Usage
- Phenazone is prescribed for mild to moderate pain relief, including headache, muscle pain, and back pain. It is also used to relieve pain and swelling associated with ear infections (otitis media) and for the removal of earwax. Additionally, it can be used for acute migraine attacks.
- Pharmacological Classification: Non-steroidal anti-inflammatory drug (NSAID) and analgesic.
- Mechanism of Action: Phenazone inhibits prostaglandin synthesis, which reduces inflammation and pain. It also possesses analgesic and antipyretic properties.
Alternate Names
- Antipyrine (USAN)
- Analgesine
- Phenazon
- Brand Names: Otigo (in combination with lidocaine), Tropex (otic solution)
How It Works
- Pharmacodynamics: Phenazone acts as an analgesic, antipyretic, and anti-inflammatory agent by inhibiting cyclooxygenase (COX) enzymes and reducing prostaglandin synthesis.
- Pharmacokinetics:
- Absorption: Well-absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations are reached within 1-2 hours.
- Distribution: Distributed throughout body fluids, including saliva and breast milk, reaching similar concentrations as in plasma.
- Metabolism: Metabolized in the liver to three major metabolites.
- Elimination: Primarily excreted in the urine, with a small amount excreted in bile. Elimination half-life is approximately 12 hours.
- Mode of Action: Phenazone inhibits COX enzymes, thus reducing prostaglandin synthesis. Prostaglandins are key mediators of inflammation, pain, and fever. The exact mechanism underlying its analgesic and antipyretic effects is not fully elucidated, but it’s believed to involve inhibition of prostaglandin synthesis in the central nervous system.
- Receptor Binding, Enzyme Inhibition or Neurotransmitter Modulation: Phenazone primarily works through inhibition of COX enzymes, particularly COX-1 and COX-2. It does not have significant receptor binding or neurotransmitter modulation activity.
- Elimination Pathways: Primarily eliminated by hepatic metabolism and subsequent renal excretion.
Dosage
Standard Dosage
Adults:
- Oral: 500 mg to 1 g every 4-8 hours. Maximum daily dose: 4 g.
- Otic: 4-6 drops of a 0.5% solution 3-4 times daily in the affected ear.
Children:
- 12-15 years: 500 mg once or twice daily. Maximum daily dose: 1 g.
- Over 15 years: Same as adult dose.
- Pediatric Safety Considerations: Use with caution in children under 12 years of age, as dosage guidelines are not well-established.
Special Cases:
- Elderly Patients: Use with caution. Start with a lower dose and adjust according to response and tolerance due to age-related decrease in renal and hepatic function.
- Patients with Renal Impairment: Reduce dosage based on the degree of impairment.
- Patients with Hepatic Dysfunction: Use with caution and reduce dosage as needed.
- Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular disease, diabetes, or a history of gastrointestinal bleeding.
Clinical Use Cases
Phenazone is not typically used in clinical settings such as intubation, surgical procedures, mechanical ventilation, or ICU use. Its use is primarily limited to pain and fever relief.
Dosage Adjustments
Dosage adjustments should be made based on individual patient characteristics, including renal function, hepatic function, age, and other medical conditions.
Side Effects
Common Side Effects
- Nausea
- Dizziness
- Drowsiness
- Stomach pain
- Chills
- Feeling of illness
- Fever
- Difficulty breathing
Rare but Serious Side Effects
- Agranulocytosis
- Leucopenia
- Hypersensitivity reactions
- Nephrotoxicity
- Skin eruptions (erythema multiforme, Stevens-Johnson syndrome)
- Hepatotoxicity
- Convulsive crisis
- Coma (with large oral doses)
Long-Term Effects
Chronic complications from prolonged use are rare but can include renal or hepatic damage.
Adverse Drug Reactions (ADR)
Severe skin reactions, agranulocytosis, and hepatotoxicity are serious ADRs that require immediate medical attention.
Contraindications
- Allergy to pyrazolones or other NSAIDs
- G6PD deficiency
- Porphyria
- Perforated eardrums (for otic use)
Drug Interactions
- May affect the metabolism of drugs metabolized by liver enzymes.
- Metabolism may be affected by liver enzyme inhibitors or inducers.
- May interact with other NSAIDs, anticoagulants, antihypertensives, and certain antidepressants.
- Alcohol consumption should be avoided while taking phenazone.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not recommended for use during pregnancy unless absolutely necessary. Potential fetal risks are not well-established.
- Breastfeeding: Not recommended for use during breastfeeding. Phenazone is excreted in breast milk and may pose risks to the neonate.
Drug Profile Summary
- Mechanism of Action: NSAID that inhibits prostaglandin synthesis.
- Side Effects: Nausea, dizziness, drowsiness, stomach pain, agranulocytosis (rare), skin reactions.
- Contraindications: Allergy to pyrazolones, G6PD deficiency, porphyria, perforated eardrums.
- Drug Interactions: Liver enzyme inhibitors/inducers, other NSAIDs, anticoagulants.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 500mg-1g every 4-8 hours (max 4g/day); Otic: 4-6 drops of 0.5% solution 3-4 times daily. Children: Dosage adjustments needed.
- Monitoring Parameters: Monitor for signs of hypersensitivity, blood counts, and liver and kidney function with prolonged use.
Popular Combinations
Phenazone is sometimes combined with lidocaine for otic use to provide both analgesic and local anesthetic effects. Combinations with other analgesics are generally not recommended.
Precautions
- General Precautions: Screen for allergies, G6PD deficiency, porphyria, and renal/hepatic dysfunction.
- Pregnant Women: Avoid use unless absolutely necessary.
- Breastfeeding Mothers: Avoid use.
- Children & Elderly: Use with caution and adjust dosage as needed.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Phenazone?
A: Adults: 500 mg to 1 g orally every 4-8 hours (maximum 4 g/day). Otic: 4-6 drops of a 0.5% solution 3-4 times daily. Children: Dosage must be adjusted based on age and weight.
Q2: What are the primary uses of Phenazone?
A: Mild to moderate pain relief, ear infections, and earwax removal.
Q3: What are the common side effects of Phenazone?
A: Nausea, dizziness, drowsiness, and stomach pain.
Q4: Is Phenazone safe to use during pregnancy?
A: No, it’s generally not recommended unless the benefits clearly outweigh the risks.
Q5: Can Phenazone be used while breastfeeding?
A: No, it’s not recommended as it can be excreted in breast milk.
Q6: Are there any serious side effects I should be aware of?
A: Yes, though rare, serious side effects can include agranulocytosis, hepatotoxicity, and severe skin reactions.
Q7: What are the contraindications for Phenazone use?
A: Allergy to pyrazolones, G6PD deficiency, porphyria, and perforated eardrums (for otic use).
Q8: Does Phenazone interact with other medications?
A: Yes, it can interact with other NSAIDs, anticoagulants, liver enzyme inhibitors/inducers, and some antidepressants.
Q9: How does Phenazone work to reduce pain and inflammation?
A: It inhibits COX enzymes, thus reducing prostaglandin production, which are mediators of pain and inflammation.
Q10: How long does Phenazone take to start working?
A: Oral forms typically reach peak plasma concentrations within 1-2 hours.
