Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DOLENE AP-65 vs ANEXSIA 5/325
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
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.
Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic effects, primarily through central COX-2 inhibition and activation of descending serotonergic pathways.
Pain relief (visceral, colicky),Postoperative pain,Fever reduction
Management of moderate to moderately severe pain where an opioid analgesic is appropriate
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.
1-2 tablets orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
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)
Oxycodone: terminal half-life 3.2-4.3 hours (immediate-release); prolonged in hepatic impairment. Acetaminophen: terminal half-life 2-3 hours (therapeutic doses); prolonged in hepatic impairment or overdose.
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.
Hydrocodone: primarily hepatic via CYP3A4 and CYP2D6 to active metabolites (hydromorphone). Acetaminophen: hepatic metabolism via conjugation (glucuronidation, sulfation) and CYP2E1-mediated oxidation to toxic NAPQI.
Renal: 90% (50% as acetaminophen glucuronide, 30% as sulfate, 5% as cysteine, 3% as unchanged drug, 2% as other metabolites); Fecal: <5%
Oxycodone: renal excretion of metabolites (conjugated and unconjugated) and parent drug; ~10% excreted unchanged. Acetaminophen: renal excretion of metabolites (glucuronide and sulfate conjugates); ~2-4% excreted unchanged.
10-25% bound to plasma proteins (mainly albumin) at therapeutic concentrations; binding is minimal and not saturable
Oxycodone: 38-45% bound to albumin and alpha-1-acid glycoprotein. Acetaminophen: 10-25% bound to albumin at therapeutic concentrations.
0.9-1.0 L/kg; indicates distribution into total body water; slightly higher in females and elderly
Oxycodone: Vd 2.0-3.0 L/kg; distributes extensively into tissues. Acetaminophen: Vd 0.8-1.0 L/kg; relatively uniform distribution.
Oral: 85-90% (first-pass metabolism reduces bioavailability slightly); Rectal: 80-90%
Oxycodone: oral bioavailability 60-87% (immediate-release). Acetaminophen: oral bioavailability 88-98% (therapeutic doses).
Contraindicated in severe renal impairment (e GFR <30 m L/min). For moderate impairment (e GFR 30-59 m L/min): extend dosing interval to every 8 hours. Monitor for propoxyphene accumulation.
GFR 30-50 m L/min: use with caution, increase dosing interval to every 6 hours; GFR <30 m L/min: avoid use due to hydrocodeone accumulation.
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.
Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% and monitor; Child-Pugh C: contraindicated.
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.
Not recommended for children under 18 years due to risk of respiratory depression.
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.
Start with lowest dose (1 tablet every 6 hours), monitor renal and hepatic function, and avoid in frail elderly due to increased fall and cognitive impairment risk.
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.
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; and hepatotoxicity from acetaminophen overdose.
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.
Risk of opioid addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; hepatotoxicity; adrenal insufficiency; severe hypotension; gastrointestinal obstruction; seizure; and serotonin syndrome.
Hypersensitivity to dipyrone or propantheline,History of agranulocytosis,Bone marrow suppression,Gastrointestinal obstruction,Myasthenia gravis,Narrow-angle glaucoma,Prostatic hypertrophy
Hypersensitivity to hydrocodone or acetaminophen; significant respiratory depression; acute or severe bronchial asthma; GI obstruction; known or suspected paralytic ileus; severe hepatic impairment; and concurrent use of MAOIs within 14 days.
Avoid alcohol and grapefruit juice (may alter tramadol metabolism). High-fat meals may delay absorption but not overall effect. No other significant food interactions.
Avoid alcohol. Grapefruit juice may enhance side effects; limit intake. Take with food to reduce gastrointestinal discomfort.
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.
First trimester: Associated with increased risk of neural tube defects and cardiovascular malformations; avoid use. Second and third trimesters: Chronic exposure may cause fetal renal toxicity, oligohydramnios, and premature closure of ductus arteriosus. Use only if clearly needed.
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.
Paracetamol and hydrocodone are excreted in breast milk. M/P ratio: paracetamol ~1.0, hydrocodone ~1.0-2.0. Use with caution; monitor infant for drowsiness and respiratory depression. Consider risk of infant sedation with long-term use.
No specific dose adjustments recommended; however, propoxyphene is generally avoided in pregnancy due to neonatal withdrawal risk. Acetaminophen dose adjustments not typically needed, but monitor for hepatotoxicity, as pregnancy may alter hepatic metabolism. Use lowest effective dose for shortest duration.
Increased clearance in pregnancy may require dose adjustment. Monitor for pain control and adverse effects; no fixed dose change recommended. Consider lower starting dose due to potential fetal risks. Avoid chronic use; taper if possible.
DOLENE AP-65 is a combination of tramadol (opioid analgesic) and acetaminophen. Monitor for serotonin syndrome when used with other serotonergic drugs. Avoid in patients with severe hepatic impairment or acute alcoholism. Maximum daily acetaminophen dose is 4 g; beware of hidden sources. Tramadol may lower seizure threshold; use cautiously in epilepsy or head trauma. CYP2D6 poor metabolizers may have reduced efficacy.
ANEXSIA 5/325 contains hydrocodone 5 mg and acetaminophen 325 mg. Maximum acetaminophen dose from all sources should not exceed 4 g/day in adults; avoid in severe hepatic impairment. Hydrocodone is a Schedule II controlled substance with abuse potential; monitor for respiratory depression, especially in opioid-naive patients. Use with caution in patients with COPD, sleep apnea, or increased intracranial pressure. Consider naloxone co-prescription for high-risk patients. For acute pain, limit duration to 3-7 days.
Do not exceed 8 tablets per day due to acetaminophen liver toxicity risk.,Avoid alcohol while taking this medication.,Do not combine with other products containing acetaminophen.,May cause drowsiness or dizziness; avoid driving until effects are known.,Report signs of serotonin syndrome (confusion, rapid heart rate, fever) or seizures.,Do not stop abruptly to prevent withdrawal; taper under doctor guidance.
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.,Do not consume alcohol or other sedatives (e.g., benzodiazepines) while taking this medication.,Avoid other products containing acetaminophen (e.g., Tylenol, cold remedies) to prevent liver damage.,This medication may cause drowsiness or dizziness; do not drive or operate machinery until you know how it affects you.,Store securely out of reach of others; dispose of unused medication via drug take-back programs.,Seek emergency help if you have trouble breathing, severe drowsiness, or signs of allergic reaction.
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 DOLENE AP-65 vs ANEXSIA 5/325, answered by our medical review team.
DOLENE AP-65 is a Opioid Analgesic Combination that works by 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.. ANEXSIA 5/325 is a Opioid Analgesic Combination that works by Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic effects, primarily through central COX-2 inhibition and activation of descending serotonergic pathways.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between DOLENE AP-65 and ANEXSIA 5/325 depend on the specific clinical indication. These are both Opioid Analgesic Combination agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of DOLENE AP-65 is: 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.. The standard adult dose of ANEXSIA 5/325 is: 1-2 tablets orally every 4-6 hours as needed for pain; maximum 8 tablets per day.. 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 DOLENE AP-65 and ANEXSIA 5/325 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. DOLENE AP-65 is classified as Category C. 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 trim. ANEXSIA 5/325 is classified as Category C. First trimester: Associated with increased risk of neural tube defects and cardiovascular malformations; avoid use. Second and third trimesters: Chronic exposure may cause fetal re. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.