mean weight 64.5 kg [range 40-120]). Theophylline serum concentrations were measured by fluorescence polarization immunoassay in a TDx analyzer (Abbott Laboratories, North Chicago, IL). A data collection form was used to record information relevant to the study, including patient age, gender, weight, height, theophylline dosage schedules, concomitant medications, prior medical history, time of last dose before sample collection, blood sampling time, and adverse effects. After the assimilation and analysis of all of the elements, we individualized, characterized, and evaluated the results obtained to establish the optimal posology for each patient. The one-compartmental model was assumed for all calculations, and in many situations we merely applied the algorithms for dosage and therapeutic monitoring of theophylline proposed by Mangues et al.s Figure I illustrates the dosage adjustments performed in our population. About 75 percent of the dosing schedules were changed, with a high percentage of subtherapeutic situations. The results of this study show, in accordance with previously published data,6.7 that a large percentage of patients receiving aminophylline or theophylline therapy are either under- or overdosed when treatment is based on conventional dose regimens. Advantages of theophylline monitoring include therapy improvement, a decrease in prescribing of potentially more-aggressive drugs, and a positive evolution of the cost-benefit ratio. AMILCAR C. FALcAo
Doctor of Pharmacy Student Assistant Professor
MARGARIDA CARAMONA, Pharrn.D. Associate Professor Laboratory ofPharmacology Faculty ofPharmacy Coimbra University Largo D. Diniz 3000 Coimbra Portugal
6. Capps N, Watkins K, Jordan P, Sewell GJ. General practice theophylline audit in the Exeter Health District. J Clin Pharmacol Ther 1990: 15:101-7. 7. Mason BJ. Subtherapeutic serum drug concentrations and compliance (letter). D1CPAnn Pharmacother 1991;25:103-4.
Comment: patterns of isotretinoin prescribing TO THE EDITOR: I am writing in response to the article by Doering et al., entitled "Patterns of Prescribing Isotretinoin: Focus on Women of Childbearing Potential" (Ann Pharmacother 1992;26: 155-61). Since January 1989, my colleagues and I have been conducting a survey of isotretinoin (Accutane) use in women to assess the effectiveness of the manufacturer's Pregnancy Prevention Program (this survey is sponsored by Hoffman-La Roche). In their discussion of fmdings from their survey of prescribers, Doering et al. cited a previous publication which reported that we had found that "about one-third of the pregnancies associated with isotretinoin have been in women who were pregnant at the time they started the drug."' The information in that reference is incorrect. The figure of 33 percent is derived from an earlier report,' and is also found in a study published this year'; estimates from both studies were derived from pregnancies that occurred among women who started isotretinoin in 1988 or earlier. In contrast, results of our survey, which began in 1989, revealed that the equivalent proportion was 12 percent (unpublished data, presented before Food and Drug Administration advisory committee, Rockville, MD, May 20,1991). We caution that these differences not be viewed as evidence of a decline in the proportion of women who are pregnant at the time of isotretinoin prescription, since the earlier figure of 33 percent was derived from spontaneous reports and our figure of 12 percent was derived from a systematic survey. ALLEN A. MITCHELL, M.D.
REFERENCES
Research Professor ofPublic Health Slone Epidemiology Unit Boston University School ofMedicine 1371 Beacon Street Brookline, Massachusetts 02146
I. Burkle WS. Development and implementationof clinical pharrnacokinetic services. Am] Hosp Pharm 1990;47:391-4.
REFERENCES
2. McLeod DC, Taylor WJ. Therapeutic drug monitoring as a standard of care. Drug Intell Clin Pharm 1985;6:473-4. 3. Cannon DJ. Therapeutic drug monitoring (letter). Clin Chem 1991;37: 141.
4. Ho K, Spino M. Theophylline in asthma: once versus twice-daily dosing. Can] Hosp Pharm 1989;42:173-218. 5. Mangues MA, Bonal J, Farre R, MassOJF. Algorithms for dosage and therapeutic monitoring of theophylline. Drug Intell Clin Pharm 1988; 22:893-4.
40
30
20
10
I. Marwick C. Additional steps proposed to ensure antiacne drug used only in appropriate patient population. ]AMA 1990;263:3125-6. 2. Lammer EJ, Chen DT, Hoar RM, Narsingh D, Benke PJ, Braun PJ, et al, Retinoic acid embryopathy. N EnglJ Med 1985;313:837-41. 3. Dai W, LaBraico JM, Stern RS. Epidemiology of isotretinoinexposure during pregnancy.J Am Acad DermatoI1992;26:599-606.
AUTHOR'S REPLY: In the "Methods" section of our article, we did not indicate the time frame in which the survey research was performed. It may be important to know this because the comprehensive Pregnancy Prevention Program for Women on Accutane initiated by Hoffman-La Roche had just gotten underway in late 1988. This program was not fully implemented until mid-1989. Our survey was developed in late 1988 and was mailed in mid-December of that year. A period of eight weeks was allowed for return of the questionnaire. Thus, it is likely that some survey recipients had received our survey packet before they had been informed of the new Pregnancy Prevention Program. How many had been informed of this program by the time they received our survey cannot be determined. At least some respondents had been advised of the Pregnancy Prevention Program because they sent us the informed consent form they had been given in the packet of materials. We did not know that the Pregnancy Prevention Program was to be implemented when we started our study. Likewise, we do not know if the program has changed the way our survey respondents are now prescribing isotretinoin. Perhaps a follow-up survey would be useful to document improvements in the patterns of isotretinoin prescribing.
