Ampyra Information
Ampyra () Indications And Usage
Ampyra () (dalfampridine) is indicated as a treatment to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed
Ampyra () Dosage And Administration
The maximum recommended dose of Ampyra () is one 10 mg tablet twice daily, taken with or without food, and should not be exceeded. Doses should be taken approximately 12 hours apart. Patients should not take double or extra doses if a dose is missed.
No additional benefit was demonstrated at doses greater than 10 mg twice daily and adverse reactions and discontinuations because of adverse reactions were more frequent at higher doses. Tablets should only be taken whole; do not divide, crush, chew, or dissolve.
Ampyra () is contraindicated in patients with moderate or severe renal impairment . The risk of seizures in patients with mild renal impairment (CrCl 51–80 mL/min) is unknown, but Ampyra () plasma exposure in these patients may approach that seen at a dose of 15 mg twice daily, a dose that may be associated with an increased risk of seizures; estimated CrCl should be known before initiating treatment with Ampyra ()
Ampyra () Dosage Forms And Strengths
Ampyra () is available in a 10 mg strength and is a film-coated, white to off-white, biconvex, oval shaped, non-scored tablet with flat edge, debossed with "A10" on one side.
Ampyra () Contraindications
The use of Ampyra () is contraindicated in the following conditions:
Ampyra () Warnings And Precautions
Ampyra () is contraindicated in patients with a history of seizures . Increased incidence of seizures has been observed at 20 mg twice daily in controlled clinical studies of 9–14 weeks duration with dalfampridine in patients with MS. There was one seizure seen in the placebo group (0.4%) and at a dose of 10 mg twice daily (0.25%), no seizure seen at 15 mg twice daily and 2 seizures (3.5%) seen at 20 mg twice daily. In open label extension trials in MS patients, the incidence of seizures during treatment with dalfampridine 15 mg twice daily (1.7/100PY) was over 4 times higher than the incidence during treatment with 10 mg twice daily (0.4/100PY).
Ampyra () has not been evaluated in patients with a history of seizures or with evidence of epileptiform activity on an EEG, as these patients were excluded from clinical trials. The risk of seizures in patients with epileptiform activity on EEG is unknown, and could be substantially higher than that observed in Ampyra () clinical studies. Ampyra () should be discontinued and not restarted in patients who experience a seizure while on treatment.
Ampyra () is eliminated through the kidneys primarily as unchanged drug
Because patients with renal impairment would require a dose lower than 10 mg twice daily and no strength smaller than 10 mg is available, Ampyra () is contraindicated in patients with moderate or severe renal impairment [Creatinine Clearance (CrCl) ≤50mL/min] . The risk of seizures in patients with mild renal impairment (CrCl 51–80 mL/min) is unknown, but dalfampridine plasma levels in these patients may approach those seen at a dose of 15 mg twice daily, a dose that may be associated with an increased risk of seizures . If unknown, CrCl should be estimated prior to initiating treatment with Ampyra () . CrCl can be estimated using the following equation (multiply by 0.85 for women):
Ampyra () Adverse Reactions
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
The following adverse reactions are described in more detail in the Warnings and Precautions section of the label: Seizures and Urinary Tract Infections.
Ampyra () Drug Interactions
In humans, dalfampridine is eliminated predominately unchanged by the kidneys. No clinically significant drug interaction was identified .
Ampyra () Use In Specific Populations
Clinical studies of Ampyra () did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. A population PK analysis showed that dalfampridine clearance modestly decreased with increasing age, but not sufficiently to necessitate a modification of dose with age. Other reported clinical experience has identified no differences in responses between the elderly and younger patients.
Ampyra () is known to be substantially excreted by the kidney and the risk of adverse reactions, including seizures, is greater with increasing exposure of dalfampridine. Because elderly patients are more likely to have decreased renal function, it is particularly important to know the estimated creatinine clearance (CrCl) in these patients
Ampyra () Drug Abuse And Dependence
No studies on the abuse or dependence potential of Ampyra () have been performed.
Ampyra () Overdosage
Three cases of overdose were reported in controlled clinical trials with Ampyra () , involving two MS patients. The first patient took six times the currently recommended dose (60 mg) and was taken to the emergency room with altered mental state. The second patient took 40 mg doses on two separate occasions. In the first instance, she experienced a complex partial seizure and, in the second instance, a period of confusion. Both patients recovered by the following day without sequelae.
Several cases of overdose are found in the scientific literature in which various formulations of dalfampridine were used, resulting in numerous adverse events including seizure, confusion, tremulousness, diaphoresis and amnesia. In some instances, patients developed status epilepticus, requiring intensive supportive care and were responsive to standard therapy for seizures. In one published case report, an MS patient who ingested 300 mg of 4-aminopyridine (dalfampridine) developed a condition that resembled limbic encephalitis. This patient developed weakness, reduced awareness, memory loss, hypophonic speech, and temporal lobe hyperintensities on MRI. The patient's speech and language and ambulation improved over time, and an MRI at 4 months after the overdose no longer showed signal abnormalities. At one year, the patient continued to have difficulty with short term memory and learning new tasks.
