From the Guidelines
Daptomycin is not significantly associated with liver dysfunction, as evidenced by the lack of significant hepatotoxicity reports in clinical use. The provided evidence [ 1 ] focuses on the treatment of infections due to multidrug-resistant organisms, including vancomycin-resistant enterococci (VRE), and does not highlight liver dysfunction as a concern with daptomycin use. While the study discusses various aspects of daptomycin treatment, including dosage, combination therapy, and comparisons with other antibiotics, it does not mention liver dysfunction as a notable side effect.
Key Points to Consider
- The primary concerns with daptomycin are related to its potential to cause muscle toxicity (myopathy), which is monitored through creatine phosphokinase (CPK) levels, not liver function tests [ 1 ].
- Routine monitoring of liver function tests is not typically required during daptomycin therapy unless a patient has pre-existing liver disease or is taking other medications that may affect the liver.
- If a patient develops unexplained elevations in liver enzymes while on daptomycin, other causes should be investigated, and the medication can be continued with appropriate monitoring in most cases.
Clinical Implications
- Daptomycin has a favorable hepatic safety profile compared to some other antibiotics, making it a suitable option for patients with liver impairment when an appropriate indication exists [ 1 ].
- The absence of significant liver dysfunction associated with daptomycin supports its use in clinical practice for treating serious infections, including those caused by VRE, without undue concern for hepatotoxicity.
From the FDA Drug Label
The pharmacokinetics of daptomycin were evaluated in 10 adult subjects with moderate hepatic impairment (Child-Pugh Class B) and compared with those in healthy adult volunteers (N=9) matched for gender, age, and weight. The pharmacokinetics of daptomycin were not altered in subjects with moderate hepatic impairment No dosage adjustment is warranted when daptomycin for injection is administered to patients with mild to moderate hepatic impairment. The pharmacokinetics of daptomycin in patients with severe hepatic impairment (Child-Pugh Class C) have not been evaluated.
Daptomycin does not cause liver dysfunction in patients with mild to moderate hepatic impairment, as the pharmacokinetics of daptomycin were not altered in these patients. However, the pharmacokinetics of daptomycin in patients with severe hepatic impairment have not been evaluated.
- Key points:
- Daptomycin pharmacokinetics were not altered in patients with moderate hepatic impairment.
- No dosage adjustment is needed for patients with mild to moderate hepatic impairment.
- The effect of daptomycin on patients with severe hepatic impairment is unknown. 2
From the Research
Daptomycin and Liver Dysfunction
- Daptomycin has been associated with liver dysfunction in several case reports, including acute liver failure 3, 4 and asymptomatic elevated transaminases 5, 6.
- The mechanism of daptomycin-induced liver injury is unclear, but it is thought to be rare and possibly dose-dependent 3, 4.
- Studies have reported that daptomycin can cause liver damage with or without elevations in creatine kinase (CK) levels 4, 5.
- Monitoring liver function tests at baseline and weekly thereafter, along with CK levels, is recommended, especially in patients requiring long-term daptomycin therapy 4.
- The importance of daptomycin dosage on clinical outcome has been highlighted, with doses ≥8mg/kg potentially needed to adequately treat vancomycin-resistant enterococci infection in liver transplant recipients 7.
Case Reports
- A 73-year-old male developed acute liver failure after receiving daptomycin for diabetic left foot osteomyelitis, with significant improvement after discontinuation of the drug 3.
- A 49-year-old female presented with alteration in mental status and acute liver failure after being treated with daptomycin for methicillin-resistant Staphylococcus aureus (MRSA) endocarditis, with resolution of liver failure after withdrawal of the drug 4.
- A patient being treated for MRSA bacteremia with daptomycin developed asymptomatic elevated transaminases, which returned to normal levels after discontinuation of the drug 5.
- A patient receiving daptomycin developed asymptomatic transaminitis and hyperbilirubinemia, which was attributed to daptomycin and resolved after discontinuation 6.