Ampyra

Name: Ampyra

Ampyra Usage

Ampyra comes as a tablet to be taken by mouth with or without food. It is usually taken 2 times each day about 12 hours apart. Ampyra tablets should be taken whole. Do not break, crush, chew or dissolve Ampyra tablets.

If you miss a dose of Ampyra, do not make up the missed dose. Do not take 2 doses at the same time. Take your next dose at your regular scheduled time.

Warnings

Contraindications

Hypersensitivity

Moderate or severe renal impairment (CrCl ≤50 mL/min)

History of seizure

Cautions

Discontinue if seizure occurs and do not restart; majority of seizures happened within days to weeks after starting the recommended dose and occurred in patients having no history of seizures

Age-related decreases in renal function, and mild renal impairment is common after age 50 yr, even when serum creatinine is normal; renal function should be assessed by estimating creatinine clearance

Do not take with other forms of 4-aminopyridine (4-AP, fampridine) to avoid adverse reaction due to the same active ingredient

Estimate CrCl before initiating (see Contraindications and Renal Impairment)

Do not double dose or take extra if dose missed

Anaphylaxis and severe allergic reactions; signs and symptoms have included respiratory compromise, urticaria, and angioedema of the throat and or tongue; discontinue immediately and do not restart (see Contraindications)

UTIs reported more frequently in clinical trials vs. placebo

Pregnancy & Lactation

Pregnancy Category: C

Lactation: Unknown if excreted in breast milk; discontinue drug or breast feeding

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Uses for Ampyra

Multiple Sclerosis

Used to improve walking in patients with multiple sclerosis (MS);1 designated an orphan drug by FDA for relief of symptoms of MS.23

In clinical studies in MS patients who received the recommended dalfampridine dosage, walking improvement was demonstrated by increased walking speed in a timed 25-foot walk (T25FW).1 2 3 20 In those who responded to dalfampridine (approximately 35–43%), walking speed increased 25–29%2 3 20 and was maintained until the drug was discontinued.2 20

Although only a portion of MS patients respond to dalfampridine treatment with walking improvement, improved walking during such treatment has been demonstrated in all MS disease types (relapsing remitting, primary progressive, secondary progressive, progressive relapsing).2 20 It is not clear what magnitude of improvement in walking speed results in improved walking ability or quality of life.20 Although consistent improvements in walking speed were shown to be associated with improvements on patient self-assessment of ambulatory disability (12-item Multiple Sclerosis Walking Scale; MSWS-12), the average MSWS-12 score during dalfampridine treatment was not different than that reported with placebo.1 20

The magnitude of walking improvement reported with dalfampridine is independent of concomitant therapy with biologic response modifiers used for the management of MS (interferon, glatiramer acetate, natalizumab).1 2

Data insufficient regarding safety and efficacy for management of other MS symptoms (e.g., motor function assessed using manual muscle testing, visual function, cognitive function, fatigue).6 12 14 18 20

Commonly used brand name(s)

In the U.S.

  • Ampyra

Available Dosage Forms:

  • Tablet, Extended Release

Therapeutic Class: Central Nervous System Agent

Pharmacologic Class: Potassium Channel Blocker

What do I need to tell my doctor BEFORE I take Ampyra?

  • If you have an allergy to dalfampridine or any other part of Ampyra (dalfampridine).
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have ever had a seizure.
  • If you have kidney disease.
  • If you are taking or will be taking another drug like this one.
  • If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Ampyra with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Contraindications

The use of Ampyra is contraindicated in the following conditions:

  • History of seizure
  • Moderate or severe renal impairment (CrCl≤50 mL/min)
  • History of hypersensitivity to Ampyra or 4-aminopyridine

Use in specific populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of Ampyra in pregnant women. Administration of dalfampridine to animals during pregnancy and lactation resulted in decreased offspring viability and growth at doses similar to the maximum recommended human dose (MRHD) of 20 mg/day. Ampyra should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In developmental toxicity studies in rats and rabbits, dalfampridine was administered orally at doses up to 10 and 5 mg/kg/day, respectively, during the period of organogenesis. These doses are approximately 5 times the MRHD on a body surface area (mg/m 2) basis. No evidence of developmental toxicity was found in either species at the highest doses tested, which were maternally toxic. Oral administration of dalfampridine (at doses of 1, 3, and 9 to 6 mg/kg/day; high dose reduced during the second week of dosing) to rats throughout the pregnancy and lactation periods resulted in decreased offspring survival and growth. The no-effect dose for pre- and postnatal developmental toxicity in rats (1 mg/kg) is approximately 0.5 times the MRHD on a mg/m 2 basis.

