Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PHENYLBUTAZONE vs ACTRON
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Phenylbutazone is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, thereby causing anti-inflammatory, analgesic, and antipyretic effects. It also inhibits leukocyte migration and lysosomal enzyme release.
Acetaminophen (paracetamol) is a non-opioid analgesic and antipyretic. Its mechanism is not fully understood but involves inhibition of cyclooxygenase (COX) enzymes in the central nervous system, reducing prostaglandin synthesis. It also modulates the endocannabinoid system and serotonergic pathways.
Relief of pain and inflammation in ankylosing spondylitis,Acute gouty arthritis,Osteoarthritis,Rheumatoid arthritis (short-term management),Off-label: Use in veterinary medicine for musculoskeletal disorders
Mild to moderate pain,Fever
Oral: 100-200 mg three times daily with food; maximum 600 mg/day. For acute gout: initial 400 mg followed by 200 mg every 4-6 hours for 1-2 days, then reduce.
Oral: 400 mg every 4-6 hours as needed for pain; maximum 1200 mg/day.
Terminal elimination half-life is 50–65 hours, but exhibits dose-dependent kinetics; can extend to 72–100 hours with repeated dosing or in elderly.
Terminal elimination half-life 2-4 hours; prolonged to 6-12 hours in elderly or renal impairment (Cr Cl <30 m L/min).
Hepatic metabolism via CYP2C9 and CYP3A4; major metabolite is oxyphenbutazone; minor pathways include hydroxylation and glucuronidation.
Primarily metabolized in the liver via glucuronidation (UGT1A1, UGT1A6, UGT1A9), sulfation (SULT1A1, SULT1A3), and oxidation (CYP2E1, CYP3A4) to form the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified by glutathione.
Primarily hepatic metabolism; renal excretion of metabolites (<1% unchanged). Biliary/fecal excretion accounts for ~20% of total elimination.
Renal: 90% as unchanged drug; biliary/fecal: 10% as metabolites.
98–99% bound, primarily to albumin.
>99% bound to albumin.
0.05–0.1 L/kg, indicating limited extravascular distribution; increased in hypoalbuminemia.
0.1-0.2 L/kg; indicates limited extravascular distribution.
Oral: 100% absorbed, though systemic availability may be reduced by first-pass metabolism (bioavailability ~90%). Intramuscular: near 100%.
Oral: 70-90% (first-pass metabolism minimal); IV: 100%.
GFR 10-50: use 50% of normal dose. GFR <10: contraindicated due to accumulation of active metabolite oxyphenbutazone.
GFR <30 m L/min: Avoid use. GFR 30-50 m L/min: Reduce dose to 50% of normal, maximum 600 mg/day.
Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated due to risk of hepatotoxicity.
Child-Pugh Class B: Reduce dose by 50%; maximum 600 mg/day. Child-Pugh Class C: Contraindicated.
Not recommended in children under 14 years due to risk of Reye-like syndrome and hypersensitivity; safety and efficacy not established.
Children ≥12 years: 400 mg orally every 6-8 hours as needed; maximum 1200 mg/day. Children <12 years: Not recommended.
Initiate at lowest effective dose (100 mg once or twice daily); monitor closely for fluid retention, GI bleeding, and renal impairment; avoid long-term use.
Initiate at 200 mg every 6-8 hours; maximum 600 mg/day due to increased risk of gastrointestinal bleeding and renal impairment.
WARNING: Aplastic anemia, agranulocytosis, and other blood dyscrasias have been associated with phenylbutazone. Use only when other NSAIDs have failed due to serious adverse effects. Monitor blood counts regularly. Risk is dose-related and increased with prolonged use.
Acetaminophen has been associated with cases of acute liver failure, sometimes resulting in liver transplant and death. Most cases involve use of acetaminophen at doses exceeding 4000 mg per day, often involving more than one acetaminophen-containing product.
Risk of bone marrow suppression (aplastic anemia, agranulocytosis); gastrointestinal ulceration and bleeding; renal toxicity (especially in elderly, dehydrated, or those with pre-existing renal impairment); hepatic dysfunction; hypersensitivity reactions; sodium and water retention; increased cardiovascular risk; use lowest effective dose for shortest duration.
