BUTAZOLIDIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BUTAZOLIDIN (BUTAZOLIDIN).
Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2), thereby reducing prostaglandin synthesis. Also has uricosuric effect at higher doses.
| Metabolism | Hepatic metabolism via oxidation (hydroxylation) and conjugation (glucuronidation). Major enzyme: CYP2C9, with minor contributions from CYP3A4 and CYP2C19. |
| Excretion | Primarily renal: ~60% as unchanged drug and glucuronide conjugates; biliary/fecal: ~40% (enterohepatic circulation). |
| Half-life | Terminal half-life: 50-100 hours (prolonged in elderly or hepatic/renal impairment; accumulation risk evident within 5-7 days). |
| Protein binding | 98-99% bound primarily to albumin. |
| Volume of Distribution | 0.1-0.15 L/kg indicating limited extravascular distribution (confined to plasma and interstitial fluid). |
| Bioavailability | Oral: 80-90% (high, with food slightly reducing rate); IM: ~100% (complete absorption); Rectal: ~70-80%. |
| Onset of Action | Oral: 2-4 hours (anti-inflammatory); IM: 30-60 min; Rectal: 1-2 hours. |
| Duration of Action | Oral: 6-12 hours (single dose, anti-inflammatory); accumulation extends duration; analgesic effect lasts 4-6 hours. |
| Molecular Weight | 225 |
Butazolidin (phenylbutazone) is typically administered orally at 100-200 mg 3 times daily with meals, not to exceed 600 mg/day. Initial loading dose of 400 mg may be given on day 1, followed by 300-400 mg/day in divided doses. Duration should be limited to 7-10 days.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated in patients with severe renal impairment (GFR <30 mL/min). For GFR 30-60 mL/min, reduce dose by 50% and monitor closely. Do not use if GFR <30 mL/min. No data for dialysis patients. |
| Liver impairment | Contraindicated in Child-Pugh Class B or C. For Child-Pugh Class A, use with caution at 50% of normal dose, monitoring hepatic function closely. Avoid in severe hepatic impairment. |
| Pediatric use | Not recommended for children under 14 years of age due to risk of serious adverse effects. No established pediatric dosing guidelines. |
| Geriatric use | Elderly patients are at increased risk of toxicity. Use lowest effective dose, typically 100-200 mg/day, and limit duration. Avoid use if possible due to high risk of gastrointestinal bleeding, renal impairment, and fluid retention. |
| 1st trimester | Avoid during first trimester due to risk of teratogenicity (association with cardiovascular and central nervous system defects). Nonsteroidal anti-inflammatory drugs (NSAIDs) should generally be avoided, and butazolidin is particularly contraindicated due to potential for fetal harm. |
| 2nd trimester | Avoid during second trimester. Use is contraindicated due to risk of premature closure of ductus arteriosus, oligohydramnios, and fetal renal impairment. Butazolidin is a potent NSAID and poses significant risk. |
| 3rd trimester | Avoid during third trimester. Contraindicated due to risk of premature closure of ductus arteriosus, oligohydramnios, neonatal renal impairment, and inhibition of labor. Butazolidin is absolutely contraindicated in late pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for BUTAZOLIDIN (BUTAZOLIDIN).
| Placental transfer | Butazolidin crosses the placenta. Studies indicate significant transfer with fetal plasma concentrations approaching maternal levels. Associated with fetal toxicity and adverse pregnancy outcomes. |
■ FDA Black Box Warning
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 occur early in treatment and may increase with duration of use. Butazolidin is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
Hypersensitivity to butazolidin or other NSAIDsHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsActive peptic ulcer disease or gastrointestinal bleedingSevere heart failure (NYHA Class III-IV)Severe renal impairment (eGFR <30 mL/min/1.73 m²)Severe hepatic impairment (Child-Pugh Class C)Third trimester of pregnancyHistory of blood dyscrasias (e.g., agranulocytosis, aplastic anemia)Concomitant use of other NSAIDs or anticoagulants (relative contraindication, but absolute in practice due to high risk of bleeding)Known hypersensitivity to pyrazolone derivatives (e.g., metamizole)
| Precautions | Cardiovascular risk (increased risk of thrombotic events); gastrointestinal risk (bleeding, ulceration, perforation); hepatic toxicity (elevated liver enzymes, hepatitis); renal toxicity (fluid retention, renal failure); hematologic effects (agranulocytosis, aplastic anemia); hypersensitivity reactions (e.g., anaphylaxis, Stevens-Johnson syndrome). |
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| Breastfeeding |
| Butazolidin is excreted into breast milk in small amounts. However, due to its long half-life, potential for serious adverse effects (e.g., hematologic toxicity, renal impairment) in the nursing infant, and availability of safer alternatives, breast-feeding is generally not recommended during therapy. Discontinue drug or discontinue breastfeeding, considering importance of drug to mother. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Avoid unless benefit outweighs risk; associated with cardiac defects and gastroschisis in some epidemiological studies. Second/third trimester: Use with caution; may cause premature closure of ductus arteriosus, oligohydramnios, and necrotizing enterocolitis. Avoid near term due to risk of neonatal bleeding and renal impairment. |
| Fetal Monitoring | Maternal: Monitor for signs of gastrointestinal bleeding, renal impairment (serum creatinine, BUN), hepatic function (LFTs), and complete blood count (CBC) for anemia/leukopenia. Fetal: Ultrasound to assess for oligohydramnios and ductus arteriosus patency if used in third trimester. |
| Fertility Effects | May impair fertility in females via prostaglandin inhibition affecting ovulation and implantation. In males, may reduce sperm count and motility. Effects are reversible upon discontinuation. |
| Food/Dietary | Avoid alcohol; may increase risk of gastrointestinal bleeding. Take with food to minimize gastric irritation. Avoid high-potassium foods if used with potassium-sparing diuretics or ACE inhibitors. |
| Clinical Pearls | Butazolidin (phenylbutazone) is a nonsteroidal anti-inflammatory drug (NSAID) with potent anti-inflammatory effects but significant toxicity; reserve for short-term use in severe ankylosing spondylitis or acute gout only after other NSAIDs have failed. Monitor for agranulocytosis, aplastic anemia, and gastrointestinal bleeding; obtain baseline CBC and LFTs, and recheck weekly during therapy. Avoid in elderly, renal impairment, and pregnancy (third trimester). Not recommended for routine analgesia. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Report any signs of infection (fever, sore throat), unusual bleeding/bruising, or skin rash immediately. · Avoid alcohol and other NSAIDs or aspirin while on this medication. · Do not use for more than 7 days unless directed by your doctor. · If pregnant, planning to become pregnant, or breastfeeding, inform your doctor before taking this drug. |