BRANDED VS GENERIC PHARMACEUTICALS

Branded Preferred

Clinicians discuss the settings in which they prefer branded drugs and why.

By Virginia Pickles, Contributing Editor

Despite increasing utilization and acceptance of generic drugs, some ophthalmologists worry about therapeutic equivalency of topical ocular solutions compared with the branded drugs on which they are based. Although not opposed to generics in general — they know a generic drug may be the only option for some patients — they are particularly vigilant for reduced efficacy and adverse side effects when a generic is on board, especially in the following settings.

CORNEAL TRANSPLANTATION

Postoperative complications are always a concern, but never more so than after corneal transplantation. “Preventing graft rejection is uppermost in my mind, and the primary preventative is a corticosteroid, which patients may use for several years,” says Keith A. Walter, MD, professor of ophthalmology at Wake Forest University School of Medicine, Winston-Salem, N.C. “When they start their course of treatment, patients may receive name-brand Pred Forte (prednisolone acetate, Allergan) as prescribed, but at some point, they may be switched to a generic. When I see a patient with signs of rejection, nine times out of 10, I find he is either using nothing at all or he is using a generic version of the branded drug.”

Dr. Walter attributes reduced efficacy of some generic suspensions to variations in manufacturing processes. “Because of differences in milling processes,¹ some generics tend to not stay in suspension, either on the pharmacy shelf or at the patient’s home,” he says. “Even when a patient shakes the bottle as directed, the medicine may clump inside, so he ends up getting mostly vehicle. The effect is almost immediate. If I see the patient soon enough after this happens and switch him back to the name-brand drug, the effects reverse, and I can save the graft.”

William B. Trattler, MD, a cornea specialist practicing in Miami and a volunteer faculty member at Florida International University Herbert Wertheim College of Medicine, also prefers branded prednisolone acetate. “I haven’t seen toxicity with generic prednisolone acetate, but it doesn’t seem to be as efficacious as similar branded products, and patients have to know to shake the bottle, or there could be some uniformity issues,” he says. “The newer brand-name formulations, particularly difluprednate (Durezol, Alcon) and loteprednol gel (Lotemax Gel, Bausch + Lomb), which do not have generic alternatives, don’t require shaking, which means dosing is uniform from the first drop to the last drop, as compared with generic prednisolone. For patients who don’t have insurance coverage, I prescribe a generic prednisolone, but for others, particularly surgical patients who have high visual expectations, I prescribe brand-name Durezol or Lotemax Gel.”

Gregg J. Berdy, MD, who specializes in corneal and external disease in St. Louis and is an assistant professor of clinical ophthalmology at Washington University School of Medicine, has more confidence in generic products that are manufactured by the same company that produces the brand-name drug. “If Alcon is making a generic EconoPred, for example, then I know the formulation is the same,” he says. “If a foreign company is making it, I can’t be sure what’s in that bottle. The formulation of the drug, including binders, pH, emollients, and solubility, may not be the same as the branded drug. There may be a significant difference in any of the components of the solution, which could affect efficacy and tolerability.”

POST CATARACT AND REFRACTIVE SURGERY

“Patients have high expectations for cataract surgery and laser vision correction,” Dr. Trattler says. “They want to see well. They want to see fast, and they want to be comfortable. They talk to their friends about their experiences, and if they don’t get a good result right away — even if they eventually achieve good vision several months later — they don’t blame the medication. They blame the doctor. The experience is as important to patients as it is for us, particularly with online rating systems and word-of-mouth referrals to friends and family.

“That said,” Dr. Trattler continues, “I’ve found some generic NSAIDs are toxic to the ocular surface in many patients, particularly those who have dry eye and ocular surface disease. In my experience, generic ketorolac and bromfenac specifically, can cause significant irritation, leading to discomfort and reduced vision. In contrast, brand-name NSAIDs, including Prolensa (bromfenac, B+L), Ilevro (nepafenac, Alcon) and Acuvail (ketorolac, Allergan), have proven to be safe for the ocular surface. I feel strongly that it’s important to use brand-name NSAIDs in my surgery patients to avoid toxicity.”

Dr. Walter agrees with Dr. Trattler’s assessment of the NSAIDs. “Topical NSAIDs are notorious for causing problems,” Dr. Walter says. “One of the worst offenders is generic ketorolac. It’s very toxic to the eye.² I’m not sure we really know why, but something — possibly the preservative or the pH — is different. Clinically, I’ve seen significant postoperative punctate epithelial keratopathy as a result of using a generic NSAID.

