Potassium Channel Blocker

Ampyra

Approved 22 Jan 2010OralTablet, extended release

Indications

AMPYRA is 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) ]. AMPYRA ® (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 AMPYRA is 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 AMPYRA 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 AMPYRA or 4-aminopyridine ( 4 )

Warnings and precautions

AMPYRA can cause seizures; the risk of seizures increases with increasing AMPYRA doses; discontinue AMPYRA 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 ) AMPYRA can cause anaphylaxis. Discontinue and do not restart AMPYRA if this occurs ( 5.4 )

5.1Seizures

AMPYRA 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 9–14 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. AMPYRA 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 risk of seizures in patients with epileptiform activity on an EEG is unknown, and could be substantially higher than that observed in AMPYRA clinical studies.

At a glance

Brand name: Ampyra
Active substance: dalfampridine
Pharmacologic class: Potassium Channel Blocker
Route: Oral
Dosage form: Tablet, extended release
Applicant: Merz
Status: Prescription
FDA approval: 22 Jan 2010
Application: NDA022250-001

Indications

Contraindications

Warnings and precautions

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 AMPYRA 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 Acorda Therapeutics at 1-800-367-5109 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 AMPYRA 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 AMPYRA and that led to discontinuation more frequently compared to placebo were headache (AMPYRA 0.5%, placebo 0%), balance disorder (AMPYRA 0.5%, placebo 0%), dizziness (AMPYRA 0.5%, placebo 0%), and confusional state (AMPYRA 0.3%, placebo 0%). Table 1 lists adverse reactions that occurred in ≥2% of patients treated with AMPYRA 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 AMPYRA-Treated Adult MS Patients and More Frequent with AMPYRA Compared to Placebo in Controlled Clinical Trials Adverse Reaction Placebo (N=238) % AMPYRA 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 AMPYRA has been evaluated in a total of 1,952 subjects, including 917 MS patients.

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

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.

Ampyra

Indications

Contraindications

Warnings and precautions

5.1Seizures

At a glance

Two medicines in one question?

Ampyra

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

Official product information