Usage
Oxyphenbutazone + Paracetamol is a combination drug containing a nonsteroidal anti-inflammatory drug (NSAID), oxyphenbutazone, and an analgesic and antipyretic, paracetamol (acetaminophen). While previously used for rheumatic disorders like ankylosing spondylitis, osteoarthritis, and rheumatoid arthritis, oxyphenbutazone has been largely withdrawn from many markets due to serious side effects, notably bone marrow suppression. Paracetamol is commonly used to treat fever and mild to moderate pain. The combination may still be available in certain regions, but its use is limited. It’s pharmacological classifications are NSAID (oxyphenbutazone) and analgesic/antipyretic (paracetamol). Paracetamol’s mechanism of action involves inhibiting cyclooxygenase (COX) enzymes in the central nervous system, reducing prostaglandin synthesis, which contributes to pain and fever. Oxyphenbutazone inhibits COX enzymes, reducing prostaglandin synthesis, leading to decreased inflammation and pain.
Alternate Names
Oxyphenbutazone was formerly marketed under the brand name Tandearil (now discontinued). Chemical names include 4-Butyl-2-(4-hydroxyphenyl)-1-phenylpyrazolidine-3,5-dione monohydrate, Oxibutazona (Spanish), and Oxyphenylbutazon (German). Paracetamol is also known as acetaminophen, particularly in North America.
How It Works
Paracetamol:
- Pharmacodynamics: Primarily acts centrally to reduce pain and fever by inhibiting COX enzymes in the CNS, reducing prostaglandin synthesis.
- Pharmacokinetics: Well-absorbed orally. Metabolized in the liver, primarily by glucuronidation and sulfation, and excreted in the urine.
- Mode of action: Centrally acting COX inhibitor.
- Elimination: Renal excretion, hepatic metabolism.
Oxyphenbutazone:
- Pharmacodynamics: Inhibits COX enzymes, reducing prostaglandin synthesis, therefore reducing inflammation and pain.
- Pharmacokinetics: Well-absorbed orally. Metabolized in the liver and excreted in the urine.
- Mode of action: Non-selective COX inhibitor.
- Elimination: Primarily renal excretion, hepatic metabolism.
Dosage
Due to safety concerns associated with oxyphenbutazone, dosage information for the combination is not readily available and should be determined with extreme caution in consultation with regional guidelines and resources. The following information focuses primarily on paracetamol dosing:
Standard Dosage
Adults:
Paracetamol: 500mg - 1000mg every 4-6 hours as needed, not to exceed 4000mg in 24 hours.
Children:
Paracetamol: 15mg/kg per dose every 4-6 hours as needed. Calculate the dose based on the child’s weight, ensuring it doesn’t exceed the maximum daily limit. Use age-appropriate formulations.
Special Cases:
- Elderly Patients: Start with a lower dose and monitor closely due to potential age-related decline in liver and kidney function.
- Patients with Renal Impairment: Dose adjustment needed based on creatinine clearance.
- Patients with Hepatic Dysfunction: Dose reduction may be required.
- Patients with Comorbid Conditions: Consider individual patient factors and adjust accordingly.
Clinical Use Cases
Due to safety concerns with oxyphenbutazone, this combination is not generally recommended for these clinical settings. Paracetamol alone, or other more appropriate analgesics/anti-inflammatory agents, would be considered.
Dosage Adjustments
Dose modifications should be considered based on factors such as renal/hepatic dysfunction, other medical conditions, and concomitant medications. Always consult regional guidelines and appropriate resources when considering the use of this combination, if encountered.
Side Effects
Common Side Effects (Paracetamol):
Nausea, vomiting, constipation.
Rare but Serious Side Effects (Paracetamol):
Allergic reactions, liver damage (especially with high doses or prolonged use).
Common Side Effects (Oxyphenbutazone):
Gastrointestinal issues, fluid retention, rash, dizziness.
Rare but Serious Side Effects (Oxyphenbutazone):
Bone marrow suppression, severe skin reactions (e.g., Stevens-Johnson syndrome), gastrointestinal bleeding, liver and kidney damage.
