Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ALEVE vs CODOXY
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Naproxen, a nonsteroidal anti-inflammatory drug (NSAID), inhibits cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing prostaglandin synthesis. This leads to decreased inflammation, pain, and fever.
Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia. Oxycodone is combined with aspirin to provide additive analgesic effects.
Rheumatoid arthritis,Osteoarthritis,Ankylosing spondylitis,Juvenile arthritis,Tendonitis,Bursitis,Acute gout,Primary dysmenorrhea,Mild to moderate pain,Fever
Management of moderate to moderately severe pain where the use of an opioid analgesic is appropriate
220 mg orally every 8 to 12 hours as needed; maximum 660 mg per day.
1-2 capsules orally every 4-6 hours as needed for pain, not to exceed 8 capsules per day. Each capsule contains 5 mg hydrocodone bitartrate and 325 mg acetaminophen.
Terminal elimination half-life is 12-17 hours; allows twice-daily dosing for steady-state concentrations.
Terminal half-life is 3.5 hours in patients with normal renal function; extends to 5-8 hours in moderate renal impairment.
Naproxen is extensively metabolized in the liver primarily via CYP2C9 to 6-O-desmethyl naproxen, and less than 5% is excreted unchanged in urine.
Oxycodone is metabolized by CYP3A4 and CYP2D6. N-demethylation to noroxycodone (via CYP3A4) is the primary metabolic pathway. CYP2D6-mediated O-demethylation to oxymorphone is a minor pathway but produces a more potent metabolite.
Renal (95% as unchanged drug and metabolites); biliary/fecal (5%)
Renal excretion of unchanged drug accounts for approximately 70% of elimination; biliary/fecal excretion accounts for 30%.
>99% bound to albumin; saturable at high concentrations.
Approximately 92% bound to albumin.
0.16 L/kg; indicates distribution primarily in extracellular fluid.
2.4 L/kg; indicates extensive tissue distribution.
Oral: ~95%; immediate-release formulation.
Oral: 60-70% due to first-pass metabolism.
GFR 30-59 m L/min: reduce dose and avoid long-term use; GFR <30 m L/min: contraindicated.
For GFR 30-50 m L/min: administer every 8 hours. For GFR 10-29 m L/min: administer every 12 hours. For GFR <10 m L/min: use not recommended.
Child-Pugh class A: no adjustment; Child-Pugh class B or C: avoid use.
Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% and extend interval to every 8 hours. Child-Pugh Class C: contraindicated.
2-12 years: 2.5-5 mg/kg/dose orally every 8-12 hours; maximum 10 mg/kg/day. 12 years and older: same as adult.
For children ≥2 years: 0.1-0.2 mg/kg hydrocodone component every 4-6 hours as needed, maximum 6 doses per day. Use weight-based dosing; do not exceed acetaminophen 75 mg/kg/day.
Initiate at lowest effective dose (220 mg every 12 hours); maximum 440 mg per day; monitor renal function and GI bleeding risk.
Initiate at lowest effective dose (e.g., 1 capsule every 6 hours) due to increased risk of respiratory depression and falls. Titrate cautiously. Maximum 6 capsules per day.
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors may be at greater risk. Naproxen is contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease or GI bleeding are at greater risk.
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 interactions with drugs affecting cytochrome P450 isoenzymes.
Cardiovascular thrombotic events,Gastrointestinal bleeding, ulceration, and perforation,Hypertension,Heart failure and edema,Renal toxicity,Anaphylactoid reactions,Serious skin reactions (e.g., Stevens-Johnson syndrome),Hematologic toxicity (inhibition of platelet aggregation),Exacerbation of asthma,Hepatic effects,Pregnancy: avoid during third trimester
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; severe hypotension; gastrointestinal obstruction; seizures; serotonin syndrome; adrenal insufficiency; and androgen deficiency.
History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs,Peri-operative pain in the setting of CABG surgery,Advanced renal disease,History of gastrointestinal bleeding or perforation related to previous NSAID therapy,Active gastrointestinal bleed
Significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected gastrointestinal obstruction, including paralytic ileus; hypersensitivity to oxycodone, aspirin, or any component of the formulation.
Avoid concurrent use of alcohol as it increases GI bleeding risk. No specific food restrictions; taking with food or milk may reduce dyspepsia. High potassium foods (e.g., bananas, spinach) may increase hyperkalemia risk in patients with renal impairment.
Avoid alcohol and grapefruit juice. Alcohol potentiates CNS depression. Grapefruit juice may increase codeine metabolism via CYP3A4, leading to variable effects. No significant food restrictions otherwise; take with food if GI upset occurs.
