CHAPTER 15

Trade-Name and Generic Drugs

Drugs often have several names. When a drug is first discovered, it is given a chemical name, which describes the atomic or molecular structure of the drug. The chemical name is thus usually too complex and cumbersome for general use. Next, a shorthand version of the chemical name or a code name (such as RU 486) is developed for easy reference among researchers.

When a drug is approved by the Food and Drug Administration (FDA—the government agency responsible for ensuring that drugs marketed in the United

WHAT’S IN A NAME?

States are safe and effective), it is given a generic (official) name and a trade (proprietary or brand) name. The trade name is developed by the company requesting approval for the drug and identifies it as the exclusive property of that company. For example, phenytoin is the generic name and Dilantin is a trade name for the same drug. When a drug is under patent protection, the company markets it under its trade name. When the drug is off-patent (no longer protected by patent), the company may market its product under either the generic name or trade name. Other companies that file for approval to market the off-patent drug must use the same generic name but can create their own trade name. As a result, the same generic drug may be sold under either the generic name or one of many trade names.

In the United States, an official body—the United States Adopted Names (USAN) Council—assigns the generic name. The company that manufactures the drug develops the trade name. Generic and trade names must be unique to prevent one drug from being mistaken for another when drugs are prescribed and prescriptions are dispensed. To prevent this possible confusion, the FDA must agree to every proposed trade name.

Government officials, doctors, researchers, and others who write about the new compound use the drug’s generic name because it refers to the drug itself, not to a particular company’s brand of the drug or a specific product. However, doctors often use the trade name on prescriptions, because it is easier to remember and doctors usually learn about new drugs by the trade name.

Generic names are usually more complicated and harder to remember than trade names. Many generic names are a shorthand version of the drug’s chemical name, structure, or formula. In contrast, trade names are usually catchy, often related to the drug’s intended use, and relatively easy to remember, so that doctors will prescribe the drug and consumers will look for it by name. Trade names often suggest a characteristic of the drug. For example, Lopressor lowers blood pressure, Vivactil is an antidepressant that might make a person more vivacious, Glucotrol controls high blood sugar (glucose) levels, and Skelaxin relaxes skeletal muscles. Sometimes, the trade name is simply a shortened version of the drug’s generic name—for example, Minocin for minocycline.

The term generic, when applied to such items as foods and household products, is used to describe a less expensive, sometimes less effective or lower-quality copycat version of a trade-name product. However, most generic drugs, although less expensive than the comparable trade-name drug, are as effective and of the same quality as the trade-name drug. In fact, generic drug makers manufacture many trade-name products for companies that control the trade names. Sometimes, more than one generic version of a drug is available. For example, many manufacturers sell versions of acetaminophen.

Patent Protection

In the United States, a company that develops a new drug can be granted a patent for the drug itself, for the way the drug is made, for the way the drug is to be used, and even for the method of delivering and releasing the drug into the bloodstream. Thus, a company often owns more than one patent for a drug. Patents grant the company exclusive rights to a drug for 20 years. Additional patents can some-times be filed to extend the patent life. Usually, about 10 years elapse between the time a drug is discovered (when the patent is obtained) and the time the drug is approved for human use, leaving the company only about half of the patent time to exclusively market a new drug. The FDA may choose to accelerate the approval process for drugs to treat AIDS, cancer, and other life-threatening disorders when no current effective treatment exists.

After a patent has expired, other companies may produce and sell a generic version of the drug as long as the FDA has approved it. They typically sell their product at a lower price than the original trade-name drug because the generic manufacturer does not have to recover the original costs of drug development and usually spends much less on marketing. A generic drug may be sold under its generic name or under a trade name (a branded generic drug) but not under the trade name used by the original patent-holder.

Not all off-patent drugs have generic versions. Sometimes a drug is too hard to duplicate, or adequate tests are not available to prove that the generic drug acts the same as the trade-name drug. Sometimes the market for the drug is so small that producing another version does not make good business sense.

Nonprescription Generic Drugs

Generic versions of some nonprescription (over-the-counter) drugs are often sold as house brands by drug chains or cooperatives, usually at a lower cost. These drugs are evaluated in the same way that generic prescription drugs are evaluated and must meet the same requirements.

Pharmacists can advise which generic over-the-counter drug products should be as effective as the original. However, a consumer may prefer one product to another because of appearance, taste, consistency, or other characteristics.

