Simulation of the AUC Changes after Generic Substitution in Patients

다국어 초록 (Multilingual Abstract)

To address the debate on the safety of generic substitution quantitatively, the author

compared the change in AUC in virtual patients who were simulated for several different

scenarios of generic substitution. In four scenarios of original (branded) to

generic and generic to generic substitution, 5,000 virtual patients were simulated per

scenario using the programming software R. The mean population AUC of generics

ranged from 90-110% (scenarios A and B) and 80-123.5% (scenarios C and D)

of the AUC of the original. Those patients who had an AUC change (ratio) as a result

of drug substitution of less than 0.67 or greater than 1.5 were considered to be in

potential danger due to the substitution. We found that less than 6% of patients fell

outside of the cutoff range of 0.67-1.5 as a result of original to generic substitution.

However, in the case of generic to generic substitution, the proportion was as high

as 9-12%. This alerts us to the potential danger of generic substitution, especially

for drugs with narrow therapeutic indices.

참고문헌 (Reference)

1 Hendeles L, "Treatment failure after substitution of generic pancrelipase capsules. Correlation with in vitro lipase activity" 263 : 2459-2461, 1990

2 Williams RL, "Therapeutic equivalence of generic drugs: response to National Association of Boards of Pharmacy"

3 Sakshaug S, "Switching statins in Norway after new reimbursement policy-a nationwide prescription study" 64 : 476-481, 2007

4 Todd JS, "Substitution of NTI drugs: physicians must maintain control" 86 : 121-123, 1997

5 Ross MB, "Status of generic substitution: problematic drug classes reviewed" 24 : 441-444, 1989

6 Hellstrom J, "Side effects of generic competition?" 5 : 203-208, 2004

7 Brust M, "Physicians’ attitudes toward generic drug substitution by pharmacists" 86 : 45-49, 1990

8 Kjoenniksen I, "Patients’ attitudes towards and experiences of generic drug substitution in Norway" 28 : 284-289, 2006

9 Allenet B, "Opinion and behaviour of pharmacists towards the substitution of branded drugs by generic drugs: survey of 1,000 French community pharmacists" 25 : 197-202, 2003

10 Richton-Hewett S, "Medical and economic consequences of a blinded oral anticoagulant brand change at a municipal hospital" 148 : 806-808, 1988

11 Burns M, "Management of narrow therapeutic index drugs" 7 : 137-143, 1999

12 Reiffel JA, "Issues in the use of generic antiarrhythmic drugs" 16 : 23-29, 2001

13 Andersson K, "Impact of a generic substitution reform on patients’ and society’s expenditure for pharmaceuticals" 81 : 376-384, 2007

14 Himmel W, "Hummers-Pradier E. What do primary care patients think about generic drugs?" 43 : 472-479, 2005

15 Andersen ML, "How do patients evaluate the newly introduced system of substituting prescriptions?" 162 : 6066-6069, 2000

16 Bongiorno RA, "Generic warfarin: implications for clinical practice and perceptions of anticoagulation providers" 30 : 619-626, 2004

17 Wasserfallen JB, "Generic drug prescribing: pilot study on the impact of the new drug pricing system on costs and potential savings" 2 : 865-866, 2006

18 Beecroft G, "Generic drug policy in Australia: a community pharmacy perspective" 4 : 7-, 2007

19 Reiffel JA, "Generic antiarrhythmics are not therapeutically equivalent for the treatment of tachyarrhythmias" 85 : 1151-1153, 2000

20 Sabatini S, "Drug substitution in transplantation: a National Kidney Foundation White Paper" 33 : 389-397, 1999

21 Andermann F, "Compulsory generic switching of antiepileptic drugs: high switchback rates to branded compounds compared with other drug classes" 48 : 464-469, 2007

22 Rosenbaum DH, "Comparative bioavailability of a generic phenytoin and Dilantin" 35 : 656-660, 1994

23 Trottet L, "Are all aciclovir cream formulations bioequivalent?" 304 : 63-71, 2005

24 Banahan BF 3rd, "A physician survey on generic drugs and substitution of critical dose medications" 157 : 2080-2088, 1997