Diltiazem co‐treatment in renal transplant patients receiving microemulsion cyclosporin

• Published in: British journal of clinical pharmacology Vol. 56; no. 6; pp. 670 - 678
• Main Authors: Kumana, Cyrus R., Tong, Matthew K. L., Li, Chun‐Sang, Lauder, Ian J., Lee, Joseph S. K., Kou, Maybelle, Walley, Tom, Haycox, Alan, Chan, Tak Mao
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-12-2003; Blackwell Science; Blackwell Science Inc
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Cost Savings; cost‐effectiveness analysis; cyclosporin Neoral; Cyclosporine - administration & dosage; Cyclosporine - economics; diltiazem; Diltiazem - administration & dosage; Diltiazem - economics; dosage conservation; Double-Blind Method; double‐blind randomized trial; Drug Interactions; Drug Therapy, Combination; Female; Humans; Immunomodulators; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - economics; Kidney Transplantation; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Quality of Life; Transplantation, Homologous; Treatment Outcome; Antianginal agent; Coronary vasodilator agent; Calcium antagonist; cyclosporin NeoralR; Benzothiazepine derivatives; Homograft; Transplantation; Kidney; Dose activity relation; Randomization; Graft; Ciclosporin; dosage conservation; Cost efficiency analysis; Kidney disease; Human; Drug combination; Urinary system disease; Antiarrhythmic agent; Diltiazem; cost-effectiveness analysis; Chemotherapy; Treatment; double-blind randomized trial; Health economy; Double blind study; Immunosuppressive agent
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.2003.01908.x

Background  Usage of cyclosporin (the Hong Kong Hospital Authority's single largest item of drug expenditure) continues to increase, mainly due to increasing numbers of renal allograft patients taking it as long‐term antirejection therapy. Diltiazem, an antihypertensive agent, interferes with the first pass extraction of oral cyclosporin, thus serving to conserve its dosage.
Aims  In renal transplant patients, to assess whether diltiazem co‐treatment could achieve worthwhile dosage conservation of Neoral® (a relatively new microemulsified cyclosporin formulation), safely.
Methods  A randomized, placebo‐controlled, double‐blind clinical trial was undertaken at three local hospitals. Renal transplant recipients receiving Neoral® as prophylactic immunosuppression were randomized to two treatment arms. Active treatment consisted of diltiazem tablets 30 or 60 mg twice daily for patients weighing < 60 or ≥ 60 kg, respectively. One hundred and ten eligible patients gave their informed consent, and were followed up for at least six months. The mean difference in the dollar cost in the sixth month was the primary outcome. Secondary/ancillary outcomes included changes in cyclosporin dosage and blood level, and untoward clinical events including rejection. Outcomes were evaluated by intention to treat analyses.
Results  During weeks 23–26 (sixth month) post randomization, diltiazem co‐treatment yielded an estimated average cost saving per patient on drugs of 15%[the 95% confidence interval (CI) of the difference being HK$609 ± 517 or £50 ± 42], with no apparent excess of untoward or adverse events, complications, hospitalization, outpatient visits, or inferior quality of life.
Conclusions  This diltiazem co‐treatment regime applied to the nearly 1800 surviving renal allograft patients followed up in Hospital Authority hospitals could have saved approximately HK$ 14.3 million (£1.17 million) annually, without adverse sequelae.