CurrentPremera BluecrossPolicy 5.01.527

Ampyra (Dalfampridine)

Policy governing medical necessity and prior authorization criteria for dalfampridine (generic) and Ampyra (brand) for improvement in walking in adults with multiple sclerosis under the pharmacy benefit; includes initial and re-authorization requirements and duration of approval.

Policy Summary

PayerPremera Bluecross

PolicyAmpyra (Dalfampridine)

Policy CodePolicy 5.01.527

Change TypeUpdated authorization lengthbrand step requirement clarified

Effective DateJun 1, 2026

Next Review Date

Key ActionInitial prescriptions must be prescribed by a neurologist and meet the listed medical necessity criteria; initial and re-authorizations require prior authorization and may be approved up to 12 months.

SourceLink

POLICY UPDATE CHANGES

Updated initial authorization for dalfampridine and Ampyra (dalfampridine) from 6 months to 12 months.

Added requirement that Ampyra requires prior trial and inadequate response or intolerance to generic dalfampridine (documentation required).

Clarified that medications listed in this policy are subject to the product's FDA dosage and administration prescribing information.

1Covered Drug (generic dalfampridine)

1Brand requiring prior generic trial (Ampyra)

12Maximum months per authorization

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This policy (5.01.527) governs medical necessity and prior authorization for dalfampridine (generic) and Ampyra (brand) under the pharmacy specialty benefit. Both agents are covered with criteria for improvement in walking speed in adults with multiple sclerosis. Initial and re-authorization requests may be approved for up to 12 months. Key thresholds include age >= 18 years, baseline T25FW measurement required, and creatinine clearance (CrCl) must be > 50 mL/min. Ampyra additionally requires prior trial and inadequate response or intolerance to generic dalfampridine and a dose limit of 20 mg per day (10 mg twice daily).

Key Eligibility Thresholds

Age>= 18 years

Creatinine Clearance (CrCl)> 50 mL/min

Timed 25-Foot Walk (T25FW)Baseline T25FW required

Ampyra dose limit20 mg per day (10 mg twice daily)

Initial Therapy Criteria

Dalfampridine (generic) - Initial Authorization (Medical Necessity)

Dalfampridine may be considered medically necessary for adult individuals when ALL of the following criteria are met:

Age: The individual is aged 18 years or older>= 18 years
Diagnosis: Has a diagnosis of multiple sclerosis
Seizure history: Does not have a history of seizures
Renal function: Has creatinine clearance (CrCl) greater than 50 mL/min> 50 mL/min
Baseline T25FW: Has completed a baseline timed 25-foot walk (T25FW)Baseline T25FW required
Prescriber: Initial prescription is prescribed by a neurologist

Ampyra (brand) - Initial Authorization (Medical Necessity)

Ampyra (dalfampridine) may be considered medically necessary for adult individuals when ALL of the following criteria are met:

Age: The individual is aged 18 years or older>= 18 years
Diagnosis: Has a diagnosis of Multiple Sclerosis
Seizure history: Does not have a history of seizures
Renal function: Has Creatinine Clearance (CrCl) greater than 50 mL/min> 50 mL/min

Contraindications and Denials

Coverage is precluded for individuals with a history of seizures and for those with creatinine clearance ≤ 50 mL/min; these contraindications will result in denial of coverage. The policy notes a seizure safety signal observed at higher doses, and documents that seizure risk informed the contraindication for history of seizures and for moderate or severe renal impairment.

Denial Risk

Contraindications that will preclude coverage

Coverage will be denied for individuals with a history of seizures or with creatinine clearance ≤ 50 mL/min.

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required and Prescriber Specialty

Initial prescriptions must be prescribed by a neurologist and meet the listed medical necessity criteria; initial and re-authorizations require prior authorization and may be approved up to 12 months.

Documentation Required

Baseline and follow-up documentation for walking function

Document baseline timed 25-foot walk (T25FW) prior to initiation and chart notes documenting improvement in T25FW from baseline for re-authorization.

Documentation Required

Renal function documentation

Document creatinine clearance greater than 50 mL/min at baseline and provide recent kidney function showing CrCl > 50 mL/min at time of re-authorization.

Billing Rule

Benefit application

Dalfampridine and Ampyra are specialty pharmacy drugs managed under the pharmacy benefit.

Step Therapy

Brand use requirement

Ampyra (brand) requires trial and inadequate response or intolerance to generic dalfampridine with documentation prior to approval.

Clinical Evidence

35% vs 8%MS-F203 responder rate: dalfampridine 35% vs placebo 8% (p<0.0001); mean T25FW difference ~0.88s

42.9% vs 9.3%MS-F204 responder rate: dalfampridine 42.9% vs placebo 9.3% (p<0.0001); mean T25FW difference ~0.5s

Seizure riskSeizure signal noted at higher doses; contraindicated with history of seizures or CrCl <50 mL/min

Clinical evidence showed statistically significant increases in T25FW responder rates (e.g., 35% vs 8% and 42.9% vs 9.3% in phase III trials), but the absolute mean change in walk time versus placebo was modest (approximately 0.5–0.9 seconds). Safety considerations include an increased seizure risk at higher doses and concern in patients with renal impairment; seizures were observed with higher doses (notably 20 mg twice daily in a dose-ranging study), which contributed to contraindications and the development of the sustained-release formulation.

Background & Definitions

Dalfampridine is a potassium channel blocker approved by the FDA to improve walking speed in individuals with multiple sclerosis. Approval was based on two phase III trials using the timed 25-foot walk (T25FW) responder endpoint, which demonstrated higher responder rates with dalfampridine versus placebo. Clinical trial context includes specific inclusion/exclusion criteria and trial durations, and safety considerations emphasize seizure risk (especially at higher doses) and issues with renal impairment, which guided labeling and use recommendations.

Timed 25-foot walk (T25FW): a standardized test used to assess walking speed. The policy requires a documented baseline T25FW prior to initiation and follow-up T25FW measurements (chart notes documenting improvement from baseline) for re-authorization decisions; these baseline and follow-up measurements are required for coverage and re-authorization.

Revision History

2026-06-01revisedLatest

Updated initial authorization for dalfampridine and Ampyra (dalfampridine) from 6 months to 12 months.

2025-04-01clarified

Clarified that the medications listed in this policy are subject to the product's FDA dosage and administration prescribing information; clarified non-formulary exception review authorizations for all drugs may be approved up to 12 months.

revised

Added requirement that Ampyra requires prior trial and inadequate response or intolerance to generic dalfampridine (documentation required) and specified dose limit for Ampyra as 20 mg/day (10 mg twice daily).