropoxyphene, which has a long half-life and can accumulate, causing CNS toxicity. Due to safety concerns, it has been withdrawn from many markets; avoid in patients with substance use disorder, renal impairment, or those taking CNS depressants. Monitor for QTc prolongation if used with other QT-prolonging agents.
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.
Take exactly as prescribed; do not increase dose or frequency due to risk of serious side effects including seizures and cardiac arrhythmias.,Avoid alcohol and other CNS depressants (e.g., benzodiazepines, sedatives) as they increase risk of respiratory depression and sedation.,Do not stop abruptly after prolonged use; withdrawal symptoms may occur.,Store securely out of reach of children; dispose of unused medication properly.,Use caution when driving or operating machinery; may cause dizziness or drowsiness.,Report new or worsening shortness of breath, irregular heartbeat, or fainting to your healthcare provider.
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-N vs ACTIQ, answered by our medical review team.
DARVON-N is a Opioid Analgesic that works by Propoxyphene is a weak mu-opioid receptor agonist that produces analgesia by binding to opioid receptors in the central nervous system, altering the perception of and response to pain. Its metabolite norpropoxyphene has local anesthetic and sodium channel blocking effects, which may contribute to cardiac toxicity.. 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-N 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-N is: 100 mg orally every 4 hours as needed for pain; maximum 600 mg per 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-N 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-N is classified as Category C. First trimester: Limited data; potential for neural tube defects with first-trimester exposure. Second and third trimesters: Risk of premature closure of ductus arteriosus, oligohy. 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.