Generics can help with adherence ...

... but some doctors aren’t sure if these glaucoma drops are as effective as the brands they're modeled on.

By Karen Blum, Contributing Editor

The availability of glaucoma medications has lowered costs for many patients, thus helping to improve adherence, but it also has raised some ophthalmologists’ worries about variability, efficacy and side effects.

While generics generally cost less than brand-name medications and work well for many patients, they may not perform identically, even if they have satisfied the FDA’s requirement to show bioequivalence, says Malik Kahook, MD, the Slater Family Endowed Chair in Ophthalmology and vice chair of clinical and translational research at the University of Colorado School of Medicine in Aurora.

Variability

Ophthalmologists need to be aware that makers of generics change characteristics, including the bottle’s material, shape and size; cap color; and drop size.¹

While branded-medication clinical trials test a bottle’s usability (shape, size, compressibility), generic drug manufacturers are not required to do so. Some generic eyedrop bottles are round and more rigid than their brand name counterparts. Older glaucoma patients could have difficulty squeezing them, potentially lowering their medication adherence and wasting drops.

Cap colors of branded drops are intended to be coordinated based on the drug category, Dr. Kahook says, but the generic drug bottle-cap color could differ even though the FDA attempts to keep this consistent. His studies have shown that patients use cap color over drug name as the method to identify their drops, and that patients and physicians might use different color descriptors to describe the caps.^2,3 For example, he says, while industry considers the latanoprost (Xalatan, Pfizer) cap turquoise, patients may call it “off-blue” or “light green,” which could cause physicians to think they are discussing a different medication.

Also, a generic bottle’s eyedrop size can vary from as much as 25 to 75 μL per drop, in part because of the hole size at the bottle’s tip. Patients could run through the drops sooner if larger amounts are dispensed at once.⁴

This type of variability accounts for why some ophthalmologists prefer branded drugs.

“I’m generally a fan of brand names overall,” says I. Paul Singh, MD, a glaucoma specialist with The Eye Centers of Racine & Kenosha, Wis. Dr. Singh says he likes branded drops because of their consistency — some studies indicate there is a 10% to 12% difference in efficacy between generics and brand names.⁵ “I have no worries [patients] are getting a different product.”

The inactive ingredients of a medication also can play an important role in the efficacy and tolerability of the active compound, he says. “Inconsistency in the inactive ingredients and bottle can potentially cause fluctuation in IOPs and overall activity.”

Consider the patient’s condition

Robert Noecker, MD, MBA, an ophthalmologist with Ophthalmic Consultants of Connecticut in Fairfield and assistant clinical professor of ophthalmology at Yale University School of Medicine says patients expect ophthalmologists to recommend what they think is best. “Maybe a generic is okay, maybe it’s not, but at least we can say with some certainty from clinical trial data what you’re going to get [from] a branded product.”

And that matters with disease severity.

The less severe a patient’s disease is, “the more wiggle room” exists to try generics, Dr. Noecker explains. “You don’t have to lower the eye pressure as much, and if you don’t get it low enough, you have time to get it right.” But as the disease becomes more severe, the more skittish the patient becomes about generics. “The problem with glaucoma is you don’t get do-overs. If you miss, permanent optic nerve damage can occur, and that ship has sailed. You have to be careful about how much risk you’re willing to take.”

Health plan constraints

Complicating the situation, many patients don’t have a choice regarding which medication they receive because of health plan constraints or the fact that each pharmacy contracts with a different drug manufacturer for a certain price, says Marcos Reyes, MD, assistant professor of clinical ophthalmology at the School of Medicine, University of Missouri Health System in Columbia. As contracts expire, the pharmacy might move to a different manufacturer so patients picking up a refill could be presented with a different bottle.

Most patients “can’t pay out of pocket any more for a generic or brand name if they just want it because they’re all so expensive that they’re almost unaffordable,” adds E. Randy Craven, MD, associate professor of ophthalmology at the Johns Hopkins University School of Medicine in Baltimore and chief of glaucoma at King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia. “They’re stuck with what’s on their health plan for the most part. It might be prostaglandin brand X or generic Y and that’s it.”

