CurrentCentenePolicy CP PHAR.248

Clinical Policy: Dalfampridine (Ampyra)

Clinical coverage policy for dalfampridine (Ampyra) to improve walking in patients with multiple sclerosis; defines initial and continued therapy criteria, contraindications, dosing, and approval durations for Centene lines of business.

Policy Summary

PayerCentene

PolicyDalfampridine (Ampyra) clinical policy

Policy CodePolicy CP PHAR.248

Change TypeNo material change

Effective Date08.01.16

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

10 mg BIDTypical MS dose

20 mg/dayMaximum daily dose

CrCl <50Contraindicated if

>18 yrsAge requirement

10 mg tabletProduct form

Coverage Criteria

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.

inv-01: Initial Therapy — Covered when ALL of the following are met (Initial Approval).

Covered when ALL of the following are met (Initial Approval):

Initial Approval - MS: 1. Diagnosis of multiple sclerosis.

Prescriber requirement: 2. Prescribed by or in consultation with a neurologist.

Age requirement: 3. Age > 18 years.

Functional status: 4. Member has sustained walking impairment but is able to walk with or without assistance.

Brand-to-generic redirection: 5. If request is for brand Ampyra, member must use generic dalfampridine unless contraindicated or clinically significant changes are experienced.

Dose limit: 6. Dose does not exceed 20 mg (2 tablets) per day.<= 20 mg/day

Approval durations differ by line of business.

inv-02: Continuation Therapy — Covered when ALL of the following are met (Continued Therapy).

Covered when ALL of the following are met (Continued Therapy):

Continued Therapy - eligibility: a) Member is currently receiving medication via Centene benefit or has previously met initial approval criteria; OR b) Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations.

Refer to state-specific addendums for continuity of care where applicable.

Response to therapy: Member is responding positively to therapy.

Brand-to-generic redirection: If request is for brand Ampyra, member must use generic dalfampridine unless contraindicated or clinically significant changes are experienced.

Dose limit for continued therapy: If request is for a dose increase, the new dose does not exceed 20 mg (2 tablets) per day.

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized. Requests for coverage of off‑label uses must include sufficient documentation of efficacy and safety according to the applicable off‑label use policies (e.g., CPCPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or the member’s evidence of coverage.

When state Medicaid coverage provisions conflict with this clinical policy, state Medicaid coverage provisions take precedence. Providers and reviewers should consult the applicable state Medicaid manual for any specific coverage provisions that apply to the member.

Dalfampridine (Ampyra) is contraindicated and therefore not covered for patients with a history of seizure and for patients with moderate or severe renal impairment defined as creatinine clearance (CrCl) < 50 mL/min. Also contraindicated in individuals with a known hypersensitivity to Ampyra or 4‑aminopyridine.

Dosing, Lab Thresholds, and Codes

Creatinine clearance (CrCl) — renal function thresholds

Contraindication thresholdContraindicated if creatinine clearance (CrCl) < 50 mL/min.

Caution rangeUse with caution when CrCl is 51-80 mL/min; patients may exhibit levels approaching those seen at higher doses with increased seizure risk.

Assessment requirementEstimate or know CrCl prior to initiating therapy (CrCl can be estimated using Cockcroft-Gault).

Dose

Typical dosing10 mg orally twice daily (approximately 12 hours apart).

Maximum daily doseDo not exceed 20 mg per day (two 10 mg tablets).

Risk with higher dosesUse of doses above 10 mg twice daily may increase the risk of seizures; no evidence of additional benefit at higher doses.

Provider Responsibilities and Prior Authorization

Prior Authorization

Initial and Continued Therapy Requirements — Prior authorization

Prior authorization requires that the member meet all Initial Therapy criteria for multiple sclerosis and that the prescriber is a neurologist or has consulted a neurologist. Requests must document age > 18, a diagnosis of multiple sclerosis, sustained walking impairment while able to walk with or without assistance, and dosing not to exceed 20 mg (2 tablets) per day. For brand Ampyra requests, the member must use generic dalfampridine first unless contraindicated or a clinically significant change has occurred. For continued therapy, the member must be currently receiving medication via the Centene benefit or have previously met initial approval criteria, and the member must be responding positively to therapy; continuity of care provisions may apply per state/product addenda.

Initial Therapy: diagnosis of MS; prescriber is or consulted with a neurologist; age > 18; sustained walking impairment but ambulatory; dose ≤ 20 mg/day.
Brand-to-generic: brand Ampyra requires prior trial of generic dalfampridine unless contraindicated or clinically significant change.
Continued Therapy: currently receiving medication through Centene or previously met initial criteria, and demonstrated positive response to therapy; state continuity of care rules may apply.

Denial Risk

Reasons for Potential Denial

Requests lacking adequate clinical documentation that the member meets the approval criteria may be denied. Requests for non‑FDA approved indications not addressed in this policy will be denied unless sufficient evidence of efficacy and safety is provided in accordance with applicable off‑label use policies and evidence of coverage documents. Providers must submit supporting documentation (e.g., office chart notes, lab results, or other clinical information) demonstrating that the member meets all approval criteria.

Missing documentation of diagnosis, neurologist consult, age, walking impairment, dosing, or response to therapy may lead to denial.
Non‑FDA indications require sufficient evidence per CPCPA.09 (commercial), HIM.PA.154 (HIM), CP.PMN.53 (Medicaid) or applicable evidence of coverage to be considered.
Provider documentation requirement: submit office notes, labs, and other clinical information to support all criteria.

Documentation Required

Provider Responsibility and Coverage Decision Dependencies

Provider responsibility: providers must exercise professional medical judgment and are responsible for medical advice and treatment. Coverage decisions depend on all terms, conditions, exclusions, and limitations of the member's coverage document. The Health Plan retains the right to change, amend, or withdraw this clinical policy and related prior authorization requirements.

Policy is a guide to medical necessity and does not replace provider clinical judgment.
Coverage and benefits are subject to the member's plan terms, exclusions, and limitations.
The Health Plan may modify or withdraw this clinical policy at any time.

Note

Unlabeled Provider Action

Definitions

creatinine clearance (CrCl) — definition

AbbreviationCrCl = creatinine clearance.

UseCrCl is used to assess renal function prior to initiating dalfampridine therapy.

EstimationCrCl can be estimated using the Cockcroft-Gault formula (see policy General Information).

Improve walking in patients with multiple sclerosis — FDA indication

FDA-approved indicationTo improve walking in patients with multiple sclerosis (MS) as demonstrated by an increase in walking speed.

Therapeutic goalIncrease walking speed in MS patients.

ScopeIndication reflects use specifically for gait/walking improvement in MS patients.

Clinical policy — definition as used in this document

PurposeA clinical policy provides guidance on medical necessity to assist in coverage decisions and administering benefits; it does not constitute medical advice or a provider treatment directive.

Development sourcesDeveloped by licensed health care professionals based on accepted standards of practice, peer-reviewed literature, agency approvals, guidelines, and expert opinion.

LimitationsCoverage decisions remain subject to plan terms, conditions, exclusions, limitations, state/federal requirements, and Health Plan administrative policies; the Health Plan may change or withdraw this policy.

OpenPayer

Clinical Policy: Dalfampridine (Ampyra)

Coverage Criteria

Dosing, Lab Thresholds, and Codes

Provider Responsibilities and Prior Authorization

Background

Definitions