Ampyra

Dalfampridine · Tablet, Film Coated, Extended Release · Oral

Prescription (Rx) Potassium Channel Blocker

Uses

1 INDICATIONS AND USAGE AMPYRA is indicated as a treatment to improve walking in adult patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed [see Clinical Studies (14) ]. AMPYRA ® (dalfampridine) is a potassium channel blocker indicated to improve walking in adult patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed ( 1 , 14 ).

Dosage and administration

The maximum recommended dosage is 10 mg twice daily (approximately 12 hours apart). There is no evidence of additional benefit with doses greater than 10 mg twice daily. Adverse reactions, including seizures, were more frequent at higher doses. ( 2.1 ) Take with or without food. Administer tablets whole; do not divide, crush, chew, or dissolve ( 2.2 ) Patients should not take double or extra doses if they miss a dose. ( 2.2 ) Estimated creatinine clearance (CrCl) should be known before initiating treatment with AMPYRA. In patients with mild renal impairment (CrCl 51–80 mL/min), AMPYRA may reach plasma levels associated with a greater risk of seizures, and the potential benefits of AMPYRA should be carefully considered against the risk of seizures in these patients ( 2.3 , 5.2 , 8.6 ) 2.1 Dosage Information The maximum recommended dosage of AMPYRA is one 10 mg tablet twice daily and should not be exceeded. Take doses approximately 12 hours apart. There is no evidence of additional benefit at doses greater than 10 mg twice daily. Adverse reactions, including seizures, and discontinuations because of adverse reactions were more frequent at higher doses. 2.2 Administration Instructions AMPYRA can be taken with or without food. Administer tablets whole; do not divide, crush, chew, or dissolve AMPYRA tablets. If a dose is missed, patients should not take double or extra doses. 2.3 Renal Monitoring Prior to and During Treatment Estimated creatinine clearance (CrCl) should be known before initiating treatment with AMPYRA, and monitored at least annually during treatment with AMPYRA. CrCl can be estimated using the following equation (multiply by 0.85 for women): crcl-eqn-102716.jpg 2.4 Dosage in Patients with Renal Impairment In patients with mild renal impairment (CrCl 51–80 mL/min), AMPYRA plasma levels may approach those seen at a dose of 15 mg twice daily, a dose that is 1.5 times the maximum recommended dose and may be associated with an increased risk of seizures. As mild renal impairment is common after age 50, estimating CrCl is particularly important in these patients. The potential benefits of AMPYRA should be carefully considered against the risk of seizures in these patients [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ]. AMPYRA is contraindicated in patients with moderate or severe renal impairment (CrCl≤50 mL/min).

Dosage forms and strengths

3 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. 10 mg tablets ( 3 )

Contraindications

The use of AMPYRA is contraindicated in the following conditions: History of seizure [ see Warnings and Precautions (5.1) ] Moderate or severe renal impairment (CrCl≤50 mL/min) [see Warnings and Precautions (5.2) ] History of hypersensitivity to AMPYRA or 4-aminopyridine; reactions have included anaphylaxis [see Warnings and Precautions (5.4) ] History of seizure ( 4 ) Moderate or severe renal impairment (CrCl≤50 mL/min) ( 4 ) History of hypersensitivity to AMPYRA or 4-aminopyridine ( 4 )

Warnings and precautions

5 WARNINGS AND PRECAUTIONS AMPYRA can cause seizures; the risk of seizures increases with increasing AMPYRA doses; discontinue AMPYRA and do not restart if a seizure occurs ( 5.1 ) Avoid concomitant use with other forms of 4-aminopyridine (4-AP, fampridine), since the active ingredient is the same ( 5.3 ) AMPYRA can cause anaphylaxis. Discontinue and do not restart AMPYRA if this occurs ( 5.4 ) 5.1 Seizures AMPYRA can cause seizures. Increased incidence of seizures has been observed at 20 mg twice daily (2 times the maximum recommended dosage) in controlled clinical studies of 9–14 weeks duration with dalfampridine in patients with MS. 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). In the post-marketing period seizures have been reported. The majority of seizures occurred at the recommended dose and in patients without a history of seizures, and 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, as these patients were excluded from clinical trials. The risk of seizures in patients with epileptiform activity on an EEG is unknown, and could be substantially higher than that observed in AMPYRA clinical studies. Permanently discontinue AMPYRA in patients who have a seizure while on treatment. AMPYRA is contraindicated in patients with a history of seizures [see Contraindications (4) ] . 5.2 Renal Impairment AMPYRA is eliminated through the kidneys primarily as unchanged drug [see Clinical Pharmacology (12.3) ]. Because patients with moderate to severe renal impairment (CrCl ≤50mL/min) would require a dose lower than 10 mg twice daily and no strength smaller than 10 mg is available, AMPYRA is contraindicated in these patients [see Contraindications (4) ] . In patients with mild renal impairment (CrCl 51–80 mL/min), AMPYRA plasma levels may approach those seen at a dose of 15 mg twice daily, a dose that may be associated with an increased risk of seizures [see Warnings and Precautions (5.1) ] . 5.3 Concurrent Treatment with Other Forms of 4-Aminopyridine Avoid concomitant use with other forms of 4-aminopyridine (4-AP, fampridine) since the active ingredient is the same. Instruct patients to discontinue use of any product containing 4-aminopyridine prior to initiating treatment with AMPYRA in order to reduce the potential for dose-related adverse reactions. 5.4 Anaphylaxis AMPYRA can cause anaphylaxis and severe allergic reactions. Signs and symptoms have included respiratory compromise, urticaria, and angioedema of the throat and or tongue. AMPYRA is contraindicated in patients with a history of hypersensitivity to AMPYRA or 4-aminopyridine. Inform patients of the signs and symptoms of anaphylaxis and instruct them to discontinue AMPYRA and seek immediate medical care should these signs and symptoms occur.

