No abstract

Everolimus is an immunosuppressant that blocks growth factor-mediated proliferation of haematopoietic and nonhaematopoietic cells. Oral everolimus 0.75 or 1.5mg twice daily significantly reduced the incidence of the primary composite endpoint, efficacy failure 6 months after transplantation, compared with azathioprine 1-3 mg/kg/day, in adult cardiac transplant recipients. All patients also received baseline immunosuppression with cyclosporin and corticosteroids. The incidence of efficacy failure remained significantly lower in everolimus recipients than in those receiving azathioprine 1 and 2 years after cardiac transplantation. However, graft and patient survival rates at 1 year were similar in patients receiving everolimus or azathioprine. The incidence of graft vasculopathy 2 years after transplantation was significantly lower in cardiac transplant recipients receiving everolimus 0.75 mg twice daily than in those receiving azathioprine. The combined incidence of biopsy-confirmed acute rejection, graft loss, death, or loss to follow-up was similar in adult patients receiving everolimus 1.5 or 3 mg/day or mycophenolate mofetil (MMF) 2 g/day 1 or 3 years after renal transplantation. Patients also received baseline immunosuppression with cyclosporin and corticosteroids. Compared with azathioprine and MMF, everolimus is associated with a lower incidence of cytomegalovirus infection in cardiac and renal transplant recipients. Everolimus has been associated with thrombocytopenia, leucopenia and elevated serum lipids and creatinine.

Tenofovir disoproxil fumarate (tenofovir DF) is a prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor. In two large, well designed, placebo-controlled clinical trials, tenofovir DF 300 mg/day resulted in significant reductions in HIV-1 RNA from baseline compared with placebo at 24 weeks in antiretroviral-experienced patients with HIV infection. Patients in both treatment groups continued to receive existing stable antiretroviral therapy. In an extension phase of one trial, these reductions in viral load were maintained after 96 weeks of treatment with tenofovir DF. Preliminary data from a large, 3-year comparative trial suggest the clinical efficacy of tenofovir DF in combination with baseline antiretroviral therapy is similar to that of stavudine in antiretroviral-naive patients with HIV infection. Virological substudies showed that viral suppression was maintained in patients who developed new reverse transcriptase mutations during tenofovir DF therapy (in combination with existing stable antiretroviral drugs) for up to 48 weeks. Isolates of HIV infrequently developed the K65R mutation during 96 weeks of tenofovir DF therapy. Tenofovir DF is generally well tolerated. The most commonly observed adverse events seen with tenofovir DF (in combination with other antiretroviral drugs) were predominantly of a gastrointestinal nature.

Basiliximab reduces acute rejection without increasing the incidence of adverse events, including infection and malignancy, in renal transplant recipients when combined with standard dual- or triple-immunotherapy. The overall incidence of death, graft loss or acute rejection was significantly reduced at 3 years; there was no significant difference for this endpoint 5 years after transplantation. Malignancy was not increased at 5 years. The overall efficacy, tolerability, ease of administration and cost effectiveness of basiliximab make it an attractive option for the prophylaxis of acute renal transplant rejection.

Once-daily lercanidipine is an effective and well tolerated antihypertensive agent in patients with mild-to-moderate hypertension.