CurrentAvMedPolicy N/A

Nitisinone products prior authorization

Defines prior authorization and step-edit criteria for nitisinone products (Harliku, Nityr, Orfadin, generic nitisinone) for AvMed members, including initial and reauthorization requirements for Hereditary Tyrosinemia Type 1 (HT-1) and Alkaptonuria (AKU). Affects prescribers and members covered by AvMed plans.

Policy Summary

PayerAvMed

PolicyNitisinone products prior authorization

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization and submit required documentation including diagnosis, relevant labs (plasma/urinary succinylacetone, urinary HGA, CBC), weight and dosing, and ophthalmologic exam when applicable.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

6 monthsInitial authorization duration

12 monthsReauthorization duration

2 mg/kg/dayMax dose (weight-based)

2 mg/dayMax dose (clause)

NCApplicable state(s)

Coverage Criteria for Nitisinone Products

Initial authorization — HT-1

Covered when ALL of the following are met

HT-1 initial criteria: Member must have a diagnosis of hereditary tyrosinemia type 1 (HT-1); using the prescribed medication as an adjunct to dietary restriction of tyrosine and phenylalanine; member's current plasma tyrosine level is maintained at <500 mcmol/L (submit documentation); a baseline urinary or plasma succinylacetone test completed within the last 30 days; baseline ophthalmologic slit lamp examination with normal result; a complete blood count completed within the last 30 days and submitted; for Nityr and Brand Orfadin capsule requests, member must have trial and failure of generic nitisinone capsules with chart notes documenting clinically significant adverse effects and submission of a completed FDA MedWatch form; for Orfadin suspension requests, provider must submit documentation confirming the member is unable to swallow nitisinone capsules; member's current weight documented and maximum approved dosage will be 2 mg/kg/day

All criteria must be met for 6-month initial authorization

Reauthorization — HT-1

Covered when ALL of the following are met

HT-1 reauth criteria:

Policy Summary

PayerAvMed

PolicyNitisinone products prior authorization

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

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.

Initial authorization — AKU (adult)

Covered when ALL of the following are met

AKU initial criteria: Member has a diagnosis of alkaptonuria (AKU) and is 18 years of age or older; prescribed by or in consultation with an endocrinologist or a metabolic/genetic disease specialist; diagnosis confirmed by ONE of: baseline urinary HGA excretion >0.4 g/24 hours OR HGD biallelic gene mutation by genetic testing; member's current weight documented with maximum approved dosage 2 mg/kg/day; for Nityr and Brand Orfadin capsule requests, member must have trial and failure of generic nitisinone capsules (chart notes documenting clinically significant adverse effects and submission of completed MedWatch form are required); for Orfadin suspension requests, provider must submit documentation confirming inability to swallow capsules; for Harliku requests, member must have trial and failure of BOTH generic nitisinone and Brand Orfadin unless contraindicated (documentation and completed FDA MedWatch form required for adverse reactions); member must not be using two different nitisinone products concurrently

All criteria must be met for 6-month initial authorization

Clinical Targets and Lab Thresholds

inv-07: Plasma tyrosine level

ThresholdPlasma tyrosine level maintained at <500 mcmol/L (submit documentation)

ContextRequired for initial authorization for hereditary tyrosinemia type 1 (HT-1)

Documentation timingCurrent plasma tyrosine level must be documented with the request

inv-08: Urinary succinylacetone reauthorization target

Reauthorization targetUrinary succinylacetone decreased to <1 mmol/mol creatinine from baseline

ApplicabilityOne of the criteria that can satisfy HT-1 reauthorization when submitted with documentation

DocumentationSubmit lab results demonstrating decrease from baseline

inv-09: Plasma succinylacetone reauthorization target

Reauthorization targetPlasma succinylacetone decreased to <0.1 micromol/L from baseline

ApplicabilityAlternate biochemical criterion for HT-1 reauthorization if documented

DocumentationSubmit plasma succinylacetone lab results showing decrease from baseline

inv-10: Baseline urinary HGA for AKU diagnosis

Diagnostic thresholdBaseline urinary HGA excretion greater than 0.4 g/24 hours

UseOne acceptable method to confirm alkaptonuria (AKU) for initial authorization in adults

DocumentationSubmit baseline 24-hour urinary HGA test results with the request

Provider Requirements and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for generic nitisinone capsules, Brand Orfadin (capsules/suspension), and Nityr. Requests for Nityr, generic nitisinone, Nityr, or Brand Orfadin capsules/suspension require prior authorization before dispensing.

