drugs
Bioequivalence and Interchangeability of Generic Drugs
Interchangeability and substitution
Theoretically, any generic drug that is bioequivalent to its brand-name counterpart may be interchanged with it. For drugs that are off patent, the generic drug may be the only form available. To limit costs, many doctors write prescriptions for generic drugs whenever possible. Even if the doctor has prescribed a brand-name drug, the pharmacist may dispense a generic drug unless the doctor wrote on the prescription that no substitution can be made. Also, insurance plans and managed care organizations may require that generic drugs be prescribed and dispensed whenever possible to save money. Some insurance plans may allow a consumer to select a more expensive brand-name product prescribed by the doctor as long as the consumer pays the difference in cost. However, in some state-run programs, the consumer may not have a choice. If the doctor prescribes a generic drug, the pharmacist must dispense a generic drug. In most states, the consumer may insist on a brand-name drug even if the doctor and pharmacist recommend a generic drug. Sometimes generic substitution may not be appropriate. For example, some available generic versions may not be precisely bioequivalent to the brand-name drug. Such generic drugs may still be used, but they may not be substituted for the brand-name product. In cases in which small differences in the amount of drug in the bloodstream can make a very large difference in the drug’s effectiveness, generic drugs are often not substituted for brand-name drugs, although bioequivalent generic products are available.Warfarin, an anticoagulant, andphenytoin, an antiseizure drug, are examples of such drugs. Finally, a generic product may not be appropriate if it contains an inactive ingredient to which the person is allergic. Thus, if a doctor specifies a brand-name drug on the prescription and the consumer wants an equivalent generic version, the consumer or pharmacist should discuss the matter with the doctor. Drugs that must be given in very precise amounts are less likely to be interchangeable, because the difference between an effective dose and a harmful dose (the margin of safety) or ineffective dose is small.Digoxin, used to treat people with heart failure, is an example. Switching from the brand-name version ofdigoxinto a generic product may cause problems, because the two versions may not be sufficiently bioequivalent. However, some generic versions ofdigoxinhave been certified as bioequivalent by the FDA. Pharmacists and doctors can answer questions about which generic drugs are interchangeable for their brand-name counterparts and which are not. A book published by the FDA each year and updated periodically also provides guidance about which drugs are interchangeable. This book,Approved Drug Products With Therapeutic Equivalence Evaluations(also known as "the orange book" because it has a bright orange cover), is available both in print and online to anyone but is intended for use by doctors and pharmacists. (SeeApproved Drug Products With Therapeutic Equivalence Evaluations.) The substitution of a generic drug can sometimes cause other problems for the consumer (see table). A doctor may write a prescription for a brand-name product and discuss the brand-name product with the consumer. If a pharmacist dispenses an equivalent generic product and the label does not also list the reference (brand-name product), the consumer may not know how the generic product relates to the drug the doctor prescribed. To prevent this confusion, most pharmacies now include the reference brand name on the label when a generic product is substituted. Caution should be exercised when considering switching brands of drugs that entered the market before the 1938 Federal Food, Drug, and Cosmetic Act took effect (for example,digoxin,codeine, andphenobarbital). The few drugs in this category that are still prescribed are exempt from generic drug requirements. Switching among different versions of these drugs is unwise because no standards are available by which to compare them. Other drugs for which generic substitution may not be appropriate include drugs that are said to have a narrow margin of safety because the toxic dose is too close to the effective dose for the drug to be used safely. 