ADVERTISEMENT

Generic drugs: The benefits and risks of making the switch

The Journal of Family Practice. 2010 November;59(11):634-640
November 1, 2010|Family Medicine
Pawel Lewek, MD;Przemyslaw Kardas, MD, PhD
Author and Disclosure Information

Pawel Lewek, MD
Przemyslaw Kardas, MD, PhD
The First Department of Family Medicine, Medical University of Lodz, Poland
pawel.lewek@umed.lodz.pl

Dr. Kardas reported that he receives research support from Polpharma SA and serves as a consultant to Boehringer Ingelheim, Egis Pharmaceuticals, and Polpharma SA. Dr. Lewek reported no potential conflict of interest relevant to this article.

When is it safe to substitute a generic drug for a brandname medication, and when should a switch be avoided? Here’s a look at the evidence.

Psychotropic agents. There has been a number of case reports of problems occurring following a switch from a brand-name antidepressant to a generic—or from 1 generic antidepressant to another. (See “Did a switch to a generic antidepressant cause relapse?” J Fam Pract. 2008;58:109-114.) In fact, the FDA cites some psychotropic drugs for which generic formulations may not be interchangeable—including amitriptyline/ perphenazine and venlafaxine—and others for which generic formulations may not be bioequivalent at all doses.22

Thyroid medication. There are also concerns about levothyroxine (LT4) administration, and major medical societies debate the use of generic substitution. According to a recent survey from the American Association of Clinical Endocrinologists, the American Thyroid Association, and The Endocrine Society, clinical use of generic LT4 continues to be associated with adverse outcomes.23 Most of the adverse events (89%) reported by survey respondents were associated with a change, either from a brand-name drug to a generic or from 1 particular generic LT4 to another.

TABLE
Generic substitution of antiepileptic agents: Where the American Academy of Neurology stands18

The AAN opposes:
  • generic substitution of anticonvulsant drugs for the treatment of epilepsy without the attending physician’s approval.
  • generic substitution of anticonvulsants for patients with epilepsy at the point of sale without prior consent of both the physician and the patient.
  • state and federal legislation that would impede the ability of physicians to determine which anticonvulsant drugs to prescribe for the treatment of patients with epilepsy.
The AAN believes:
  • formulary policies should recognize and support physician autonomy in prescribing, and patients in accessing, the full range of anticonvulsants for epilepsy.
The AAN supports:
  • legislation that would require informed consent of physicians and patients before generic substitutions of anticonvulsants are made at the point of sale.
The AAN recognizes:
  • that different strategies may be appropriate in using anticonvulsants for the treatment of conditions other than epilepsy.

Modified-release formulations may also pose a problem
Problems may also occur with generics in modified-release formulations, which may not have the same pharmacokinetic profiles as their brand-named counterparts. The British National Formulary has advised that prescriptions for modified-release diltiazem hydrochloride, nifedipine, and theophylline be filled with the brand-name drug only.24,25 Morever, a recent study concluded that 2 modified-release products of methylphenidate and nifedipine had concentration profiles that strongly diverged during the period of absorption, although the formulations met the regulatory criteria for bioequivalence. 26

The type of salt used to form a compound is also important. Salt-joining makes a hydrophobic molecule hydrophilic; the result, especially in psychoactive drugs, is improved kinetics, absorption, or physico-chemical properties (eg, stability, hygroscopicity, fluidity).27 This may be the reason for differences identified between generic and brand-name amitriptyline, nortriptyline, desipramine, and trimipramine.28 To avoid problems, physicians should prescribe generics containing the same salt as their brand-name counterparts.

When in doubt …

Brand-name drugs are, and always will be, the best proven therapy, because of the number and extent of clinical trials they go through. In most cases, however, there is no evidence-based reason to avoid generic substitution for patients who cannot afford the brand-name drug. When in doubt, consult the FDA’s Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations, available at https://www.accessdata.fda.gov/scripts/cder/ob/default.cfm, before making a switch.

CORRESPONDENCE Pawel Lewek, MD, The First Department of Family Medicine, Medical University of Lodz,60 Narutowicza Street, 90-136 Lodz, Poland; pawel.lewek@umed.lodz.pl

ADVERTISEMENT
ADVERTISEMENT
ADVERTISEMENT