Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PHENYLBUTAZONE vs ACULAR LS
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.
Selective COX-2 inhibitor; inhibits prostaglandin synthesis, reducing ocular inflammation and pain.
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
FDA: Treatment of postoperative inflammation in patients who have undergone cataract surgery,Off-label: Relief of ocular pain, photophobia, and inflammation associated with corneal abrasion or refractive surgery
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.
1 drop in the affected eye(s) four times daily
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.
The terminal elimination half-life is approximately 1.8 hours (range 1.2–2.5 hours) following topical ocular administration. This short half-life is consistent with rapid clearance from the systemic circulation.
Hepatic metabolism via CYP2C9 and CYP3A4; major metabolite is oxyphenbutazone; minor pathways include hydroxylation and glucuronidation.
Primarily hepatic via CYP2C9; undergoes glucuronidation and oxidation to inactive metabolites.
Primarily hepatic metabolism; renal excretion of metabolites (<1% unchanged). Biliary/fecal excretion accounts for ~20% of total elimination.
Renal excretion of metabolites and unchanged drug accounts for approximately 26% of the dose. Fecal excretion accounts for approximately 74% of the dose, primarily as metabolites.
98–99% bound, primarily to albumin.
Ketorolac is highly protein bound, approximately 99% bound to plasma proteins, primarily albumin.
0.05–0.1 L/kg, indicating limited extravascular distribution; increased in hypoalbuminemia.
The volume of distribution is approximately 0.12 L/kg, indicating distribution primarily into extracellular fluid with limited tissue penetration.
Oral: 100% absorbed, though systemic availability may be reduced by first-pass metabolism (bioavailability ~90%). Intramuscular: near 100%.
Ophthalmic bioavailability is approximately 2% of the administered dose due to extensive nasolacrimal drainage and systemic absorption. Oral bioavailability of ketorolac is approximately 80-100%, but this route is not used for ophthalmic formulations.
GFR 10-50: use 50% of normal dose. GFR <10: contraindicated due to accumulation of active metabolite oxyphenbutazone.
No dosage adjustment required for renal impairment
Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated due to risk of hepatotoxicity.
No dosage adjustment required for hepatic impairment but use with caution in severe hepatic disease due to potential for increased systemic exposure
Not recommended in children under 14 years due to risk of Reye-like syndrome and hypersensitivity; safety and efficacy not established.
Safety and efficacy in pediatric patients below 2 years of age have not been established; for children 2 years and older, same as adult dosing
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.
No specific dose adjustment recommended; use with caution due to increased incidence of age-related ocular conditions
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.
None
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.
Increased risk of bleeding and bleeding-related adverse events due to platelet inhibition,May prolong bleeding time,Cross-sensitivity with aspirin and other NSAIDs,Caution in patients with prior history of corneal epithelial defects or ocular surgery,Not for intraocular injection
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.
Hypersensitivity to ketorolac tromethamine or any component of the formulation,Patients with active peptic ulcer disease, recent GI bleeding, or perforation,Patients with advanced renal disease or at risk for renal failure,Patients with known history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
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.
No known food interactions for ophthalmic ketorolac. However, maintain good hydration and nutrition to support corneal healing.
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.
Ketorolac tromethamine, the active ingredient in ACULAR LS, is a nonsteroidal anti-inflammatory drug (NSAID). In animal reproduction studies, administration of ketorolac during organogenesis resulted in increased embryofetal mortality, delayed ossification, and increased incidence of skeletal abnormalities at doses less than the maximum recommended human ophthalmic dose. However, systemic exposure following ocular administration is very low. NSAIDs are generally avoided during pregnancy, especially in the third trimester, due to the risk of premature closure of the ductus arteriosus and oligohydramnios. The risk is considered low for ophthalmic use but should be used only if clearly needed.
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.
It is not known whether ketorolac is excreted in human milk after ophthalmic administration. Systemic levels are low, and following oral administration, ketorolac is excreted in breast milk at low concentrations (M/P ratio approximately 0.37). Due to the potential for adverse effects on the nursing infant, caution should be exercised. The low systemic absorption likely poses minimal risk.
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.
No dosing adjustments are necessary for ophthalmic use during pregnancy due to negligible systemic absorption. Standard dosing (1 drop in the affected eye(s) four times daily) is recommended. Systemic NSAIDs may require dose adjustment due to increased volume of distribution and renal changes, but this does not apply to topical ocular ketorolac.
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.
ACULAR LS (ketorolac tromethamine ophthalmic solution 0.4%) is a nonsteroidal anti-inflammatory drug (NSAID) indicated for the reduction of ocular pain and photophobia following corneal refractive surgery. Use with caution in patients with known bleeding tendencies or those on anticoagulants due to increased risk of ocular bleeding. Avoid concurrent use with other NSAIDs or steroids to minimize corneal adverse effects. Monitor for corneal epithelial breakdown or delayed healing.
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.
Do not touch the dropper tip to any surface to avoid contamination.,Remove contact lenses before instillation and wait at least 10 minutes before reinserting.,Use only in the affected eye(s) as prescribed; do not use for longer than directed.,Temporary stinging or burning may occur upon instillation.,Report any persistent pain, redness, or visual changes to your doctor immediately.,Avoid driving or operating machinery if vision is blurred after use.
"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 ACULAR LS, 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.. ACULAR LS is a NSAID Ophthalmic that works by Selective COX-2 inhibitor; inhibits prostaglandin synthesis, reducing ocular inflammation and pain.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between PHENYLBUTAZONE and ACULAR LS 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 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 ACULAR LS is: 1 drop in the affected eye(s) four times daily. 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 ACULAR LS 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. ACULAR LS is classified as Category C. Ketorolac tromethamine, the active ingredient in ACULAR LS, is a nonsteroidal anti-inflammatory drug (NSAID). In animal reproduction studies, administration of ketorolac during org. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.