ModifiedPremera BluecrossPolicy N/A

Ampyra (Dalfampridine) - Coverage Criteria

Defines medical necessity, authorization, and re-authorization requirements for dalfampridine (generic) and Ampyra (dalfampridine) under the pharmacy benefit for adults with multiple sclerosis.

Policy Summary

PayerPremera Bluecross

PolicyAmpyra (Dalfampridine) - Coverage Criteria

Policy CodePolicy N/A

Change TypeMaterial: initial authorization extended to 12 months

Effective DateJun 1, 2026

Next Review DateMay 11, 2026

Key ActionObtain prior authorization under the pharmacy benefit; initial and re-authorizations may be approved up to 12 months when criteria are met.

SourceLink

POLICY UPDATE CHANGES

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

Removed reference to non-formulary exception reviews.

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

Added Related Medical Policy: 5.01.644 Medical Pharmacologic Treatment of Multiple Sclerosis.

18+minimum age for coverage

CrCl >50renal function requirement

20 mg/dayAmpyra dose limit

12 months

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria for Dalfampridine (Ampyra)

Initial Therapy (generic dalfampridine)

Covered when ALL of the following are met

Initial coverage criteria for generic dalfampridine: Member is age 18 years or older; diagnosis of multiple sclerosis; no history of seizures; creatinine clearance (CrCl) > 50 mL/min; completed a baseline timed 25-foot walk (T25FW); initial prescription is prescribed by a neurologist.

Initial authorization may be approved up to 12 months.

Initial Therapy (Ampyra)

Covered when ALL of the following are met

Initial coverage criteria for Ampyra (dalfampridine): Member is age 18 years or older; diagnosis of Multiple Sclerosis; no history of seizures; creatinine clearance (CrCl) > 50 mL/min; completed a baseline timed 25-foot walk (T25FW); has tried and had an inadequate response or intolerance to generic dalfampridine (documentation required); initial prescription is prescribed by a neurologist; dose limited to 20 mg per day (10 mg twice daily).20 mg/day

Initial authorization may be approved up to 12 months.

Continuation Therapy / Re-authorization

Re-authorization may be approved up to 12 months when ALL of the following are met

Re-authorization: Chart notes documenting improvement in the timed 25-foot walk (T25FW) from baseline; chart notes documenting recent kidney function with creatinine clearance greater than 50 mL/min.

Reassessment of kidney function required at time of request; approvals up to 12 months.

Dalfampridine is contraindicated in individuals with a history of seizures due to an increased seizure risk observed in clinical trials, particularly at higher doses. The product is also contraindicated in individuals with moderate or severe renal impairment (CrCl < 50 mL/min) because reduced renal clearance increases systemic exposure and seizure risk. These contraindications are grounds for exclusion from coverage under this policy.

Operational language referencing non‑formulary exception reviews has been removed from this policy. The 2026 update deletes prior references to non‑formulary exception review processes; authorization decisions should follow the policy criteria and standard prior authorization processes described herein.

Use of dalfampridine (including Ampyra) is not medically necessary and will be denied for individuals with a history of seizures or with a measured creatinine clearance of ≤ 50 mL/min. A recent creatinine clearance > 50 mL/min is required to meet medical necessity; reassessment of kidney function is required at re‑authorization.

Initial Authorization Requirements

Initial therapy (generic)

Initial therapy coverage criteria

Initial generic dalfampridine: Age ≥ 18 years; diagnosis of multiple sclerosis; no history of seizures; creatinine clearance (CrCl) > 50 mL/min; baseline timed 25-foot walk (T25FW) completed; prescriber is a neurologist.

Initial authorization may be approved up to 12 months.

Initial therapy (Ampyra)

Initial therapy coverage criteria for branded Ampyra

Initial Ampyra: Meets all initial generic dalfampridine criteria AND documentation of trial and inadequate response or intolerance to generic dalfampridine is provided; dose limit 20 mg/day (10 mg twice daily); prescriber is a neurologist.20 mg/day

Documentation of prior trial of generic dalfampridine required for branded Ampyra.

Re-authorization and Long-term Use

Re-authorization

Re-authorization requirements for continued coverage

Continuation therapy nodes: Documentation of clinical benefit demonstrated by improvement in T25FW from baseline; recent creatinine clearance > 50 mL/min.

Reassessment of kidney function required at time of request; approvals up to 12 months.

Long-term use

Long-term safety and efficacy were evaluated in open-label extensions; policy notes outcomes but maintains coverage per prior authorization rules.