Ampyra () Description
Ampyra () (dalfampridine) is a potassium channel blocker, available in a 10 mg tablet strength. Each tablet contains 10 mg dalfampridine, formulated as an extended release tablet for twice-daily oral administration. Dalfampridine is also known by its chemical name, 4-aminopyridine, with the following structure:
Ampyra () (dalfampridine) Extended Release tablets are available in a 10 mg strength and are a white to off-white, biconvex, oval shaped, film-coated, non-scored tablet with flat edge, debossed with "A10" on one side, containing 10 mg of dalfampridine. Inactive ingredients consist of colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide.
Dalfampridine is a fine white powder with a molecular weight of 94.1, CAS 504-24-5 and a molecular formula of CHN. At ambient conditions, dalfampridine is soluble in water, methanol, acetone, tetrahydrofuran, isopropanol, acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, and ethanol.
Ampyra () Clinical Studies
The effectiveness of Ampyra () in improving walking in patients with multiple sclerosis was evaluated in two adequate and well controlled trials involving 540 patients. Patients in these two clinical trials had a mean disease duration of 13 years and a mean Kurtzke Expanded Disability Status Scale (EDSS) score of 6.
Trial 1 was a randomized, placebo-controlled, parallel group, 21-week study (one week post screening, two-week, single-blind placebo run-in, 14-week double-blind treatment, and 4-week no treatment follow-up) in 301 patients with multiple sclerosis at 33 centers in the U.S. and Canada: 229 patients assigned to Ampyra () 10 mg twice daily and 72 patients assigned to placebo. A total of 283 patients (212 Ampyra () and 71 placebo) completed all study visits. Patient inclusion criteria included the ability to walk 25 feet in 8–45 seconds. Patient exclusion criteria included a history of seizures or evidence of epileptiform activity on a screening EEG, and onset of an MS exacerbation within 60 days.
Trial 2 was a randomized, placebo-controlled, parallel group, 14-week study (one week post-screening, two weeks of single-blind, placebo run-in, nine weeks of double-blind treatment, and two weeks of no-treatment follow-up) in 239 patients with multiple sclerosis at 39 centers in the U.S. and Canada: 120 patients assigned to 10 mg twice daily and 119 assigned to placebo. A total of 227 patients (113 Ampyra () and 114 placebo) completed all study visits. The patient inclusion and exclusion criteria used in Trial 1 were employed in Trial 2, and in addition patients with severe renal impairment were also excluded.
The primary measure of efficacy in both trials was walking speed (in feet per second) as measured by the Timed 25-foot Walk (TF25W), using a responder analysis. A responder was defined as a patient who showed faster walking speed for a least three visits out of a possible four during the double-blind period than the maximum value achieved in the five non-double-blind no treatment visits (four before the double-blind period and one after).
A significantly greater proportion of patients taking Ampyra () 10 mg twice daily were responders, compared to patients taking placebo, as measured by the T25FW (Trial 1: 34.8% vs. 8.3%; Trial 2: 42.9% vs. 9.3%). The increased response rate in the Ampyra () group was observed across all four major types of MS disease course.
During the double-blind treatment period, a significantly greater proportion of patients taking Ampyra () 10 mg twice daily had increases in walking speed of at least 10%, 20%, or 30% from baseline, compared to placebo (Figure 1 and Figure 2).
In Trial 1 and Trial 2, consistent improvements in walking speed were shown to be associated with improvements on a patient self-assessment of ambulatory disability, the 12-item Multiple Sclerosis Walking Scale (MSWS-12), for both drug and placebo treated patients. However, a drug-placebo difference was not established for that outcome measure.
The majority of patients in these trials (63%) were using immunomodulatory drugs (interferons, glatiramer acetate, or natalizumab), but the magnitude of improvement in walking ability was independent of concomitant treatment with these drugs. No differences in effectiveness based on degree of impairment, age, gender, or body mass index were detected. There were too few non-Caucasians in the patient population to evaluate the effect of race.
Ampyra () How Supplied/storage And Handling
Ampyra () (dalfampridine) extended release tablets, 10 mg are a film-coated, white to off-white, biconvex, oval shaped, non-scored tablets with flat edge. The tablets are identified by a debossed code "A10" on one side and are available in bottles of 60.
Ampyra () Patient Counseling Information
Ampyra () Fda-approved Patient Labeling
Read this Medication Guide before you start taking Ampyra () and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.
Ampyra () can cause seizures.
Ampyra () is a prescription medicine used to help improve walking in people with multiple sclerosis (MS). This was shown by an increase in walking speed.
It is not known if Ampyra () is safe or effective in children less than 18 years of age.
Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.
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The most common side effects of Ampyra () include:
Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of Ampyra () . For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Keep Ampyra () and all medicines out of the reach of children.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Ampyra () for a condition for which it was not prescribed. Do not give Ampyra () to other people, even if they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about Ampyra () . If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Ampyra () that is written for health professionals.
For more information, go to www.Ampyra () .com or call 1-800-367-5109.
Distributed by: Acorda Therapeutics, Inc.Hawthorne, NY 10532
Issued 01/2010
Ampyra ()
Ampyra ()
