Oxyphenbutazone

Usage

• Oxyphenbutazone is a non-steroidal anti-inflammatory drug (NSAID) indicated for the symptomatic relief of acute and chronic inflammatory conditions, including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and gout. It was also prescribed for other painful musculoskeletal conditions. However, it’s use has been restricted significantly.
• Pharmacological Classification: Non-Steroidal Anti-inflammatory Drug (NSAID), Analgesic, Antipyretic.
• Mechanism of Action: Oxyphenbutazone primarily inhibits cyclooxygenase (COX) enzymes, responsible for prostaglandin synthesis. Prostaglandins mediate inflammation, pain, and fever. By inhibiting COX, oxyphenbutazone reduces prostaglandin production, thus alleviating these symptoms.

Alternate Names

• p-Hydroxyphenylbutazone
• Brand Names: Tandearil (withdrawn from the market in many countries due to serious side effects).

How It Works

• Pharmacodynamics: Oxyphenbutazone exerts its anti-inflammatory, analgesic, and antipyretic effects through COX inhibition, reducing prostaglandin synthesis.
• Pharmacokinetics:
  • Absorption: Rapidly absorbed from the gastrointestinal tract, reaching peak plasma concentrations in 2-4 hours.
  • Metabolism: Extensively metabolized in the liver, primarily by oxidation and conjugation with glucuronic acid. A major active metabolite is gamma-hydroxyphenylbutazone.
  • Elimination: Excreted primarily in urine as metabolites, with a small amount eliminated in feces. The elimination half-life is approximately 70 hours, but this varies considerably among individuals.
• Mode of Action: Inhibits COX-1 and COX-2 enzymes, thereby reducing prostaglandin production.
• Receptor binding, enzyme inhibition, or neurotransmitter modulation: Primarily inhibits COX-1 and COX-2 enzymes.
• Elimination Pathways: Primarily renal excretion of metabolites, with some hepatic excretion.

Dosage

Please note: Due to the potential for serious side effects, oxyphenbutazone use is severely restricted. The information below reflects historical dosage practices and should not be interpreted as current recommendations. Consult local guidelines for the most up-to-date information.

Standard Dosage

Adults:

Historically, the initial adult dosage ranged from 200-600 mg/day, divided into multiple doses. Due to the risk of toxicity, it was advised to promptly reduce the dosage to the lowest effective level for maintenance, not to exceed 400 mg/day.

Children:

Due to potential risks, oxyphenbutazone is generally contraindicated in children under 14 years of age.

Special Cases:

• Elderly Patients: Due to an increased risk of toxicity, oxyphenbutazone use is generally avoided in the elderly. If deemed necessary, use lowest effective dose for the shortest possible duration.
• Patients with Renal Impairment: Contraindicated in severe renal impairment. Reduce dosage in mild to moderate impairment.
• Patients with Hepatic Dysfunction: Contraindicated in severe hepatic dysfunction. Adjust dosage based on liver function.
• Patients with Comorbid Conditions: Use with caution in patients with cardiovascular, gastrointestinal, or hematological disorders.

Clinical Use Cases

Previously, oxyphenbutazone might have been used in some of these settings. It is crucial to emphasize that its use in such situations is currently highly restricted or contraindicated due to safety concerns. Please consult updated local guidelines for appropriate therapeutic options.

• Intubation: Not recommended.
• Surgical Procedures: Not recommended.
• Mechanical Ventilation: Not recommended.
• Intensive Care Unit (ICU) Use: Not recommended.
• Emergency Situations: Not recommended.

Dosage Adjustments

Dosage adjustments are based on patient factors such as renal/hepatic function, age, and response to therapy. Monitor for adverse effects. Given its restricted use, consultation with a specialist is crucial if oxyphenbutazone is considered.

Side Effects

Common Side Effects

• Nausea, vomiting, abdominal pain, diarrhea, indigestion, flatulence, fluid retention.

Rare but Serious Side Effects

• Gastric ulceration and bleeding, hepatitis, jaundice, renal failure, aplastic anemia, agranulocytosis, thrombocytopenia, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis.

Long-Term Effects

• Cardiovascular risks, including hypertension, heart attack, and stroke.
• Renal toxicity, especially in those with pre-existing kidney conditions.
• Bone marrow suppression.

