Ingrida S. Sketris

Effect of Calcium-Channel Blockers on Cyclosporine Clearance and Use in Renal Transplant Patients

OBJECTIVE: To determine the effect of calcium-channel blockers (CCBs) on cyclosporine dose, clearance, and cost, and their effect on kidney graft function and survival in patients who underwent kidney transplant. DESIGN: A total of 176 adults receiving 177 transplants were studied retrospectively. Patients were stratified as follows: no CCB (n=57), diltiazem (n=13), nifedipine (n=37), and verapamil (n=70). Patients received cyclosporine 3–4 mg/kg by continuous infusion for 5 days followed by cyclosporine 10 mg/kg/d po to maintain initial whole blood concentrations of 300–400 ng/mL. Clearance of intravenously administered cyclosporine was calculated following at least 48 hours of the same dose by continuous infusion. The amount and cost of cyclosporine used during the first 10 days of oral therapy were also calculated. RESULTS: Patients receiving diltiazem, but not verapamil or nifedipine, had decreased clearance of intravenously administered cyclosporine compared with that of the mean control group. The mean clearance of intravenously administered cyclosporine ± SD in patients receiving no CCB was 5.1 ± 1.5 mL/min/kg, diltiazem was 3.7 ± 0.8 mL/min/kg, nifedipine was 6.4 ± 1.9 mL/min/kg, and verapamil was 5.2 ± 2.2 mL/min/kg. The amount and cost of 10 days of oral cyclosporine therapy was decreased in the verapamil group (5.7 ± 1.5 g and

Coprescribing of nonsteroidal anti-inflammatory drugs and cytoprotective and antiulcer drugs in Nova Scotia's senior population

257 ± 69) compared with that of the control group (6.7 ± 1.6 g and

Cyclosporine Absorption in Two Patients with Short-Bowel Syndrome

304 ± 72) (p<0.001). There was no significant difference among the groups with respect to immediate graft function, 1-year serum creatinine concentration, or 1-year graft survival. CONCLUSIONS: Diltiazem decreased the clearance of intravenously administered cyclosporine. Although verapamil did not decrease the clearance of intravenously administered cyclosporine, it allowed a significant reduction in oral cyclosporine cost without apparent adverse effects on graft function. Further work is needed to determine the effect of CCBs on cyclosporine pharmacokinetics, especially with respect to their metabolism by gut and hepatic cytochrome P-450 enzymes, and their effect on patient outcome.

Eight Days of Cyclosporine Overdose: A Case Report

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for the elderly and are commonly prescribed with cytoprotective or antiulcer drugs to prevent or treat gastrointestinal side effects. The objective of this study was to examine the utilization and drug costs of NSAIDs, and to examine coprescription of cytoprotective and antiulcer drugs with NSAIDs in the Nova Scotia population aged 65 years and older. The study used data from the Nova Scotia Seniors Pharmacare program database, which contains data on claims for all filled prescriptions to persons 65 years of age and older. We examined claims for the period April 1, 1993, to March 31, 1994. Aspirin accounted for the largest percentage of the total days supply of NSAIDs (25.2%), followed by diclofenac (18.8%) and naproxen (12.9%). Diclofenac accounted for the largest share of expenditures for NSAIDs (27.6%). Overall, 17.1% of the total days supply of NSAIDs were coprescribed with a cytoprotective or antiulcer drug. Histamine2 blockers accounted for most coprescribed days supply (83.6%) followed by sucralfate (8.1%), misoprostol (4.5%), and omeprazole (2.3%). The appropriateness and cost-effectiveness of these coprescriptions must be examined.

DEVELOPING A QUALITY ASSURANCE PROGRAM FOR DRUG INFORMATION REQUESTS ANSWERED BY STAFF PHARMACISTS

We present the cases of two patients with short-bowel syndrome who failed to achieve therapeutic cyclosporine serum concentrations on oral drug but were successful on intravenous administration. One patient received cyclosporine after renal transplantation for renal failure secondary to enteric oxalosis; the second received cyclosporine for active Crohns disease. The rapid bowel transit time was the critical factor in limiting cyclosporine absorption in both cases. In studying oral and intravenous pharmacokinetic profiles, we support a zero-order kinetic model for oral cyclosporine absorption.

Effect of coadministration of acyclovir and cyclosporine on kidney function and cyclosporine concentrations in renal transplant patients.

A 25–year‐old woman was admitted to the hospital because of rising trough cyclosporine concentrations thought to be due to self‐administration of 4 times the normal dosage of the drug for 8 days. Her symptoms included colicky central abdominal pains and urinary retention; her serum creatinine concentrations were elevated. Whole blood cyclosporine and metabolite concentrations were measured by high‐performance liquid chromatography and monoclonal radioimmunoassays. The highest reported trough cyclosporine concentration was 5877 ng/ml, and AM1 (M17) concentration was 3425 ng/ml. A cyclosporine half‐life of 91 hours was calculated. Nine days after the agent was discontinued the patients serum creatinine concentration had returned to normal and her symptoms resolved. Due to the availability of three sizes of cyclosporine capsules, and the need for frequent dosage changes, continued vigilance is necessary to ensure that patients understand their drug regimen.

Cost-effectiveness of interferon beta-1b in slowing multiple sclerosis disability progression: First estimates

A quality assurance program was developed at an 800-bed tertiary care hospital to determine if pharmacists working outside a formal drug information center were providing adequate responses and appropriately documenting drug information requests, and if requesters were satisfied with the service. Two instruments, an audit form that could be used by peers to examine written documentation and a satisfaction questionnaire sent to requesters, were constructed. All drug information requests were evaluated for a four-week period. Seventy-eight questions were documented, 57 of which had sufficient information to allow user satisfaction questionnaires to be sent. Compliance with documentation was generally good, except for the name of the requester (73%) and the location and/or pager of the requester (65%). The drug information responses given met audit standards for 85% of requests. Eight questions were judged to need further referral, eg, to the drug information center. Replies from the user questionnaire demonstrated that information was primarily used in direct patient care. The quality assurance program identified subject areas of weakness, eg, drugs and pregnancy, which need to be addressed in continuing education programs and highlighted areas in which documentation could be improved.

Erythromycin-cyclosporine interaction

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