RxPRODUCT NEWS PROFILE: Cubicin

Christian Hartman, PharmD, and Claudio Faria, PharmD
Published Online: Saturday, May 1, 2004

Background

The treatment of Staphylococcus aureus?related bacterial infections has become more difficult due to the increased prevalence of resistance to antibiotics. The FDA reports that nearly 70% of bacteria that cause infections in hospitals are resistant to at least 1 of the drugs most commonly used to treat the infection.1 Cubicin is a novel antibacterial agent marketed by Cubist Pharmaceuticals Inc and manufactured by Abbott Laboratories. It is indicated for the treatment of complicated skin and skin structure infections caused by strains of gram-positive microorganisms: S aureus (including methicillinresistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp equisimilis, and Enterococcus faecalis (vancomycin-susceptible strains only).

Pharmacology

Cubicin, a cyclic lipoprotein, causes rapid depolarization of membrane potentials. This action leads to impediment of bacterial cell DNA and RNA production and ultimately to cell death.2

Clinical Trials

Two similar randomized, multicenter, investigator-blinded clinical trials (9801 and 9901) comparing Cubicin (4 mg/kg intravenous [IV] q 24 h) with either vancomycin (1 g IV q 12 h) or a semisynthetic penicillin (ie, nafcillin, oxacillin, cloxacillin, or flucloxacillin; 4-12 g IV/day) were conducted in adult patients with clinically documented complicated skin and skin structure infections. Patients were randomized to receive Cubicin 4 mg/kg IV q 24 h, vancomycin 1 g IV q 12 h, or a semisynthetic penicillin (eg, nafcillin, oxacillin) 4-12 g IV qd. Patients were switched to oral therapy after a minimum of 4 days of IV therapy if clinical improvement was observed.2,3

In the first study, a total of 534 patients were treated with Cubicin, and 558 were treated with comparative agents, with most patients (89.7%) receiving only IV therapy throughout the trial. Clinical success rates were used as efficacy end points in both trials for the intent-to-treat (ITT) and the clinically evaluable (CE) population. Results varied; overall, however, Cubicin showed comparative success rates in both groups (ITT and CE) when tested side by side against other comparator drugs.

In the 9801 study, the ITT group presented a 62.5% and a 60.9% success rate, and the CE group presented a 76.0% and a 76.7% success rate, when comparing Cubicin to comparator agents, respectively. In the 9901 study, the ITT group exhibited a 80.4% and a 80.5% success rate and the CE group exhibited a 80.9% and a 90.4% success rate, when comparing Cubicin to comparator drugs, respectively.2,3

Safety

The most common adverse events (>2% of patients) noted in trials were constipation, nausea, diarrhea, vomiting, injection-site reactions, headache, insomnia, dizziness, rash, pruritus, abnormal liver function test results, elevated creatine phosphokinase (CPK), fungal infections, urinary tract infections, hypotension, renal failure, anemia, and dyspnea.2 As with other antibacterial agents, Cubicin may alter normal intestinal flora. Therefore, it is important to identify patients with diarrhea prior to initiating therapy. Additionally, caution is advised when using Cubicin concomitantly with warfarin and HMG-CoA reductase inhibitors because of limited available information.2 The international normalized ratio should be monitored closely when using warfarin and Cubicin together.2 CPK levels also should be watched closely, since both Cubicin and HMG-CoA reductase inhibitors have been shown to increase these levels.2 It is recommended that HMG-CoA reductase inhibitors be temporarily suspended at the initiation of treatment with Cubicin.2

Outlook

Cubicin is available as a sterile lyophilized powder in either 250-mg or 500-mg single-use vials. It is administered at 4 mg/kg over 30 minutes (in 0.9% sodium chloride) intravenously every 24 hours for 7 to 14 days.2 If creatinine clearance is <30 mL/min, it is recommended that Cubicin be administered at 4 mg/kg every 48 hours.2 Cubicin is as safe and effective as other comparable agents used for complicated skin or skin structure infections. Results from future trials could broaden the use of Cubicin in other infectious diseases due its potential to treat resistant strains of bacteria. See prescribing information for complete microbiologic species susceptibility.

Dr. Hartman is medication safety officer at UMass Memorial Medical Center, Worcester, Mass. He also is a clinical assistant professor at Northeastern University and an adjunct assistant professor at Massachusetts College of Pharmacy. Dr. Faria is senior research pharmacist at Brigham and Women's Hospital, Boston, Mass.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. D. Ryan, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: dryan@mwc.com.



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