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Product-to-product variability
DRUGS AND THE ELDERLY Product-to-Product Variability :--..
~=-Y-T-O-D-D------- ferences
~ave you ever noticed a change in / older person's response to medicar~on that Occurred for no apparent IIIason? Perhaps a woman with forsuerly stable diabetes begins spilling a gar. The patient on phenytoin has ti~.unexpectedincrease in seizure ac10 tty. Or the elder who has tolerated geng.-term digitalis therapy for conopShve heart failure suddenly devels profound bradycardia. spAny of these uncharacteristic reino~es could be caused by a change SOurce of the patient's drug Prode uct. ChA ~eneric name denotes a specific inenllcal substance that is contained bisa P~armaceutical dosage form. flavSO~Vlng agents, fillers, binders, ing OT1?gs, preservatives, and other Ch re~lents are needed to make this dr~1l11cal substance into a finished fig product. flo ~01l1 a regulatory perspective, the 0 ga and Drug Administration rethrds these additives as inert, but Coere is longstanding evidence to the ce~trary. Some of the agency's confec~s about the pharmacologic efeVids of these extra ingredients are aboent in recent FDA statements 6te ut the allergic potential of sulas s added to some bronchodilators, lin \VeIl as a 1982 FDA advisory on ll1aa~proved generic drugs on the .; et(l,2). Stathe formularies of the United tio es Pharmacopeia and the Naan~al Formulary define chemical bllt Physical standards for drugs, fOr they do not specify methods or Proll1ulas for manufacturing drug ~. Company-to-company dif-
.1le1sy T : - - - - - - - - - - - - nUrs
odd, RN, OS, is a part-time staff
lias e. at the Frances Schervier Home and
tantltal, Bronx. NY. and a lecturer/consulOn drug use among elderly persons.
in inert ingredients and manufacturing processes account for the different effects that are sometimes seen when one company's product is replaced by another company's version of the same drug. Nurses often see physical evidence of product-to-product differences. One drug capsule contains a fine powder; another company's capsule of the same drug may be filled with coarser granules. One drug is easy to crush into a fine powder; another company's brand is difficult to break down. One tablet is easy to swallow; another company's version is the same size but patients complain that it sticks in their throats.
Consumers take note: all versions of one drug aren't the same.
Product-to-product variability is not a matter of effective, safe drugs versus nonpotent, unsafe drugs. An expensive drug or an original brandname product is not necessarily better than less expensive generic products. Both drug products may be pure and consistent from tablet to tablet; the potential problem is that they may not be interchangeable. Therapeutically, the differences between two companies' versions of the same drug are sometimes significant and sometimes not. In a dramatic 1979 episode, the FDA confirmed four cases in which patients' conditions worsened because a generic furosemide product was substituted for Lasix, the brand of furosemide manufactured by Hoechst-
Roussel Pharmaceuticals(3). The percentage of active ingredient contained in a drug product that actually enters the circulation in unchanged form determines that drug's bioavailability. Hundreds of studies have confirmed that there are variations in the bioavailability of different versions of digitalis, insulin, lithium, phenytoin, prednisone, the sulfonylureas, tetracycline, thyroid preparations, and many other drugs. The total drug absorbed, time to peak blood levels, and halflife for elimination are all part of a drug's pharmacokinetic profile. These properties are influenced by the effects of inert ingredients and manufacturing process, and, in turn, these properties affect the drug's bioavailability. If every drug's therapeutic effect could be directly correlated with blood levels of the drug, it would be easy to set bioavailability standards to which all versions of the same drug must conform. Unfortunately, a direct correlation isn't always possible, so it is difficult to devise a "lab testable" definition of product-toproduct equivalency. Most drug-product comparisons are based on bioavailability data from healthy young adults. Because of the wide variability in drug response among older people, drugs used primarily by the elderly probably require separate bioavailability studies. Protecting Older Adults
It is advisable to investigate any changes in the medication source whenever an older person's response to drug therapy changes-whether it is an enhanced or diminished therapeutic effect, or a change in the pattern of adverse reactions. Different companies' products are most likely Geriatric Nursing January/February 198557