Labor and Delivery

The effect of Ampyra on labor and delivery in humans is unknown.

Nursing Mothers

It is not known whether dalfampridine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from dalfampridine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

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

Geriatric Use

Clinical studies of Ampyra did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than 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 kidneys 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 [see Warnings and Precautions (5.2)].

Impaired Renal Function

Clearance of dalfampridine is decreased in patients with renal impairment and is significantly correlated with creatinine clearance (CrCl) [see Clinical Pharmacology (12.4)] . Ampyra is contraindicated in patients with moderate or severe renal impairment (CrCl ≤50 mL/min) [see Contraindications (4)]. 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, estimated creatinine clearance should be calculated prior to initiating treatment with Ampyra [see Dosage and Administration (2) and Warnings and Precautions (5.2)] .

Ampyra - Clinical Pharmacology

Mechanism of action

The mechanism by which dalfampridine exerts its therapeutic effect has not been fully elucidated. Dalfampridine is a broad spectrum potassium channel blocker. In animal studies, dalfampridine has been shown to increase conduction of action potentials in demyelinated axons through inhibition of potassium channels.

Pharmacodynamics

Ampyra does not prolong the QTc interval and does not have a clinically important effect on QRS duration.

Pharmacokinetics

Absorption and Distribution:

Orally administered dalfampridine is rapidly and completely absorbed from the gastrointestinal tract. Absolute bioavailability of extended release Ampyra tablets has not been assessed, but relative bioavailability is 96% when compared to an aqueous oral solution. The extended release tablet delays absorption of dalfampridine relative to the solution formulation, giving a slower rise to a lower peak concentration (Cmax), with no effect on the extent of absorption (AUC). Single Ampyra tablet 10 mg doses administered to healthy volunteers in a fasted state gave peak concentrations ranging from 17.3 ng/mL to 21.6 ng/mL occurring 3 to 4 hours post-administration (Tmax). In comparison, Cmax with the same 10 mg dose of dalfampridine in an oral solution was 42.7 ng/mL and occurred approximately 1.3 hours after dosing. Exposure increased proportionally with dose.

Dalfampridine is largely unbound to plasma proteins (97–99%). The apparent volume of distribution is 2.6 L/kg.

There is no apparent difference in pharmacokinetic parameter values following administration of Ampyra tablets to either healthy volunteers or patients with MS.

When dalfampridine is taken with food, there is a slight increase in Cmax (12–17%) and a slight decrease in AUC (4–7%). These changes in exposure are not clinically significant, and therefore the drug may be taken with or without food [see Dosage and Administration (2)].

Metabolism and 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. Most of the excreted radioactivity in urine was parent drug (90.3%). 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.

The apparent elimination half-life of dalfampridine following administration of the extended release tablet formulation of Ampyra is 5.2 to 6.5 hours. The plasma half-life of the sulfate conjugate is approximately 7.6 hours and the half-life of 3-hydroxy-4-aminopyridine could not be calculated because concentrations for most subjects were close to or below the limit of quantitation.

In vitro studies with human liver microsomes indicate that CYP2E1 was the major enzyme responsible for the 3-hydroxylation of dalfampridine. The identity of the CYP enzymes suspected of playing a minor role in the 3-hydroxylation of dalfampridine could not be established unequivocally.

Special Populations

Pediatric

The safety and effectiveness of Ampyra in patients younger than 18 years of age have not been established.

Geriatric

A population pharmacokinetic analysis showed that dalfampridine clearance modestly decreased with increasing age, but not sufficiently to necessitate a modification of dose.

Gender

A population pharmacokinetic analysis suggested that female patients would be expected to have higher maximum dalfampridine plasma concentration than male patients. The magnitude of these differences is small and does not necessitate any dose modification.

Renal Impairment [see Contraindications (4) and Warnings and Precautions (5.2)].

The pharmacokinetics of dalfampridine was studied in 9 male and 11 female subjects with varying degrees of renal function. Elimination of the drug is significantly correlated with the creatinine clearance. Total body clearance of dalfampridine was reduced by about 45 % in patients with mild renal impairment (CrCl 51–80 mL/min), by about 50% in patients with moderate renal impairment (CrCl = 30–50 mL/min), and by about 75% in patients with severe renal impairment (CrCl <30 mL/min). The terminal half-life of dalfampridine is about 3.3 times longer in patients with severe renal impairment but is not prolonged in patients with mild or moderate renal impairment.

Hepatic Impairment

The pharmacokinetics of dalfampridine in hepatically impaired subjects has not been studied. Since dalfampridine is primarily excreted unchanged in the urine, hepatic impairment is not expected to significantly affect dalfampridine pharmacokinetics or recommended dosing.

