Each time a generic drug is released on the market, doctors must evaluate the risk versus the reward to their patients and navigate whether or not to prescribe. Among eyecare professionals, generics are a complicated and controversial topic. One of the latest to spark conversation and investigation is the new generic formulation of cyclosporine ophthalmic emulsion 0.05%.
In early February, the FDA approved a generic version of AbbVie’s top-selling Restasis
. Launching a generic has been underway for over a decade, with 16 different FDA research trials, 9 different companies vying for approval, and Mylan Pharmaceuticals Inc., a subsidiary of Viatris Global, winning out.
We interviewed optometrists to find out what they think about the viability of this generic version of the widely popular dry eye drop.
What is Restasis?
As the first FDA-approved dry eye
medication, Restasis has been a go-to treatment since its release by Allergan in 2003. Its formulation of 0.05% cyclosporine and Refresh Endura is devised to bring immediate relief to patients upon instillation, stimulate natural tear production, and increase goblet cell density. The drug comes in both single-use vials and in a multi-dose, preservative-free option.
The most common side effect with Restasis is ocular burning, as reported by 17% of patients. Less than 5% of patients complained of blurred vision, epiphora, conjunctival hyperemia, redness
, or discharge. The lack of serious adverse effects is a key component of Restasis’ success.
Leading up to this newest development, Restasis already brought with it an interesting history. The drug, which is reported to have generated $1.2 billion
in sales for AbbVie last year, was originally patented and produced by Allergan. To protect their patent, the company went as far as to bestow patent rights to the St. Regis Mohawk Tribe
. However, this effort failed, leading to the approval of the current generic incarnation.
What is Restasis used for?
Restasis, also known as cyclosporine ophthalmic emulsion 0.05%, is a calcineurin inhibitor used to treat chronic dry eye disease.
How does Restasis work?
Unlike traditional artificial tears, which provide tears, Restasis reduces inflammation and stimulates the patient’s body to produce more tears.
How long does it take Restasis to work?
Taken as directed—one drop in each eye twice a day, every day, at least 12 hours apart—Restasis may take up to 3 months in some patients to increase tear production. For significant tear production increase, patients may need to continue use for 6 months.
What are the side effects of Restasis?
The most commonly reported side effects from Restasis are temporary burning or stinging. Patients have also complained of redness, itching, stinging, watering, blurred vision, and discharge.
How much does Restasis cost?
A 30-day supply of Restasis has a list price of $586. However, Restasis is widely covered through insurance and Medicare.
Are generic drugs as good as brand names?
The fundamental question at the bottom of this article is whether or not the generic—and specifically this formulation of cyclosporine ophthalmic emulsion 0.05%— is equivalent to its brand name counterparts and should be prescribed interchangeably.
According to the FDA
, their rigid standards ensure that “generic drug products are safe, effective and meet the same high-quality standards as their brand name counterparts.” However the administration acknowledges that, due to having more involved active ingredient formulations and delivery routes, complex generics are more challenging
. After conducting 16 research projects related to cyclosporine ophthalmic emulsion, they deemed Mylan had achieved an acceptable bioequivalent.
When asked about generic equivalence, the overall consensus from the ODs we asked was “no, not necessarily.” Across the board, each cited that a drug's effectiveness depends not only on its active ingredient, but on its inactive ingredients as well.
“While generics are required to have the same active ingredient as the brand-name medication, they are not required to have the same inactive ingredients. Although this may not seem like a major concern, it can have a significant impact on efficacy as certain inactive ingredients can be critical components of a branded drug,” said Cory Lappin, OD, MS, FAAO, who practices at Phoenix Eye Care and the Dry Eye Center of Arizona.
Dr. Lappin went on to explain that the vehicle used to deliver the drug to the target site is often an inactive ingredient, which determines how efficiently the drug will penetrate and behave. According to Dr. Lappin, “If the generic version has a drastically different vehicle, it may not be as effective as its brand-name counterpart. Additionally, the inactive ingredients used by different generic manufacturers can vary which may lead to unpredictability in side effects and efficacy.”
Mahnia Madan, BSc, OD, FAAO, a dry eye specialist in Vancouver, British Columbia, where a generic version of Restasis has been available since 2018, echoed this sentiment: “You want to make sure you’re getting the brand name because there's more consistency in it. I have experience with Restasis for the last 15 years. It's not just the active ingredient in a drug: it's all the other molecules and how they work together.”
Main concerns about generic Restasis
As with any medication, the main concerns are efficacy and side effects. Absorption and the drops' effect on the ocular surface are also alarming factors, as the inactive ingredients are unknowns in the equation.
“The formulations we currently have are formulated in the way they are for a reason. There's a lot of research, money, and time that goes into understanding how the drug is delivered to the ocular surface, how it absorbs into the cornea, epithelial cells, and conjunctiva. That's a really big part of how medication works,” stated Hardeep Kataria, OD, FAAO, a practicing optometrist in Los Angeles with a focus on dry eye and medical glaucoma. “And so with a generic, I am concerned about the delivery, the formulation, how it will affect the ocular surface . . . all those things.”
As Dr. Lappin pointed out, cyclosporine is naturally hydrophobic, making penetrating the aqueous component of the tear film challenging. Restasis addressed this issue by utilizing an anionic oil-in-water emulsion vehicle to allow for better compatibility with the tear film and ocular surface. This, in turn, leads to greater absorption and, ultimately, efficacy.
