Ampyra

— THERAPEUTIC CATEGORIES —
  • Multiple sclerosis
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Ampyra Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Dalfampridine 10mg; ext-rel tabs.

    Pharmacological Class

    Potassium channel blocker.

    How Supplied

    Tabs—60

    Storage

    Store at 25°C (77°F). Excursions permitted 15ºC to 30ºC (59ºF to 86ºF).

    Manufacturer

    Acorda Therapeutics

    Generic Availability

    YES

    Ampyra Indications

    Indications

    To improve walking in patients with multiple sclerosis (demonstrated by an increase in walking speed).

    Ampyra Dosage and Administration

    Prior to Treatment Evaluations

    Assess estimated creatinine clearance before initiating treatment and monitor at least annually during treatment.

    Adult

    Swallow whole. ≥18yrs: max 10mg every 12hrs.

    Children

    <18yrs: not established.

    Ampyra Contraindications

    Contraindications

    History of seizures. Moderate or severe renal impairment (CrCl ≤50mL/min). Hypersensitivity to 4-aminopyridine.

    Ampyra Boxed Warnings

    Not Applicable

    Ampyra Warnings/Precautions

    Warnings/Precautions

    Assess renal function before initiation; monitor at least annually. Mild renal impairment (CrCl 51–80mL/min): increased risk of seizures. Discontinue if signs/symptoms of anaphylaxis occurs. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Seizures

    • Ampyra can cause seizures; increased incidence observed at 20mg twice daily (2 times max recommended dosage).
    • Seizures have also been reported (post-marketing) at recommended doses and in patients with a history of seizures; generally within days to weeks of starting therapy.
    • Ampyra has not been evaluated in patients with a history of seizures or with evidence of epileptiform activity on an EEG.
    • Permanently discontinue Ampyra in patients who have a seizure.
    • Treatment is contraindicated in patients with a history of seizures.

    Renal Impairment

    • Ampyra is eliminated primarily through the kidneys as unchanged drug.
    • Moderate to severe renal impairment: Ampyra is contraindicated as these patients would require a dose lower than 10mg twice daily and no strength smaller than 10mg is available.
    • Mild renal impairment: Ampyra levels may approach those seen at a dose of 15mg twice daily, which may be associated with an increased risk of seizures.

    Anaphylaxis

    • Ampyra can cause anaphylaxis and severe allergic reactions.
    • Signs/symptoms: Respiratory compromise, urticaria, angioedema of the throat/tongue.
    • Contraindicated in patients with a history of hypersensitivity to Ampyra or 4-aminopyridine.
    • Discontinue Ampyra if anaphylaxis develops.

    Pregnancy Considerations

    There are no adequate data on the developmental risk associated with use of Ampyra in pregnant women.

    Nursing Mother Considerations

    There are no data on the presence of dalfampridine in human milk, the effects of dalfampridine on the breastfed infant, or the effects on milk production. Consider the benefits to the mother vs the potential risks to the infant.

    Pediatric Considerations

    Safety and effectiveness in patients younger than 18 years of age have not been established. 

    Geriatric Considerations

    Clinical studies of Ampyra did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. Consider renal function as the drug is substantially excreted by the kidneys.

    Renal Impairment Considerations

    Clearance of dalfampridine is decreased in patients with renal impairment and is significantly correlated with creatinine clearance. Estimated CrCl should be calculated prior to starting treatment. Mild impairment may result in an increased risk of seizures as dalfampridine plasma levels in these patients may approach those seen at a dose of 15mg twice daily. Treatment is contraindicated in moderate to severe impairment.

    Ampyra Pharmacokinetics

    Absorption

    Rapidly and completely absorbed from the gastrointestinal tract. Single Ampyra tablet 10mg doses administered to individuals in a fasted state gave peak concentrations ranging from 17.3ng/mL to 21.6ng/mL occurring 3 to 4 hours post administration (Tmax).

    Distribution

    Dalfampridine is largely unbound to plasma proteins (97–99%).

    Metabolism

    Two metabolites were identified: 3-hydroxy-4-aminopyridine (4.3%) and 3-hydroxy-4-aminopyridine sulfate (2.6%). These metabolites have been shown to have no pharmacologic activity on potassium channels. CYP2E1 was the major enzyme responsible for the 3-hydroxylation of dalfampridine.

    Elimination

    Dalfampridine and metabolites elimination is nearly complete after 24 hours, with 95.9% of the dose recovered in urine and 0.5% recovered in feces. Elimination half-life of dalfampridine is 5.2 to 6.5 hours.

    Ampyra Interactions

    Interactions

    Discontinue other forms of 4-aminopyridine prior to initiating. Concomitant OCT2 inhibitors (eg, cimetidine) may potentiate the risk of seizures.

    Ampyra Adverse Reactions

    Adverse Reactions

    UTI, insomnia, dizziness, headache, nausea, asthenia, back pain, balance disorder, MS relapse, paresthesia, nasopharyngitis, constipation, dyspepsia, throat pain; seizures (possible at higher doses), severe allergic reactions.

    Ampyra Clinical Trials

    Clinical Trials

    The effectiveness of Ampyra in improving walking in patients with multiple sclerosis was evaluated in 2 adequate and well controlled trials involving 540 patients. Patients in these studies had a mean disease duration of 13 years and a mean Kurtzke Expanded Disability Status Scale (EDSS) score of 6.

    Trial 1

    • Randomized, placebo-controlled, parallel group, 21-week study in 301 patients with multiple sclerosis.
    • 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.
    • Exclusion criteria: History of seizures or evidence of epileptiform activity on a screening EEG, and onset of an MS exacerbation within 60 days.

    Trial 2

    • Randomized, placebo-controlled, parallel group, 14-week study in 239 patients with MS.
    • A total of 227 patients (113 AMPYRA and 114 placebo) completed all study visits.
    • Same inclusion and exclusion criteria as in Trial 1.

    Primary endpoint: Walking speed (in feet per second) as measured by the Timed 25-foot Walk (T25FW), using a responder analysis. A responder was defined as a patient who showed faster walking speed for at least 3 visits out of a possible 4 during the double-blind period than the maximum value achieved in the 5 non-double-blind no treatment visits.

    Results: A significantly greater proportion of patients taking Ampyra 10mg twice daily were responders, compared with patients taking placebo (Trial 1: 34.8% vs 8.3%; Trial 2: 42.9% vs. 9.3%). Increased response rate was observed across all 4 major types of MS disease course. Compared with placebo, a significantly greater proportion of patients taking Ampyra had increases in walking speed of at least 10%, 20%, or 30% from baseline. The magnitude of improvement in walking ability was independent of concomitant drugs (63% of patients were using immunomodulatory drugs). No differences observed based on degree of impairment, age, gender, or BMI; the effect on race could not be evaluated.

    Ampyra Note

    Not Applicable

    Ampyra Patient Counseling

    Patient Counseling

    Can cause seizures; discontinue treatment if seizure occurs.

    Do not take a double dose after a missed dose as this may increase seizure risk. Max 2 tablets in a 24-hour period with a 12-hour interval between doses.

    Discontinue treatment if anaphylaxis occurs.

    CNS-related adverse reactions such as vertigo and dizziness may occur with treatment and might affect ability to drive or use machinery.

    Cost Savings Program

    Ampyra Patient Support Services

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