Bioequivalence and Interchangeability of Generic Drugs

When a company develops a generic version of a trade-name drug, the company’s experts in drug formulation must figure out how to make it. It is not enough for them to simply reproduce the trade-name drug’s chemical structure or to buy the active ingredient from a chemical manufacturer. Although 250 milligrams (mg) of a trade-name chemical is identical to 250 mg of the same generic chemical, a 250-mg generic pill containing that chemical may or may not have the same effect in the body as a 250-mg trade-name pill. That is because everything that is used in a particular product formulation affects how it is absorbed into the bloodstream. Inactive ingredients such as coatings, stabilizers, fillers, binders, flavorings, diluents, and others are necessary to turn a chemical into a usable drug product. These ingredients may be used to provide bulk so that a tablet is large enough to handle, to keep a tablet from crumbling between the time it is manufactured and the time it is used, to help a tablet dissolve in the stomach or intestine, or to provide a pleasant taste and color. Inactive ingredients are usually harmless substances that do not affect the body. However, because inactive ingredients can cause unusual and sometimes severe allergic reactions in a few people, one version, or brand, of a drug may be preferable to another. For example, chemicals called bisulfites (such as sodium metabisulfite), which are used as preservatives in many products, cause asthmatic allergic reactions in many people. Consequently, drug products containing bisulfites are prominently labeled as such.

Bioequivalence: Manufacturers must conduct studies to determine whether their version is bioequivalent to the original drug—that is, that the generic version releases its active ingredient (the drug) into the bloodstream at virtually the same speed and in virtually the same amounts as the original drug. Because the active ingredient in the generic drug has already been shown in testing of the trade-name drug to be safe and effective, bioequivalence studies only have to show that the generic version produces virtually the same levels of drug in the blood over time and thus require only a relatively small number (24 to 36) of healthy volunteers.

Although people generally think of oral dosage forms, such as tablets, capsules, and liquids, when they think about generic prescription drugs, generic versions of other drug dosage forms, such as injections, patches, inhalers, and others, must also meet a bioequivalence standard. The FDA sets bioequivalence standards for different drug dosage forms.

The manufacturer of the trade-name drug also must prove bioequivalence before a new form of an approved drug can be sold. New forms include new dosage forms or strengths of an existing trade-name drug product and any other modified form that is developed, as well as new generic drugs. Sometimes the form that was originally tested is modified for commercial reasons. For example, tablets may need to be made sturdier, flavoring or coloring may be added or changed, or inactive ingredients may be changed to increase consumer acceptance.

Evaluation and Approval Procedures: The FDA evaluates every generic version of a drug. The FDA approves a generic drug if studies indicate that the original trade-name drug and the generic version are essentially bioequivalent. The FDA also makes sure that a new generic drug contains the appropriate amount of the active (drug) ingredient, that it is manufactured according to federal standards (Good

