DOLENE AP-65
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DOLENE AP-65 (DOLENE AP-65).
DOLENE AP-65 is a combination of dipyrone (metamizole) and propantheline. Dipyrone is a non-opioid analgesic and antipyretic that acts centrally and peripherally via inhibition of cyclooxygenase and activation of the endocannabinoid system. Propantheline is an anticholinergic agent that inhibits muscarinic acetylcholine receptors, reducing gastrointestinal motility and spasm.
| Metabolism | Dipyrone is metabolized primarily in the liver via CYP450 enzymes (CYP2C9, CYP2C19) to active metabolites (4-methylaminoantipyrine and 4-aminoantipyrine). Propantheline is metabolized hepatic via ester hydrolysis and conjugation. |
| Excretion | Renal: 90% (50% as acetaminophen glucuronide, 30% as sulfate, 5% as cysteine, 3% as unchanged drug, 2% as other metabolites); Fecal: <5% |
| Half-life | 2-3 hours in adults with normal hepatic function; prolonged in hepatic impairment (up to 5-10 hours) and in neonates (up to 3-5 hours) |
| Protein binding | 10-25% bound to plasma proteins (mainly albumin) at therapeutic concentrations; binding is minimal and not saturable |
| Volume of Distribution | 0.9-1.0 L/kg; indicates distribution into total body water; slightly higher in females and elderly |
| Bioavailability | Oral: 85-90% (first-pass metabolism reduces bioavailability slightly); Rectal: 80-90% |
| Onset of Action | Oral: 30-60 minutes; peak analgesic effect at 1-2 hours |
| Duration of Action | 4-6 hours; analgesic effect correlates with plasma concentrations; may be shorter in children or patients with rapid metabolism |
DOLENE AP-65 (propoxyphene napsylate 100 mg and acetaminophen 650 mg). Adult: 1 tablet orally every 4 hours as needed for pain. Maximum: 6 tablets per day.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (eGFR <30 mL/min). For moderate impairment (eGFR 30-59 mL/min): extend dosing interval to every 8 hours. Monitor for propoxyphene accumulation. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For moderate impairment (Child-Pugh class B): reduce dose by 50% and monitor liver function. Use with caution in class A. |
| Pediatric use | Contraindicated in children under 12 years due to risk of respiratory depression. For adolescents 12-18 years: administer as per adult dosing if clinically appropriate; monitor closely. |
| Geriatric use | Start with one tablet every 6 hours due to increased sensitivity and reduced clearance. Maximum: 4 tablets per day. Avoid in patients with renal impairment, respiratory compromise, or concurrent CNS depressants. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DOLENE AP-65 (DOLENE AP-65).
| Breastfeeding | Propoxyphene is excreted in breast milk; M/P ratio approximately 0.5. Low levels in milk; however, due to risk of neonatal opioid toxicity and respiratory depression, caution advised. Acetaminophen is considered compatible with breastfeeding. Consider alternative analgesics. |
| Teratogenic Risk | First trimester: Propoxyphene (component of Dolene AP-65) is classified as FDA Pregnancy Category C; animal studies show fetal harm but no adequate human studies. Second/third trimester: Prolonged use may cause opioid withdrawal in neonate (neonatal abstinence syndrome). Acetaminophen (AP-65 component) is generally considered low risk but high doses may be hepatotoxic. Avoid use during pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Dipyrone may cause agranulocytosis, a severe and potentially fatal decrease in white blood cells. Use is contraindicated in patients with known hypersensitivity to dipyrone or other pyrazolones.
| Serious Effects |
["Hypersensitivity to dipyrone or propantheline","History of agranulocytosis","Bone marrow suppression","Gastrointestinal obstruction","Myasthenia gravis","Narrow-angle glaucoma","Prostatic hypertrophy"]
| Precautions | Risk of agranulocytosis with dipyrone; monitor blood counts. Anticholinergic effects of propantheline (e.g., urinary retention, constipation, blurred vision). Caution in elderly, renal/hepatic impairment, and history of gastrointestinal obstruction. |
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| Fetal Monitoring | Monitor maternal symptoms: respiratory rate, sedation, constipation, and liver function if prolonged acetaminophen exposure. Fetal monitoring: assess for signs of opioid withdrawal in neonate (e.g., excessive crying, tremors, poor feeding). No specific maternal-fetal monitoring required beyond standard obstetric care. |
| Fertility Effects | No evidence of direct effects on fertility. Opioids may cause hypothalamic-pituitary-gonadal axis suppression, potentially leading to menstrual irregularities or anovulation, but data specific to propoxyphene is limited. Acetaminophen has no known significant fertility effects at therapeutic doses. |