HCPCS
J0598
1 unit = 10 IU
Phase 1
Identify what you're billing
Confirm the unit basis (10 IU/unit), prophylaxis indication, and HAE class context.
HAE drug class — 5-drug comparison Class verified May 2026
Cinryze sits inside a tightly defined class. The split that drives every payer policy: prophylaxis vs on-demand, IV vs SC.
Hereditary angioedema therapies divide cleanly into two indication tracks (routine prophylaxis vs. acute on-demand) and two routes (IV vs. SC). Mis-mapping a drug to the wrong track is the most common reason HAE claims deny. Cinryze is plasma-derived C1-INH for IV prophylaxis; its on-demand counterpart Berinert is the same molecule, different indication.
| Drug | HCPCS | Class / molecule | Route | Indication | Schedule |
|---|---|---|---|---|---|
| Cinryze (this page) | J0598 (10 IU) | Plasma C1-INH | IV ~10 min | Prophylaxis | 1,000 IU q3-4d |
| Haegarda | J0599 (10 IU) | Plasma C1-INH (CSL) | SC | Prophylaxis | ~60 IU/kg q3-4d |
| Takhzyro | J0593 (1 mg) | Lanadelumab (anti-kallikrein mAb) | SC | Prophylaxis | 300 mg q2wk → q4wk |
| Berinert | J0597 (10 IU) | Plasma C1-INH (same as Cinryze) | IV ~5–10 min | On-demand (acute) | 20 IU/kg per attack |
| Ruconest | J0596 (10 IU) | Recombinant C1-INH | IV ~5 min | On-demand (acute) | 50 IU/kg per attack |
Cinryze vs. Berinert: identical molecule (plasma-derived, pasteurized, nanofiltered C1 esterase inhibitor),
different FDA indications and different HCPCS codes. Cinryze (J0598) bills only against prophylaxis ICD-10 / clinical
documentation. Berinert (J0597) bills only against acute attack documentation. The pharmacy buy-and-bill purchase
is brand-specific — you cannot substitute one carton for the other.
Class shift since 2018: SC therapies (Haegarda 2017, Takhzyro 2018) eliminated infusion chair time for
prophylaxis. Many commercial payers now prefer Takhzyro or Haegarda for new prophy starts; Cinryze remains covered
for established patients, IV-only preference, or Takhzyro/Haegarda failures. Verify per-payer step therapy.
Dosing & unit math FDA label verified May 2026
From FDA prescribing information (BLA 125267).
Adult & adolescent (≥12 years)
- 1,000 IU IV every 3 to 4 days for routine prophylaxis (weight-independent fixed dose)
- Reconstitute with 5 mL Sterile Water for Injection per 500 IU vial → 100 IU/mL solution
- Two 500 IU vials → 10 mL of 100 IU/mL solution
- Infuse at 1 mL/min → ~10-minute infusion for the standard 1,000 IU dose
- 10 IU = 1 billable unit → 1,000 IU = 100 units J0598
Pediatric (6–11 years)
- 500 IU IV every 3 to 4 days for routine prophylaxis
- One 500 IU vial = 50 billable units; infuse 5 mL of 100 IU/mL solution at 1 mL/min over ~5 min
- Not approved for prophylaxis <6 years
Worked example — full year of routine prophylaxis (adult, 1,000 IU q3.5d)
# Dose math — CRITICAL: 10 IU = 1 unit
Dose per infusion: 1,000 IU
Billable units per dose: 1,000 IU ÷ 10 IU/unit = 100 units
Vials per dose: 2 × 500 IU single-dose vials
HCPCS: J0598 · Modifier: JZ · Admin CPT: 96365 (10-min IV non-chemo)
# Annual schedule (q3-4d → ~104 doses/year average)
Total doses: 104
Total billable units (year): 10,400 (104 × 100)
Total drug cost (Q2 2026 ASP+6% × 10,400 units): ~$681,210 before sequestration
Dose per infusion: 1,000 IU
Billable units per dose: 1,000 IU ÷ 10 IU/unit = 100 units
Vials per dose: 2 × 500 IU single-dose vials
HCPCS: J0598 · Modifier: JZ · Admin CPT: 96365 (10-min IV non-chemo)
# Annual schedule (q3-4d → ~104 doses/year average)
Total doses: 104
Total billable units (year): 10,400 (104 × 100)
Total drug cost (Q2 2026 ASP+6% × 10,400 units): ~$681,210 before sequestration
No premedication required
Cinryze is a plasma-derived protein replacement. Hypersensitivity is rare but possible — observe per FDA label. Routine premed (acetaminophen, antihistamine, steroid) is not required. Manage acute infusion reactions symptomatically; consider transition to recombinant Ruconest if reactions to plasma-derived product.
