Multiple sclerosis (MS) affects approximately 400,000 Americans and 2.5 million adults worldwide. It is currently ranked as the second leading cause of neurologic disability in North America, which in turn may lead to an increase in dependence on others and caregiver burden.1

The earliest symptoms of MS include functional abnormalities of cognitive impairment, emotional lability, fatigue, sensory loss, dysphagia, vision loss, incoordination, ataxic tremors, pain, as well as, bladder, bowel, and sexual dysfunction.1,2 These symptoms are caused by changes in the normal functioning of the central nervous system due to inflammation of both the white and gray matter. These changes cause a delay in conduction and block demyelinated axons.3

MS can be divided into four basic categories (see Categories of MS). This information is important to keep in mind when determining appropriate treatment options for patients with MS.

The primary goals in the treatment of MS include: to prevent relapse; and to delay the progressive worsening by limiting disability progression and by reducing cognitive dysunction.2

Ambulatory impairment is one of the most common symptoms of MS, and there have been efforts to restore conduction defects and provide functional improvement. Through research, it has been shown that medications that inhibit potassium channels can improve conduction deficiencies secondary to neuronal demyelination in MS.2,4

FDA approval

The FDA approved orphan drug status for dalfampridine extended-release tablets, which will be marketed under the brand name Ampyra. Its use is indicated to improve walking in patients with MS.5 Ampyra will be manufactured under licenses from Elan of Dublin, Ireland, and distributed by Acorda Therapeutics Inc. of New York. Ampyra is a novel agent that targets MS symptoms, especially improving walking ability demonstrated by improved walking speed.6

Mechanism of action

Ampyra is an extended-release formulation. Ampyra nonspecifically blocks potassium channels causing a prolongation of the duration of the action potential by preventing potassium efflux during the repolarization phase of the action potential. This blockage of potassium can improve neuronal conduction. In turn, skeletal muscle fiber twitch activity strengthens, improving peripheral motor neurologic function.7

Pharmacokinetics

Early studies of Ampyra were done with an immediate-release formulation. This product produced a high peak serum concentration and rapid elimination, along with 90% of the drug excreted unchanged in the urine.1,7 Due to potential adverse events associated with the high concentrations and the rapid fluctuations in the plasma levels, a sustained-release oral formulation was developed. Ampyra is able to provide lower peak concentrations and a more consistent steady-state concentration.8

Dosing and administration

Ampyra is dosed orally at 10 mg every 12 hours. The maximum daily dose is 20 mg; there is no additional benefit with doses over 20 mg/day. The dose can be taken orally with or without food. Do not crush, chew, or break the tablet, due to the extended formulation of the product. No dose adjustments are needed in the geriatric population. The manufacturer recommends no specific dosing adjustment for patients with mild renal impairment (CrCl 51-80 mL/minute) However, it has been noted that there is an increased risk of seizure secondary to reduced clearance. In those with moderate-to-severe renal impairment (CrCl of 50 mL/minute or less), the use of Ampyra is contraindicated.

Contraindications

There are only a few contraindications associated with the use of Ampyra. Ampyra should not be used in patients who have a history of seizures. Another group are those who have moderate-to-severe renal impairment. Patients with a CrCl of 50 mL/minute or less should avoid the use of Ampyra due to the contraindication associated with the product.7

Adverse reactions

Throughout the clinical trials, adverse reactions related to the use of Ampyra are usually mild and dose-related. The most common include dizziness, paresthesia, and confusion. The adverse reactions that occur with the correct dosing are generally tolerable. Other adverse reactions include headache, balance disorder, urinary tract infection, and insomnia.7,9,10

Drug interactions

There are no documented drug interactions associated with the use of Ampyra. But keep in mind that Ampyra can induce seizures, so use caution if using it concomitantly with other medications that can lower the seizure threshold.2,8

Clinical pearls

When considering using Ampyra in patients with MS, NPs should keep in mind the following:

* Ampyra is the first drug of its kind that helps improve walking and increase walking speed in patients with MS.

* The tablet should be swallowed whole. Do not crush, chew, or break the tablet. Doing so will release the medication too quickly and increase the potential to develop a seizure and other adverse reactions.7

* The dosing of Ampyra is 10 mg by mouth every 12 hours.

* Do not use in patients with renal dysfunction who have a CrCl of 50 mL/minute or less.

* Ampyra is pregnancy category C.

* Ampyra should not be used while breastfeeding.

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