PAUL L. DOERING, M.S. A Dose/Day (%) Figure 1. Distribution of the dosage alterations performed, Doses per day were calculated as a function of ideal body weight and represent the anhydrous theophylline contents. A dose/day = [(dose/day before adjustment- dose/day after adjustment)/ dose/day after adjustment] x lOO.
1302
•
The Annals ofPharmacotherapy
•
Professor ofPharmacy Practice College ofPharmacy University ofFlorida Box 100486 Gainesville, Florida 326/0
1992 October, Volume 26
Doctor of Pharmacy Student Assistant Professor
MARGARIDA CARAMONA, Pharrn.D. Associate Professor Laboratory ofPharmacology Faculty ofPharmacy Coimbra University Largo D. Diniz 3000 Coimbra Portugal
6. Capps N, Watkins K, Jordan P, Sewell GJ. General practice theophylline audit in the Exeter Health District. J Clin Pharmacol Ther 1990: 15:101-7. 7. Mason BJ. Subtherapeutic serum drug concentrations and compliance (letter). D1CPAnn Pharmacother 1991;25:103-4.
Comment: patterns of isotretinoin prescribing TO THE EDITOR: I am writing in response to the article by Doering et al., entitled "Patterns of Prescribing Isotretinoin: Focus on Women of Childbearing Potential" (Ann Pharmacother 1992;26: 155-61). Since January 1989, my colleagues and I have been conducting a survey of isotretinoin (Accutane) use in women to assess the effectiveness of the manufacturer's Pregnancy Prevention Program (this survey is sponsored by Hoffman-La Roche). In their discussion of fmdings from their survey of prescribers, Doering et al. cited a previous publication which reported that we had found that "about one-third of the pregnancies associated with isotretinoin have been in women who were pregnant at the time they started the drug."' The information in that reference is incorrect. The figure of 33 percent is derived from an earlier report,' and is also found in a study published this year'; estimates from both studies were derived from pregnancies that occurred among women who started isotretinoin in 1988 or earlier. In contrast, results of our survey, which began in 1989, revealed that the equivalent proportion was 12 percent (unpublished data, presented before Food and Drug Administration advisory committee, Rockville, MD, May 20,1991). We caution that these differences not be viewed as evidence of a decline in the proportion of women who are pregnant at the time of isotretinoin prescription, since the earlier figure of 33 percent was derived from spontaneous reports and our figure of 12 percent was derived from a systematic survey. ALLEN A. MITCHELL, M.D.
REFERENCES
Research Professor ofPublic Health Slone Epidemiology Unit Boston University School ofMedicine 1371 Beacon Street Brookline, Massachusetts 02146
I. Burkle WS. Development and implementationof clinical pharrnacokinetic services. Am] Hosp Pharm 1990;47:391-4.
REFERENCES
2. McLeod DC, Taylor WJ. Therapeutic drug monitoring as a standard of care. Drug Intell Clin Pharm 1985;6:473-4. 3. Cannon DJ. Therapeutic drug monitoring (letter). Clin Chem 1991;37: 141.
4. Ho K, Spino M. Theophylline in asthma: once versus twice-daily dosing. Can] Hosp Pharm 1989;42:173-218. 5. Mangues MA, Bonal J, Farre R, MassOJF. Algorithms for dosage and therapeutic monitoring of theophylline. Drug Intell Clin Pharm 1988; 22:893-4.
40
30
20
10
I. Marwick C. Additional steps proposed to ensure antiacne drug used only in appropriate patient population. ]AMA 1990;263:3125-6. 2. Lammer EJ, Chen DT, Hoar RM, Narsingh D, Benke PJ, Braun PJ, et al, Retinoic acid embryopathy. N EnglJ Med 1985;313:837-41. 3. Dai W, LaBraico JM, Stern RS. Epidemiology of isotretinoinexposure during pregnancy.J Am Acad DermatoI1992;26:599-606.
AUTHOR'S REPLY: In the "Methods" section of our article, we did not indicate the time frame in which the survey research was performed. It may be important to know this because the comprehensive Pregnancy Prevention Program for Women on Accutane initiated by Hoffman-La Roche had just gotten underway in late 1988. This program was not fully implemented until mid-1989. Our survey was developed in late 1988 and was mailed in mid-December of that year. A period of eight weeks was allowed for return of the questionnaire. Thus, it is likely that some survey recipients had received our survey packet before they had been informed of the new Pregnancy Prevention Program. How many had been informed of this program by the time they received our survey cannot be determined. At least some respondents had been advised of the Pregnancy Prevention Program because they sent us the informed consent form they had been given in the packet of materials. We did not know that the Pregnancy Prevention Program was to be implemented when we started our study. Likewise, we do not know if the program has changed the way our survey respondents are now prescribing isotretinoin. Perhaps a follow-up survey would be useful to document improvements in the patterns of isotretinoin prescribing.
PAUL L. DOERING, M.S. A Dose/Day (%) Figure 1. Distribution of the dosage alterations performed, Doses per day were calculated as a function of ideal body weight and represent the anhydrous theophylline contents. A dose/day = [(dose/day before adjustment- dose/day after adjustment)/ dose/day after adjustment] x lOO.
1302
•
The Annals ofPharmacotherapy
•
Professor ofPharmacy Practice College ofPharmacy University ofFlorida Box 100486 Gainesville, Florida 326/0
1992 October, Volume 26
