atients (1.9%) than in those that received comparators (0.5%). Therefore, it is recommended that:• Plasma CPK should be measured at baseline and at regular intervals (at least once weekly) during therapy in all patients.• It cannot be ruled out that those patients with CPK greater than 5 times upper limit of normal at baseline may be at increased risk of further increases during daptomycin therapy. This should be taken into account when initiating daptomycin therapy and, if daptomycin is given, these patients should be monitored more frequently than once weekly.• CPK should be measured more frequently than once weekly in patients who are at higher risk of developing myopathy. These patients include those with severe renal insufficiency (creatinine clearance 40 kg/m2 but with creatinine clearance > 70 ml/min, the AUC0- daptomycin was significantly increased (mean 42% higher) compared with non-obese matched controls. There is limited information on the safety and efficacy of daptomycin in the very obese and so caution is recommended. However, there is currently no evidence that a dose reduction is required.The use of antibiotics may promote the overgrowth of non-susceptible micro-organisms. If super infection occurs during therapy, appropriate measures should be taken.Antibiotic-associated colitis and pseudomembranous colitis have been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or shortly following treatment.
Interactions
Daptomycin undergoes little to no Cytochrome P450 (CYP450) mediated metabolism. In vitro studies have determined that daptomycin does not inhibit or induce the activities of clinically significant human CYP isoforms (1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4). Therefore, no CYP450-related drug interactions are to be expected.There is limited experience regarding concomitant administration of daptomycin with other medicinal products that may trigger myopathy. However, some cases of marked rises in CPK levels and cases of rhabdomyolysis occurred in patients taking one of these medications at the same time as Cubicin. It is recommended that other medications associated with myopathy should if possible be temporarily discontinued during treatment with Cubicin unless the benefits of concomitant administration outweigh the risk. If co-administration cannot be avoided, CPK levels should be measured more frequently than once weekly and patients should be closely monitored for any signs or symptoms that might represent myopathy. See Special Precautions and Adverse Reactions.Daptomycin is primarily cleared by renal filtration and so plasma levels may be increased during co-administration with medicinal products that reduce renal filtration (e.g. NSAIDs and COX-2 inhibitors). In addition, there is a potential for a pharmacodynamic interaction to occur during co-administration due to additive renal effects. Therefore, caution is advised when daptomycin is co-administered with any other medicinal product known to reduce renal filtration.During post-marketing surveillance, cases of interference between daptomycin and a particular reagent used in some assays of Prothrombin Time/International Normalised Ratio (PT/INR) have been reported. This interference led to an apparent prolongation of PT and elevation of INR. If unexplained abnormalities of PT/INR are