Hepatotoxicity: risk increased with chronic alcohol use, liver disease, or use of other acetaminophen-containing products. Avoid exceeding 4000 mg/day. Severe skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis. Hypersensitivity reactions: anaphylaxis.
Hypersensitivity to phenylbutazone or other NSAIDs; history of aplastic anemia or agranulocytosis; active peptic ulcer disease; severe renal or hepatic impairment; advanced age; concomitant use with other NSAIDs or anticoagulants; pregnancy (third trimester) and lactation.
Severe hepatic impairment or active liver disease. Known hypersensitivity to acetaminophen or any component of the formulation.
Avoid taking with alcohol as it may increase the risk of gastrointestinal bleeding and hepatotoxicity. Grapefruit juice may increase drug levels and toxicity; avoid concurrent consumption. High-fat meals can delay but do not significantly reduce absorption; take with food or milk to minimize gastrointestinal irritation. Maintain adequate hydration unless contraindicated due to fluid retention concerns.
Avoid alcohol; may increase risk of GI bleeding. No specific food restrictions, but taking with food can reduce gastrointestinal irritation. Maintain adequate hydration to prevent renal impairment.
First trimester: Increased risk of cardiovascular malformations and neural tube defects due to inhibition of prostaglandin synthesis. Second and third trimesters: Risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment. Avoid in all trimesters unless absolutely necessary.
First trimester: Based on animal studies and limited human data, possible increased risk of cardiovascular and neural tube defects. Second/third trimester: Risk of premature closure of ductus arteriosus and oligohydramnios with prolonged use. Avoid after 30 weeks gestation.
Excreted into breast milk in low concentrations. M/P ratio is approximately 0.1–0.2. Potential for adverse effects in the infant, including platelet dysfunction and renal impairment. Avoid breastfeeding during therapy.
Excreted in breast milk; M/P ratio 0.15. Low oral bioavailability to infant; considered compatible with breastfeeding. Monitor infant for sedation or feeding problems.
Increased renal clearance and volume of distribution in pregnancy may reduce serum drug levels. However, due to significant teratogenic and fetal risks, use is contraindicated in pregnancy. No dosing adjustment justified.
Dose adjustment not typically required; however, due to increased renal clearance and volume of distribution in pregnancy, higher doses may be needed to achieve therapeutic effect. Use lowest effective dose for shortest duration.
Phenylbutazone is a nonsteroidal anti-inflammatory drug (NSAID) with potent anti-inflammatory, antipyretic, and analgesic effects, but its use is severely limited due to high risk of serious adverse effects including agranulocytosis, aplastic anemia, and hepatotoxicity. It is reserved for short-term treatment of severe conditions such as ankylosing spondylitis, acute gouty arthritis, and acute exacerbations of rheumatoid arthritis when other therapies are ineffective or contraindicated. Due to its long half-life (50-100 hours), dosing should be carefully adjusted, and complete blood counts (CBC) and liver function tests must be monitored regularly. It inhibits prostaglandin synthesis and can cause sodium and water retention, exacerbating hypertension and heart failure. Avoid concomitant use with other NSAIDs, anticoagulants, or methotrexate due to increased bleeding risk and toxicity.
ACTRON (ketorolac tromethamine) is a nonsteroidal anti-inflammatory drug (NSAID) for short-term management of moderate to severe acute pain, typically not exceeding 5 days due to risk of GI bleeding, renal impairment, and cardiovascular events. Avoid in patients with active peptic ulcer disease, bleeding diathesis, or advanced renal disease. Monitor renal function and signs of bleeding. Use lowest effective dose for shortest duration. May cause bronchospasm in aspirin-sensitive asthma.
Take this medication exactly as prescribed; do not exceed the recommended dose or duration of therapy due to risk of serious side effects.,Report any signs of infection (fever, sore throat, mouth ulcers), unusual bleeding or bruising, skin rash, or jaundice immediately.,Avoid alcohol and aspirin-containing products while taking this drug.,This medication may cause dizziness or drowsiness; avoid driving or operating heavy machinery until you know how it affects you.,Use effective contraception if you are of childbearing age; this drug may be harmful to an unborn baby and should not be used in late pregnancy.,Do not take this drug with other NSAIDs (e.g., ibuprofen, naproxen) or corticosteroids without consulting your doctor.
