Cefditoren Pivoxil Tablets—A New Cephalosporin

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

Pharmacology Update

Cefditoren is a new semisynthetic "third/ fourth generation" cephalosporin recently approved by the FDA. It has good antimicrobial activity against common pathogens of the respiratory tract such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. TAP Pharmaceuticals licensed cefditoren pivoxil from a Japanese pharmaceutical company. The drug has been in wide use in Japan for 7 years, where 41 million prescriptions have been dispensed. Cefditoren is marketed by TAP as Spectracef.

Indications

Cefditoren is indicated for use in adults or adolescents for the treatment of the following infections: acute bacterial exacerbation of chronic bronchitis caused by H influenzae, Streptococcus parainfluenzae, S pneumoniae, or M catarrhalis; pharyngitis/tonsillitis caused by Streptococcus pyogenes; uncomplicated skin and skin-structure infections caused by Staphylococus aureus, or S pyogenes.1

Dosage

The recommended dose for acute bacterial exacerbation of chronic bronchitis is 400 mg twice daily for 10 days. For pharyngitis/tonsillitis or uncomplicated skin and skin structure infections, the dose is 200 mg twice daily for 10 days. The drug should be taken with meals to improve absorption. It should not be taken with antacids, histamine-2 receptor antagonists, and, possibly proton pump inhibitors. No dose adjustment is required in patients with mild renal impairment or mild-to-moderate hepatic impairment.1

Potential Advantages

Cefditoren has demonstrated in vitro activity against intermediate and penicillin-resistant strains of S pneumoniae as well as beta lactam and macrolide resistant S pyogenes.1-3

Potential Disadvantages

Cefditoren, as with other cephalosporins, is not active against atypical respiratory pathogens such as Chlamydia pneumonia, Mycoplasma pneumoniae, and Legionella pneumophilia. It is not recommended for long-term use as pivalate-containing compounds have been associated with carnitine deficiency when used over a period of months. Patients with milk protein hypersensitivity should not take cefditoren as the tablets contain sodium caseinate.1 The most frequent side effect is diarrhea (12-14%) and the primary reason for discontinuation of therapy is diarrhea or nausea.

Approximately 2-3% of patients discontinue therapy.1

Comments

Cefditoren pivoxil is considered a "third/fourth" generation cephalosporin. It is administered as the prodrug (pivoxil) which is hydrolyzed by esterases after oral absorption. It has excellent in vitro activity against many respiratory tract pathogens such as S pneumonia, H influenzae, and M catarrhalis. It is not active against atypical respiratory pathogens, Pseudomonas aeruginosa or B fragilis. Data from clinical trials indicate that the efficacy and safety of cefditoren are comparable to other similar antibiotics in the treatment of acute exacerbation of chronic bronchitis, pharyngitis, sinusitis, and uncomplicated skin and skin structure infections.4,5 Comparative antibiotics included penicillin VK for pharyngitis, cefuroxime or clarithromycin for acute exacerbation of chronic bronchitis, cefadroxil or cefuroxime for uncomplicated skin and skin structure infections, and amoxicillin/clavulanate for acute maxillary sinusitis.

Cefditoren is expected to be launched in December. Costs are not available at this time.

Clinical Implications

Cefditoren appears to be safe and efficacious for approved indications but does not appear to offer any clear clinical advantages over available agents. It is currently not approved for community-acquired pneumonia or sinusitis. Antibiotic resistance is regarded by several expert committees as a major public health threat. Misuse and overuse of antibiotics is considered a major driver.7 Therefore, judicious use of cefditoren or any antibiotic is essential.

References

1. Spectrocef Product Information. TAP Pharmaceutical Inc. August 2001.

2. Thornsberry C, et al. Chemotherapy. 2001;47:332-343.

3. Hardy DJ, Ludlow MB. Poster presented at: American Society for Microbiology 101st General Meeting, May 20-24, 2001; Orlando, FL.

4. Hom R, et al. Poster presented at: Infectious Diseases Society of America 38th Annual Meeting, Sept. 7-10, 2000; New Orleans, LA.

5. Henry DC, et al. J Resp Dis. 2001:22(8 suppl):S69-74.

6. Ramirez JA, et al. J Resp Dis. 2001;22(8 suppl): S75-S80.

7. FDA Task Force on Antimicrobial Resistance. Key Recommendations and Report. December 2000.

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, Calif.