Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
AZITHROMYCIN vs COMBOGESIC
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting m RNA translation and thus protein synthesis. Exhibits concentration-dependent bactericidal activity.
COMBOGESIC (acetaminophen and tramadol) combines a centrally acting analgesic (tramadol) that binds to mu-opioid receptors and inhibits serotonin and norepinephrine reuptake, with an antipyretic (acetaminophen) that inhibits cyclooxygenase (COX) in the CNS.
Acute bacterial exacerbations of chronic obstructive pulmonary disease due to H. influenzae, M. catarrhalis, or S. pneumoniae,Acute bacterial sinusitis due to H. influenzae, M. catarrhalis, or S. pneumoniae,Community-acquired pneumonia due to C. pneumoniae, H. influenzae, M. pneumoniae, or S. pneumoniae,Pharyngitis/tonsillitis due to S. pyogenes,Uncomplicated skin and skin structure infections due to S. aureus, S. pyogenes, or S. agalactiae,Urethritis/cervicitis due to C. trachomatis or N. gonorrhoeae,Genital ulcer disease due to H. ducreyi,Acute otitis media due to H. influenzae, M. catarrhalis, or S. pneumoniae,Prevention of disseminated M. avium complex disease in advanced HIV infection,Pertussis (off-label)
Management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate in adults
500 mg orally once daily for 3 days, or 500 mg IV once daily for at least 2 days followed by 500 mg orally to complete 7-10 days of therapy for community-acquired pneumonia. For other indications, typical adult dose is 500 mg orally on day 1 then 250 mg orally once daily on days 2-5.
One tablet (acetaminophen 500 mg / tramadol 37.5 mg) orally every 4 to 6 hours as needed for pain, not to exceed 8 tablets per day.
Terminal half-life of approximately 68 hours (range 35–96 h) after multiple doses, allowing once-daily dosing and a prolonged post-antibiotic effect.
Acetaminophen: 2-3 hours; Tramadol: 6.3 hours (slow CYP2D6 metabolizers may exceed 12 hours). Clinically, dosing interval adjusted for renal impairment.
Primarily hepatic, not via cytochrome P450 system. Partially metabolized to inactive metabolites. Eliminated via biliary excretion and renal excretion (<15% unchanged).
Tramadol: primarily metabolized by CYP2D6 and CYP3A4; O-desmethyltramadol (active metabolite) via CYP2D6. Acetaminophen: primarily metabolized by glucuronidation and sulfation in the liver.
Primarily biliary/fecal (approx. 50% unchanged); renal excretion accounts for about 12% of the dose.
Renal excretion of acetaminophen metabolites (glucuronide, sulfate, cysteine, and mercapturate conjugates); 85% total. Tramadol and metabolites: 90% renal, 10% fecal.
7–51% (concentration-dependent); primarily binds to albumin.
Acetaminophen 10-25%; Tramadol 20% bound to albumin.
31.1 L/kg (range 23–50 L/kg), indicating extensive tissue penetration and sequestration (e.g., WBCs, liver, lung).
Acetaminophen 0.9 L/kg; Tramadol 2.6 L/kg. Reflects extensive tissue distribution.
Oral: 37–40% (fasting); food may decrease absorption by ~50%.
Acetaminophen oral ~88%; Tramadol oral ~75% (due to first-pass metabolism).
No dose adjustment required for GFR ≥10 m L/min. For GFR <10 m L/min, caution advised; no specific dose recommendation, consider alternative agent.
For Cr Cl 30-59 m L/min: increase dosing interval to every 12 hours, maximum 4 tablets per day. For Cr Cl <30 m L/min: not recommended. Hemodialysis: administer dose after dialysis session, use with caution.
No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A and B). Contraindicated in severe hepatic impairment (Child-Pugh class C).
Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% or extend interval; maximum 4 tablets per day. Child-Pugh Class C: contraindicated.
For otitis media and community-acquired pneumonia: 10 mg/kg orally or IV on day 1 (max 500 mg), then 5 mg/kg (max 250 mg) once daily on days 2-5. For pharyngitis/tonsillitis: 12 mg/kg orally once daily for 5 days (max 500 mg/day).
Not recommended for pediatric use. Safety and efficacy not established in children.
No specific dose adjustment required; use same dosing as younger adults. Monitor renal function due to age-related decline, but no modification needed unless severe renal impairment (Cr Cl <10 m L/min).
Initiate at lowest effective dose; consider extended dosing interval (every 8-12 hours) and monitor for adverse effects, particularly CNS and respiratory depression.
