PHENYLBUTAZONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHENYLBUTAZONE (PHENYLBUTAZONE).

How it works

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.

What the body does with it

Metabolism	Hepatic metabolism via CYP2C9 and CYP3A4; major metabolite is oxyphenbutazone; minor pathways include hydroxylation and glucuronidation.
Excretion	Primarily hepatic metabolism; renal excretion of metabolites (<1% unchanged). Biliary/fecal excretion accounts for ~20% of total elimination.
Half-life	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.
Protein binding	98–99% bound, primarily to albumin.
Volume of Distribution	0.05–0.1 L/kg, indicating limited extravascular distribution; increased in hypoalbuminemia.
Bioavailability	Oral: 100% absorbed, though systemic availability may be reduced by first-pass metabolism (bioavailability ~90%). Intramuscular: near 100%.
Onset of Action	Oral: 30–60 minutes for analgesic effect; 2–4 days for full anti-inflammatory effect. Intramuscular: 20–30 minutes for analgesic effect.
Duration of Action	Analgesic duration: 4–6 hours. Anti-inflammatory duration persists up to 24 hours due to long half-life, but accumulation leads to prolonged effects.

Classification & Brands

Dosing & administration

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.

Dosage form	TABLET
Renal impairment	GFR 10-50: use 50% of normal dose. GFR <10: contraindicated due to accumulation of active metabolite oxyphenbutazone.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated due to risk of hepatotoxicity.
Pediatric use	Not recommended in children under 14 years due to risk of Reye-like syndrome and hypersensitivity; safety and efficacy not established.
Geriatric use	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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PHENYLBUTAZONE (PHENYLBUTAZONE).

Breastfeeding	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.
Teratogenic Risk	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.

Warnings & precautions

■ FDA Black Box Warning

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.

Side Effect Profile

Serious Effects

Absolute Contraindications

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.

Clinical Precautions

Precautions

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.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

PHENYLBUTAZONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHENYLBUTAZONE (PHENYLBUTAZONE).

How it works

What the body does with it

Metabolism	Hepatic metabolism via CYP2C9 and CYP3A4; major metabolite is oxyphenbutazone; minor pathways include hydroxylation and glucuronidation.
Excretion	Primarily hepatic metabolism; renal excretion of metabolites (<1% unchanged). Biliary/fecal excretion accounts for ~20% of total elimination.
Half-life	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.
Protein binding	98–99% bound, primarily to albumin.
Volume of Distribution	0.05–0.1 L/kg, indicating limited extravascular distribution; increased in hypoalbuminemia.
Bioavailability	Oral: 100% absorbed, though systemic availability may be reduced by first-pass metabolism (bioavailability ~90%). Intramuscular: near 100%.
Onset of Action	Oral: 30–60 minutes for analgesic effect; 2–4 days for full anti-inflammatory effect. Intramuscular: 20–30 minutes for analgesic effect.
Duration of Action	Analgesic duration: 4–6 hours. Anti-inflammatory duration persists up to 24 hours due to long half-life, but accumulation leads to prolonged effects.

Classification & Brands

Dosing & administration

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.

Dosage form	TABLET
Renal impairment	GFR 10-50: use 50% of normal dose. GFR <10: contraindicated due to accumulation of active metabolite oxyphenbutazone.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated due to risk of hepatotoxicity.
Pediatric use	Not recommended in children under 14 years due to risk of Reye-like syndrome and hypersensitivity; safety and efficacy not established.
Geriatric use	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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PHENYLBUTAZONE (PHENYLBUTAZONE).

Breastfeeding	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.
Teratogenic Risk	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.