Race

There were too few non-Caucasians in the patient population to evaluate the effect of race.

Drug Interactions

Effects of Co-administered Drugs on Dalfampridine

Interferon

Dalfampridine kinetics were not affected by co-administration of subcutaneous injections of 8 million units interferon beta-1b.

Baclofen

Based on a population analysis, dalfampridine kinetics were not affected by baclofen.

Effects of Dalfampridine on Co-administered Drugs

In vitro data with human liver microsomes showed that dalfampridine was not a direct or time-dependent inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4/5. Dalfampridine is not likely to affect the pharmacokinetics of drugs that are substrates of these enzymes.

Other in vitro studies with cultured human hepatocytes with 0.025 μM, 0.25 μM, 2.5 μM, and 25 μM dalfampridine had little or no effect on CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5 enzyme activities. Consequently, the potential for dalfampridine to induce human hepatocytes at therapeutic concentrations is remote.

In vitro, dalfampridine is not a substrate or an inhibitor for the p-glycoprotein transporter. The pharmacokinetics of Ampyra are unlikely to be affected by drugs that inhibit the p-glycoprotein transporter, and dalfampridine is not likely to affect the pharmacokinetics of drugs that are substrates of the p-glycoprotein transporter.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Risk of Seizures

Inform patients that Ampyra can cause seizures, and that they must discontinue use of Ampyra if they experience a seizure.

Ampyra Dosing

Instruct patients to take Ampyra exactly as prescribed. Instruct patients not to take a double dose after they miss a dose, as this would increase their risk of seizure. Instruct patients not to take more than 2 tablets in a 24-hour period and to make sure that there is an approximate 12-hour interval between doses.

Anaphylaxis

Advise patients to discontinue Ampyra and seek medical care if they develop signs and symptoms of anaphylaxis.

Storage

Advise patients to store Ampyra at 25°C (77°F), with excursions permitted to 15–30ºC (59–86ºF). Advise patients to safely throw away Ampyra that is out of date or no longer needed.

MEDICATION GUIDE
Ampyra® (am-PEER-ah)
(dalfampridine)
Extended Release Tablets

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.

What is the most important information I should know about Ampyra?

Ampyra can cause seizures.

  • You could have a seizure even if you never had a seizure before.
  • Your chance of having a seizure is higher if you take too much Ampyra or if your kidneys have a mild decrease of function, which is common after age 50.
  • Your doctor may do a blood test to check how well your kidneys are working, if that is not known before you start taking Ampyra.
  • Do not take Ampyra if you have ever had a seizure.
  • Before taking Ampyra tell your doctor if you have kidney problems.
  • Take Ampyra exactly as prescribed by your doctor. See "How should I take Ampyra?"

Stop taking Ampyra and call your doctor right away if you have a seizure while taking Ampyra.

What is Ampyra?

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.

Who should not take Ampyra?

Do not take Ampyra if you:

  • have ever had a seizure
  • have certain types of kidney problems
  • are allergic to dalfampridine (4-aminopyridine), the active ingredient in Ampyra

What should I tell my doctor before taking Ampyra?

Before you take Ampyra, tell your doctor if you:

  • have any other medical conditions
  • are taking compounded 4-aminopyridine (fampridine, 4-AP)
  • are pregnant or plan to become pregnant. It is not known if Ampyra will harm your unborn baby. You and your doctor will decide if you should take Ampyra while you are pregnant
  • are breast-feeding or plan to breast-feed. It is not known if Ampyra passes into your breast milk. You and your doctor should decide if you will take Ampyra or breast-feed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements.

Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.

How should I take Ampyra?

  • Take Ampyra exactly as your doctor tells you to take it. Do not change your dose of Ampyra.
  • Take one tablet of Ampyra 2 times each day about 12 hours apart. Do not take more than 2 tablets of Ampyra in a 24-hour period.
  • Take Ampyra tablets whole. Do not break, crush, chew or dissolve Ampyra tablets before swallowing. If you cannot swallow Ampyra tablets whole, tell your doctor.
  • Ampyra is released slowly over time. If the tablet is broken, the medicine may be released too fast. This can raise your chance of having a seizure.
  • Ampyra can be taken with or without food.
  • If you miss a dose of Ampyra, do not make up the missed dose. Do not take 2 doses at the same time. Take your next dose at your regular scheduled time.
  • If you take too much Ampyra, call your doctor or go to the nearest hospital emergency room right away.
  • Do not take Ampyra together with other aminopyridine medications, including compounded 4-AP (sometimes called 4-aminopyridine, fampridine).

