Generic Prescribing

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Committee on Drugs

PEDIATRICS Vol. 57 No. 2 February 1976 275

Generic

Prescribing

During the last several years there has been continued pressure from consum ers, legislators, and health administrators to mandate generic prescribing. It has been proposed that requiring

physicians to prescribe by generic rather than

brand name and allowing pharmacists to

substi-tute generically equivalent drug products would

save consumers millions of dollars. These

assump-tions and the following events have stimulated the

American Academy of Pediatrics to bring this

issue to the attention of its I1embership.

(1) The report of the Office of Technology Assessment, Drug Bioequivalence Study Panel, entitled “Drug Bioequivalence,” concluded that current standards and regulatory practices do not

ensure bioequivalence for drug products,

al-though most of the analytical methodology and experimental procedures for the conduct of bioavailability studies in man are available.’

Additional work may be required to develop the

means of applying them to certain drugs and to special situations of drug use.

(2) The Drug Research Board of the National Academy of Sciences (October 25, 1974) recom-mended that the physician “should be required to delegate to the pharmacist, or explicitly to retain to himself, selection of the particular drug product to be dispensed.”2

(3) The Maximuni Allowable Cost Proposal

published in the Federal Register (November 15,

1974)1 would establish a system to fix a

“max-imum allowable cost” for reimbursement for

drugs dispensed under health financing and

service programs of the Department of Health, Education, and Welfare which have multiple sources and are deemed bioequivalent. Other provisions of this proposal call for a fixed

dispensing fee and supplying comparative price

information to physicians and pharmacists.

ANALYSIS OF THE PROBLEM

The Committee on Drugs recognizes, and is in agreement with the validity of, attempts to provide safe and efficacious medications at the lowest possible cost. Unfortunately, few drug

products have been appropriately studied for bioavailability or therapeutic equivalence in

infants and children. Such products often differ in formulation from drug products used for adults.

The bioavailability of a drug product has been defined as the rate and extent (efficiency) of absorption and distribution of the active substance to the site of action in the body.4 In

vitro tests do not suffice for the determination of

bioavailability. Data must be derived from testing in man in order to determine physiologic avail-ability of the drug.5 Differences in bioavailability may be accentuated in infants and children where there is evidence of age-related changes in the rate and extent of gastrointestinal absorption-as well as changes in vOlume of distribution, rates of metabolism, and excretion.

The term bioavailability is often confused with bioequivalence, but these are not interchangeable terms. Bioequivalence is achieved when two chemically equivalent drug products exhibit similar bioavailability characteristics.

One cannot assume that specific products will be equivalent in therapeutic effect until they have been evaluated in vivo. The clinical efficacy of a drug may be greatly modified by the rate and extent of absorption of a drug into systemic

circulation.6 Changes in physical state, such as crystal form or particle size, can affect the

dissolution of a drug. The addition of inert ingre-dients used in tablet or capsule formulations can have pronounced effects on drug absorption; and

variations in tablet structure formulation and

other aspects of manufacturing have been found to have a significant effect on bioavailability. A

number of generically equivalent products have been demonstrated to vary appreciably in their rate and extent of absorption, concentrations of drug produced in the body, and clinical

response.65’1 These differences in bioequivalency usually occur because of variations in the foregoing pharmaceutical factors. Such

ingre-dients differ from one product to another and are not usually specified in official compendia.’9’2#{176} These differences have been demonstrated in

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adults. The lack of data on bioavailability and peutic and/or toxic effects, care should be used to

bioequivalence in children precludes blanket ensure that the patient maintains therapy with support of generic prescribing for infants and the same product (the same brand).

children. The physician is ultimately responsible for

With some drugs, for example antibio- care; therefore, authority for prescribing must

tics-where (1) initial studies on bioavailability remain his prerogative. To exercise this preroga-are carried out in adults with comparison to “the live now demands increased efforts to judge

standard” product of that particular drug, critically if there is a need for any drug therapy;

(2) batch certification of biologic potency is and, having so decided, to select the right drug, carried out, and (3) therapeutic endpoints or drug product, dose, and dose schedule. To make

serum levels can be more or less accurately these decisions, the pediatrician needs heightened

defined-generic prescribing may be used with awareness, continuing education, and consulta-relatively more confidence. tion with peers and other health professionals.

The current trend in drug development is The prescribing pediatrician should insist that toward more specific agents, thereby amplifying data on bioavailability be made available to him the need for bioavailability data. These data must to choose the product most suitable for his be established in infants and children as well as in patient.

adults.

Although some lists’ evaluating risk

poten-tial (as related to relative bioequivalence) have

been made, these lists are inconclusive because

they are prepared from incomplete information

presently available and reflect no significant data

from the pediatric population.

The Committee on Drugs of the American

Academy of Pediatrics feels strongly that cost

alone should not receive the highest priority in

the choice of drug or drug product. Drug disposi-tion in the sick infant and child has not been

Pharmacists’ professional fees, acquisition

costs, overhead, profit margin (which depends on neighborhood and other local factors), the

number of tablets in a prescription, and

innu-merable other variables may determine the cost to the patient more than the wholesale list price of a drug. Assistance in product availability, quality, and price can be obtained from

commu-adequately investigated at this time; and the data which would allow the pediatrician to prescribe generically and expect consistent therapeutic

results does not exist. Therefore, the pediatrician

must acquaint himself with dose-response rela-tionships of known entities and not prescribe products with which he has no familiarity.

The Committee also recommends that the

nity pharmacists to enable the physician to pre- Department of Health, Education, and Welfare

scribe the drug product most suitable for his dedicate fiscal and manpower resources to the

patient.