None.
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risk of medication errors (combining different forms of acetaminophen leading to hepatotoxicity); serious, life-threatening, or fatal respiratory depression may occur when used with benzodiazepines or other CNS depressants.
Hepatotoxicity: hepatitis, cholestatic jaundice, hepatic necrosis, hepatic failure,QT prolongation and torsades de pointes (especially with concurrent use of other QT-prolonging agents, electrolyte abnormalities, bradycardia, or structural heart disease),Clostridioides difficile-associated diarrhea (CDAD),Aggravation of myasthenia gravis,Severe allergic reactions (angioedema, anaphylaxis, Stevens-Johnson syndrome),Infantile hypertrophic pyloric stenosis (IHPS) in neonates following oral azithromycin,Use in pregnancy: category B; avoid during breastfeeding due to potential for disruption of infant gut flora
Addiction, abuse, and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; hepatotoxicity (associated with acetaminophen); seizures; serotonin syndrome; risk of overdose; interactions with MAOIs; CYP2D6 poor metabolizers may have reduced efficacy; risk of anaphylaxis and hypersensitivity.
Hypersensitivity to azithromycin, erythromycin, or any macrolide antibiotic,History of cholestatic jaundice or hepatic dysfunction associated with prior azithromycin use,Concurrent use with ergotamine or dihydroergotamine (possible ergot toxicity)
Hypersensitivity to tramadol, acetaminophen, or any component; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment; known or suspected gastrointestinal obstruction, including paralytic ileus; concomitant use of MAOIs or within 14 days of such therapy.
Food does not significantly affect absorption; can be taken with or without food. However, avoiding high-fat meals may reduce minor GI side effects. No known specific food interactions.
Avoid alcohol while taking Combogesic, as it increases the risk of liver damage with acetaminophen and gastrointestinal bleeding with ibuprofen. Taking with food may reduce gastric irritation. No specific food restrictions.
FDA Category B. No evidence of teratogenicity in animal studies; limited human data show no increased risk of major malformations. First trimester: No significant association with birth defects. Second/third trimester: No reported fetal harm from short-term use for infections like chorioamnionitis. Use only if clearly needed.
Combogesic contains paracetamol (acetaminophen) and tramadol. Paracetamol: No increased risk of major malformations; first trimester use is generally considered low risk. Second and third trimester: No known fetal toxicity at therapeutic doses. Tramadol: First trimester: Limited data, but no major teratogenicity observed in animal studies; human data insufficient to exclude risk. Second and third trimester: Not associated with structural anomalies; chronic use may lead to fetal dependence and neonatal withdrawal syndrome. At term: Risk of neonatal respiratory depression if used near delivery; tramadol may prolong labor and increase risk of postpartum hemorrhage.
Azithromycin is excreted into breast milk in low amounts. M/P ratio approximately 0.2-0.6. Relative infant dose estimated at 2-6% of maternal weight-adjusted dose. Generally considered compatible with breastfeeding; monitor infant for diarrhea or rash.
Paracetamol: Excreted into breast milk in small amounts (M/P ratio ~0.23-0.91); considered compatible with breastfeeding. Tramadol: Excreted into breast milk (M/P ratio ~1.5-2.0); relative infant dose ~2.24% of maternal weight-adjusted dose. Monitor infant for sedation and respiratory depression; avoid in women with CYP2D6 ultra-rapid metabolizer status due to increased risk of high morphine levels in breast milk.
No dose adjustment required for pregnancy. Standard adult dosing (500 mg on day 1, then 250 mg daily for 4 days) is appropriate. Note: Pregnancy may increase volume of distribution, but pharmacokinetic studies suggest no significant decrease in AUC; no need for dose increase.
Paracetamol: No adjustment required; use lowest effective dose for shortest duration. Tramadol: Pregnancy may alter tramadol pharmacokinetics (increased clearance, decreased Cmax); however, no standard dose adjustment is recommended. Use minimal effective dose; avoid sustained-release formulations. Near term: Consider alternative analgesics to minimize neonatal effects.
Monitor for QTc prolongation especially in patients with preexisting cardiac conditions or those on other QT-prolonging drugs. Azithromycin has a long half-life (68 hours) allowing for shorter treatment courses. Use with caution in hepatic impairment; consider alternative in severe liver disease. Not recommended for pneumonia in patients with bacteremia due to increased mortality risk. Administer on an empty stomach or with food if GI upset occurs; however, absorption is unaffected by food.
