Dalfampridine - Empowering Multiple Sclerosis With Enhanced Mobility

Overview

Dalfampridine is a potassium channel blocker that helps in modifying the neurofunction. It is typically prescribed alone or in combination with other drugs to help reduce or alleviate the symptoms of multiple sclerosis. Dalfampridine is prescribed for the improvement of motor function and walking in people with Multiple Sclerosis (MS). This medication is the first drug approved for use, specifically in improving mobility in MS patients.

Dalfampridine is indicated for the symptomatic symptoms of the enhancement of walking in people with several variations of multiple sclerosis disease. The Food and Drug Administration (FDA) of the United States approved Dalfampridine on January 22, 2010. In Canada, this medication has received its approval for medical use by Health Canada from February 10, 2012.

Drug Group:

Potassium channel blockers are a group of drugs that are used for the treatment of arrhythmias. Arrhythmia refers to the abnormal beating of the heart, either too rapid or too slow. Potassium channel blockers are also used to improve movement or mobility in patients with multiple sclerosis. These drugs act by inhibiting action towards potassium effluent by means of cell membranes. Hence, these agents interfere with the conduction or electrical activity through potassium channels.

Available Doses and Dosage Forms:

• Dalfampridine is a potassium channel blocker that is available in a 10-milligram tablet strength.

• Dalfampridine is an extended-release tablet that is white to off-white in color and oval biconvex in shape.

For Patients

What Is Multiple Sclerosis?

Multiple sclerosis is a degenerative condition (due to degenerating cell changes influencing the tissues and organs) in which the myelin sheath (insulting cover) of the nerve cells in the brain is damaged. Such damage to the nerve fiber disrupts the ability of certain parts of the Central Nervous System (CNS) to transmit signals (messenger), leading to a range of signs and symptoms with physical, psychiatric, and mental health problems. Hence, multiple sclerosis is a potentially disabling condition of the brain (CNS) and spinal cord.

Signs and Symptoms of Multiple Sclerosis:

The signs and symptoms of the disabling condition multiple sclerosis vary widely from individual to individual and over the course of the disease, depending on the site of the affected nerve fibers. The most commonly encountered symptoms include the following.

• Weakness or numbness in one or more limbs usually occurs on either side of the body at a time.

• Tingling sensation.

• Electric shock feelings occur with neck movements, particularly when bending the neck frontward.

• Unsteady gait (waking style).

• Inability to walk.

• Vertigo.

• Blurred vision.

• Fatigue.

• Slurred speech.

• Cognitive or mental health problems.

• Mood disorders.

• Partial or complete vision loss is often accompanied by pain during eye movements.

• Prolonged double vision.

How Does Dalfampridine Work?

The primary treatment for multiple sclerosis consists of immunosuppressants. Physiotherapy and appropriate medications that suppress the immune system could help reduce and alleviate the symptoms while slowing the disease's progression. The other medications include chemotherapy, steroids, and anti-inflammatory medications. Physical exercise and counseling play a major role in the management of the symptoms of multiple sclerosis.

Dalfampridine is a neurofunctional modifier that is used to enhance walking in individuals with multiple sclerosis, where the nerves do not function normally and result in loss of muscle coordination, numbness, weakness, impaired vision, speech discrepancy, and problems with bladder control. Dalfampridine is either used alone or in conjunction with other medications that help relieve the symptoms of multiple sclerosis. Dalfampridine belongs to the group of pharmaceutical drugs called the potassium channel blockers. This medication works by reinforcing the signals sent by the brain through the nervous system that have been deactivated or damaged by multiple sclerosis.

What Is the Dosage of Dalfampridine?

Dalfampridine comes in extended-release tablet form. The maximum adult dosage for multiple sclerosis is 10 milligrams orally every 12 hours. The adults and geriatrics are usually advised to take a 10-milligram Dalfampridine tablet twice a day, 12 hours apart. This can be taken with or without the meal.

What Are the Things to Inform the Doctor Before Taking the Drug?

• Inform the doctor if one is hypersensitive to Dalfampridine, 4-aminopyridine, or other active ingredients in the prescribed formulation.

• Inform the doctor if one has had moderate to severe kidney disease.

• Tell the doctor if one has or has ever had seizure attacks.

• Inform the healthcare providers about the medication one takes or plans to take. This includes over-the-counter medications, prescription drugs, nutritional supplements, vitamins, and herbal products.

• Be sure to mention if one is taking other forms of 4-aminopyridine. The doctors might change the dosages of the medication or closely monitor the person for side effects.

• Inform the doctor if one has ever had an irregular or abnormal electroencephalogram (EEG). This is a test used to measure the electrical activity of the brain.

• Inform the doctor if one is pregnant or has any plans to conceive. Call and tell the doctor if one gets pregnant while taking this medication.