Side effects

The following serious adverse reactions are described in more detail elsewhere in the labeling: Seizures [see Warnings and Precautions (5.1) ] Anaphylaxis [see Warnings and Precautions (5.4) ] The most common adverse events (incidence ≥2% and at a rate greater than the placebo rate) for AMPYRA were urinary tract infection, insomnia, dizziness, headache, nausea, asthenia, back pain, balance disorder, multiple sclerosis relapse, paresthesia, nasopharyngitis, constipation, dyspepsia, and pharyngolaryngeal pain ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Acorda Therapeutics at 1-800-367-5109 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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. In three placebo-controlled clinical trials of up to 14 weeks duration, 4% (15/400) of patients treated with AMPYRA 10 mg twice daily experienced one or more adverse reactions leading to discontinuation, compared to 2% (5/238) of placebo-treated patients. The adverse reactions leading to discontinuation of at least 2 patients treated with AMPYRA and that led to discontinuation more frequently compared to placebo were headache (AMPYRA 0.5%, placebo 0%), balance disorder (AMPYRA 0.5%, placebo 0%), dizziness (AMPYRA 0.5%, placebo 0%), and confusional state (AMPYRA 0.3%, placebo 0%). Table 1 lists adverse reactions that occurred in ≥2% of patients treated with AMPYRA 10 mg twice daily, and more frequently than in placebo-treated patients, in controlled clinical trials. Table 1: Adverse Reactions with an Incidence ≥2% of AMPYRA-Treated Adult MS Patients and More Frequent with AMPYRA Compared to Placebo in Controlled Clinical Trials Adverse Reaction Placebo (N=238) % AMPYRA 10 mg twice daily (N=400) % Urinary tract infection 8 12 Insomnia 4 9 Dizziness 4 7 Headache 4 7 Nausea 3 7 Asthenia 4 7 Back pain 2 5 Balance disorder 1 5 Multiple sclerosis relapse 3 4 Paresthesia 3 4 Nasopharyngitis 2 4 Constipation 2 3 Dyspepsia 1 2 Pharyngolaryngeal pain 1 2 Other Adverse Reactions AMPYRA has been evaluated in a total of 1,952 subjects, including 917 MS patients. A total of 741 patients have been treated with AMPYRA for over six months, 501 for over one year and 352 for over two years. The experience in open-label clinical trials is consistent with the safety profile observed in the placebo-controlled clinical trials. As in controlled clinical trials, a dose-dependent increase in the incidence of seizures has been observed in open-label clinical trials with AMPYRA in patients with MS as follows: AMPYRA 10 mg twice daily 0.41 per 100 person-years (95% confidence interval 0.13–0.96); dalfampridine 15 mg twice daily 1.7 per 100 person-years (95% confidence interval 0.21–6.28). 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use with dalfampridine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: vomiting, vertigo.

Drug interactions

7 DRUG INTERACTIONS OCT2 Inhibitors: Concomitant use may cause an increased exposure and potential risk of seizures ( 7.1 ) 7.1 OCT2 Inhibitors Concurrent treatment with OCT2 inhibitors, such as cimetidine, may cause increased exposure to dalfampridine [ see Clinical Pharmacology (12.3) ]. Elevated levels of dalfampridine increase the risk of seizures [ see Warnings and Precautions (5.1 , 5.2) ]. The potential benefits of taking OCT2 inhibitors concurrently with AMPYRA should be considered against the risk of seizures in these patients. 7.2 Baclofen No interaction was identified between dalfampridine and baclofen [see Clinical Pharmacology (12.3) ].