What are the possible side effects of Ampyra?

Ampyra may cause serious side effects, including:

  • serious allergic reactions. Stop taking Ampyra and call your doctor right away or get emergency medical help if you have:
    • shortness of breath or trouble breathing
    • swelling of your throat or tongue
    • hives
  • kidney or bladder infections

See "What is the most important information I should know about Ampyra?"

The most common side effects of Ampyra include:

  • urinary tract infection
  • trouble sleeping (insomnia)
  • dizziness
  • headache
  • nausea
  • weakness
  • back pain
  • problems with balance
  • multiple sclerosis relapse
  • burning, tingling or itching of your skin
  • irritation in your nose and throat
  • constipation
  • indigestion
  • pain in your throat

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.

How should I store Ampyra?

  • Store Ampyra at 59ºF to 86ºF (15ºC to 30ºC).
  • Safely throw away Ampyra that is out of date or no longer needed.

Keep Ampyra and all medicines out of the reach of children.

General Information about the safe and effective use of Ampyra

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.

What are the ingredients in Ampyra?

Active ingredient: dalfampridine (previously called fampridine)

Inactive ingredients: colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide.

Distributed by: Acorda Therapeutics, Inc.
Ardsley, NY 10502

Issued 10/2016

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Ampyra® is a registered trademark of Acorda Therapeutics, Inc.

Manufactured for Acorda under license from Alkermes Pharma Ireland Limited (APIL), Athlone, Ireland, utilizing APIL's MatriX Drug Absorption System (MXDAS®) technology.

MXDAS® is a registered trademark of Alkermes Pharma Ireland Limited (APIL).

U.S. Patent Nos.: US 5,540,938; US 8,007,826; US 8,354,437; US 8,440,703; and US 8,663,685

© 2016 Acorda Therapeutics, Inc. All rights reserved.

1016427AK-0

PRINCIPAL DISPLAY PANEL - 10 mg Tablet Label

Ampyra®

(dalfampridine)

Extended Release

Tablets

Rx ONLY

10 mg

PHARMACIST: Dispense the accompanying

Medication Guide to each patient

60 tablets

Ampyra 
dalfampridine tablet, film coated, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:10144-427
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
DALFAMPRIDINE (DALFAMPRIDINE) DALFAMPRIDINE 10 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
HYPROMELLOSES  
SILICON DIOXIDE  
MAGNESIUM STEARATE  
TITANIUM DIOXIDE  
POLYETHYLENE GLYCOLS  
Product Characteristics
Color white (white to off-white) Score no score
Shape OVAL (biconvex) Size 13mm
Flavor Imprint Code A;10
Contains     
Packaging
# Item Code Package Description
1 NDC:10144-427-60 60 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022250 03/01/2010
Labeler - Acorda Therapeutics, Inc. (963845136)
Establishment
Name Address ID/FEI Operations
Alkermes Gainesville LLC 057585150 pack(10144-427), label(10144-427)
Establishment
Name Address ID/FEI Operations
Sharp Corporation 143696495 label(10144-427), pack(10144-427)
Establishment
Name Address ID/FEI Operations
Patheon Inc., Toronto Regional Operations 240769596 manufacture(10144-427), pack(10144-427), label(10144-427), analysis(10144-427)
Establishment
Name Address ID/FEI Operations
Alkermes Pharma Ireland Limited 896838492 manufacture(10144-427)
Revised: 03/2017   Acorda Therapeutics, Inc.

Before taking this medicine

You should not use Ampyra if you are allergic to dalfampridine, or if:

  • you have had a seizure (convulsions); or

  • you have moderate to severe kidney disease.

To make sure Ampyra is safe for you, tell your doctor if you have:

  • kidney disease; or

  • if you also take a form of this medicine obtained from a compounding pharmacy (fampridine, or 4-aminopyridine).

It is not known whether dalfampridine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether dalfampridine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Ampyra is not approved for use by anyone younger than 18 years old.

What should I avoid while taking Ampyra?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Ampyra side effects

Get emergency medical help if you have signs of an allergic reaction to Ampyra: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop taking Ampyra and call your doctor at once if you have:

  • a seizure (convulsions);

  • pain or burning when you urinate;

  • numbness, burning pain, or tingly feeling;

  • problems with balance; or

  • relapse or worsening of MS symptoms.

Common Ampyra side effects may include:

  • headache, dizziness;

  • sleep problems (insomnia);

  • nausea, constipation, upset stomach;

  • weakness;

  • stuffy nose, sinus pain, sore throat; or

  • back pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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