HARLIKU (nitisinone) — Preauthorization Required
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Preauthorization policy governing medical necessity criteria for Harliku (nitisinone) to reduce urinary homogentisic acid (HGA) in patients with alkaptonuria; applies to coverage decisions made by Blue Cross Blue Shield - Nebraska.
No material clinical or coverage changes in this revision.
Coverage Criteria for Harliku (nitisinone)
Initial therapy criteria
Covered when ALL of the following are met
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Renewal criteria
Renewal Evaluation covered when ALL of the following are met
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No FDA-labeled contraindications specific to Harliku were identified in this policy, and the policy states that Harliku does not carry any black box warnings.
Patients who do not meet all elements of the Initial Evaluation criteria described in this policy are not considered to meet medical necessity. Examples include: lacking a documented diagnosis of alkaptonuria, having a 24-hour urine homogentisic acid (HGA) measurement that is below the required threshold of >= 1 gram, failing to meet the prerequisite agent requirements (trials, inadequate response, or documented intolerance/hypersensitivity), absence of specialist involvement or consultation, presence of FDA-labeled contraindications to the requested agent, or requests for doses that exceed program limits without required justification.
Key Coding and Test Thresholds
Provider Requirements and Authorization Actions
Preauthorization required for Harliku — initial approval conditions
Prior authorization is required for Harliku (nitisinone). Initial approval requires a diagnosis of alkaptonuria and a 24‑hour urine HGA ≥ 1 gram, meeting FDA age labeling or providing clinical justification for use outside FDA age limits, specialist prescriber or documented specialist consultation, absence of any FDA‑labeled contraindications to the requested agent, and dosing within program quantity limits or meeting the program’s exception criteria for higher doses.
- Diagnosis of alkaptonuria is required (Initial Evaluation I).
- 24‑hour urine HGA ≥ 1 gram (Initial Evaluation II; medical records required).
- If the patient has an FDA‑labeled indication, patient age must be within FDA labeling or there must be support for use in that age (Initial Evaluation III).
- Prescriber must be a specialist or have consulted with a specialist (Initial Evaluation V).
- Patient must not have any FDA‑labeled contraindications to the requested agent (Initial Evaluation VI).
- Requested quantity/dose must not exceed program limits or must meet the program’s criteria for exceeding limits (Initial Evaluation VII/VIII and chunk 9).
Prerequisite agent trials and intolerance/contraindication requirements
Prior therapy/prerequisite requirements must be documented: the patient must meet ONE of the listed step‑therapy scenarios showing trial and inadequate response or intolerance/contraindication to prerequisite agents (examples given: nitisinone capsule, Nityr tablet).
- Option A: Tried and had inadequate response to TWO prerequisite agents (e.g., nitisinone capsule, Nityr tablet) not expected with the requested agent.
- Option B: Tried and had inadequate response to ONE prerequisite agent AND intolerance/hypersensitivity to ONE prerequisite agent not expected with the requested agent.
- Option C: Intolerance/hypersensitivity to TWO prerequisite agents not expected with the requested agent.
- Option D: FDA‑labeled contraindication to ALL prerequisite agents not expected with the requested agent.
Required medical records and prior‑approval documentation
Medical records must contain specific documentation for initial and renewal review: a 24‑hour urine HGA measurement of ≥ 1 gram for initial approval and documentation of reduction in urinary HGA for renewals; specialist consultation notes if the prescriber is not a specialist; and prior authorization approval record for renewals.
- Initial: 24‑hour urine homogentisic acid (HGA) ≥ 1 gram (medical records required).
- Renewal: documentation of reduction in urinary HGA demonstrating clinical benefit (medical records required).
- Specialist involvement: consultation notes if prescriber is not a specialist (Initial Evaluation V; Renewal III).
- Renewal: evidence the patient was previously approved through the plan’s Prior Authorization process (Renewal I).
Denial risks if required diagnosis, HGA, or documentation are missing
Requests risk denial when required criteria or documentation are missing: lack of a diagnosis of alkaptonuria, 24‑hour urine HGA < 1 gram/24 hr, missing prior authorization record for renewals, absent specialist involvement or consultation, presence of FDA‑labeled contraindications to the requested agent, or requested dose/quantity exceeding program limits without meeting the exception criteria.
- No documented diagnosis of alkaptonuria (Initial Evaluation I).
- 24‑hour urine HGA less than 1 gram/24 hours or missing urine HGA result (Initial Evaluation II).
- For renewals, lack of prior approval through the plan’s Prior Authorization process or missing documentation of reduction in urinary HGA (Renewal I–II).
- Prescriber is not a specialist and no documented specialist consultation (Initial V; Renewal III).
- Documented FDA‑labeled contraindication to the requested agent (Initial VI; Renewal IV).
- Requested quantity/dose exceeds program limits without meeting the program’s higher‑dose support criteria (Initial VII/VIII and chunk 9).
Background on Alkaptonuria and Nitisinone
Alkaptonuria (AKU) is an inherited metabolic disorder characterized by accumulation of homogentisic acid (HGA) due to defects in tyrosine catabolism. Elevated urinary HGA leads to progressive tissue deposition (ochronosis) and related clinical manifestations. Nitisinone (Harliku) inhibits 4-hydroxyphenylpyruvate dioxygenase in the tyrosine degradation pathway and has been shown to markedly reduce urinary HGA levels in treated patients. Clinical data cited in the policy report large reductions in urinary HGA and symptom improvement for some patients treated with nitisinone.
Definitions and Biomarkers
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