Combogesic (paracetamol/acetaminophen + ibuprofen) is a fixed-dose combination used for acute pain. Note that the maximum daily dose of acetaminophen is 4000 mg (or lower in hepatic impairment) and ibuprofen 1200 mg (or lower in renal impairment). Avoid concomitant use of other NSAIDs or acetaminophen-containing products. Use with caution in patients with a history of peptic ulcer or bleeding disorders; ibuprofen may increase bleeding risk.
Take exactly as prescribed; do not skip doses or stop early even if you feel better.,Do not take antacids containing aluminum or magnesium within 2 hours before or after this medication.,Report any signs of liver problems (nausea, vomiting, dark urine, jaundice) or severe diarrhea (watery or bloody) immediately.,Azithromycin may cause dizziness; avoid driving or operating machinery until you know how it affects you.,Inform your doctor if you have a history of QT prolongation, heart rhythm problems, or electrolyte imbalances.,Store at room temperature away from moisture and heat; discard any unused liquid after 10 days.
Do not exceed the recommended dose as it may cause liver damage or kidney problems.,Avoid taking other products containing acetaminophen or NSAIDs (e.g., ibuprofen, naproxen) while using Combogesic.,Take with food or milk to reduce stomach upset.,Report any signs of stomach bleeding (e.g., black/tarry stools, vomiting blood), rash, or swelling.,Do not use for more than 10 days for pain unless directed by a doctor.
"Azithromycin, a macrolide antibiotic, is known to prolong the QT interval by blocking cardiac potassium channels (specifically IKr), which can lead to torsades de pointes. Mifepristone also poses a risk of QT prolongation, likely via similar mechanisms. Coadministration may result in additive QTc prolongation, increasing the risk of life-threatening ventricular arrhythmias, especially in patients with preexisting cardiac conditions or electrolyte disturbances."
"Lumiracoxib is a selective COX-2 inhibitor primarily metabolized by CYP2C9 and to a lesser extent by CYP3A4. Azithromycin, a macrolide antibiotic, is a known inhibitor of CYP3A4. Concomitant use may decrease the metabolism of azithromycin, leading to increased plasma concentrations and potential toxicity, such as QT prolongation and hepatotoxicity. Elevated azithromycin levels can also enhance its antibacterial effects but raise safety concerns."
"Azithromycin, a macrolide antibiotic, inhibits the cardiac potassium channel encoded by hERG (human Ether-à-go-go-Related Gene), leading to prolonged cardiac repolarization and increased risk of QTc interval prolongation. Arformoterol, a long-acting beta-2 agonist, can also prolong the QTc interval via beta-adrenergic receptor-mediated effects on cardiac ion channels. Concurrent use may result in additive QTc prolongation, predisposing patients to potentially fatal ventricular arrhythmias such as torsades de pointes."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about AZITHROMYCIN vs COMBOGESIC, answered by our medical review team.
AZITHROMYCIN is a Macrolide Antibiotic that works by Binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting m RNA translation and thus protein synthesis. Exhibits concentration-dependent bactericidal activity.. COMBOGESIC is a Analgesic Combination (Opioid + Non-Opioid) that works by COMBOGESIC (acetaminophen and tramadol) combines a centrally acting analgesic (tramadol) that binds to mu-opioid receptors and inhibits serotonin and norepinephrine reuptake, with an antipyretic (acetaminophen) that inhibits cyclooxygenase (COX) in the CNS.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between AZITHROMYCIN and COMBOGESIC 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 AZITHROMYCIN is: 500 mg orally once daily for 3 days, or 500 mg IV once daily for at least 2 days followed by 500 mg orally to complete 7-10 days of therapy for community-acquired pneumonia. For other indications, typical adult dose is 500 mg orally on day 1 then 250 mg orally once daily on days 2-5.. The standard adult dose of COMBOGESIC is: One tablet (acetaminophen 500 mg / tramadol 37.5 mg) orally every 4 to 6 hours as needed for pain, not to exceed 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 AZITHROMYCIN and COMBOGESIC 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. AZITHROMYCIN is classified as Category A/B. FDA Category B. No evidence of teratogenicity in animal studies; limited human data show no increased risk of major malformations. First trimester: No significant association with . COMBOGESIC is classified as Category C. Combogesic contains paracetamol (acetaminophen) and tramadol. Paracetamol: No increased risk of major malformations; first trimester use is generally considered low risk. Second an. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.