Kinezia (Tablets) Instructions for Use

Marketing Authorization Holder

Valenta Pharm, JSC (Russia)

ATC Code

N07XX07 (Fampridine)

Active Substance

Fampridine (Rec.INN registered by WHO)

Dosage Form

Kinezia

Prolonged-release film-coated tablets, 10 mg: 27, 54, or 60 pcs.

Dosage Form, Packaging, and Composition

Prolonged-release film-coated tablets white or almost white, oval, biconvex, with an embossed “10” on one side; the core on the cross-section is white or almost white.

Excipients: microcrystalline cellulose (type 102), hypromellose, colloidal silicon dioxide, magnesium stearate.

Shell composition ready-made film coating (hypromellose, titanium dioxide (E171), macrogol).

9 pcs. – blister packs (3) – cardboard packs.
9 pcs. – blister packs (6) – cardboard packs.
15 pcs. – blister packs (4) – cardboard packs.

Clinical-Pharmacological Group

Drug used for diseases of the nervous system

Pharmacotherapeutic Group

Potassium channel blocker

Pharmacological Action

Fampridine is a potassium channel blocker. It improves nerve impulse conduction along demyelinated fibers. It penetrates the blood-brain barrier, blocks potassium channels in demyelinated neurons, and prevents the efflux of potassium ions from the cell, thereby prolonging repolarization and enhancing the formation of the action potential of the nerve impulse.

Pharmacokinetics

When taken orally, Fampridine is completely absorbed from the gastrointestinal tract. Food intake does not have a significant effect on the pharmacokinetics of fampridine. Fampridine is a fat-soluble drug and easily penetrates the blood-brain barrier. Plasma protein binding in humans is 3-7%. V_d 332.167 ± 59.696 L. In humans, Fampridine is metabolized by oxidation to 3-hydroxy-4-aminopyridine, then conjugated to 3-hydroxy-4-aminopyridine sulfate. The 3-hydroxylation of fampridine to 3-hydroxy-4-aminopyridine by human liver microsomes appears to be catalyzed by the CYP2E1 isoenzyme without signs of significant inhibition. There is evidence of direct inhibition of CYP2E1 by fampridine at a concentration of 30 µM (approximately 12%), which is about 100 times higher than the average plasma concentration of fampridine when used at a dose of 10 mg. Fampridine is characterized by linear pharmacokinetics. T_1/2 is about 6 hours. C_max and, to a lesser extent, AUC, increase proportionally to the administered dose. The main route of elimination of fampridine is renal excretion, with approximately 90% of the dose excreted unchanged within 24 hours. Renal clearance is significantly higher than GFR due to the active participation of the organic cation transporter 2 (OCT2). Less than 1% of the dose is excreted in feces. In patients with renal impairment, accumulation of fampridine occurs in proportion to the severity of renal impairment.

Indications

Symptomatic treatment of walking disturbances in adult patients with multiple sclerosis (4-7 points on the Expanded Disability Status Scale EDSS).

ICD codes

Dosage Regimen

Administer orally.

The recommended dose is 10 mg twice daily, approximately 12 hours apart.

Do not exceed the maximum single dose of 10 mg or the maximum daily dose of 20 mg.

Swallow the tablet whole; do not crush, split, or chew.

Take with or without food; maintain consistent timing of doses relative to meals.

Discontinue treatment if no clinical benefit is observed.

Assess renal function before initiating therapy; this regimen is contraindicated in patients with a creatinine clearance below 80 mL/min.

Monitor renal function periodically during treatment, especially in elderly patients.

Immediately discontinue use if a seizure occurs.

Missed Dose: If a dose is missed, skip it and take the next dose at the regularly scheduled time. Do not take a double dose.

Adverse Reactions

Infections and infestations very common – urinary tract infections; common – acute respiratory diseases, nasopharyngitis, viral infections.

Immune system disorders frequency unknown – hypersensitivity reactions (including angioedema, skin rashes, urticaria, anaphylactic reactions).

Nervous system disorders common – insomnia, anxiety, dizziness, headache, balance disorder, paresthesia, tremor; frequency unknown – seizures, trigeminal neuralgia.

Cardiac disorders common – palpitations; frequency unknown – tachycardia, arterial hypotension.

Respiratory, thoracic and mediastinal disorders common – dyspnea, throat pain.

Gastrointestinal disorders common – nausea, vomiting, constipation, dyspepsia.

Musculoskeletal and connective tissue disorders common – back pain.

General disorders and administration site conditions common – asthenia; frequency unknown – chest discomfort.

Contraindications

Hypersensitivity to fampridine; concurrent use of different dosage forms of fampridine or 4-aminopyridine; history of seizures; renal failure (CrCl <80 ml/min); concurrent use with drugs that are inhibitors of OCT2 (e.g., cimetidine); children and adolescents under 18 years of age.

With caution

Renal failure (CrCl >80 ml/min), presence of factors that may lower the seizure threshold, history of allergic reactions, arrhythmia, dizziness, balance disorder, decreased white blood cell count.

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding is not recommended.

Use in Hepatic Impairment

Dose adjustment is not required.

Use in Renal Impairment

Contraindication: renal failure (CrCl <80 ml/min).

In patients with renal impairment, accumulation of fampridine occurs in proportion to the severity of renal impairment.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Renal function monitoring is required before starting and during treatment.

Special Precautions

In patients with impaired renal function, higher plasma concentrations of fampridine may be observed, which is associated with a higher risk of adverse effects, especially from the nervous system. Assessment of renal function before treatment and its regular monitoring during treatment is recommended for all patients (especially in elderly patients, in whom renal function may be impaired).

If seizures occur during treatment with Fampridine, it should be discontinued.

If anaphylaxis or other serious allergic reactions develop, fampridine should be discontinued.

Dizziness and balance disorders observed while taking fampridine may increase the risk of falls and also affect the ability to drive vehicles. Therefore, patients should use walking aids if necessary.

The occurrence of infectious diseases and impairment of the immune response during treatment cannot be ruled out.

Effect on ability to drive vehicles and operate machinery

Given the possibility of dizziness and other side effects, during treatment one should refrain from engaging in potentially hazardous activities.

Drug Interactions

Concomitant treatment with other medicines containing Fampridine (4-aminopyridine) is contraindicated due to the possible increase in side effects.

OCT2 is the transporter responsible for the active secretion of fampridine by the kidneys. Therefore, the concomitant use of fampridine with drugs that are inhibitors of OCT2, for example, cimetidine, is contraindicated. Concomitant use of fampridine with drugs that are substrates of OCT2, for example, carvedilol, propranolol, and metformin, requires caution.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.