In a new study, the changing shape or color of generic pills is singled out as a factor in the misuse, underuse or overuse of prescribed drugs. (Amy Sancetta/AP)

Generic medications that are identical on the inside can look different on the outside, depending on the manufacturer. But those differences in shape and color could be causing confusion among patients, leading some to stop taking much-needed medications, according to a study published Monday in the Annals of Internal Medicine.

Researchers from Brigham and Women’s Hospital in Boston studied the pill-taking habits of more than 10,000 patients across the country who had been hospitalized after a heart attack between 2006 and 2011. In the first year after such an event, it is critical that patients take certain medications, such as beta blockers and cholesterol-lowering statins.

But the study found that when patients went for a refill and the color or shape of their generic pills changed, the odds that they would stop taking the drug or not refill the prescription jumped dramatically: 34 percent for a change in pill color and 66 percent for a change in shape. That could mean numerous unnecessary complications, deaths and an overall increase in health-care costs, the researchers concluded.

“When you go get your monthly refill and your circular pink pill is now an oblong yellow pill . . . it’s a little jarring,” said Aaron Kesselheim, a Harvard Medical School professor and a senior investigator on the study. “You can imagine how this might cause confusion.”

Patients with all kinds of conditions commonly do not adhere properly to taking their prescribed medications. The reasons vary, from drug costs to side effects to simply not remembering. And Monday’s study admittedly had limitations: Researchers evaluated only three classes of drugs being taken by heart patients, and they didn’t have access to certain information about the patients, such as socioeconomic status or enrollment in automatic refill programs.

Still, the available data singled out the changing shape and color of generic pills as a troubling factor in the misuse, underuse or overuse of prescribed drugs, Kesselheim said.

“It doesn’t explain all the nonadherence, certainly,” he said. “But it is a statistically significant and clinically meaningful amount.”

Often, the changes arise when a pharmacy switches suppliers or a patient starts buying pills online, and suddenly the exact same cholesterol medication comes in a different-looking pill.

The Food and Drug Administration does not require a consistent appearance for generic drugs that are otherwise clinically interchangeable — the agency ensures that the medication inside is chemically identical — and often the color and shape of such drugs vary by manufacturer.

Last year, however, the agency acknowledged its concern that differences in the physical characteristics of identical drugs “may affect patient compliance and acceptability of medication regimens or could lead to medication errors.” Given that concern, the FDA issued nonbinding guidance to manufacturers, recommending that they consider the effect on patients when developing the shape and color of generic drugs.

The authors of Monday’s paper said the FDA perhaps should require the appearance of new generic drugs to match that of the original brand-name products. The effects, they wrote, are not just aesthetic but also “clinically relevant.”

In addition to any public policy actions, the authors said doctors should proactively inform patients about potential changes in pill colors and shapes, and reassure them that the medicines should work identically despite differing appearances. Without such warnings, many patients could end up confused, frustrated and ultimately in danger of not getting the treatment they need.