First trimester: Risk of spontaneous abortion and cardiac defects (odds ratio 1.86 for NSAIDs). Second trimester: Possible fetal renal dysfunction and oligohydramnios; ductus arteriosus premature closure risk begins. Third trimester: High risk of premature closure of ductus arteriosus, oligohydramnios, necrotizing enterocolitis, intracranial hemorrhage, and renal impairment; avoid after 30 weeks.
No human data; animal studies not available. Avoid during pregnancy, especially first trimester, due to potential oxycodone-induced neural tube defects.
Excreted in breast milk in low concentrations (M/P ratio ~0.12); relative infant dose <1% of maternal weight-adjusted dose. Compatible with breastfeeding; monitor infant for potential adverse effects (gastrointestinal upset, rash) at higher doses.
Oxycodone is excreted into breast milk; M/P ratio ~3.6:1. Risk of infant sedation and respiratory depression. Contraindicated during breastfeeding.
No specific pharmacokinetic-based dose adjustments; however, use lowest effective dose for shortest duration, especially after 20 weeks. Avoid use after 30 weeks gestation due to fetal risks. Increased volume of distribution may reduce serum concentrations but no dose adjustment recommended.
No established dose adjustments; increased clearance in pregnancy may require higher doses for analgesia, but use is contraindicated.
ALEVE (naproxen sodium) is a nonsteroidal anti-inflammatory drug (NSAID) with a longer half-life (12-17 hours) allowing twice-daily dosing. It carries a boxed warning for cardiovascular and gastrointestinal risk. Use lowest effective dose for shortest duration. Contraindicated in patients with aspirin allergy, perioperative pain in CABG surgery, and significant renal impairment. Monitor renal function in elderly, volume-depleted patients, and those on ACE inhibitors or diuretics.
CODOXY is a fixed-dose combination of codeine (opioid) and doxylamine (antihistamine). Use lowest effective dose for shortest duration due to opioid dependence and respiratory depression risk. Avoid in children <12 years for post-tonsillectomy pain and in those <18 with respiratory compromise. Monitor for CNS depression, especially with alcohol. Doxylamine adds anticholinergic effects (constipation, dry mouth, urinary retention). Caution in elderly, renal impairment, and breastfeeding.
Take with food or milk to reduce GI upset.,Do not exceed 2 tablets (440 mg) in 24 hours unless directed by a doctor.,Avoid alcohol consumption to lower risk of GI bleeding.,Stop use and seek medical help if you experience chest pain, weakness, slurred speech, or signs of stomach bleeding (black/tarry stools, vomit that looks like coffee grounds).,Do not use with other NSAIDs (e.g., ibuprofen, aspirin) unless prescribed.
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.,This medication may cause drowsiness, dizziness, or blurred vision; avoid driving or operating machinery until you know how it affects you.,Avoid alcohol and other sedatives (e.g., benzodiazepines, sleep aids) as they increase risk of severe drowsiness and breathing problems.,Do not use with other products containing codeine or antihistamines (including cough/cold medicines).,Store securely away from children; misuse can cause addiction, overdose, or death.,If you are pregnant, plan to become pregnant, or are breastfeeding, inform your healthcare provider before use.,Common side effects: constipation, dry mouth, nausea. Increase fluid intake and fiber to prevent constipation.,Seek emergency help if you experience slow or shallow breathing, confusion, or fainting.
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 ALEVE vs CODOXY, answered by our medical review team.
ALEVE is a Nonsteroidal Anti-inflammatory Drug (NSAID) that works by Naproxen, a nonsteroidal anti-inflammatory drug (NSAID), inhibits cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing prostaglandin synthesis. This leads to decreased inflammation, pain, and fever.. CODOXY is a Antitussive Combination that works by Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia. Oxycodone is combined with aspirin to provide additive analgesic effects.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ALEVE and CODOXY depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of ALEVE is: 220 mg orally every 8 to 12 hours as needed; maximum 660 mg per day.. The standard adult dose of CODOXY is: 1-2 capsules orally every 4-6 hours as needed for pain, not to exceed 8 capsules per day. Each capsule contains 5 mg hydrocodone bitartrate and 325 mg acetaminophen.. 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 ALEVE and CODOXY 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. ALEVE is classified as Category C. First trimester: Risk of spontaneous abortion and cardiac defects (odds ratio 1.86 for NSAIDs). Second trimester: Possible fetal renal dysfunction and oligohydramnios; ductus arter. CODOXY is classified as Category C. No human data; animal studies not available. Avoid during pregnancy, especially first trimester, due to potential oxycodone-induced neural tube defects.. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.