Dalfampridine

The mechanism by which dalfampridine exerts its therapeutic effect has not been fully elucidated. Dalfampridine is a broad spectrum potassium channel blocker.

• Dalfampridine extended-release tablets are 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) ].ICD-10: G35

• The use of dalfampridine extended-release tablets are 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 dalfampridine extended-release tablets 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 dalfampridine extended-release tablets or 4-aminopyridine (4)contraindicated

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 dalfampridine extended-release tablets. In patients with mild renal impairment (CrCl 51 to 80 mL/min), dalfampridine extended-release tablets may reach plasma levels associated with a greater risk of seizures, and the potential benefits of dalfampridine extended-release tablets 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 dalfampridine extended-release tablet 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 Dalfampridine extended-release tablet can be taken with or without food. Administer tablets whole; do not divide, crush, chew, or dissolve dalfampridine extended-release tablets. If a dose is missed, patients should not take double or extra doses.

Dalfampridine extended-release tablets can cause seizures; the risk of seizures increases with increasing dalfampridine extended-release tablets doses; discontinue dalfampridine extended-release tablets 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 ) Dalfampridine extended-release tablets can cause anaphylaxis. Discontinue and do not restart dalfampridine extended-release tablets if this occurs (5.4) 5.1 Seizures Dalfampridine extended-release tablets 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 to 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. Dalfampridine extended-release tablets 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 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 dalfampridine extended-release tablets 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 Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) 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 dalfampridine extended-release tablets 10 mg twice daily experienced one or more adverse reactions leading to discontinuation, compared to 2% (5/238) of placebo-treated patients.

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 dalfampridine extended-release tablets treatment ( 4 , 5.2 , 8.6 ) 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of dalfampridine extended-release tablets 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, 5mg/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.

Metabolism

Absorption and Distribution Orally administered dalfampridine is rapidly and completely absorbed from the gastrointestinal tract. Absolute bioavailability of dalfampridine extended-release tablets has not been assessed, but relative bioavailability is 96% when compared to an aqueous oral solution.

Three cases of overdose were reported in controlled clinical trials with dalfampridine extended-release tablets, 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.

• Jan 22, 2010NDANDA022250Merz
• Jan 23, 2017ANDAANDA206811Aurobindo Pharma
• Jan 23, 2017ANDAANDA206836Actavis Labs Fl Inc
• Jul 11, 2018ANDAANDA206863Accord Hlthcare
• Jul 30, 2018ANDAANDA206765Alkem Labs Ltd
• Mar 11, 2019ANDAANDA210158Micro Labs
• May 21, 2019ANDAANDA208292Sun Pharm

1. 1Gait Disturbance10,96415%
2. 2Drug Ineffective8,29912%
3. 3Fall7,32410%
4. 4Fatigue5,5117.7%
5. 5Balance Disorder4,8976.9%
6. 6Multiple Sclerosis Relapse4,7666.7%
7. 7Therapy Cessation4,5106.3%
8. 8Dizziness3,9865.6%
9. 9Urinary Tract Infection3,7345.2%
10. 10Condition Aggravated3,4814.9%
11. 11Asthenia3,4564.9%
12. 12Insomnia3,3054.6%
13. 13Headache3,2594.6%
14. 14Multiple Sclerosis3,1164.4%
15. 15Mobility Decreased2,9954.2%

