Usage
Topiroxostat is prescribed for the treatment of hyperuricemia (high blood uric acid levels) in patients with gout. It belongs to the pharmacological class of xanthine oxidase inhibitors. Its mechanism of action involves selectively inhibiting xanthine oxidase, an enzyme crucial for uric acid production. By reducing uric acid levels, it aids in preventing gout flares and joint damage associated with urate crystal deposition.
Alternate Names
Topiroxostat is also known as Topiloric, Uriadec or FYX-051.
How It Works
Pharmacodynamics: Topiroxostat selectively and competitively inhibits xanthine oxidase, thereby reducing uric acid production. This leads to a decrease in serum and urine uric acid levels, preventing the formation of urate crystals in joints and other tissues.
Pharmacokinetics:
- Absorption: Topiroxostat exhibits good oral bioavailability.
- Metabolism: Primarily metabolized in the liver. Main metabolites include N-oxide, N1-glucuronide and N2-glucuronide. It demonstrates strong inhibition of CYP2C8/9 and weak inhibition of CYP1A1/2, 3A4 and 2C19. It shows no inhibition of CYP2A6, 2B6, 2D6 and 2E1, and does not induce CYP enzymes.
- Elimination: Excreted via both renal and hepatic routes, with a higher proportion through hepatic elimination. It inhibits renal transporters OAT1, OAT3, BCRP and OATP1B1.
Dosage
Standard Dosage
Adults:
Initial dose: 20 mg twice daily (BID), orally.
Maintenance dose: 60 mg BID, orally.
Maximum dose: 80 mg BID, orally.
Dosage titration: The dose can be gradually increased (e.g., by 20 mg increments every 2-4 weeks) based on serum uric acid levels and patient response, up to the maximum dose.
Children:
The safety and efficacy of Topiroxostat have not been established in pediatric patients.
Special Cases:
- Elderly Patients: Careful monitoring is recommended, though dosage adjustments are not typically required based on age alone. Renal and hepatic function should be assessed.
- Patients with Renal Impairment: Dose adjustments are necessary for patients with moderate to severe renal impairment. With creatinine clearance (CrCl) 30-50 mL/min, a maximum dose of 60 mg/day is recommended. With CrCl < 30 mL/min, the drug is contraindicated. Regular monitoring of renal function is advised.
- Patients with Hepatic Dysfunction: Caution is advised, though specific dosage adjustments are not explicitly defined. Monitoring of liver function tests is recommended.
- Patients with Comorbid Conditions: Consider individual patient factors and potential drug interactions when prescribing to patients with comorbid conditions.
Clinical Use Cases
The use of topiroxostat in specific medical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations has not been established and is not recommended.
Dosage Adjustments
Dose modifications may be necessary based on serum uric acid levels, renal function, hepatic function, concomitant medications, and individual patient response.
Side Effects
Common Side Effects
- Elevated liver enzymes
- Gastrointestinal issues (diarrhea, nausea, vomiting, abdominal pain)
- Headache
- Drowsiness
- Skin rash
- Fatigue
Rare but Serious Side Effects
- Hypersensitivity reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)
- Liver damage
- Severe hematological abnormalities (e.g., decreased white blood cell or platelet counts)
Long-Term Effects
Limited data exists on long-term complications. However, long-term monitoring is recommended for potential renal or hepatic issues, as well as hematological abnormalities.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe hypersensitivity reactions and liver dysfunction.
Contraindications
- Hypersensitivity to Topiroxostat
- Severe renal impairment (CrCl < 30 mL/min)
- Concomitant use of azathioprine or mercaptopurine
Drug Interactions
- Theophylline
- Azathioprine
- Mercaptopurine
- Warfarin
- Other medications metabolized by CYP2C8/9, CYP1A1/2, CYP3A4 and CYP2C19
Pregnancy and Breastfeeding
Topiroxostat should generally be avoided during pregnancy and breastfeeding unless the potential benefits outweigh the risks. Animal studies have shown some transfer of the drug to milk. Consult with a specialist regarding potential risks and alternative treatment options.
Drug Profile Summary
- Mechanism of Action: Selective xanthine oxidase inhibitor.
- Side Effects: Elevated liver enzymes, gastrointestinal issues, skin rash, fatigue, headache, drowsiness.
- Contraindications: Hypersensitivity, severe renal impairment, concomitant azathioprine/mercaptopurine.
- Drug Interactions: Theophylline, azathioprine, mercaptopurine, warfarin, and drugs metabolized by certain CYP enzymes.
- Pregnancy & Breastfeeding: Avoid unless benefits outweigh risks.
- Dosage: Initial 20 mg BID, titrate up to 80 mg BID.
- Monitoring Parameters: Serum uric acid, liver function tests, renal function tests, complete blood count.
Popular Combinations
NSAIDs or colchicine may be used for acute gout flares alongside chronic topiroxostat therapy for long-term management of hyperuricemia.
Precautions
- Pre-existing liver or kidney disease: Careful monitoring is necessary.
- Hypersensitivity: Monitor for allergic reactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Topiroxostat?
A: Initial: 20 mg BID. Maintenance: 60 mg BID. Maximum: 80 mg BID. Titrate based on serum uric acid and patient response.
Q2: What is the mechanism of action of Topiroxostat?
A: Topiroxostat is a selective xanthine oxidase inhibitor, reducing uric acid production.
Q3: What are the common side effects of Topiroxostat?
A: Common side effects include elevated liver enzymes, gastrointestinal issues, headache, skin rash, fatigue and drowsiness.
Q4: What are the contraindications for Topiroxostat?
A: Contraindications include hypersensitivity to topiroxostat, severe renal impairment (CrCl < 30 mL/min), and concomitant use of azathioprine or mercaptopurine.
Q5: Can Topiroxostat be used during pregnancy or breastfeeding?
A: Generally avoided unless benefits clearly outweigh risks. Consult with a specialist regarding potential risks and safer alternatives.
Q6: What are the potential drug interactions with Topiroxostat?
A: Topiroxostat may interact with theophylline, azathioprine, mercaptopurine, warfarin, and certain drugs metabolized by CYP enzymes.
Q7: How should Topiroxostat dosage be adjusted for patients with renal impairment?
A: Reduce the dose or avoid its use in patients with moderate to severe renal impairment. If CrCl is 30-50 mL/min, the maximum recommended dose is 60 mg/day. With CrCl < 30 mL/min, the drug is contraindicated.
Q8: What should be monitored in patients taking Topiroxostat?
A: Monitor serum uric acid levels, liver function tests, renal function, and complete blood count.
Q9: What is the role of Topiroxostat in gout management?
A: It prevents gout flares and joint damage associated with urate crystal deposition by lowering uric acid levels. It’s not for acute gout attacks.
Q10: Can Topiroxostat be used with other medications for gout?
A: Yes, it can be used in combination with NSAIDs or colchicine for acute attacks.