Use in specific populations

Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) Geriatric use: Because elderly patients are more likely to have decreased renal function, it is particularly important to know the estimated CrCl in these patients before initiating AMPYRA treatment ( 4 , 5.2 , 8.6 ) 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of AMPYRA in pregnant women. Administration of dalfampridine to animals during pregnancy and lactation resulted in decreased offspring viability and growth at clinically relevant doses [see Data ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of dalfampridine to pregnant rats and rabbits throughout organogenesis resulted in no evidence of developmental toxicity in either species. The highest doses tested (10 mg/kg/day in rats, 5 mg/kg/day in rabbits), which were associated with maternal toxicity, are approximately 5 times the MRHD on a body surface area (mg/m 2 ) basis. Oral administration of dalfampridine (0, 1, 3, and 9 to 6 mg/kg/day; high dose reduced during the second week of dosing) to female rats throughout pregnancy and lactation resulted in decreased offspring viability at the highest dose tested and decreased body weight in offspring at the mid and high doses. The no-effect dose for pre- and postnatal developmental toxicity in rats (1 mg/kg/day) is less than the MRHD on a mg/m 2 basis. 8.2 Lactation Risk Summary 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. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for AMPYRA and any potential adverse effects on the breastfed infant from AMPYRA or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in patients younger than 18 years of age have not been established. 8.5 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) ]. 8.6 Impaired Renal Function Clearance of dalfampridine is decreased in patients with renal impairment and is significantly correlated with creatinine clearance (CrCl) [see Clinical Pharmacology (12.3) ] . 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 (2.3) and Warnings and Precautions (5.2) ] .

Pregnancy

8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of AMPYRA in pregnant women. Administration of dalfampridine to animals during pregnancy and lactation resulted in decreased offspring viability and growth at clinically relevant doses [see Data ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of dalfampridine to pregnant rats and rabbits throughout organogenesis resulted in no evidence of developmental toxicity in either species. The highest doses tested (10 mg/kg/day in rats, 5 mg/kg/day in rabbits), which were associated with maternal toxicity, are approximately 5 times the MRHD on a body surface area (mg/m 2 ) basis. Oral administration of dalfampridine (0, 1, 3, and 9 to 6 mg/kg/day; high dose reduced during the second week of dosing) to female rats throughout pregnancy and lactation resulted in decreased offspring viability at the highest dose tested and decreased body weight in offspring at the mid and high doses. The no-effect dose for pre- and postnatal developmental toxicity in rats (1 mg/kg/day) is less than the MRHD on a mg/m 2 basis.

Pediatric use

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

Geriatric use

8.5 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) ].

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.

Description

(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 white to off-white, biconvex, oval shaped, film-coated, non-scored tablets 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 C 5 H 6 N 2 . At ambient conditions, dalfampridine is soluble in water, methanol, acetone, tetrahydrofuran, isopropanol, acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, and ethanol. Chemical Structure

Mechanism of action

12.1 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.

How supplied

(dalfampridine) extended release tablets, 10 mg are 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. NDC 10144-427-60 bottles of 60 tablets Store at 25°C (77°F). Excursions permitted 15°C to 30°C (59°F to 86°F).

Storage

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

Patient 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 [ see Warnings and Precautions (5.1) ]. 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 [ see Dosage and Administration (2.1 , 2.2) ]. Anaphylaxis Advise patients to discontinue AMPYRA and seek medical care if they develop signs and symptoms of anaphylaxis [ see Warnings and Precautions (5.4) ]. Effects on Driving or Using Machinery Counsel patients that central nervous system-related adverse reactions, such as vertigo and dizziness, associated with the use of AMPYRA might impair their ability to drive or use machinery should they develop these symptoms. Drug Interactions Instruct patients to notify their healthcare provider prior to starting any new medication, including over-the-counter drugs. Storage Advise patients to store AMPYRA at 25°C (77°F), with excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). Advise patients to safely throw away AMPYRA that is out of date or no longer needed.

Label text from the FDA structured product label by Merz Pharmaceuticals, LLC (revised Jan 16, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Dalfampridine in 2 products

Ampyra NDC products (2)

NDC	Strength & form	Labeler	Type
0259-5010	Dalfampridine 10 mg/1 Tablet, Film Coated, Extended Release	Merz Pharmaceuticals, LLC	NDA
10144-427	Dalfampridine 10 mg/1 Tablet, Film Coated, Extended Release	Merz Pharmaceuticals, LLC	NDA

Frequently asked questions

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Who makes Ampyra?

Ampyra is listed by 1 labeler in the FDA NDC directory, including Merz Pharmaceuticals, LLC.