• Be certain to inform the doctor if one is breastfeeding.

How Is Dalfampridine Administered?

• Follow the doctor’s directions and prescription label guidelines for taking Dalfampridine correctly.

• One must use the medication exactly as per the directions.

• Space and take the medications in 12 hours part in a day.

• One must not take more than two Dalfampridine tablets in one day or 24 hours.

• Dalfampridine can be taken with or without a meal.

• Swallow the Dalfampridine tablet as a whole. One should not chew, crush, or break the tablet.

• Breaking the Dalfampridine tablet can cause the release of too much of the drug at one time, increasing the risk of seizure.

• One should not take the tablet that has been broken or crushed.

Warnings:

• Dalfampridine tablets can cause seizures even in people who have had attacks before.

• Taking more Dalfampridine can increase the risk of seizures.

• One might be at an increased risk of seizure if one has any kidney problems and is older than 50 years of age.

• The healthcare providers recommend a kidney function test before imitating Dalfampridine therapy.

• One should stop taking the medication and reach out to the professionals if experiencing a seizure attack.

What Are the Side Effects of Dalfampridine?

Dalfampridine can induce allergic reactions in people hypersensitive to the drug. One should get emergency medical care promptly if experiencing any of the following signs.

• Hives.

• Rashes.

• Difficulty breathing.

• Swelling of the face.

• Swelling of the lips, throat, or tongue.

Moreover, one should stop taking the medication and seek professional help straight away if experiencing any seizures.

Common Side Effects:

The following side effects are common in people taking Dalfampridine. These can resolve on their own with time. However, one should reach out to the doctor and seek medical care if any of the symptoms are not relieving or distressing the daily life.

• Weakness.

• Multiple sclerosis relapse.

• Dizziness.

• Balance problems.

• Sleep problems, including insomnia.

• Headache.

• Back pain.

• Stuffy nose.

• Sinus pain.

• Sinus throat.

• Nausea.

• Constipation.

• Stomach upset.

• Numbness or tingling sensation.

• Painful urination.

Serious Side Effects:

Dalfampridine can cause serious side effects in some instances. Call the healthcare provider and inform them once if experiencing any of the following issues.

• Pain or burning sensation while urinating.

• Relapse or worsening of multiple sclerosis symptoms.

Dietary Considerations: People taking Dalfampridine can follow the Jairam and classic diet guidelines unless the doctors utter any changes or restrictions. Discuss with the healthcare providers the restrictions, beverages, food, and activities while taking Dalfampridine medication.

Missed Dose: Take the missed dose as soon as one has the thought. One can skip the missed dose and go with the subsequent one at the regularly scheduled time if it is almost time for the next one. Never use two doses of Dalfampridine at one time for compensation.

Overdose:

Seek poison helpline services or emergency medical attention promptly if one has taken an overdose of Dalfampridine. Overdose can cause undesirable reactions, including confusion and seizures.

Storage

Keep the Dalfampridine medication in the container that came with it. Store the medications at a room temperature of about 25 degrees Celsius. It is crucial to store them away from excess moisture and heat to prevent contamination.

Any medication should be kept out of the sight and reach of children.

For Doctors

Indication:

Dalfampridine is a neurofunctional modifier that can improve the walking speed in individuals with Multiple Sclerosis (MS).

Dose:

Dalfampridine is an extended-release form of tablet with a strength of 10 milligrams.

Multiple Sclerosis:

• Dalfampridine helps improve walking in individuals with multiple sclerosis by increasing walking speed.

• The recommended dosage of Dalfampridine is 10 milligrams orally twice daily 12 hours apart. This can be taken with or without food.

Dosing Considerations: Renal Impairment

• In moderate to severe renal impairment cases with creatinine clearance of less than 50 milliliters per minute, Dalfampridine is contraindicated since it increases the risk of seizure attacks.

• The risk of seizure is unknown and undetermined in mild degrees of renal impairment. However, plasma levels can be the same as the levels of 15 milligrams twice daily, a dosage that is potentially associated with seizure risk.

Hepatic Impairment

• The usage and safety of Dalfampridine in people with hepatic impairment have not been studied.

• However, it is not predicted to change the dosing recommendation.

What Are the Pharmacological Aspects of Dalfampridine?

Pharmacodynamics

Dalfampridine belongs to broad-spectrum lipophilic potassium channel blockers. This drug class binds more favorably to the open state of the potassium channel than the closed state in the central nervous system (CNS). The significant and potential target of Dalfampridine is the potassium channels susceptible in multiple sclerosis patients. Moreover, Dalfampridine does not prolong the duration of the QTc interval.

