Fampridine

N07X - Other nervous system drugs ATC N07XX07 Small molecule approved 2010 Oral Natural product

JFDA label: Fampyra 10mg

Mechanism of Action

Blocker of Voltage-gated potassium channel — Voltage-gated potassium channel blocker

Target	Action	Gene / class
Voltage-gated potassium channel efficacy	BLOCKER

Indications

Approved

Multiple Sclerosis — multiple sclerosis

Off-label

Carpal Tunnel Syndrome
Guillain-Barre Syndrome
Ischemic Stroke
Memory, Short-Term
Multiple Sclerosis, Chronic Progressive
Multiple Sclerosis, Relapsing-Remitting
Muscle Spasticity
Muscular Atrophy, Spinal
Prostatic Diseases
Sleep Apnea, Obstructive
Spinal Cord Injuries
Stroke
Trauma, Nervous System
Wounds and Injuries

Contraindications

Source: Lexicomp

Additional contraindications (not in U.S. labeling): Mild, moderate, severe renal impairment (CrCl ≤80 mL/minute) Absolute
Hypersensitivity to dalfampridine, 4-aminopyridine, or any component of the formulation Absolute
concomitant use with compounded 4-aminopyridine or other forms of fampridine Absolute
concomitant use with drugs that inhibit organic cation transporter 2 (OCT2), such as cimetidine or quinidine Absolute
history of seizure Absolute
moderate or severe renal impairment (CrCl ≤50 mL/minute) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (5)

Common dizziness · equilibrium disturbance · headache · Insomnia · paresthesia

Gastrointestinal disorders (3)

Common constipation · dyspepsia · Nausea

Musculoskeletal and connective tissue disorders (3)

Common acute exacerbations of multiple sclerosis · back pain · Weakness

Other (1)

Very Common Genitourinary: Urinary tract infection

Respiratory, thoracic and mediastinal disorders (2)

Common Nasopharyngitis · pharyngolaryngeal pain

Dosing

Source: Lexicomp

Multiple sclerosis: Oral: 10 mg every 12 hours (maximum daily dose: 20 mg); no additional benefit seen with doses >20 mg daily Missed doses: Do not administer double or extra doses if a dose is missed.

Refer to adult dosing.

Note: Creatinine clearance is estimated with Cockcroft-Gault formula. U.S. labeling: Mild renal impairment (CrCl 51-80 mL/minute): No dosage adjustment recommended by the manufacturer; however, use with extreme caution as risk of seizure may be increased secondary to reduced clearance. Moderate-to-severe renal impairment (CrCl ≤50 mL/minute): Use is contraindicated. Canadian labeling: Mild-to-severe impairment (CrCl ≤80 mL/minute): Use is contraindicated.

No dosage adjustment required; drug undergoes minimal metabolism and is primarily excreted unchanged in the urine.

Warnings & Precautions

Source: Lexicomp

Anaphylaxis

May cause anaphylaxis or severe allergic reactions; symptoms have included respiratory compromise, urticaria, and angioedema (throat and tongue). Discontinue immediately and administer appropriate medical care if a severe allergic reaction occurs.

Seizures

Associated with a dose-dependent risk of seizure; seizures may occur within days to weeks after treatment initiation and have been reported more frequently in patients with no history of seizures. Discontinue use and do not reinitiate therapy if seizure occurs during treatment. Use is contraindicated in patients with a history of seizures. Assess risk of seizure prior to treatment initiation; use caution or avoid in patients who may have a lower seizure threshold due to predisposing factors.

Urinary tract infection

Urinary tract infections were reported more frequently in patients receiving dalfampridine (compared to placebo), Disease-related concerns:

Renal impairment

Use in renal impairment is associated with an increased risk of seizure and other adverse events, primarily neurologic effects, due to increased serum concentrations; elimination is predominately via the kidneys as unchanged drug. U.S. labeling contraindicates use in moderate-to-severe renal impairment (CrCl ≤50 mL/minute). Canadian labeling contraindicates use in mild, moderate, and severe renal impairment (CrCl ≤80 mL/minute). Concurrent drug therapy issues:

4-aminopyridine formulations

Sustained release products available in the U.S. (dalfampridine) or in Canada (fampridine) should not be administered with other 4-aminopyridine formulations (eg, compounded immediate release fampridine). Other warnings/precautions:

Name confusion

The chemical entity of 4-aminopyridine is referred to with a generic name of dalfampridine in the U.S. and with a generic name of fampridine in Canada.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed in animal reproduction studies, including decreased growth and death.

Lactation

Avoid

It is not known if dalfampridine is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the decision to discontinue dalfampridine or to discontinue breast-feeding is not recommended should take into account the importance of treatment to the mother.

Monitoring

Clinical pearl	Renal function (baseline and at least annually thereafter); EEG; walking ability

Chemistry & Properties

Formula	C5H6N2
Molecular weight	94.12 g/mol
IUPAC name	pyridin-4-amine
CAS	504-24-5
PubChem CID	1727
InChIKey	`NUKYPUAOHBNCPY-UHFFFAOYSA-N`
logP	0.66 (XLogP 0.3)
Polar surface area	38.91 Å²
H-bond acceptors / donors	2 / 1
Drug-likeness (QED)	0.51
Lipinski violations	0

SMILES

Nc1ccncc1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP2C8	Inhibitor	—
CYP2D6	Inhibitor	—
CYP3A4	Inhibitor	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT2 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)OCT2 (Substrate)P-gp (Substrate)

Drug–drug interactions (19, DDInter)

Interacting drug	Severity	Management
Bupropion	major
Iohexol	major
Iopamidol	major
Cimetidine	moderate
Crizotinib	moderate
Encorafenib	moderate
Ketoconazole	moderate
Lenvatinib	moderate
Lindane	moderate
Megestrol acetate	moderate
Metformin	moderate
Olaparib	moderate
Picosulfuric acid	moderate
Polyethylene glycol (3350 with electrolytes)	moderate
Ribociclib	moderate
Rucaparib	moderate
Sodium sulfate	moderate
Tafenoquine	moderate
Vandetanib	moderate

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Fampyra	Tablet 10 mg	56 tab	Jarash Drug Store	—