The introduction of cyclosporin significantly improved solid organ transplantation outcomes. However, the costs associated with immunosuppressive therapy increased from approximately $US1000 to $US2000 per patient per year with azathioprine (AZA) and prednisone to $US5000 to $US8000 per patient per year with the addition of cyclosporin (1997 values). Because of the financial demands placed on medical care in the current era, research has been directed towards developing drug combinations which potentiate the therapeutic effect of cyclosporin whereby reducing the amount of drug administered and consequently the costs of long term immunosuppressive therapy. To date, many drugs that interact with cyclosporin have been recognised. Included in this list are the azole antifungal drugs, ketoconazole, fluconazole and itraconazole; the calcium channel blockers, diltiazem, verapamil and nicardipine; and the macrolide antibacterials, erythromycin and related compounds. Although all of these drugs increase cyclosporin drug concentrations when used concomitantly, ketoconazole and diltiazem appear to be the best candidates on the basis of reducing financial pressures of chronic immunosuppressive therapy without sacrificing patients' well-being. Studies of various regimens involving the combined use of ketoconazole and cyclosporin have shown that cyclosporin dosages can be reduced by approximately 70 to 85% while maintaining therapeutic blood concentrations in renal, cardiac and liver transplant recipients. The calcium channel blocker, diltiazem, allows a decrease in cyclosporin dosage by approximately 30 to 50% in this same group of organ transplant patients. These reductions in cyclosporin dosage have been achieved with no reported severe adverse effects that would discourage the use of these agents concurrently in practice. The combined use of cyclosporin and ketoconazole or diltiazem could reduce medication costs by approximately $US915 to $US3000 per year per patient. If all patients treated with cyclosporin are considered, these combinations could reduce medication costs by hundreds of millions of dollars per year in the US alone. While these are promising approaches, further characterisation of these drug interactions is necessary before this practice is adopted as standard protocol worldwide. The objective of this paper is to review the clinical and economic potential of cyclosporin-sparing agents such as the azole antifungal drugs and calcium channel blockers in an attempt to decrease the costs associated with this expensive immunosuppressive agent.

The tetracycline antibiotics have pleiotropic anti-inflammatory properties that may explain their therapeutic benefit in rheumatoid arthritis and acne. As these agents suppress both cellular and humoral immune responses, they may be of benefit in treating asthma and other allergic disorders. The purpose of this study was to determine whether minocycline therapy of asthma has steroid sparing effects beyond its inherent antibiotic properties. Adult asthmatic patients (n = 17) were treated with minocycline 150 mg p.o. twice daily or placebo for 8 weeks in a randomized, double-blind, placebo-controlled crossover study. Patients were evaluated for clinical improvement in oral steroid requirements, spirometry, and symptom scores (Asthma Quality of Life Questionnaire). They underwent assessment for preexisting infection (CT facial sinuses, Chlamydia pneumoniae nasopharyngeal culture, and C. pneumoniae and Mycoplasma pneumoniae serology). Minocycline use was associated with a 30% reduction in mean daily prednisone use compared with placebo (8.8 mg versus 14.4 mg, respectively; p = 0.02). Pulmonary function testing showed improvement in forced vital capacity (FVC; percent predicted; p = 0.03) and improvement in actual FVC and forced expiratory volume in 1 second (percent predicted) approached statistical significance (p = 0.05 and 0.08, respectively). Minocycline treatment was associated with significant improvement in asthma symptoms brought on by environmental triggers (p = 0.01). This preliminary study of minocycline therapy showed oral steroid-sparing properties for those with moderate persistent and severe persistent asthma.

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Since 145 of 146 EMBs (99%) demonstrated no or minimal allograft rejection, a large cost savings could be realized if EMBs were performed only when clinically indicated during the 14-day OKT3 induction course in cardiac transplant recipients. Appropriate immunologic monitoring and echocardiographic testing may obviate the need for performing costly EMBs during OKT3 induction without an adverse clinical outcome.