Recent PubMed references pinned to Dalfampridine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Sustainable RP-HPLC Method Development for Simultaneous Estimation of Fampridine and Monomethyl Fumarate in Lipid Nanocarriers and Biological Fluids: Application of AQbd Principles.
  Archiv der Pharmazie · 2026 · Muppayyanamath A, Mastiholimath V
  PMID 42246625DOI 10.1002/ardp.70274
• Kv1.3 Channel Blockade by Dalfampridine Attenuates NLRP3 Inflammasome-Driven Demyelination via the NEK7/Ripk1/FADD Pathway, Matching the Efficacy of Broad P2X7 Antagonism by Suramin in EAE.
  Drug development research · 2026 · Kamel AS, Shalaby HN, El-Said YAM, et al.
  PMID 42145136DOI 10.1002/ddr.70318
• 4-aminopyridine-loaded topical gel for promoting skin regeneration in burn injuries.
  Biomaterials · 2026 · Ellur G, Kamaraj M, Rahul VG, et al.
  PMID 42134250DOI 10.1016/j.biomaterials.2026.124293
• Hyaluronic acid conjugated gold nanoparticles/chitosan/4-aminopyridine intranasal nanocomposites for myelin repair in multiple sclerosis.
  Journal of pharmaceutical sciences · 2026 · Affrald R J, Narayan S
  PMID 41974374DOI 10.1016/j.xphs.2026.104279
• Efficacy and Safety of Amifampridine in Myasthenia Gravis: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial.
  Neurology · 2026 · Remijn-Nelissen L, Bakker WR, van Gelder T, et al.
  PMID 41945880DOI 10.1212/WNL.0000000000214715
• Effect of Dalfampridine on cognition, gait and fatigue in patients with multiple sclerosis: a randomized placebo-controlled study.
  Multiple sclerosis and related disorders · 2026 · Abdeldayem MME, Abdelnasser A, Khalil SH, et al.
  PMID 41850121DOI 10.1016/j.msard.2026.107137
• N, N-Dimethyl-4-Aminopyridine- and Aluminum Isopropoxide-Catalysed Ring-Opening Polymerizations of β-Butyrolactone for the Antimicrobial Oligohydroxybutyrate.
  International journal of molecular sciences · 2026 · Bao Q, So PK, Leung SL, et al.
  PMID 41596644DOI 10.3390/ijms27020999
• Mapping the secondary response to traumatic brain injury using spatial transcriptomics shows acute 4-aminopyridine treatment mitigates axonal and molecular pathology.
  Acta neuropathologica communications · 2026 · Sullivan GM, Radomski KL, He S, et al.
  PMID 41508250DOI 10.1186/s40478-025-02219-1

The 10 most recently updated of 101 ClinicalTrials.gov registrations naming Dalfampridine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Double Dose 4-AP on Functional Recovery After Spinal Cord Injury
  Recruiting · Phase 1 · Phase 2 · Interventional · 27 enrolled · Shirley Ryan AbilityLab
  NCT06853015updated 2026-06-03
• Effects of 4-AP on Functional SCI Recovery
  Completed · Early phase 1 · Interventional · 26 enrolled · Shirley Ryan AbilityLab
  NCT05447676updated 2026-06-03
• Preoperative Imatinib and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor
  Recruiting · Phase 1 · Interventional · 18 enrolled · University of California, San Diego
  NCT07171203updated 2026-05-27
• Clemastine Fumarate as Remyelinating Treatment in Internuclear Ophthalmoparesis and Multiple Sclerosis
  Terminated · Phase 3 · Interventional · 47 enrolled · Amsterdam UMC, location VUmc
  NCT05338450updated 2026-05-06
• The Role of Potassium Channels in Working Memory Impairments of Chronic Cocaine Users
  Not yet recruiting · Interventional · 40 enrolled · Boris Quednow
  NCT07532460updated 2026-04-20
• 4-Aminopyridine to Treat Skin Burns
  Recruiting · Phase 2 · Interventional · 200 enrolled · John Elfar
  NCT06596434updated 2026-03-05
• Dalfampridine Combined With Physical Therapy for Mobility Impairment in Multiple Sclerosis
  Recruiting · Phase 4 · Interventional · 48 enrolled · MGH Institute of Health Professions
  NCT06136728updated 2026-02-27
• 4AP for Carpal Tunnel Syndrome (CTS)
  Not yet recruiting · Phase 2 · Interventional · 160 enrolled · John Elfar
  NCT06294821updated 2026-01-26
• 4-aminopyridine Treatment for Nerve Injury
  Recruiting · Phase 2 · Phase 3 · Interventional · 70 enrolled · John Elfar
  NCT03701581updated 2025-12-17
• Cross-over Study on the Influence of Fampridine on Working Memory in Mild to Moderate Depression
  Recruiting · Phase 2 · Interventional · 38 enrolled · University of Basel
  NCT06751784updated 2025-12-12

Frequently asked questions

How does Dalfampridine work?

The mechanism by which dalfampridine exerts its therapeutic effect has not been fully elucidated. Dalfampridine is a broad spectrum potassium channel blocker.

What is Dalfampridine used for?

According to FDA labeling, Dalfampridine carries indications including: Dalfampridine extended-release tablets are 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) ].. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Dalfampridine?

Dalfampridine is classified as Other nervous system drugs, Potassium Channel Blocker, Potassium Channel Antagonists, Increased Central Nervous System Organized Electrical Activity.

What are the brand names for Dalfampridine?

Dalfampridine is marketed under brand names including Ampyra.

What are the contraindications for Dalfampridine?

Dalfampridine labeling lists contraindications including: The use of dalfampridine extended-release tablets are 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 dalfampridine extended-release tablets 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 dalfampridine extended-release tablets or 4-aminopyridine (4). Always consult the full prescribing information and a clinician.