With generic Restasis, efficacy and side effects are inextricably linked, as its effectiveness is directly tied to patient compliance, which primarily depends on the level of discomfort they experience upon instillation. Irritation proves the leading cause for discontinuation of Restasis. If the generic does not address this issue, it may lead to an even greater abandonment of the treatment.
According to Sathi Maiti, OD, an Ocular Surface Disease Clinical Research Fellow at Periman Eye Institute, “Due to the hydrophobic, lipophilic nature of cyclosporine, the vehicle is quite important in order for the drug to penetrate well while also feeling comfortable for regular use. It would be unfortunate if the generic has a lot of side effects, like burning and stinging, making it less expensive but potentially non-tolerable to many patients.”
Having had experience with the generic version of cyclosporine 0.05%, Dr. Madan has seen this firsthand. “What I have seen is that the tolerability differences are huge,” she stated. “Some patients will report more side effects with the generic, saying it stings, burns, and irritates more.”
How much less will generic Restasis cost?
Of course, the foremost reason generics are created is purportedly to off-set cost for the consumer by offering a lower price.
Generic medications typically cost about 80% to 85% less than the same brand-name drug. With a 30-Day supply of Restasis having a list price of $586
, this means the generic should be approximately $117. For patients paying out of pocket, this could mean the difference in being able to opt for the most appropriate and advantageous treatment.
“I think one of the most difficult aspects of treating dry eye is how expensive most of the advanced treatment options are to patients including immunomodulators like cyclosporine and Lifitegrast,” Dr. Maiti said, “Many patients end up not being able to access these medications due to cost and difficulty with insurance coverage. Many patients simply cannot afford to treat their dry eye and have to just live with the symptoms.”
Overall, the doctors have not found Restasis to be cost-prohibitive, noting that of all the prescription dry eye medications
it tends to have the best insurance coverage
, likely due to its two decades on the market. “Restasis has been around for 20 plus years. It's the first immunomodulatory drug to be available. And, it has great coverage. That's one of the main reasons that I can write it so widely at my practice for the appropriate patient—because it is covered, and patients don't have high co-pays with it,” Dr. Kataria said.
Also, in Canada, Dr. Madan did not see nearly the expected price difference with the generic and questions whether we will in the US, especially with no market competition to spur competitive pricing, as only one generic has been approved. She stated, “In my experience, the price just hasn't been that different. Here, we don't see a 65% drop, so I would be cautious.”
Insurance policies around the new generic could dictate other changes for practices:
- Insurance companies may demand the generic be tried first, for a given period of time, before brand-name Restasis can be prescribed.
- Alternatively, if a patient fails on the generic, insurers who would not previously cover Restasis may be forced to do so.
- Having a generic option could potentially drive down the cost of Restasis, and as a result Xiidra and Cequa as well.
Patient education on dry eye disease
With ad campaigns and the FDA promoting generics as equal but cheaper—and, therefore, more desirable than brand names—patients are bound to inquire about “generic Restasis.”
Dr. Kataria has already experienced this since the drug’s launch and feels an obligation to educate patients on the aforementioned concerns and remind them that this solution will be applied directly to their ocular surface and warrants deep consideration. “My role is to educate,” Dr. Kataria said. “I have more knowledge than the consumer and the patient. My responsibility is to tell the patient my knowledge on the subject, and then say ‘I encourage you to do your own research, if you so wish, and then I want you to make the decision.’”
Dr. Madan has also had to address the difference between brand/generic with patients who are not experiencing improvement. She explained, “Oftentimes when patients come back and they’re not getting better, the question we have to ask now is whether they’re on generic Restasis or regular.”
The future of generic cyclosporine 0.05%
Due to the aging population and increased screen time, the prevalence of dry eye
is ever increasing. According to the Eyes On Eyecare 2021 Dry Eye Report
, optometrists estimated over half of their patients suffered from some level of dry eye disease and that 38.7% of their clinical focus would be focused on the diagnosis and treatment of dry eye.
Taking this into consideration, having effective and affordable treatment options is a major concern for eyecare professionals. Our optometrists all agree that though having a less expensive alternative could prove positive, there are simply too many variables and unknowns about generic cyclosporine 0.05% to factor it into the future of dry eye treatment at this time.
Dr. Lappin cautions against using the generic for patients who have previously failed on Restasis, either due to poor clinical response or intolerance of side effects, or switching a patient who is responding well to a brand-name treatment to the generic, unless insurance demands you do so.
Dr. Madan agrees: “I always look for any in-office treatments that I can do to help enhance [Restasis], whether it is treating the meibomian glands, making sure we can optimize that with, perhaps, Intense Pulsed Light (IPL). There's so many treatments in our toolbox, whether you want to try an autologous serum or PRP or do bloodwork to rule out any other causes. In terms of just drugs, I might try Xiidra or increase the Restasis. We just got Cequa in Canada, as of two weeks ago, so I can try it on these patients.”
With innovations and medications leading to an ever-expanding arsenal for the treatment of dry eye disease
, doctors can afford to cautiously prescribe the new generic to patients who, due to cost barriers, cannot obtain Restasis. In the end, the goal is patient safety, relief from symptoms, and overall satisfaction.
As stated by Dr. Maiti, “We already work hard to offer our patients all the available treatments we can, so this [generic] will be a welcome addition—if it is affordable, tolerable, and effective.”
What Doctors Think About the New Generic of Restasis? Click here to read insights from four ODs on thenewly FDA-approved generic version of cyclosporine ophthalmic emulsion 0.05%