Mechanism of Action

In multiple sclerosis, the axons (nerve fibers) are progressively demyelinated, exposing the potassium channels in the CNS. This results in the leakage and release of potassium ions, causing depolarization of the cells and a decline in neuronal excitability. The impact of multiple sclerosis is the impairment of neuromuscular transmission, making it more difficult to trigger the action potential.

Dalfampridine inhibits the voltage-gated potassium channels exposed in the central nervous system. This helps maintain the transmembrane potential while prolonging the action potential. Therefore, the drug Dalfampridine ensures that the potential is high enough to precipitate the conduction in those demyelinated nerve fibers exposed in multiple sclerosis patients. Dalfampridine also expedites synaptic and neuromuscular transmission by releasing the conduction blocks from the demyelinated axons.

Pharmacokinetics

Absorption:

• Dalfampridine undergoes rapid and complete absorption from the gastrointestinal tract following oral administration.

• The time to maximum plasma concentration (Tmax) is one hour for the immediate-release form and 3.5 hours for the extended-release form.

• The Cmax of 10 mg extended-release Dalfampridine is 17.3 to 21.6 ng/mL.

• The relative bioavailability of 10 milligrams of extended-release Dalfampridine tablets compared to the aqueous solution is 96 percent.

Distribution:

• The volume of distribution of 10 milligrams of extended-release Dalfampridine is 2.6 liters per kilogram.

• The protein binding capacity of 10 milligrams of extended-release Dalfampridine is one to three percent.

Metabolism:

• Dalfampridine does not undergo extensive metabolism by the liver.

• Hence, the drugs influencing the cytochrome P450 enzyme that is co-administered with the Dalfampridine are not anticipated to interact with each other.

• The metabolites are 3-hydroxy-4-aminopyridine sulfate and 3-hydroxy-4-aminopyridine, but both metabolites are inactive.

• Cytochrome P2E1 is the significant enzyme responsible for the three-hydroxylation of Dalfampridine.

Elimination:

• The kidneys eliminate most dosages of Dalfampridine and their metabolites after one day (24 hours) of administration.

• 90 to 96 percent of the total dose of Dalfampridine is excreted in urine as an unchanged form, and about 0.5 percent is excreted in feces.

Half-Life:

The absolute half-life period of Dalfampridine in the immediate-release form is 3.5 hours, and the extended-release form is 5.47 hours.

Toxicity:

The Toxic overdose or lethal dose of 50 percent (LD50) orally in mice is determined to be 19 milligrams per kilogram and, in rats, is 21 milligrams per kilogram.

Adverse Effects of Dalfampridine:

The most common adverse effect experienced in people taking Dalfampridine is urinary tract infection. Other adverse reactions tend to occur in about one to ten percent of patients are as follows.

• Dizziness.

• Headache.

• Insomnia.

• Nausea.

• Asthenia (lack of energy or physical weakness).

• Multiple sclerosis relapse.

• Back pain.

• Balance disorder.

• Constipation.

• Dyspepsia.

• Drug and dose-related increased risk for seizures.

• Pharyngolaryngeal pain.

• Paresthesia.

Post-marketing Reports:

• Seizures have been reported in 4.6 numbers per 1000 patients in years of use.

• Vomiting.

• Vertigo.

What Are the Contraindications of Dalfampridine?

The use of the drug Dalfampridine is strictly contraindicated in these conditions.

• History of seizures.

• Moderate to severe degrees of renal impairment with creatinine clearance of values less than 50 milliliters per minute.

• History of hypersensitivity or allergic reaction to Dalfampridine.

Specific Considerations:

• Pediatric: The safety and efficacy have not been determined in children younger than 18 years of age.

• Geriatrics: The clinical research of Dalfampridine did not include an adequate number of people aged 65 and above to assess whether geriatrics show different responses than younger subjects. Analysis suggests that Dalfampridine clearance could be reduced with increased age, but this does not necessarily influence or modify the dosage with age. The kidneys significantly excrete Dalfampridine with an increased risk of adverse reactions, especially seizures. As geriatric patients are more likely to have reduced renal function, it is crucial to determine the creative clearance in elderly patients before administration.

• Lactation: No data suggests the presence of Dalfampridine in human breast milk, its effects on the infant, and milk production. However, one should consider the health and developmental benefits of breastfeeding and estimate them with the clinical need for Dalfampridine and its potential adverse effects on the infant.

• Gender: An analysis suggests that female patients would be more likely to have increased and maximum Dalfampridine plasma concentration than males. Nevertheless, the eminence of these differences is substantially less and does not require any dosage modification.

• Pregnancy: No adequate data embrace the developmental risks and complications associated with the use of Dalfampridine in pregnant women. The administration of Dalfampridine to animals during pregnancy and lactation resulted in reduced offspring viability and progression with clinically appropriate doses.