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FDA Approves First 3D-Printed Epilepsy Drug Experts Assess the Benefits and Caveats

ARTICLE IN BRIEF

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A new three-dimensional manufacturing process for levetiracetam aims to make the drug easier to swallow.

An epilepsy drug manufactured using three-dimensional printing techniques that will soon hit the market aims to make it easier for patients who have trouble swallowing pills to comply with their therapeutic regimen.

The drug, a version of the commonly prescribed anticonvulsant levetiracetam, is designed to dissolve in the mouth with a sip of liquid, according to the manufacturer, Aprecia Pharmaceuticals.

In August, the US Food and Drug Administration (FDA) approved the 3D-printed version of the drug, which will be marketed as Spritam (levetiracetam) when it becomes available in 2016. It is described as the first drug manufactured using a three-dimensional printing process.

The proprietary printing technique, which was developed at the Massachusetts Institute of Technology, involves building a pill one layer at a time by spreading powdered medication and depositing liquid layer by layer until the desired dosage is achieved. It allows for a high dose of medicine — up to 1,000 mg — to be layered into a relatively compact pill.

The pill is porous, enabling it to disintegrate quickly with a sip of liquid, said Don Wetherhold, the chief executive officer of Aprecia, a privately held company based in New Jersey.

“It has a unique capacity to dissolve at higher-dose loads,” Wetherhold told Neurology Today. “There clearly are some patients who would benefit — children, the elderly, people who have some other condition that may make it hard to swallow, such as cerebral palsy, stroke, or Alzheimer's disease.”

Levetiracetam, sold under the brand name Keppra, is already available in varying strengths in tablet, liquid, and extended-release formulations. The drug is used as an adjuvant therapy to treat partial-onset seizures, myoclonic seizures, and primary generalized tonic-clonic seizures in adults and children with epilepsy.

The company said a 1,000 mg dose has a diameter of about the size of a nickel and a thickness similar to a stack of four nickels, though the pill is lightweight and extremely porous. The pills will be individually packaged.

Research shows that anywhere from about 30 to 50 percent of epilepsy patients don't adhere to their prescribed drug regimens, Wetherhold said, though the reasons for non-compliance are varied.

THE BENEFITS, CAVEATS

Several neurologists not involved with the marketing of the drug agreed that it is potentially beneficial for some patients. “If this pill is easier to take, then it makes sense that it could improve compliance for some patients,” said Nathan Fountain, MD, a professor of neurology and director of the Comprehensive Epilepsy Program at the University of Virginia. For example, he said, “some children and adults are medically unable to swallow pills or have a psychological aversion to swallowing a pill.”

The more pills a person has to take a day, the greater the likelihood of non-compliance, Dr. Fountain added. Missed doses are especially problematic for epilepsy patients, who can have a seizure at any time without proper medication.

Jacqueline A. French, MD, FAAN, a professor of neurology at New York University Langone Medical Center and a member of the Neurology Today editorial advisory board, noted that she did some short-term consulting for Aprecia during its drug development stage. She said it has both advantages and disadvantages.

“Compliance is a huge issue when it comes to people with epilepsy and their medication,” Dr. French told Neurology Today. While the new version of levitiracetam might be helpful for some patients, she noted that there are already other dosing options available, including the liquid and extended-release forms and varying dosages of regular tablets. She said the 1,000 mg tablet is a “large pill,” but patients can take multiple smaller doses if they prefer.

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DON WETHERHOLD: “It has a unique capacity to dissolve at higher-dose loads. There clearly are some patients who would benefit — children, the elderly, people who have some other condition that may make it hard to swallow, such as cerebral palsy, stroke, or Alzheimers disease.”

“Swallowing can be a problem for everyone, but it is more of an issue for kids and the elderly,” Dr. French said. One advantage of the new drug, she noted, is that “you can put it in your mouth and don't have to worry about finding water.” Also, “you can throw a couple of pill packs in your pocket or purse and take them with you.”

But Dr. French said there are downsides to the drug, too. For instance, many patients like to use weekly pillboxes to stay on track with their medicines, and individually packaged pills aren't conducive to that approach. Also, just because a pill dissolves in the mouth, that doesn't necessarily mean that a patient will remember to take it.

Dr. French said physicians should talk to their patients about the pill-taking approach that works best for them. It may take a bit of tinkering to get dosing right, she noted, and it may also take some experimentation to find the medication formulation that best suits a patient.

“I think many doctors talk with their patients about compliance in a punitive way,” she said. “I like to approach it like, ‘Let's talk about what your barriers are and how we can overcome them.’”

Good compliance with medication is essential for epilepsy patients, she added. “There are a lot of medical conditions where missing one pill doesn't matter. But with epilepsy, it's not enough to say, ‘I am perfect 99 percent of the time.’”

Dr. Fountain said the new dissolvable pill could improve the quality of life for some epilepsy patients.

“People with epilepsy have to take medication for a long time,” he said. “It's worthwhile to get things fine-tuned both in terms of seizure control and in terms of convenience and compatibility with their lifestyle.”

Wetherhold said pricing for Spritam has not been set, though he said it will be in line with other branded versions of the drug. The pills will be manufactured at the company's New Jersey site and later at a new facility in Ohio.

He added that Aprecia is planning to use 3D printing to make drugs for other disorders involving the central nervous system, and will later expand to other therapeutic areas where high-dose medications are prescribed. He said the company is also exploring opportunities to use the 3D technology to manufacture over-the-counter medications and nutritional supplements.

EXPERTS: ON A 3D-PRINTED FORM OF LEVETIRACETAM

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DR. JACQUELINE A. FRENCH said that while the new version of levitiracetam might be helpful for some patients, there are already other dosing options available, including the liquid and extended-release forms and varying dosages of regular tablets. She said the 1,000 mg tablet is a “large pill,” but patients can take multiple smaller doses if they prefer.

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DR. NATHAN FOUNTAIN: “If this pill is easier to take, then it makes sense that it could improve compliance for some patients. Some children and adults are medically unable to swallow pills or have a psychological aversion to swallowing a pill.”

LINK UP FOR MORE INFORMATION:

•. FDA prescribing information for Spritam (levetiracetam): http://bit.ly/FDA-spritam
    •. More information about Spritam (levetiracetam): www.spritam.com