CAREER OPPORTUNITIES Advertisements include those from individuals seeking positions, or from institutions regarding special programs and position openings, and other announcements of professional interest. All advertising copy is subject to Geriatric Nursing editor's approval. Publication of an advertisement does not conslilute endorsement. Classified advertising is charged at $15.00 per printed line. Display advertising rates on request. Ad copy or cancellation must be received in our office NO LATER than the 25th of the second month preceding date of issue. For example, copy for the JulyAugust issue must be received no later than May 25. $75 minimum per ad. Mail your order to: Classified Advertising Department
Geriatric Nursing 555 W. 5751. New York, New York 10019 DIRECTOR OF NURSING-Well respected and established skilled nuroinq facility in the Loa ADgeles County area i. seeking An energetic RN for Administrative position and Patient Care supervision. Top .Alary offered commenBurate with experience and qualificahoDs FrinQ8 benefitl include vacation, holiday, sick leave, health Insurance, continuing education and Profit Sharinq plan. Will assist with relocation e.pens••. Excellent environment to study the Geriatric Patient and Alzheimer's Diseaa•. Pleaoe contact Jellrey Allan, AdmInIstrator, at Clear View SanItariUm, 15823 South Western Avenue, Gardena, CA 90247 (213) 538-2323/ (213) 770-3131 CHAIRPERSON, GERONTOLOGICAL NURSING SPECIALTY -MSN Proqra'm for non-nursinq colle98 oraduat.a .eeks full-time senior faculty with expertise in Gerontological DurBinq for Fall, 1985. Opportunity to inteqrate teaching, practice, research in an interdisciplinary settinq. Clinical expertise, prevIous co11eQ'iate teachinQ', evidence of scholarship And reaearch required Doctoral de9ree and Masters in nurainQ' r~quir.d. Submit curriculum vitae to: Barbara Wilson, R.N., M.S., Chairperson, Gerontoloqical Nursinq Search CommiHee, MGH Ins"tute of Health Professions, Boston, MA 02114. An Affirmative Action/Equal Opportunity Employer. CLINICAL SPECIALIST IN GERONTOLOGICAL NURSING-The Division of Nuroinq hao funded an Advanced Nurse Traininq Grant to prepare clinical nursinq _specialists ingerontolog-icel nurainq at the University of Alabama School of Nurslnq. The proqram can be completed in one year of full-time study or on a p_art-time ba.is. Contact: Graduate Programs, University of Alabama School of Nuroinq, Univeraity of Alabama in Birmingham; University Stahon, Birminqham, AL 35294. (205) 9346680.
c+-aAmerican Heart vAssociafion WE'RE FIGHTING FOR YOUR LIFE 58 Geriatric Nursing January/February 1985
to enter the picture in the following situations: • A generic substitute is purchased instead of the product the patient has taken previously. Many pharmacists now label all prescription vials with generic drugs names, digoxin, for instance, even though a well-known brand name such as Lanoxin might have been dispensed. Don't assess the contents of a vial solely by the generic or brand name on the label; also take a look at the color, shape, and size of the contents. • The patient "shops "from drugstore to drugstore. refilling prescriptions at a different place each time. Pharmacies use many suppliers, and different stores frequently purchase their stocks from different distributors. • The patient is discharged from the hospital with a new prescription to fill. Companies that supply hospital pharmacies in large quantities are often different from the companies used by the neighborhood pharmacist to whom the patient takes a prescription. Ironically, great effort may be expended to stabilize a patient on a particular drug regimen in the hospital, but when the patient continues therapy at home, he or she may purchase a different company's version of the same drug. If treatment response varies, the patient may be readmitted to the hospital, perhaps even labeled noncompliant, only to begin the cycle again by switching back to the drug supply used by that hospital. • Patients in long-term care settings. Drug distributors periodically offer reduced prices. Pharmacists in long-term care institutions are likely to vary their purchases regularly in an effort to keep costs down, and this results in cyclical variations in the residents' drug supply. Again, when changes occur in drug products, there mayor may not be clinically significant differences in therapeutic results. But the increased sensitivity of the elderly to drug constituents, including inert ingredients, may make this group particularly prone to an erratic drug response when changes occur.
Advise consumers to develop a r9 lationship with one reputable phatj macy, and to ask questions a~~1 cost and manufacturer reputatI° ' Both nurses and consumers would d~ well to get out the magnifyinS glasses and examine tablets, to le~~;' the names and symbols used by 1 ferent manufacturers. r Once stabilized on a partiCula C company's product, it's good prabe' tice for the consumer to ask t. pharmacist who the manufacturer l~~ to continue with that companY product, and to check with each r~ fill that the same company's drug I dispensed. d Most important, consumers neCg to learn that all versions of one dr~ are not the same, that company·t a company variations do occur. If rt. person "feels different" after sta ing a new refill, or if lab res~l~ change unexpectedly, the pres cnbvi needs to consider whether a ne e drug source has affected the cours of therapy.
