orespiratory adverse events were higher in CUBICIN-treated patients than in comparator-treated patients. These differences were due to lack of therapeutic effectiveness of CUBICIN in the treatment of CAP in patients experiencing these adverse events [see Indications and Usage (1.3) ].
Laboratory Changes
Complicated Skin and Skin Structure Infection Trials
In Phase 3 cSSSI trials of CUBICIN at a dose of 4 mg/kg, elevations in CPK were reported as clinical adverse events in 15/534 (2.8%) CUBICIN-treated patients, compared with 10/558 (1.8%) comparator-treated patients. Of the 534 patients treated with CUBICIN, 1 (0.2%) had symptoms of muscle pain or weakness associated with CPK elevations to greater than 4 times the upper limit of normal (ULN). The symptoms resolved within 3 days and CPK returned to normal within 7 to 10 days after treatment was discontinued [see Warnings and Precautions (5.2) ]. Table 6 summarizes the CPK shifts from Baseline through End of Therapy in the cSSSI trials.
Table 6. Incidence of CPK Elevations from Baseline during Therapy in Either the CUBICIN Treatment Group or the Comparator Treatment Groups in Phase 3 cSSSI Trials Change in CPK All Patients Patients with
Normal CPK at Baseline
CUBICIN
(N=430) ComparatorComparator: vancomycin (1 g IV q12h) or an anti-staphylococcal semi-synthetic penicillin (i.e., nafcillin, oxacillin, cloxacillin, or flucloxacillin; 4 to 12 g/day IV in divided doses).
(N=459) CUBICIN
(N=374) Comparator
(N=392)
% n % n % n % n
Note: Elevations in CPK observed in patients treated with CUBICIN or comparator were not clinically or statistically significantly different.
No Increase 90.7 390 91.1 418 91.2 341 91.1 357
Maximum Value >1× ULNULN (Upper Limit of Normal) is defined as 200 U/L. 9.3 40 8.9 41 8.8 33 8.9 35
>2× ULN 4.9 21 4.8 22 3.7 14 3.1 12
>4× ULN 1.4 6 1.5 7 1.1 4 1.0 4
>5× ULN 1.4 6 0.4 2 1.1 4 0.0 0
>10× ULN 0.5 2 0.2 1 0.2 1 0.0 0
Note: Elevations in CPK observed in patients treated with CUBICIN or comparator were not clinically or statistically significantly different.
S. aureus Bacteremia/Endocarditis Trial
In the S. aureus bacteremia/endocarditis trial, at a dose of 6 mg/kg, 11/120 (9.2%) CUBICIN-treated patients, including two patients with baseline CPK levels >500 U/L, had CPK elevations to levels >500 U/L, compared with 1/116 (0.9%) comparator-treated patients. Of the 11 CUBICIN-treated patients, 4 had prior or concomitant treatment with an HMG-CoA reductase inhibitor. Three of these 11 CUBICIN-treated patients discontinued therapy due to CPK elevation, while the one comparator-treated patient did not discontinue therapy [see Warnings and Precautions (5.2) ].
The following adverse reactions have been identified during postapproval use of CUBICIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or establish a causal relationship to drug exposure.
Immune System Disorders: anaphylaxis; hypersensitivity reactions, including pruritus, hives, shortness of breath, difficulty swallowing, truncal erythema, and pulmonary eosinophilia [see Contraindications (4), Warnings and Precautions (5.1) ]
Infections and Infestations: Clostridium difficile–associated diarrhea [se