NDC reference FDA NDC Directory verified May 2026
| NDC (10/11-digit) | Package | Use |
|---|---|---|
42227-081-05 / 42227-0081-05 |
500 IU lyophilized powder, single-dose vial — 1 vial per carton (with diluent + transfer device) | Standard adult dose uses 2 cartons per infusion (= 1,000 IU) |
Use 11-digit NDC on the claim form (24A shaded). Convert
42227-081-05 to 11-digit
42227-0081-05 with the N4 qualifier, EA (each) unit of measure, and quantity = number of vials used.
For a 1,000 IU dose: N4 42227-0081-05 EA 2.
Sister Takeda HAE product: Cinryze (J0598, IV prophy) and Firazyr (icatibant, J1744, SC on-demand)
share Takeda OnePath enrollment infrastructure. Some HAE patients carry both: Cinryze prophylaxis + Firazyr rescue.
Phase 2
Code the claim
Non-chemo IV admin (96365), JZ on virtually every claim, HAE-specific ICD-10.
Administration codes CPT verified May 2026
Cinryze is a plasma-derived protein replacement — non-chemotherapy IV admin codes apply.
| Code | Description | When to use |
|---|---|---|
96365 |
IV infusion, for therapy/prophylaxis/diagnosis; initial, up to 1 hour | Primary code for Cinryze. ~10-min infusion fits comfortably inside the 1-hour window. |
96366 |
IV infusion, for therapy/prophylaxis/diagnosis; each additional hour | Rarely needed for Cinryze monotherapy. Pair with 96365 only for combo therapy or extended observation. |
96374 |
IV push (single, initial), ≤15 min | Some payers reclassify Cinryze IV-push billing given the ~10 min infusion time. Verify per payer policy — default is 96365. |
96413 / 96415 |
Chemotherapy IV administration | NOT appropriate. Cinryze is not a chemotherapeutic, monoclonal antibody, or biologic immune modulator. Do not use chemo admin codes. |
Home infusion alternative: Many HAE prophylaxis patients self-administer or have nurse-supervised
home infusion via specialty home infusion vendors (POS 12). Home infusion typically bills S9329 (per diem
infusion administration) plus 99601/99602 nursing visit codes through the home infusion vendor, separate from the
drug claim. UHC and Aetna often steer Cinryze prophy to home infusion to reduce site-of-care cost.
Modifiers CMS verified May 2026
JZ — required on virtually every Cinryze claim
Effective July 1, 2023, CMS requires the JZ modifier on all single-dose container claims when no drug is discarded. Cinryze's standard 1,000 IU prophylaxis dose uses two 500 IU single-dose vials with zero waste (the dose is weight-independent and aligns to whole vials). JZ applies to virtually every adult Cinryze claim, and to most pediatric 500 IU claims as well.
JW — partial-vial waste (rare for Cinryze)
JW reports the discarded portion of a single-dose vial. Because Cinryze prophy dosing is the fixed weight-independent 1,000 IU (or pediatric 500 IU), partial-vial waste is unusual. JW becomes relevant only if the prescriber orders an off-label fractional dose (e.g., 750 IU during a dose taper) that produces partial waste. One of JZ or JW must be on every J0598 claim per CMS's July 2023 single-dose container policy.
Common error: Submitting J0598 with neither JZ nor JW. CMS auto-rejects unmodified single-dose
container claims at the MAC edit layer. Add JZ (no waste) on every standard 1,000 IU prophy claim.
Modifier 25 — same-day E/M
Use modifier 25 on the E/M code when a significant, separately identifiable evaluation and management service is performed on the same day as the infusion (e.g., quarterly HAE specialist visit). Routine pre-infusion clinical check is bundled.
340B modifiers (JG, TB)
For 340B-acquired Cinryze, follow your MAC's current 340B modifier policy. Takeda's HCP coding guide does not provide 340B-specific instructions.