Long-term use summary: Long-term safety and efficacy of dalfampridine were evaluated in open-label extensions of Phase 3 trials; these data are noted but continuing coverage is contingent on meeting re-authorization criteria demonstrating clinical benefit.

Operational coverage follows standard re-authorization requirements (see Re-authorization block).

Coding

Codingmixed

No codes listed

Creatinine Clearance Requirement

Creatinine clearance requirement> 50 mL/min

Contraindication thresholdCrCl ≤ 50 mL/min is contraindicated (moderate or severe renal impairment)

Reassessment at re-authorizationRecent creatinine clearance > 50 mL/min must be documented for re-authorization

RationaleRenal impairment increases risk (seizure risk is higher with impaired clearance); policy requires >50 mL/min for safety

Provider Requirements and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization required under the pharmacy benefit for dalfampridine (generic) and Ampyra (dalfampridine). Initial and re-authorizations may be approved for up to 12 months when criteria are met. Drug requests are managed through the specialty pharmacy benefit.

Initial and continuation requests handled via pharmacy prior authorization
Authorization duration: up to 12 months when criteria are satisfied

Denial Risk

Contraindications and Denial Triggers

Requests will be denied if the individual has any contraindication or meets policy-level denial triggers. Specifically, a history of seizures or creatinine clearance (CrCl) ≤ 50 mL/min are contraindications that will preclude meeting medical necessity. Requests inconsistent with the product's FDA dosing or not meeting the prior authorization criteria (including missing required documentation) may be denied.

Step Therapy / Formulary Preference

Step	Requirement	Documentation / Notes	Coverage
1	Trial of generic dalfampridine is required prior to approval of branded Ampyra (dalfampridine)	Documentation must show trial and inadequate response or intolerance to generic dalfampridine; initial prescription must be prescribed by a neurologist	Branded Ampyra requires prior trial of generic dalfampridine

Item	Historical note	Policy action / preference	Coverage
Generic-before-brand preference (2019)	Policy history documents addition of a generic preference in 2019	Policy historically required use of generic dalfampridine prior to branded Ampyra; formulary preference noted	Continues to require generic trial before brand; preference documented in history

Quantity Limits

Ampyra (dalfampridine) — Quantity Limit / Maximum Daily Dose

Maximum daily dose (quantity limit)20 mg per day (taken as 10 mg twice daily)

Policy quantity limit unitLimit expressed as milligrams per day (mg/day)

Source of dosing guidanceDose limit and prescribing information referenced from product labeling (Ampyra prescribing information)

ApplicationApplies to branded Ampyra when criteria met; initial and re-authorizations follow same dose limit

Site of Care / Benefit

Note

Managed under the pharmacy benefit (specialty drug)

Dalfampridine and Ampyra (dalfampridine) are managed under the pharmacy benefit as specialty pharmacy drugs.

Site of care: home (specialty pharmacy drug managed under the pharmacy benefit).

Background

Multiple sclerosis (MS) is a demyelinating disease that impairs nerve conduction and commonly causes walking difficulty. Dalfampridine is a potassium channel blocker formulated as an extended‑release tablet (Ampyra) intended to improve walking speed in adults with MS. It provides symptomatic benefit for walking as measured by the timed 25‑foot walk (T25FW), but it does not alter the underlying disease course. Safety considerations include an increased risk of seizure — the primary safety concern — and common adverse events such as urinary tract infection, dizziness, insomnia, and headache.

Definitions

T25FW — Timed 25-foot Walk

DefinitionTimed 25-foot walk (T25FW): a standardized test measuring walking speed over 25 feet, used to assess walking ability in multiple sclerosis.

Role as baseline measureA baseline T25FW must be completed prior to initiation and documented in the chart.

Role as outcome measureFor re-authorization, chart notes must document improvement in T25FW from baseline to demonstrate clinical benefit.

Use in policy decisionsT25FW results are required evidence of walking improvement to meet continuation/re-authorization criteria.

Ampyra (dalfampridine) — Drug Definition and Indication

Drug definitionAmpyra (dalfampridine): extended-release tablet formulation of dalfampridine indicated to improve walking in adults with multiple sclerosis (per product labeling).

Revision History

2019annual_review

Reviewed dalfampridine prescribing information and primary literature search (1/1/18–3/29/19); no evidence found requiring policy changes.

2024annual_review

Reviewed dalfampridine prescribing information; no new information identified that would impact the policy.

2025clarification

Clarified that non‑formulary exception review authorizations for drugs in this policy may be approved up to 12 months and reiterated that medications are subject to the FDA dosing and administration prescribing information.