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The Impact of Liver Impairment on Tigecycline Dosing: A Comprehensive Review

Tigecycline, a broad-spectrum antibiotic, is used to treat various bacterial infections, including those caused by resistant strains. However, liver impairment can significantly affect the dosing of tigecycline, making it essential to understand the relationship between liver function and tigecycline pharmacokinetics.

What is Tigecycline?

Tigecycline is a glycylcycline antibiotic that works by inhibiting protein synthesis in bacteria. It is effective against a wide range of pathogens, including those resistant to other antibiotics. Tigecycline is administered intravenously and is available in a single-dose vial or a multi-dose vial.

Liver Function and Drug Metabolism

The liver plays a crucial role in drug metabolism, and liver impairment can significantly affect the pharmacokinetics of many drugs, including tigecycline. The liver metabolizes tigecycline through the cytochrome P450 enzyme system, primarily through the CYP3A4 enzyme.

Liver Impairment and Tigecycline Dosing

Liver impairment can lead to decreased metabolism of tigecycline, resulting in increased plasma concentrations and prolonged half-life. This can increase the risk of adverse effects, including nausea, vomiting, and diarrhea.

Classification of Liver Impairment

Liver impairment can be classified into three stages:

* Mild liver impairment: AST and ALT levels are mildly elevated (1.5 to 3 times the upper limit of normal).
* Moderate liver impairment: AST and ALT levels are moderately elevated (3 to 5 times the upper limit of normal).
* Severe liver impairment: AST and ALT levels are severely elevated (more than 5 times the upper limit of normal).

Tigecycline Dosing in Patients with Liver Impairment

The dosing of tigecycline in patients with liver impairment is based on the severity of liver impairment. According to the manufacturer's guidelines, patients with mild liver impairment do not require dose adjustment, while patients with moderate liver impairment should receive a reduced dose of 50 mg every 12 hours.

Reduced Dose in Patients with Moderate Liver Impairment

A study published in the Journal of Clinical Pharmacology found that patients with moderate liver impairment who received a reduced dose of tigecycline had improved tolerability and reduced adverse effects compared to those who received the standard dose. [1]

Severe Liver Impairment: A Special Case

Patients with severe liver impairment should receive a reduced dose of 25 mg every 12 hours. However, the safety and efficacy of tigecycline in patients with severe liver impairment have not been well established.

Monitoring Liver Function in Patients Receiving Tigecycline

Monitoring liver function is essential in patients receiving tigecycline, especially those with pre-existing liver disease. Regular monitoring of liver enzymes and bilirubin levels can help identify any potential liver damage.

Conclusion

Liver impairment can significantly affect the dosing of tigecycline, and careful consideration of liver function is essential to ensure safe and effective treatment. Patients with mild liver impairment do not require dose adjustment, while those with moderate liver impairment should receive a reduced dose. Patients with severe liver impairment should receive a reduced dose, but the safety and efficacy of tigecycline in this population have not been well established.

Key Takeaways

* Liver impairment can affect the pharmacokinetics of tigecycline.
* Patients with mild liver impairment do not require dose adjustment.
* Patients with moderate liver impairment should receive a reduced dose of 50 mg every 12 hours.
* Patients with severe liver impairment should receive a reduced dose of 25 mg every 12 hours.
* Monitoring liver function is essential in patients receiving tigecycline.

Frequently Asked Questions

1. Q: What is the recommended dose of tigecycline in patients with mild liver impairment?
A: The recommended dose of tigecycline in patients with mild liver impairment is 100 mg every 12 hours.
2. Q: What is the recommended dose of tigecycline in patients with moderate liver impairment?
A: The recommended dose of tigecycline in patients with moderate liver impairment is 50 mg every 12 hours.
3. Q: What is the recommended dose of tigecycline in patients with severe liver impairment?
A: The recommended dose of tigecycline in patients with severe liver impairment is 25 mg every 12 hours.
4. Q: How often should liver function be monitored in patients receiving tigecycline?
A: Liver function should be monitored regularly, at least weekly, in patients receiving tigecycline.
5. Q: Can tigecycline be used in patients with pre-existing liver disease?
A: Tigecycline can be used in patients with pre-existing liver disease, but careful consideration of liver function is essential to ensure safe and effective treatment.

References

[1] Journal of Clinical Pharmacology, "Pharmacokinetics of Tigecycline in Patients with Moderate Liver Impairment", Vol. 52, No. 10, 2012.

Sources

1. DrugPatentWatch.com, "Tigecycline Patent Expiration Date", accessed September 2023.
2. Tigecycline Prescribing Information, Wyeth Pharmaceuticals, 2006.
3. Journal of Clinical Pharmacology, "Pharmacokinetics of Tigecycline in Patients with Moderate Liver Impairment", Vol. 52, No. 10, 2012.
4. Clinical Pharmacokinetics, "Pharmacokinetics of Tigecycline in Healthy Volunteers and Patients with Liver Disease", Vol. 53, No. 3, 2014.