Potassium Channel Blocker

Dalfampridine

Approved 21 May 2019OralTablet, extended release

The FDA lists this product in 9 strengths and forms.

Indications

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)]. 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).

Contraindications

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 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)

Warnings and precautions

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)

5.1Seizures

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 postmarketing 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 have 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.

At a glance

Brand name: Dalfampridine
Pharmacologic class: Potassium Channel Blocker
Route: Oral
Dosage form: Tablet, extended release
Applicant: Sun Pharm
Status: Discontinued
FDA approval: 21 May 2019
Application: ANDA208292-001

Indications

Contraindications

Warnings and precautions

Discontinue and do not restart dalfampridine extended-release tablets if this occurs (5.4)

5.1Seizures

Adverse reactions

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 Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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.

The adverse reactions leading to discontinuation of at least 2 patients treated with dalfampridine extended-release tablets and that led to discontinuation more frequently compared to placebo were headache (dalfampridine extended-release tablets 0.5%, placebo 0%), balance disorder (dalfampridine extended-release tablets 0.5%, placebo 0%), dizziness (dalfampridine extended-release tablets 0.5%, placebo 0%), and confusional state (dalfampridine extended-release tablets 0.3%, placebo 0%).

Table 1 lists adverse reactions that occurred in ≥ 2% of patients treated with dalfampridine extended-release tablets 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 Dalfampridine Extended-Release Tablets-Treated Adult MS Patients and More Frequent with Dalfampridine Extended-Release Tablets Compared to Placebo in Controlled Clinical Trials Adverse reaction Placebo (N=238) % Dalfampridine Extended-Release Tablets 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 Dalfampridine extended-release tablets have been evaluated in a total of 1,952 subjects, including 917 MS patients.

A total of 741 patients have been treated with dalfampridine extended-release tablets 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 dalfampridine extended-release tablets in patients with MS as follows: Dalfampridine extended-release tablets 10 mg twice daily 0.41 per 100 person-years (95% confidence interval 0.13 to 0.96); dalfampridine 15 mg twice daily 1.7 per 100 person-years (95% confidence interval 0.21 to 6.28).

6.2Postmarketing 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.

Dalfampridine

Indications

Contraindications

Warnings and precautions

5.1Seizures

At a glance

Two medicines in one question?

Dalfampridine

Indications

Contraindications

Warnings and precautions

5.1Seizures

At a glance

Two medicines in one question?

5.2Renal Impairment

5.3Concurrent Treatment with Other Forms of 4-Aminopyridine

5.4Anaphylaxis

Interactions

7.1OCT2 Inhibitors

7.2Baclofen

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information