Journal of Pharmacy Technology

To present a case of cefotetan-associated hypoprothrombinemia and to review the literature concerning cephalosporin-associated hypoprothrombinemia.

Information was collected by conducting a MEDLINE search for cases, clinical trials, reviews, and other articles pertaining to cephalosporin use and the development of hypoprothrombinemia.

Studies, cases, and letters were selected if they addressed the development of hypoprothrombinemia in cephalosporin-treated patients.

A case of hypoprothrombinemia is described in an 82-year-old woman who received cefotetan for the treatment of a urinary tract infection. A review of the literature revealed more than 50 reported cases and multiple clinical studies evaluating this adverse effect. The postulated mechanism behind this occurrence is the inhibition of the synthesis of vitamin K-dependent clotting factors by the N-methyl-thiotetrazole (NMTT) moiety found in certain cephalosporin side chains. Risk factors associated with the development of this adverse effect include advanced age, renal and hepatic impairment, recent surgical procedures, malnutrition, and the use of H₂-antagonists.

Cephalosporins containing the NMTT side chain are associated with the development of hypoprothrombinemia and possibly bleeding, especially in high-risk patients.

To establish the pharmacokinetic parameters of gentamicin in elderly patients and to compare predicted concentrations based on the Dettli method, with actual concentrations.

Measurement of gentamicin concentrations and pharmacokinetic parameters in a consecutive patient sample with comparison to ones predicted by the Dettli method.

Medical and surgical units in a Veterans Affairs Medical Center.

Forty-six consecutive elderly men treated with gentamicin for documented or presumed infection and had stable, normal renal function.

The following information was calculated or measured: elimination rate constant (k_el), elimination half-life, volume of distribution (V_d), and peak and trough concentrations.

The mean k_el (0.16 ± 0.05 h⁻¹) was not significantly different (p=0.2) from the Dettli method prediction, and the mean V_d (0.36 ± 0.1 L/kg) was 37 percent higher than that usually reported. Actual peak and trough concentrations were significantly lower (both p<0.01) than predicted concentrations.

Based on our findings, higher than recommended loading doses and longer dosage intervals may be required in the elderly. The Dettli method is useful to estimate k_el in the elderly.

For the pharmacist to be able to practice good professional and scientific procedures, appropriate literature sources are provided to enable rational, appropriate decisions for extemporaneous compounding.

The bibliography consists of articles listed from the key word “compounding” in International Pharmaceutical Abstracts.

The list of references are compiled in alphabetical order according to the title of the reference in terms of generic name, the clinical condition, or the subject heading.

Many of the extemporaneous formulations are published in accessible professional pharmacy journals, including American Druggist, American Journal of Hospital Pharmacy, The Annals of Pharmacotherapy, and US Pharmacist.

The pharmacist must determine if the referenced expiration date was determined either by chemical stability or by successful clinical experience. The assignment of an expiration date by chemical stability is the accepted standard of the pharmaceutical industry. Assigning an expiration date by clinical response does not give the clinician any quantification of chemical potency or an indication of the absence or presence of degradation products in a formulation.

With extemporaneous compounding, there must not be any careless formulation of prescription products without adequate scientific and professional judgment. For this reason, pharmacists are encouraged to use the current pharmaceutical literature to enhance their professional judgment. To make pharmacists' searches of the pharmaceutical literature for extemporaneous formulations a time-efficient procedure, a bibliography is presented.

To introduce the reader to the fundamentals involved in using decision analysis as a tool in evaluating the associated costs and effectiveness of comparable therapeutic agents.

Currently available literature citations were used to provide the reader with basic references whose purpose is to provide a step-by-step approach for using Decision Analysis in conducting a cost-effective comparison of three commonly used antibiotics. Data were gathered from a previously conducted retrospective chart review where the three antibiotics were used for either prophylactic, empiric, or documented infections. Although this study was limited by its retrospective nature, the reader can use the data to appreciate the fundamentals of decision analysis.

The continually changing climate in healthcare and the added visibility of pharmacologic agents in the treatment and prevention of disease has increased pressure on pharmacy departments to provide therapeutic agents that are cost-effective. Decision analysis can be used to compare therapeutic agents, in terms of financial as well as clinical outcomes, in a structured fashion that all members of the health care team can understand. The application of Decision analysis is appropriate for many therapeutic agents, not just antibiotics.