Adverse Drug Reactions (ADR)

• Agranulocytosis, aplastic anemia, hepatic failure, renal failure, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis.

Contraindications

• Hypersensitivity to oxyphenbutazone or other NSAIDs.
• Active gastrointestinal bleeding or peptic ulcer disease.
• Severe cardiovascular, renal, or hepatic impairment.
• Blood disorders.
• Pregnancy and breastfeeding.
• Asthma or aspirin-induced allergy.

Drug Interactions

• Other NSAIDs, including aspirin: Increased risk of gastrointestinal bleeding.
• Anticoagulants (e.g., warfarin): Increased risk of bleeding.
• Antihypertensives (e.g., ACE inhibitors, beta-blockers): Reduced efficacy.
• Diuretics: Reduced efficacy.
• Lithium: Increased lithium levels and potential toxicity.
• CYP450 interactions: May interact with other drugs metabolized by CYP enzymes, acting as an inducer or inhibitor.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Contraindicated. Potential for fetal harm, including premature closure of the ductus arteriosus.
• Breastfeeding: Contraindicated. Excreted in breast milk and may cause adverse effects in infants.

Drug Profile Summary

• Mechanism of Action: Inhibits COX enzymes, reducing prostaglandin synthesis.
• Side Effects: Nausea, vomiting, gastrointestinal issues; serious effects include bleeding, bone marrow suppression, and organ damage.
• Contraindications: Hypersensitivity, active GI bleeding, severe organ impairment, pregnancy, breastfeeding.
• Drug Interactions: Other NSAIDs, anticoagulants, antihypertensives, lithium, CYP450 substrates.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: Historically 200-600 mg/day initially, reduced to maintenance; now restricted/contraindicated.
• Monitoring Parameters: Complete blood count, renal and liver function tests, blood pressure.

Popular Combinations

Due to its risk profile, combining oxyphenbutazone with other medications is generally avoided.

Precautions

• Evaluate renal and hepatic function, cardiovascular status, and gastrointestinal history before initiating therapy.
• Close monitoring for adverse events, especially during long-term use.
• Caution in patients with pre-existing medical conditions like diabetes, hypertension, and heart failure.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Oxyphenbutazone?

A: Oxyphenbutazone has restricted usage due to its side effects profile. It’s crucial to consult up-to-date local or national guidelines for any current recommendations on dosage. Historically, dosages ranged from 200-600 mg daily in adults, subsequently reduced to the minimum effective level. However, this information should not be used to guide current practice.

Q2: What are the serious side effects of Oxyphenbutazone?

A: Serious side effects include gastrointestinal bleeding, aplastic anemia, agranulocytosis, liver damage, renal failure, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Q3: In which patients is Oxyphenbutazone contraindicated?

A: Patients with hypersensitivity to oxyphenbutazone or other NSAIDs, active GI bleeding, severe cardiovascular, renal, or hepatic impairment, blood disorders, pregnant or breastfeeding women, and individuals with aspirin-induced allergies should not take this medication.

Q4: What are the drug interactions of Oxyphenbutazone?

A: It interacts with other NSAIDs, anticoagulants like warfarin, antihypertensives, lithium, and drugs metabolized by CYP enzymes.

Q5: Can Oxyphenbutazone be used in pregnancy?

A: No, it is contraindicated in pregnancy due to potential harm to the fetus.

Q6: Can Oxyphenbutazone be used during breastfeeding?

A: No, it is contraindicated during breastfeeding as it is excreted in breast milk and can affect the infant.

Q7: What monitoring parameters are essential while using Oxyphenbutazone?

A: Regular monitoring of complete blood count, renal and liver function tests, and blood pressure is necessary.

Q8: Why is Oxyphenbutazone use restricted?

A: Its usage is severely restricted due to the risk of serious adverse reactions, particularly bone marrow suppression and other blood disorders.

Q9: Are there any alternative medications for the conditions that Oxyphenbutazone was used to treat?

A: Yes, safer NSAIDs and other anti-inflammatory and analgesic drugs are available. Consult with a physician or specialist for appropriate alternative options based on the patient’s condition.

This information is current as of February 16, 2025, and might change with time. Always consult updated guidelines and resources.