Nearly a third of HIV-positive patients with kidney impairment received incorrect prescriptions for nucleoside reverse transcript inhibitors (NRTIs) at a university-based clinic in the United States, according to a report published in the September 1st edition of Clinical Infectious Diseases.
These prescribing errors led to serious clinical consequences for two individuals, with one patient experiencing renal failure and the other lactic acidosis. Investigators also established that the use of coformulated NRTI medicines, the dose of which cannot be adjusted, was particularly associated with prescribing errors for patients with renal impairment.
Antiretroviral prescribing errors can have serious consequences, leading to the failure of anti-HIV therapy and the development of drug-resistant HIV is suboptimal doses are prescribed, or a risk of side-effects if excess doses of medicines are used.
It is possible that the increasing number of antiretroviral drugs and complexity of anti-HIV treatment regimens will lead to more cases of prescribing error. However, relatively little is known about the frequency of antiretroviral prescribing errors or the factors associated with them.
Fixed-dose combination NRTI tablets have lead to a decrease in the number of pills involved in daily antiretroviral therapy. But as the dose of such products cannot be adjusted for patients with health issues such as renal impairment, the potential for dosing errors exists.
Investigators at the HIV outpatient clinic at the University of Alabama at Birmingham wished to determine the frequency of NRTI dosing errors and the related factors. They hypothesised that errors would be more frequent in patients with kidney impairment and that the use of fixed-dose combination NRTI products would increase the risk of errors.
An analysis of NRTI prescriptions issued using the clinic’s electronic prescribing system between 2004 and 2006 was performed. Four categories of NRTI dosing errors were defined:
- Weight errors, defined as failure to adjust a dose to a patient’s weight.
- Renal errors, defined as failure to adjust a dose for patients with impaired creatinine clearance.
- Failure to adjust the dose of ddI (didanosine, Videx) when prescribed with tenofovir (Viread).
- Use of non-standard doses.
A total of 907 prescriptions issued to 603 patients were analysed. The median age of patients was 40 years, 51% were white, 76% were male, 28% were uninsured, 49% were cared for by a nurse practitioner and 12% had renal impairment. Median CD4 cell count was 256 cells/mm3 and median viral load was 10,000 copies/ml.
A total of 53 (6%) NRTI prescribing errors were observed, but 41 (31%) of the 132 prescriptions provided to patients with renal impairment were incorrect. The NRTI most frequently misprescribed was ddI, with 22 (28%) of 78 prescriptions being misdosed. One patient experienced kidney failure and another lactic acidosis as a consequence of receiving the wrong dose of ddI.
In multivariate analysis, ddI use (odds ratio [OR], 11.51), older age (OR, 1.75 per ten years), and belonging to an ethnic minority (OR, 2.69) were significantly related to dosing errors.
The investigators hypothesised that the increased risk of prescribing errors seen in patients of older age and patients of minority ethnicity was associated with the increased risk of impaired renal function in these groups. To test this, the investigators added renal function to their multivariate model. Age and ethnicity ceased to be significant predictor of prescribing error.
Analysis was then performed to see if dosing errors were associated with the use of combination NRTI products in patients with renal impairment. The investigators found that coformulated NRTIs (OR, 3.73) and race and ethnicity (OR, 8.12) were significantly associated with dosing errors.
“Our findings highlight the importance of renal impairment in NRTI dosing errors and identify the demographic groups at greatest risk of dosing errors”, write the investigators. They add, “coformulated NRTIs must be used carefully among renally impaired patients. Software that generates NRTI dosing recommendations on the basis of renal function, weight, coadministered drugs, and standard recommendations may greatly reduce NRTI dosing errors”. Such software is being developed at the investigators’ centre.
Willig JH et al. Nucleoside reverse-transcriptase inhibitor dosing errors in an outpatient HIV clinic in the electronic medical record era. Clin Infect Dis 45: 658 – 661, 2007.