Substitution guidelines

In response to the increasingly common trend of substituting generic medications for brand-name ones, the National Kidney Foundation issued new recommendations for the safe and effective use of generic immunosuppressant medications in solid organ transplant recipients.

Particularly popular with managed care organizations, which want to rein in rising prescription drug costs, drug substitution is usually innocuous. The Food and Drug Administration holds every generic product to a standard of bioequivalence, and the variation in efficacy is usually lower than 30%. In some instances, pharmacists can switch a patient's prescription from a brand-name product to a generic one without consulting a physician.

According to the National Kidney Foundation, substituting a critical-dose drug in a kidney transplant patient should not be done without the approval of the prescribing physician and the patient.

Despite the possible advantages associated with drug substitution - including lower cost and better compliance - there are also potential dangers such as overdose, underdose and unexpected side effects.

"Our goal is to ensure that patients are fully aware of their unique drug regimens and involved in the decision-making process when changes or substitutions occur," said Joel Kopple, M.D., president of the National Kidney Foundation.

Published in the foundation's American Journal of Kidney Disease (Vol. 33, No. 2), the recommendations include the following:

•Â The immunosuppressive agents cyclosporine and tacrolimus should be included in lists of critical-dose drugs. In the future, new immunosuppressive agents should be evaluated to determine whether they also meet these criteria.

•Â For critical-dose drugs, replicate design studies to determine subject-by-formulation interactions should be required as part of the Food and Drug Administration approval process for both innovator drugs and their generic equivalents.

•Â Health care providers should educate the patient about generic drugs and include him or her in the decision of whether to switch drugs.

•Â The pharmacist should inform the prescribing physician and patient whenever a prescribed immunosuppressive drug for a transplant patient is to be switched.

Casting a critical eye

The authors of the recommendations also called on the Food and Drug Administration to review its methodology for establishing and approving bioequivalence, calling the current testing "limited."

They pointed out that bioequivalence is currently tested in healthy and usually young male volunteers, who may absorb medicines differently than some patients.

For critical-dose drugs, they recommended that replicate design studies be used to determine subject-by-formulation interactions.

The authors also recommended that the Food and Drug Administration should "request that generic manufacturers obtain bioequivalence data in subpopulations of patients for whom, based on evidence in the literature, the drug is likely to exhibit visible bioavailability that differs substantially from the norm."

The authors wrote their findings based on a conference of 45 experts from diverse clinical disciplines and transplant patients who met in April 1998.

For an executive summary of the drug substitution guidelines, call (800) 622-9010. PR