----------_.--' References
rf
fi I. Hecht, Annabel, and Willis, Judith. sul : ",. preservauves that can go wrong. FDA Cons .' er 17.10, Sept 1983. ,0' 2. U. S. Food and Drug Administration. ~en~oo, hIO S , FDA Advisory on Generic Drugs, Wa. DC. The Administration, March 18. 1982. "s)
3. FDA recalls three versions of drugs. (ot . AJN 79(6):1042, June 1979.
~=-Y-T-O-D-D------- ferences
~ave you ever noticed a change in / older person's response to medicar~on that Occurred for no apparent IIIason? Perhaps a woman with forsuerly stable diabetes begins spilling a gar. The patient on phenytoin has ti~.unexpectedincrease in seizure ac10 tty. Or the elder who has tolerated geng.-term digitalis therapy for conopShve heart failure suddenly devels profound bradycardia. spAny of these uncharacteristic reino~es could be caused by a change SOurce of the patient's drug Prode uct. ChA ~eneric name denotes a specific inenllcal substance that is contained bisa P~armaceutical dosage form. flavSO~Vlng agents, fillers, binders, ing OT1?gs, preservatives, and other Ch re~lents are needed to make this dr~1l11cal substance into a finished fig product. flo ~01l1 a regulatory perspective, the 0 ga and Drug Administration rethrds these additives as inert, but Coere is longstanding evidence to the ce~trary. Some of the agency's confec~s about the pharmacologic efeVids of these extra ingredients are aboent in recent FDA statements 6te ut the allergic potential of sulas s added to some bronchodilators, lin \VeIl as a 1982 FDA advisory on ll1aa~proved generic drugs on the .; et(l,2). Stathe formularies of the United tio es Pharmacopeia and the Naan~al Formulary define chemical bllt Physical standards for drugs, fOr they do not specify methods or Proll1ulas for manufacturing drug ~. Company-to-company dif-
.1le1sy T : - - - - - - - - - - - - nUrs
odd, RN, OS, is a part-time staff
lias e. at the Frances Schervier Home and
tantltal, Bronx. NY. and a lecturer/consulOn drug use among elderly persons.
in inert ingredients and manufacturing processes account for the different effects that are sometimes seen when one company's product is replaced by another company's version of the same drug. Nurses often see physical evidence of product-to-product differences. One drug capsule contains a fine powder; another company's capsule of the same drug may be filled with coarser granules. One drug is easy to crush into a fine powder; another company's brand is difficult to break down. One tablet is easy to swallow; another company's version is the same size but patients complain that it sticks in their throats.
Consumers take note: all versions of one drug aren't the same.
Product-to-product variability is not a matter of effective, safe drugs versus nonpotent, unsafe drugs. An expensive drug or an original brandname product is not necessarily better than less expensive generic products. Both drug products may be pure and consistent from tablet to tablet; the potential problem is that they may not be interchangeable. Therapeutically, the differences between two companies' versions of the same drug are sometimes significant and sometimes not. In a dramatic 1979 episode, the FDA confirmed four cases in which patients' conditions worsened because a generic furosemide product was substituted for Lasix, the brand of furosemide manufactured by Hoechst-
Roussel Pharmaceuticals(3). The percentage of active ingredient contained in a drug product that actually enters the circulation in unchanged form determines that drug's bioavailability. Hundreds of studies have confirmed that there are variations in the bioavailability of different versions of digitalis, insulin, lithium, phenytoin, prednisone, the sulfonylureas, tetracycline, thyroid preparations, and many other drugs. The total drug absorbed, time to peak blood levels, and halflife for elimination are all part of a drug's pharmacokinetic profile. These properties are influenced by the effects of inert ingredients and manufacturing process, and, in turn, these properties affect the drug's bioavailability. If every drug's therapeutic effect could be directly correlated with blood levels of the drug, it would be easy to set bioavailability standards to which all versions of the same drug must conform. Unfortunately, a direct correlation isn't always possible, so it is difficult to devise a "lab testable" definition of product-toproduct equivalency. Most drug-product comparisons are based on bioavailability data from healthy young adults. Because of the wide variability in drug response among older people, drugs used primarily by the elderly probably require separate bioavailability studies. Protecting Older Adults
It is advisable to investigate any changes in the medication source whenever an older person's response to drug therapy changes-whether it is an enhanced or diminished therapeutic effect, or a change in the pattern of adverse reactions. Different companies' products are most likely Geriatric Nursing January/February 198557
CAREER OPPORTUNITIES Advertisements include those from individuals seeking positions, or from institutions regarding special programs and position openings, and other announcements of professional interest. All advertising copy is subject to Geriatric Nursing editor's approval. Publication of an advertisement does not conslilute endorsement. Classified advertising is charged at $15.00 per printed line. Display advertising rates on request. Ad copy or cancellation must be received in our office NO LATER than the 25th of the second month preceding date of issue. For example, copy for the JulyAugust issue must be received no later than May 25. $75 minimum per ad. Mail your order to: Classified Advertising Department