Take with food or milk to reduce stomach upset.,Do not take for more than 5 days as prescribed; longer use increases risk of serious side effects.,Avoid alcohol while taking this medication to lower risk of stomach bleeding.,Report any signs of bleeding (e.g., black stools, vomiting blood), unusual bruising, or decreased urination.,Do not take with other NSAIDs (e.g., ibuprofen, naproxen) or aspirin without consulting your doctor.,Inform your doctor about all medications, especially blood thinners (e.g., warfarin) and diuretics.,If you have asthma, be aware of potential bronchospasm; seek immediate help if you have breathing trouble.,Not recommended during pregnancy, especially in the third trimester.
"The combination of fenoprofen, a nonsteroidal anti-inflammatory drug (NSAID), with phenylbutazone, another NSAID with potent anti-inflammatory effects, significantly increases the risk of gastrointestinal (GI) adverse effects, including ulceration, bleeding, and perforation. This additive toxicity arises from synergistic inhibition of cyclooxygenase (COX) enzymes, leading to reduced gastroprotective prostaglandin synthesis and impaired platelet aggregation. Clinically, patients may experience increased incidence of gastric mucosal injury, occult blood loss, and potentially life-threatening GI bleeding, particularly in elderly or renally impaired individuals."
"Aprepitant, a moderate CYP3A4 inducer, can accelerate the metabolism of Phenylbutazone, a nonsteroidal anti-inflammatory drug (NSAID) primarily metabolized by CYP3A4 and CYP2C9. This leads to reduced plasma concentrations of Phenylbutazone, potentially diminishing its analgesic and anti-inflammatory efficacy. The interaction may result in inadequate symptom control in patients with chronic inflammatory conditions such as rheumatoid arthritis."
"Phenylbutazone, a nonsteroidal anti-inflammatory drug (NSAID) with potent prostaglandin synthesis inhibition, antagonizes the vasodilatory and antiplatelet effects of epoprostenol, a prostacyclin analog. This occurs because phenylbutazone reduces the production of endogenous prostacyclin and may also compete for receptor binding or downstream signaling, thereby diminishing epoprostenol's therapeutic efficacy in pulmonary arterial hypertension. Clinically, this interaction may lead to increased pulmonary vascular resistance, worsening symptoms, and elevated risk of thrombotic events."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about PHENYLBUTAZONE vs ACTRON, answered by our medical review team.
PHENYLBUTAZONE is a NSAID that works by Phenylbutazone is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, thereby causing anti-inflammatory, analgesic, and antipyretic effects. It also inhibits leukocyte migration and lysosomal enzyme release.. ACTRON is a NSAID that works by Acetaminophen (paracetamol) is a non-opioid analgesic and antipyretic. Its mechanism is not fully understood but involves inhibition of cyclooxygenase (COX) enzymes in the central nervous system, reducing prostaglandin synthesis. It also modulates the endocannabinoid system and serotonergic pathways.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between PHENYLBUTAZONE and ACTRON depend on the specific clinical indication. These are both NSAID agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of PHENYLBUTAZONE is: Oral: 100-200 mg three times daily with food; maximum 600 mg/day. For acute gout: initial 400 mg followed by 200 mg every 4-6 hours for 1-2 days, then reduce.. The standard adult dose of ACTRON is: Oral: 400 mg every 4-6 hours as needed for pain; maximum 1200 mg/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 PHENYLBUTAZONE and ACTRON 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. PHENYLBUTAZONE is classified as Category C. First trimester: Increased risk of cardiovascular malformations and neural tube defects due to inhibition of prostaglandin synthesis. Second and third trimesters: Risk of premature. ACTRON is classified as Category C. First trimester: Based on animal studies and limited human data, possible increased risk of cardiovascular and neural tube defects. Second/third trimester: Risk of premature closur. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.