DARVON-N
Clinical safety rating
cautionComprehensive clinical and safety monograph for DARVON-N (DARVON-N).
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.
| Metabolism | Primarily hepatic via CYP3A4 and CYP2D6 to norpropoxyphene (active metabolite). Propoxyphene and norpropoxyphene undergo further metabolism and conjugation. |
| Excretion | Primarily renal (approximately 70% as unchanged drug and glucuronide conjugates); minor biliary/fecal elimination (25-30%). |
| Half-life | Propoxyphene: 6-12 hours; norpropoxyphene: 30-36 hours. Accumulation of norpropoxyphene on repeated dosing increases risk of toxicity. |
| Protein binding | Propoxyphene: 70-80%; norpropoxyphene: 75-85%. Primarily bound to albumin. |
| Volume of Distribution | Propoxyphene: 12-26 L/kg; widely distributed into tissues, including CNS. |
| Bioavailability | Oral: approximately 30-70% due to extensive first-pass metabolism; interindividual variability. |
| Onset of Action | Oral: 30-60 minutes; peak effect at 2 hours. |
| Duration of Action | 4-6 hours for pain relief; analgesic effect may persist longer with accumulation. |
| Molecular Weight | 375.5 |
100 mg orally every 4 hours as needed for pain; maximum 600 mg per day.
| Dosage form | SUSPENSION |
| Renal impairment | GFR 30-89 mL/min: no adjustment; GFR <30 mL/min: reduce dose by 50% or extend interval to every 8-12 hours; not recommended for GFR <15 mL/min. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use. |
| Pediatric use | Not recommended for children under 12 years; for adolescents 12-17 years: 100 mg every 4 hours as needed, maximum 400 mg per day. |
| Geriatric use | Initiate at 50 mg every 4 hours as needed; maximum 400 mg per day; monitor for CNS depression and constipation. |
| 1st trimester | Avoid; may cause fetal harm based on animal studies and limited human data. |
| 2nd trimester | Avoid; risk of fetal dependence and respiratory depression. |
| 3rd trimester | Avoid; may cause neonatal withdrawal syndrome and respiratory depression at delivery. |
Clinical note
Comprehensive clinical and safety monograph for DARVON-N (DARVON-N).
| Placental transfer | Crosses placenta readily; detectable in fetal tissues. |
| Breastfeeding | Excreted in breast milk in low levels; however, use caution due to risk of infant sedation and respiratory depression. Monitor for signs of toxicity. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic 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. |
| Fetal Monitoring | Monitor for maternal respiratory depression, sedation, and fetal well-being. In late pregnancy, monitor ductus arteriosus via ultrasound and amniotic fluid index. Assess neonatal for withdrawal post-delivery. |
| Fertility Effects | Propoxyphene may impair female fertility via disruption of hypothalamic-pituitary axis and reduced libido. Male fertility: possible decrease in sperm count and motility. |
■ FDA Black Box Warning
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.
| Serious Effects |
Hypersensitivity to propoxyphene or any componentSignificant respiratory depressionAcute or severe bronchial asthmaParalytic ileusConcurrent use of MAOIs or within 14 daysKnown or suspected gastrointestinal obstruction
| Precautions | 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 |
| Food/Dietary | Avoid alcohol; may enhance CNS depression. No specific food interactions known, but high-fat meals may delay absorption. |
| Clinical Pearls | 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. |
| Patient Advice | 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. |
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