DOLENE
Clinical safety rating
cautionComprehensive clinical and safety monograph for DOLENE (DOLENE).
Opioid agonist, primarily mu-opioid receptor activation, leading to analgesic and euphoric effects.
| Metabolism | Hepatic via CYP2D6 and CYP3A4; active metabolite morphine-6-glucuronide. |
| Excretion | Renal: 70-80% as conjugated metabolites (mostly glucuronides), 5-10% as unchanged drug; Fecal: 5-10%; Biliary: minor. |
| Half-life | 2.5-3.5 hours; prolonged in hepatic impairment (up to 6-8 hours) and in neonates. |
| Protein binding | 20-30% bound to albumin. |
| Volume of Distribution | 1-2 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: 50-60% (first-pass metabolism); Rectal: ~50%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes. |
| Duration of Action | Oral: 4-6 hours; Intravenous: 2-4 hours. Analgesic effect lasts 3-5 hours. |
| Molecular Weight | 308.33 |
50 mg orally every 4-6 hours as needed for pain; maximum 400 mg per day.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-50 mL/min: 50 mg every 6 hours; GFR 10-29 mL/min: 50 mg every 8 hours; GFR <10 mL/min: 50 mg every 12 hours. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 50 mg every 8 hours; Child-Pugh C: not recommended. |
| Pediatric use | 1-2 mg/kg orally every 4-6 hours as needed; maximum 5 mg/kg per day or 200 mg per day, whichever is less. |
| Geriatric use | Initiate at 25 mg every 6 hours; increase cautiously to 50 mg every 6 hours if needed; maximum 300 mg per day. |
| 1st trimester | Contraindicated: Risk of neural tube defects and congenital heart malformations due to folate antagonism. |
| 2nd trimester | Contraindicated: May cause fetal growth restriction and oligohydramnios. |
| 3rd trimester | Contraindicated: Risk of premature closure of ductus arteriosus, pulmonary hypertension, and neonatal bleeding. |
Clinical note
Comprehensive clinical and safety monograph for DOLENE (DOLENE).
| Placental transfer | Readily crosses placenta; fetal concentrations may approach maternal levels. |
| Breastfeeding | Excreted into breast milk in low amounts; however, due to potential serious adverse effects (e.g., kernicterus in neonates), use is not recommended. Consider alternative agents. |
| Lactation Rating | L4 (Hazardous) |
| Teratogenic Risk | DOLENE (propoxyphene) is pregnancy category C; first trimester: no adequate human studies; potential risk of teratogenicity cannot be excluded; second and third trimesters: associated with neonatal respiratory depression, withdrawal syndrome, and fetal growth restriction with chronic use; avoid use during pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Maternal: monitor respiratory function, sedation levels, signs of abuse or dependence; Fetal: fetal heart rate monitoring for signs of distress; Neonatal: monitor for respiratory depression, withdrawal symptoms (irritability, feeding problems, tremors) after birth. |
| Fertility Effects | Propoxyphene may impair fertility in females via disruption of estrous cycle and ovulation; in males, may reduce sperm count and motility; clinical significance in humans not fully established. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; interaction with alcohol or CNS depressants; risk of opioid-induced hyperalgesia.
| Serious Effects |
Hypersensitivity to DOLENE or any componentThird trimester of pregnancyBreastfeedingActive peptic ulcer diseaseHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsSevere hepatic impairmentSevere renal impairment (CrCl <30 mL/min)Hemorrhagic diathesis or ongoing bleeding
| Precautions | Respiratory depression, particularly in elderly or debilitated; increased intracranial pressure; severe hypotension; adrenal insufficiency; serotonin syndrome; risk of seizures; severe hypotension; use in renal or hepatic impairment. |
| Food/Dietary | Avoid alcohol consumption due to additive CNS depression and increased risk of propoxyphene toxicity. No specific food interactions documented; however, maintaining a balanced diet is recommended to support overall health. |
| Clinical Pearls | DOLENE (propoxyphene) is a weak mu-opioid agonist with an active metabolite (norpropoxyphene) that has a long half-life (30-36 hours) and can accumulate, causing CNS and cardiac toxicity (QT prolongation, dysrhythmias). It is no longer marketed in many countries due to risk of fatal overdose, especially when combined with alcohol or other CNS depressants. Avoid in elderly, renal impairment, or patients with history of substance abuse. Consider ECG monitoring for QT prolongation in high-risk patients. |
| Patient Advice | Do not exceed prescribed dose; overdose risk is high even at slightly elevated doses. · Avoid alcohol and all other CNS depressants (benzodiazepines, sedatives) while taking DOLENE. · Report any signs of toxicity: confusion, dizziness, slow heartbeat, fainting, seizures. · May cause dizziness or drowsiness; avoid driving or operating machinery. · Store safely out of reach of children and dispose of unused medication properly. |
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