Dr. Craven says he tries to get patients on a branded product if possible. But, with health plan limitations, he sometimes has to look for products like bimatoprost 0.01%, (Lumigan, Allergan) because it doesn’t have a generic equivalent. When generic latanoprost became available in 2011, he says, patients came to him with different brands from different countries — such as India, Canada and Mexico — and certain drugs didn’t work at all.

Imported generics might have different manufacturing requirements, says Dr. Kahook. His 2012 study of India-manufactured latanoprost found that its active ingredients, when exposed to heat, lost more than 10% of their stability.⁶ He also found that these generics had a higher number of contaminants.

“We’re facing a very difficult budgetary ... restriction,” says Dr. Craven, some patients need but can’t get branded drugs. “Unless something is very unique or special, it’s hard to get. My hopes are there will be new drugs coming out so we can at least keep some brand names we know.”

The case for generics

But while generic medications are not equivalent to their brand-name counterparts, they still can be effective, says Dr. Reyes. “I like brand-name medications but almost always recommend generic drugs first. For a long-term chronic medication, patients are going to have to be on for the rest of their life, I try to go as cheap as possible, knowing the economic impact” the disease will have.

Most often, he says, generics “do a decent job, and the studies are pretty clear that if you give someone a medication that’s a lower cost, they’re more compliant with it.”⁷ If a patient does not do well on a generic medication, because of less than expected pressure lowering, irritation or difficulty squeezing a bottle, then he will switch to a branded medication. In those cases, he says, he and his colleagues try to manage costs by taking advantage of manufacturer prescription savings plans.

Patient communication

Dr. Singh explains his preferences to patients, giving them a simple one-page document explaining the differences between brand-name and generic medications in terms of the manufacturing, FDA oversight and refill consistency. He found this type of counseling helps some patients better appreciate the value of branded drugs, he says.

In an unpublished study, Dr. Singh looked at 20 patients with mild glaucoma who initially were prescribed a brand-name drop but came back for their follow-up visit with a generic because the pharmacist told them it was less expensive. After Dr. Singh counseled patients and gave them the one-page handout, he wrote a new script for a brand-name drop (with generic substitution okay) and told patients to ask the pharmacist to go over the price differential. Of the 20, 13 converted to brand-name medications. A greater price difference could have also been a factor. Those who converted to a brand name saw a $30 price difference; those who chose to remain on generics had an average $65 difference.

Within a reasonable price difference, he says, “A lot of patients say, ‘now I understand the value and I’m willing to go ahead and pay the extra money.’” One patient chose to give up one Starbuck’s coffee a week to help cover the difference.

“It’s not that all generics are bad — they are useful and do work well for a lot of patients,” he says. “But we just don’t know which patients they work well in. The insecurity and lack of understanding of which [generics patients] are going to be on causes me to be uncomfortable [using them] for a long-term condition.”

While the primary argument for using a generic drug is cost, in some cases the price difference between the generic drug and the branded one can be $5, Dr. Noecker says. “In those situations, I’m hard-pressed to say the cost savings is really worth it for most patients. There are good generics and not-so-good generics, and it’s sometimes hard to tell what your patient is going to get.”

Conclusion

Despite the issues involved, Dr. Kahook says the “overwhelming majority” of his patients are on generic latanoprost, mainly because of cost and access. “Most of our patients do well with generics. They have significant IOP lowering and the side effect profile is not different than the branded drug.” Just a small subset of patients don’t respond as well to generics or complain of adverse events with the generic; this group does better on the brand name drug, he says.

The other physicians interviewed here also report larger percentages of patients on generic rather than brand name drugs. Among Dr. Noecker’s patients, one-third are on generics, while Dr. Craven’s patients are a 50-50 split; 70% of Dr. Reyes patients take generics. Dr. Singh’s patients were least likely to go generic, with only an estimated 20% opting for that class of drug.

“We all use generics, but if issues come up, think about generic medications being a potential cause before shying away from an entire class of medications,” Dr. Kahook says. OM

Dr. Craven is a consultant for Alcon, Allergan and Pfizer. Dr. Kahook is a consultant for Alcon, Allergan, Aerie and Shire, and receives research support from Allergan and Alcon. Dr. Noecker is a consultant for Allergan, Alcon, Aerie and Inotek. Dr. Singh is a speaker/consultant for Alcon, Allergan and Bausch + Lomb. Dr. Reyes reported no relevant financial conflicts of interest.

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