What is the significance of elevated Creatine Kinase (CK) in a patient on daptomycin?

From the Guidelines

Elevated Creatine Kinase (CK) levels in a patient on daptomycin are a significant concern, as they may indicate muscle toxicity, and weekly monitoring of CK levels is recommended, especially in patients with renal insufficiency or those receiving concomitant statin therapy. The use of daptomycin, a lipopeptide antibiotic, has been associated with elevations in creatinine phosphokinase (CPK) levels, which are rarely treatment-limiting, but have occurred in patients receiving higher doses of the medication, such as 6 mg/kg/day 1. Key considerations for managing patients on daptomycin include:

• Monitoring for muscle pain or weakness
• Weekly determination of CPK levels
• More frequent monitoring in patients with renal insufficiency or those receiving concomitant statin therapy
• Awareness of the potential for daptomycin-induced eosinophilic pneumonia, as reported in several case reports 1. It is essential to weigh the benefits of daptomycin therapy against the potential risks, particularly in patients with pre-existing renal impairment or those receiving concomitant medications that may increase the risk of muscle toxicity. Regular assessment of renal function and adjustment of the daptomycin dose as needed can help minimize the risk of toxicity while maintaining the efficacy of the medication 1.

From the FDA Drug Label

1. 2 Myopathy and Rhabdomyolysis Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values to greater than 10 times the upper limit of normal (ULN), has been reported with the use of daptomycin for injection. Rhabdomyolysis, with or without acute renal failure, has been reported Patients receiving daptomycin for injection should be monitored for the development of muscle pain or weakness, particularly of the distal extremities In patients who receive daptomycin for injection, CPK levels should be monitored weekly, and more frequently in patients who received recent prior or concomitant therapy with an HMG-CoA reductase inhibitor or in whom elevations in CPK occur during treatment with daptomycin for injection Daptomycin for injection should be discontinued in patients with unexplained signs and symptoms of myopathy in conjunction with CPK elevations to levels >1,000 U/L (~5× ULN), and in patients without reported symptoms who have marked elevations in CPK, with levels >2,000 U/L (≥10 × ULN)

The significance of elevated Creatine Kinase (CK) in a patient on daptomycin is that it may indicate myopathy or rhabdomyolysis, which are potential adverse effects of the medication.

• Elevated CK levels, particularly those greater than 10 times the upper limit of normal (ULN), are a key indicator of myopathy.
• Patients with elevated CK levels should be monitored closely for signs and symptoms of myopathy, such as muscle pain or weakness.
• Daptomycin should be discontinued in patients with unexplained signs and symptoms of myopathy in conjunction with CK elevations to levels >1,000 U/L (~5× ULN), and in patients without reported symptoms who have marked elevations in CK, with levels >2,000 U/L (≥10 × ULN) 2.

From the Research

Significance of Elevated Creatine Kinase (CK) in a Patient on Daptomycin

• Elevated CK levels in patients on daptomycin may indicate skeletal muscle injury, which can range from mild to severe, including rhabdomyolysis 3, 4, 5, 6.
• The current package labeling recommends discontinuation of daptomycin with significant myopathy symptoms in association with a CK elevation >1000 U/L or in patients without muscle pain and a CK >10 times normal 3.
• However, some studies suggest that asymptomatic patients with elevated CK levels may be able to continue daptomycin therapy after a temporary discontinuation, also known as a "daptomycin holiday" 4, 7.
• The mechanism of daptomycin-mediated muscle injury is not fully understood, but it is thought that a reduction in daptomycin exposure via a one-dose cessation of therapy may allow for physiological restoration of sarcolemma membrane integrity 7.
• Severe cases of daptomycin-related rhabdomyolysis can be complicated by acute kidney injury and hepatic injury, highlighting the importance of timely recognition of adverse drug effects and identification of risk factors 5, 6.
• Patients on chronic statins may be at higher risk of developing daptomycin-related rhabdomyolysis, and alternative antibiotics should be considered in these cases 5.
• The combination of daptomycin and rifampin may increase the risk of adverse effects, including rhabdomyolysis, acute kidney injury, and hepatic injury, and should be used with caution 6.