The Committee on Drugs of the American Academy of Pediatrics strongly supports the use

solution of the many pressing questions and problems which stand in the way of rational drug therapy for pediatric patients.

of the least expensive medication which provides

effective therapy. However, the physician’s duty COMMITTEE ON DRUGS

to the patient is to prescribe reliable drugs with SUMNER

J.

YAFFE, M.D., Chairman reproducible therapeutic effects at a given dose. C. WARREN BIERMAN, M.D.

Therefore, until suitable bioavailability data in HOWARD M. CANN, M.D. (1974-1975) children are determined and therapeutic impor- SANFORD N. COHEN, M.D.

tance recognized, the physician should continue JOHN FREEMAN, M.D. to prescribe the products which have shown BENJAMIN M. KAGAN, M.D. significant clinical effectiveness in his hands or in RALPH KAUFFMAN, M.D.

published clinical trials. ALBERT PRUITT, M.D.

The variation in drug handling in the infant SYDNEY SEGAL, M.D. and child resulting from his various stages of

development, as well as the alterations produced

by the disease, accentuates the fact that therapy

with many drugs is individualized; and,

differ-LESTER SOYKA, M.D.

CHARLES F. WEISS, M.D. (1974-1975) consultant

GREGORY CHUDZIK, Pharm.D.

ences existing between patients are often more Liaison Representatives

significant than those existing between drug Joi C. BALLIN, Ph.D.

products. Some situations require careful

“titra-tions” of drug therapy. In these cases and those in

PIEiu S. DEL PRATO, Pharm.D.

AiN K. DONE, M.D. which blood levels closely correlate with thera- LOUIs FARCHIONE, M.D.

276 GENERIC PRESCRIBING

RECOMMENDATIONS

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AMERICAN ACADEMY OF PEDIATRICS 277 GODFREY OAKLEY, M.D.

STEVEN SAwCHUK, M.D.

C. P. Scorr, M.D.

ARTEMIS P. SIM0P0UL05, M.D.

REFERENCES

1. Drug Bioequivalence: A Report of the Office of

Tech-nology Assessment, Drug Bioequivalence Study

Panel. Government Printing Office, April 12, 1974.

2. Drug Research Board of the National Research Council: Resolution on generic prescribing, with background

statement. News release, January 21, 1975.

3. Maximum allowable cost for drugs. Federal Register,

vol 39, No. 222, November 15, 1974.

4. Bioavailability: Report of the Special Advisory Commit-tee to the Health Protection Branch, Department of National Health and Welfare. Can Med Assoc J 109:920, 1973.

5. Wagner JG: Generic equivalence and inequivalence of oral products, biopharmaceutics and relevant phar-macokinetics. Drug Intell Clin Pharm 5:115,

1971.

6. Arnold K, Gerber N, Levy C: Absorption and dissolution studies on sodium diphenylhydantoin capsules. Can

J Phammacol Sci 5:89, 1970.

7. Barr WH: Factors involved in the assessment of systemic

or biologic availability of drug products. Drug Info

Bull 59, 1969.

8. Barr WH, Cerbracht LM, Letcher K, et at: Assessment of the biologic availability of tetracycline products in man. Clin Pharmacol Ther 13:97, 1972. 9. Levy C, Hall NA, Nelson E: Studies on inactive

predni-sone tablets USP XVI. Am J Hosp Pharm 21:402, 1964.

10. Rail L: Dilantin overdosage. Med J Aust 2:339, 1968. 11. Balla J: Dilantin overdosage. Med J Aust 2:480, 1968. 12. Feldman 5: Diphenylhydantoin: The Bioavailability of

Drug Products (From APhA Bioavailability Pilot Project). Washington DC, American

Pharmaceu-tical Association, 1973.

13. Bartelloni PJ, Calia FM, Minchew BH, et at: Products in humans after oral administration. Am J Med Sci

258:203, 1969.

14. Manninen V, Melin J, Haartel C: Serum-digoxin concen-trations during treatment with different prepara-tions. Lancet 2:934, 1971.

15. Skelly JP, Knapp C: Biologic availability of digoxin tablets. JAMA 224:243, 1973.

16. Binnion PF, McDermott M, LeSher D: Bioavailability of digoxin. Lancet 1:1118, 1973.

17. Leonards JR, Levy C: Gastrointestinal blood loss from aspirin and sodium salicylate tablets in man. Clin

Pharmacol Ther 14:62, 1973.

18. Health Protectorate Branch, Department of Nutritional

Health and Welfare, Canada: Nitrofurantoin. RX Bulletin (Canada), February 1971.

19. United States Pharmacopeial Convention Inc: The

United States Pharmacopeia, rev 18. Easton, Penn-sylvania, Mack Publishing Co, 1970.

20. National Formulary, ed 9. Washington DC, American Pharmaceutical Association, 1970.

21. Barr W, Doluisio J, Fedder D, et at: Report of the Ad Hoc Committee on Drug Selection of the Academy of General Practice of Pharmacy and the Academy of Pharmaceutical Sciences. J Am Pharm Assoc NS13 6:278, 1973.

22. Busse H (chairman): Report of the Ad Hoc Committee of

the APhA Academy of Pharmaceutical Sciences.

Academy Reporter, vol 10, No. 5, 1974.

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1976;57;275

Pediatrics

Farchione, Godfrey Oakley, Steven Sawchuk, C. P. Scott and Artemis P. Simopoulos

F. Weiss, Gregory Chudzik, John C. Ballin, Pierre S. Del Prato, Alan K. Done, Louis

Benjamin M. Kagan, Ralph Kauffman, Albert Pruitt, Sydney Segal, Lester Soyka, Charles

Sumner J. Yaffe, C. Warren Bierman, Howard M. Cann, Sanford N. Cohen, John Freeman,