“For cataract surgery, I want patients on an NSAID, and I want them on a good NSAID, typically a name-brand NSAID, such as Prolensa,” Dr. Walter continues. “If generic ketorolac is substituted for the brand-name drug I prescribe, I will likely see widespread keratopathy and decreased vision at the 1- to 2-week post-op visit. These effects resolve once the patient stops using the generic drug and switches to the branded drug.”

Dr. Berdy also has observed adverse effects from generic ketorolac, particularly when patients are switched from branded NSAIDs that have different, usually less frequent, dosing schedules. “A patient who is using Prolensa or Ilevro is dosing the drug once a day,” he says. “If the patient is switched to generic ketorolac, it should be dosed four times a day for the equivalent effective dose. Unfortunately, if the patient doesn’t understand the difference in frequency of the dosing and uses the drug only once a day, the drug won’t be effective. I’ve seen patients with chronic, long-standing inflammation in the anterior chamber, as well as evidence of cystoid macular edema and poor vision in this situation.”

GLAUCOMA MANAGEMENT

Glaucoma specialists are faced with a unique dilemma. Numerous IOP-lowering drops in different drug classes, as well as fixed combinations, are available with various dosing schedules. What’s more, most of the branded drugs now have generic versions, including the most commonly prescribed prostaglandin analog, Xalatan (Pfizer). Multiple treatment options enable physicians to individualize therapy, but they also create opportunities for variable treatment responses.

Robert D. Fechtner, MD, professor and director of the glaucoma division of Rutgers-New Jersey Medical School in Newark, has studied brand-name and generic antiglaucoma medications and found the generics wanting. In a 2012 study,³ for example, he and colleagues found generic latanoprost lost 10% of its mean active concentration at temperatures at the high level of their labeled indication and within the expected duration of clinical use. In addition, the mean concentration of the preservative benzalkonium chloride was significantly lower after thermal stress testing in some generic formulations. They also found a higher number of particulates greater than 1 micron in diameter in some generic formulations. Based on their findings, they recommended that patients who are converted to generic formulations be closely monitored for signs of decreased efficacy, as well as potential side effects related to everyday use.

Dr. Fechtner’s research, research by others,⁴ and his clinical experience have placed him squarely in the branded-only (when possible) camp. “I have convinced myself in some cases that patients who were switched to a generic prostaglandin analog lost some of their pressure control but recovered it when placed back on the branded drug,” he says. “In a few instances, I re-introduced a generic because there was a big price difference, and saw the same effect again.”

The prostaglandin analogs remain the foundation of medical therapy for glaucoma, Dr. Fechtner says, but they tend to go on and off drug plans from year to year, often prompting patients who have been using a particular drug successfully to ask for a less expensive alternative. “Their question, ‘Doctor, isn’t there something cheaper I can use?’ has become as much of my discussions with patients about glaucoma care as anything else,” he says.

Many of Dr. Fechtner’s patients are referred to him and are already using antiglaucoma medications, often generics, but when he initiates therapy, he gives patients samples of branded drugs. “The best possible start I can offer is with a branded drug,” he says. “Patients can try it, and we can look at efficacy and tolerability together. I show them how to recognize and use the bottle, and they use it for a week or more to make sure it’s comfortable. If they’re comfortable with the drug and their pharmacy benefit covers it, they may have to fill their first prescription before they come back to see me, but at least they’ve had a chance to make sure it is comfortable. I can check efficacy when I see them.”

A recent development involving bimatoprost has Dr. Fechtner on alert. “A generic drug-maker is promoting its product as a generic alternative to Lumigan (Allergan),” he says. “However, the drug concentration in branded Lumigan is 0.01%, while the drug concentration in the generic is 0.03%. If I write a prescription for Lumigan and don’t specify 0.01%, a pharmacist can dispense the generic bimatoprost. I have heard some anecdotal reports of better efficacy with the generic but overall worse tolerability.”

Dr. Fechtner has also observed differences among the generic versions of Cosopt (dorzolamide-timolol, Merck). “I commonly see four different generic Cosopts in my practice,” he says. “Patients report differences in the bottle feel, drop size, and comfort.

“I would like patients to have access to the medications I understand and have studied and believe will benefit them the most in terms of tolerability, ease of use, and even bottle design,” Dr. Fechtner says. “Unless pharmacy benefit managers are more flexible or provide greater access, however, I think by controlling the dollars, they have vast coercive influence over patients’ choices.” ◆

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