Contraindications
- Hypersensitivity to either drug.
- Active gastrointestinal bleeding or peptic ulcers (especially with oxyphenbutazone).
- Severe liver or kidney disease (especially with oxyphenbutazone).
- Severe heart conditions (especially with oxyphenbutazone).
- Blood disorders (especially with oxyphenbutazone).
- Pregnancy and breastfeeding (oxyphenbutazone).
Drug Interactions
- Other NSAIDs (increased risk of gastrointestinal bleeding).
- Anticoagulants (increased risk of bleeding).
- Alcohol (increased risk of liver damage with paracetamol and increased side effects with oxyphenbutazone).
- Medications metabolized by the liver (potential for altered metabolism).
Pregnancy and Breastfeeding
Paracetamol is generally considered safe during pregnancy and breastfeeding at recommended doses. Oxyphenbutazone is contraindicated during pregnancy and breastfeeding due to potential risks.
Drug Profile Summary
(Primarily for Paracetamol)
- Mechanism of Action: Inhibits COX enzymes in the CNS, reducing prostaglandin synthesis.
- Side Effects: Nausea, vomiting, constipation; rarely, allergic reactions, liver damage.
- Contraindications: Hypersensitivity.
- Drug Interactions: Alcohol, other medications containing paracetamol.
- Pregnancy & Breastfeeding: Generally safe at recommended doses.
- Dosage: Adults: 500mg-1000mg every 4-6 hours, maximum 4000mg/day. Children: 15mg/kg/dose every 4-6 hours.
- Monitoring Parameters: Liver function tests (especially with long-term use or high doses).
Popular Combinations (Paracetamol)
Paracetamol is often combined with other analgesics, such as codeine or ibuprofen, for enhanced pain relief. These combinations should be used with caution and within recommended dosage limits. The combination with oxyphenbutazone is not generally recommended.
Precautions
- Pre-screening for allergies, metabolic disorders, organ dysfunction, and other medical conditions.
- Avoid alcohol.
- Use caution in driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Oxyphenbutazone + Paracetamol?
A: Due to safety concerns related to oxyphenbutazone, providing a specific dosage recommendation for this combination is not advisable. If this combination is encountered, refer to current regional guidelines and carefully evaluate the risks and benefits for the individual patient. Consider alternatives to oxyphenbutazone whenever possible. Dosage information here focuses on paracetamol: Adults: 500mg-1000mg every 4-6 hours, maximum 4000mg/day. Children: 15mg/kg/dose every 4-6 hours.
Q2: What are the major safety concerns with oxyphenbutazone?
A: Bone marrow suppression, severe skin reactions (e.g., Stevens-Johnson syndrome), gastrointestinal bleeding, liver damage and kidney damage.
Q3: Is Oxyphenbutazone + Paracetamol safe during pregnancy?
A: No. Oxyphenbutazone is contraindicated during pregnancy. Paracetamol is generally considered safe at recommended doses, but always consult with a healthcare professional before use during pregnancy.
Q4: What are the key drug interactions to consider with this combination?
A: Other NSAIDs, anticoagulants, and alcohol. Additionally, consider medications metabolized by the liver.
Q5: What are the potential side effects of Paracetamol?
A: Common side effects include nausea, vomiting, and constipation. Rare but serious effects include allergic reactions and liver damage.
Q6: What are the potential side effects of Oxyphenbutazone?
A: Common side effects include gastrointestinal issues, fluid retention, rash, and dizziness. Rare but serious side effects include bone marrow suppression, severe skin reactions, gastrointestinal bleeding, and liver/kidney damage.
Q7: What is the mechanism of action of paracetamol?
A: It inhibits COX enzymes, primarily in the central nervous system, reducing prostaglandin synthesis and subsequently reducing pain and fever.
A: Primarily metabolized in the liver and excreted in the urine.
Q9: Should oxyphenbutazone be used in patients with renal impairment?
A: No. It is contraindicated in patients with severe renal disease and should be used with extreme caution, if at all, in those with any degree of renal impairment.