Generic nitisinone capsules — prior authorization required
Brand Orfadin (capsules/suspension) — prior authorization required
Nityr — prior authorization required

Step Therapy

Step Therapy / Trial Requirements

Step therapy / trial requirements apply for certain brand products. For Nityr and Brand Orfadin capsule requests, the member must have trial and failure of generic nitisinone capsules with documentation of clinically significant adverse effects; a completed FDA MedWatch form is required when adverse reactions to the prerequisite therapy are claimed. For Harliku requests, the member must have trial and failure of BOTH listed preferred agents unless contraindicated or adverse effects occurred (verified by chart notes and/or pharmacy paid claims). Providers must submit documentation explaining why the preferred agent cannot be used when applicable.

Nityr and Brand Orfadin (capsules) — trial and failure of generic nitisinone capsules required (MedWatch form required for adverse reactions)
Harliku — trial and failure of BOTH preferred agents required unless contraindicated (supporting chart notes/pharmacy claims and MedWatch if adverse events)

Documentation Required

Required Documentation

Complete clinical documentation must be submitted with the prior authorization request. Incomplete documentation may delay authorization or cause denial. Required documentation includes drug details, dosing, therapy length, diagnosis with ICD-10 code when applicable, weight (if applicable) and date obtained, baseline and follow-up laboratory results, specialist consultation notes when required, and supporting chart notes for trials/failures and intolerance.

Drug name, form, strength, dosing schedule, and length of therapy
Diagnosis and ICD-10 code (if applicable)
Member weight and date weight obtained (if applicable); current weight must be noted — maximum approved dosage 2 mg/kg/day or dosing limits per indication
Baseline urinary or plasma succinylacetone level within last 30 days (for HT-1); baseline urinary HGA excretion or genetic testing for HGD mutation (for AKU) as applicable
Baseline ophthalmologic exam with normal slit lamp (for HT-1) and complete blood count within last 30 days
Laboratory results demonstrating treatment response for reauthorization (e.g., decreased urinary or plasma succinylacetone, reduced urinary HGA, or clinical improvement in joint symptoms)
Documentation of trial and failure of prior agents, including chart notes and pharmacy paid claims; completed FDA MedWatch form when adverse reactions are cited
For Orfadin suspension requests: documentation confirming inability to swallow capsules
Prescriber specialty: prescribed by or in consultation with an endocrinologist or a metabolic/genetic disease specialist when required

Documentation Required

Documentation Completeness

Ensure all checklist items are addressed and supporting records are attached. Authorization may be delayed or denied if any required item is missing, outdated, or not clearly documented. For initial requests and reauthorizations, include recent lab results (within 30 days where specified), current weight, and evidence of clinical benefit or biochemical response for continuation.

Attach all lab results, diagnostic tests, and chart notes referenced on the checklist
Ensure baseline labs/tests are within required timeframes (e.g., within 30 days where specified)
For reauthorization, submit documentation showing continued meeting of initial criteria and evidence of response (per reauthorization criteria)
Do not submit concurrent use of two different nitisinone products; confirm only one product is used

Initial Therapy

Initial therapy

Initial authorization rules

Initial therapy — HT-1: See HT-1 initial criteria set including diagnosis, use as adjunct to dietary restriction, plasma tyrosine <500 mcmol/L, baseline succinylacetone within 30 days, baseline ophthalmologic slit lamp exam, CBC within 30 days, weight documented and dosing limit 2 mg/kg/day; for Nityr and Brand Orfadin capsules require trial and failure of generic nitisinone; for Orfadin suspension document inability to swallow capsules

6-month initial authorization

Initial therapy — AKU: See AKU initial criteria set including age >=18, specialist prescriber, diagnostic confirmation (baseline urinary HGA >0.4 g/24h or biallelic HGD mutation), weight documented with max 2 mg/kg/day, required trials of preferred agents as applicable (Harliku requires trial/failure of both generic nitisinone and Brand Orfadin unless contraindicated), and member not using two different nitisinone products concurrently

6-month initial authorization

Step Therapy Requirements

Step	Requirement	Notes
1	For requests for Nityr or Brand Orfadin capsules: trial and failure of generic nitisinone capsules required unless contraindicated	Chart notes must document clinically significant adverse effects and a completed FDA MedWatch form when failure is due to adverse reaction
1	For Orfadin suspension requests: submit documentation confirming inability to swallow nitisinone capsules	Provider must document intolerance to capsules
1	For Harliku requests in AKU: trial and failure of BOTH generic nitisinone and Brand Orfadin required unless contraindicated	If failure due to adverse effects, include chart notes/paid claims and attach completed FDA MedWatch form
1	Prior authorization is required for generic nitisinone capsules, Brand Orfadin capsules/suspension, and Nityr	Medication provided by specialty pharmacy; ensure PA submitted as applicable

OpenPayer

Nitisinone products prior authorization

Coverage Criteria for Nitisinone Products

Clinical Targets and Lab Thresholds

Provider Requirements and Documentation

Background

Definitions and Dose Limits

Initial Therapy

Reauthorization / Continuation Criteria

Step Therapy Requirements

Site of Care / Dispensing