WHEN GENERIC SUBSTITUTION MAY NOT BE APPROPRIATE

DRUG CATEGORY	EXAMPLES	COMMENTS
Drugs on the market before the 1938 Federal Food, Drug, and Cosmetic Act	Despite efforts by the FDA, some brands of thyroid hormone replacement products, which are still not bioequivalent	Pre-1938 drugs are exempt from generic drug requirements, but only a few of these are still prescribed. Switching among different versions is unwise because no standards are available by which to compare them. Caution is needed when switching brands.
Drugs with little difference between a toxic dose and an effective dose (a narrow margin of safety)	Anticonvulsants such as phenytoin, carbamazepine, and valproate; digoxin (for heart failure and a very rapid heart rate); and the anticoagulant warfarin	The margin of safety is relatively small. Too little drug may not work, and too much drug may have side effects.
Antihypertensive drugs	Reserpine and reserpine plus polythiazide	Generic versions are not bioequivalent to trade-name drugs.
Antiasthmatic drugs taken by mouth	Theophylline, dyphylline, and some brands of aminophylline	Different versions are generally not bioequivalent. If one version is working, it should not be interchanged for another unless absolutely necessary.
Corticosteroid creams, lotions, and ointments	Alclometasone, amcinonide, betamethasone, clocortolone, desonide, desoximetasone, dexamethasone, diflorasone, fluocinolone, fluocinonide, flurandrenolide, fluticasone, halcinonide, halobetasol, hydrocortisone, mometasone, and triamcinolone	These products are standardized by tests of skin response, and many have been rated as bioequivalent by the FDA. But response varies, and different drug vehicles (creams, ointments, gels) can affect product potency. Response may be unpredictable. So, if one version is effective, it should not be interchanged for another.
Corticosteroid tablets	Dexamethasone, triamcinolone, and others	Many generic versions are not bioequivalent to trade-name drugs and should not be freely interchanged for them.
Hormones	Esterified estrogen (estrogen therapy in postmenopausal women), some brands of medroxyprogesterone, and most generic brands of methyltestosterone	The two brands of esterified estrogen are not bioequivalent. Hormones are usually taken in small doses, so differences in brands could produce major swings in response.
Antihyperglycemic drugs	Glyburide (for type 2 diabetes)	One version of glyburide, Diabeta, may not be interchanged for any other. All other versions are considered interchangeable.
Drugs to control gout	Colchicine	Generic versions of individual drugs are not bioequivalent to one another.
Antipsychotic drugs	Chlorpromazine tablets	Generic versions are not bioequivalent to the trade-name version.
Antidepressants	A few brands of amitriptyline and one brand of amitriptyline plus perphenazine	Not all versions are interchangeable. A pharmacist can advise whether the FDA considers a particular generic drug bioequivalent to the trade-name drug.
Potassium	Most long-acting potassium replacement products in tablet form	Long-acting potassium products in capsule (not tablet) form are considered bioequivalent and may be interchanged.
Other drugs	Fluoxymesterone, some brands of promethazine tablets and suppositories, chloramphenicol capsules, and clozapine	Generic versions may not bioequivalent. Although any version can be effective, versions should not be interchanged.
FDA = Food and Drug Administration.

Manufacturing Practices), and that the generic version differs from its trade-name counterpart in size, color, and shape—a legal requirement.

Interchangeability and Substitution: Theoretically, any generic drug that is bioequivalent to its trade-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 trade-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 plans may allow a consumer to select a more expensive trade-name product prescribed by the doctor as long as the consumer pays the difference in cost. However, in some state-run programs, the consumer has no say. If the doctor prescribes a generic drug, the pharmacist must dispense a generic drug. In most states, the consumer may insist on a trade-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 bioequivalent to the trade-name drug. Such generic drugs may still be used, but they may not be substituted for the trade-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 trade-name drugs, although bioequivalent generic products are available. Warfarin, an anticoagulant, and phenytoin, an anticonvulsant, are examples of such drugs. Finally, a generic product may not be appropriate if it contains an inactive ingredient that the person is allergic to. Thus, if a doctor specifies a trade-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 or an ineffective dose (the margin of safety) is small. Digoxin, used to treat people with heart failure, is an example. Switching from the trade-name version of digoxin to a generic product may cause problems, because the two versions may not be sufficiently bioequivalent. However, some generic versions of digoxin have been certified as bioequivalent by the FDA. Pharmacists and doctors can answer questions about which generic drugs are interchangeable for their trade-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.

The substitution of a generic drug can sometimes cause other problems for the consumer. A doctor may write a prescription for a trade-name product and discuss the trade-name product with the consumer. If a pharmacist dispenses an equivalent generic product and the label does not also list the reference (trade-name product), the consumer may not know how the generic product relates to the drug the doctor prescribed. To prevent this confusion, pharmacists should include the reference trade name on the label when a generic product is substituted.

Generic Biologic Drugs

Traditional drugs are called small-molecule agents because the active ingredient is usually a single, discrete chemical entity. Biologic drugs are complex products that can be derived from viruses, blood and body tissues, antibodies, toxins and antitoxins, vaccines, and related products used for treating disease. Until now, it has not been possible to develop generic versions of these products because of their complex manufacturing requirements and the difficulty in defining their exact composition. Companies have made several attempts to get approval for generic equivalent biological products, such as human growth hormone. However, the Food and Drug Administration has required manufacturers of the proposed products to submit for approval under new drug regulations rather than as a generic equivalent. Ongoing scientific developments may allow the creation of generic biologic products in the next several years. The advantage of generic biologic drugs for manufacturers, pharmacies, and consumers is that they could be freely interchanged and compete against one another for inclusion on a hospital or health plan drug list. Having different brands of very similar biologic products, as with epoetin, a hormone to increase red blood cell count, does not offer all the benefits of generically equivalent products.