What Worries Me About Generics

Like most pharmacists, I have a very high opinion of generic medications.

Like most pharmacists, I have a very high opinion of generic medications.

As medication experts, pharmacists understand that the FDA requires generics to have the same active ingredients, strength, dosage form, and route of administration as their corresponding brand-name product. Generics comprise more than 80% of all prescriptions filled in the United States, and they save consumers an estimated $8 billion to $10 billion a year at retail pharmacies alone.

The FDA allows variance in the bioavailability between generic medications and brand-name products. Its rules ensure that a generic’s maximum concentration and area under the curve (AUC) does not fall more than 20% below or 25% above that of the brand name.

These limits may seem exceedingly broad to many health care professionals. Still, the FDA has conducted more than 2000 studies on bioequivalence and determined that the average difference in AUC between the generic and the brand name was only 3.5%.

There are a number of reasons patients may be concerned about taking a generic medication. One reason is that generics may have different inactive ingredients than brand-name products, while another reason is that they may have a different appearance.

Patients become familiar with the shape and color of their current medication. Switching to a generic with a different appearance may cause patients to believe they have received the wrong medication. This may burden the pharmacy staff with unnecessary phone calls and complaints. Patients may also mistakenly take a double dose of a medication because they didn't know that their generic and brand-name medications are the same drug.

While these issues are important, they do not give me pause in recommending a generic medication. What really concerns me isa patient receiving a refill from a different generic manufacturer. This is critical when dispensing a narrow therapeutic index (NTI) drug, such as carbamazepine, digoxin, levothyroxine, phenytoin, or warfarin.

A generic may be 20% below or 25% above that of the brand, but what would happen if we switch from a generic that is 20% below the brand to one that is 25% above it? That’s a potentially deadly swing in drug concentration, resulting in either a subtherapeutic dose or a supratherapeutic dose.

A close friend of mine was recently discharged from the hospital on warfarin 5 mg daily. His INR was stable at 2.5 when he left the hospital. During his 6 months of therapy, he received a different generic product every single time he refilled his warfarin at his local pharmacy.

Despite his physician’s best efforts, his INR swung wildly between 1.8 (subtherapeutic) and 3.6 (supratherapeutic). He was taking no prescription, OTC, or herbal medications that interacted with warfarin. He even refrained from eating foods high in vitamin K.

Luckily, my friend is no longer taking warfarin, but I cannot shake the feeling that constantly switching between different warfarin generics contributed to his problem. This leaves me wondering why the FDA allows such broad variations in bioavailability between generic medications and brand-name products, and why a local pharmacy would stock a different generic every month.