Geriatric Nursing 555 W. 5751. New York, New York 10019 DIRECTOR OF NURSING-Well respected and established skilled nuroinq facility in the Loa ADgeles County area i. seeking An energetic RN for Administrative position and Patient Care supervision. Top .Alary offered commenBurate with experience and qualificahoDs FrinQ8 benefitl include vacation, holiday, sick leave, health Insurance, continuing education and Profit Sharinq plan. Will assist with relocation e.pens••. Excellent environment to study the Geriatric Patient and Alzheimer's Diseaa•. Pleaoe contact Jellrey Allan, AdmInIstrator, at Clear View SanItariUm, 15823 South Western Avenue, Gardena, CA 90247 (213) 538-2323/ (213) 770-3131 CHAIRPERSON, GERONTOLOGICAL NURSING SPECIALTY -MSN Proqra'm for non-nursinq colle98 oraduat.a .eeks full-time senior faculty with expertise in Gerontological DurBinq for Fall, 1985. Opportunity to inteqrate teaching, practice, research in an interdisciplinary settinq. Clinical expertise, prevIous co11eQ'iate teachinQ', evidence of scholarship And reaearch required Doctoral de9ree and Masters in nurainQ' r~quir.d. Submit curriculum vitae to: Barbara Wilson, R.N., M.S., Chairperson, Gerontoloqical Nursinq Search CommiHee, MGH Ins"tute of Health Professions, Boston, MA 02114. An Affirmative Action/Equal Opportunity Employer. CLINICAL SPECIALIST IN GERONTOLOGICAL NURSING-The Division of Nuroinq hao funded an Advanced Nurse Traininq Grant to prepare clinical nursinq _specialists ingerontolog-icel nurainq at the University of Alabama School of Nurslnq. The proqram can be completed in one year of full-time study or on a p_art-time ba.is. Contact: Graduate Programs, University of Alabama School of Nuroinq, Univeraity of Alabama in Birmingham; University Stahon, Birminqham, AL 35294. (205) 9346680.
c+-aAmerican Heart vAssociafion WE'RE FIGHTING FOR YOUR LIFE 58 Geriatric Nursing January/February 1985
to enter the picture in the following situations: • A generic substitute is purchased instead of the product the patient has taken previously. Many pharmacists now label all prescription vials with generic drugs names, digoxin, for instance, even though a well-known brand name such as Lanoxin might have been dispensed. Don't assess the contents of a vial solely by the generic or brand name on the label; also take a look at the color, shape, and size of the contents. • The patient "shops "from drugstore to drugstore. refilling prescriptions at a different place each time. Pharmacies use many suppliers, and different stores frequently purchase their stocks from different distributors. • The patient is discharged from the hospital with a new prescription to fill. Companies that supply hospital pharmacies in large quantities are often different from the companies used by the neighborhood pharmacist to whom the patient takes a prescription. Ironically, great effort may be expended to stabilize a patient on a particular drug regimen in the hospital, but when the patient continues therapy at home, he or she may purchase a different company's version of the same drug. If treatment response varies, the patient may be readmitted to the hospital, perhaps even labeled noncompliant, only to begin the cycle again by switching back to the drug supply used by that hospital. • Patients in long-term care settings. Drug distributors periodically offer reduced prices. Pharmacists in long-term care institutions are likely to vary their purchases regularly in an effort to keep costs down, and this results in cyclical variations in the residents' drug supply. Again, when changes occur in drug products, there mayor may not be clinically significant differences in therapeutic results. But the increased sensitivity of the elderly to drug constituents, including inert ingredients, may make this group particularly prone to an erratic drug response when changes occur.
Advise consumers to develop a r9 lationship with one reputable phatj macy, and to ask questions a~~1 cost and manufacturer reputatI° ' Both nurses and consumers would d~ well to get out the magnifyinS glasses and examine tablets, to le~~;' the names and symbols used by 1 ferent manufacturers. r Once stabilized on a partiCula C company's product, it's good prabe' tice for the consumer to ask t. pharmacist who the manufacturer l~~ to continue with that companY product, and to check with each r~ fill that the same company's drug I dispensed. d Most important, consumers neCg to learn that all versions of one dr~ are not the same, that company·t a company variations do occur. If rt. person "feels different" after sta ing a new refill, or if lab res~l~ change unexpectedly, the pres cnbvi needs to consider whether a ne e drug source has affected the cours of therapy.
----------_.--' References
rf
fi I. Hecht, Annabel, and Willis, Judith. sul : ",. preservauves that can go wrong. FDA Cons .' er 17.10, Sept 1983. ,0' 2. U. S. Food and Drug Administration. ~en~oo, hIO S , FDA Advisory on Generic Drugs, Wa. DC. The Administration, March 18. 1982. "s)
3. FDA recalls three versions of drugs. (ot . AJN 79(6):1042, June 1979.