ICD-10-CM for HAE prophylaxis FY2026 verified May 2026
HAE Type I (low antigenic + functional C1-INH) and HAE Type II (normal antigenic, low functional C1-INH).
| ICD-10 | Description | Notes |
|---|---|---|
D84.1 | Defects in the complement system | Primary prophy code — covers C1-INH deficiency (Type I/II HAE) |
D89.49 | Other complement disorder | Alternative supporting code for HAE |
T78.3xxx | Angioneurotic edema (HAE manifestation) | Use for documenting attack history; do NOT use as primary on prophy claim — flags as acute treatment |
T78.40xx | Allergy, unspecified | Avoid — non-specific; payers will deny |
PA documentation expectations: Most payers require (1) HAE Type I or II confirmation by C4, C1-INH
antigen, and C1-INH function lab values; (2) attack history (typically ≥1 attack/month or quality-of-life impact
documented in symptom diary); (3) HAE specialist (allergist/immunologist) consultation. ICD-10 alone is not
sufficient.
Lab values to include in PA: C4 (typically low), C1-INH antigen (low in Type I, normal in Type II),
C1-INH function (low in both). Without these, most major payers issue an information-request denial pending
confirmatory diagnostics.
Site of care & place of service Verified May 2026
UnitedHealthcare and Aetna run aggressive site-of-care UM for HAE prophylaxis drugs. UHC commonly steers Cinryze prophy to home infusion (POS 12) after initial in-clinic doses, given the q3-4d schedule and short infusion time. Aetna's site-of-care policy disfavors HOPD administration for chronic prophylactic biologics.
| Setting | POS | Claim form | Payer steering |
|---|---|---|---|
| Patient home (home infusion) | 12 | CMS-1500 (home infusion vendor) | Often preferred by UHC for chronic prophy schedule |
| Allergy/immunology office | 11 | CMS-1500 / 837P | Acceptable for in-clinic doses |
| Ambulatory infusion suite (AIC) | 49 | CMS-1500 / 837P | Acceptable |
| Hospital outpatient (on-campus) | 22 | UB-04 / 837I | Disfavored after initial induction |
| Hospital outpatient (off-campus PBD) | 19 | UB-04 / 837I | Disfavored |
| Skilled nursing facility | 31/32 | UB-04 / 837I (consolidated billing rules) | Rare; verify SNF Part B coverage |
Self-administration: Some HAE patients are trained for self-administered IV Cinryze at home (with
caregiver support). When self-administered, the drug is dispensed via specialty pharmacy under the medical benefit;
no admin CPT applies. Verify benefit pathway with the patient's plan — medical benefit (buy-and-bill) is more
common than pharmacy benefit for J-coded HAE drugs.
Claim form field mapping Takeda OnePath 2026
| Information | CMS-1500 box | Notes |
|---|---|---|
| NPI | 17b | Rendering provider |
| NDC qualifier + 11-digit NDC + UoM + qty | 24A shaded area | N4 42227-0081-05 EA 2 (2 vials for 1,000 IU dose) |
| HCPCS J0598 + JZ | 24D (drug line) | Always include JZ for standard fixed-dose prophy |
| Drug units | 24G | 100 units per 1,000 IU dose (not 1,000 — common 10x error) |
| CPT 96365 (admin line) | 24D (admin line) | ~10-min IV non-chemo infusion |
| ICD-10 | 21 | D84.1 primary; supporting codes per HAE specialist documentation |
| PA number | 23 | Required by all major payers for HAE biologics |
Phase 3
Get paid
PA confirmation of HAE Type I/II + attack frequency is the gating step for every commercial payer.
Payer policy snapshot Reviewed May 2026
All major payers require PA with HAE Type I/II diagnosis confirmation, attack frequency documentation, and specialist consultation.
| Payer | PA? | Coverage criteria | Site-of-care UM |
|---|---|---|---|
| UnitedHealthcare HAE Medical Drug Policy |
Yes | HAE Type I or II (lab confirmation: C4, C1-INH antigen, C1-INH function); ≥1 attack/month or symptom diary; HAE specialist consult; documented Takhzyro/Haegarda failure may be required for new starts | Aggressive: steers to home infusion (POS 12) after induction |
| Aetna CPB + Medical Drug policies |
Yes | HAE Type I/II diagnosis with lab confirmation; attack frequency; allergist/immunologist consultation | Yes (separate Site-of-Care policy; HOPD disfavored after initial doses) |
| BCBS plans Vary by plan |
Yes | Generally aligned with US HAEA + WAO/EAACI guidelines; lab confirmation + attack history | Plan-specific; many have HAE-class site-of-care steering |
| Cigna / Express Scripts Specialty drug policy |
Yes | Step through Takhzyro or Haegarda for new prophy starts in many plans | Yes; AccredoHealth home infusion preferred |
Step therapy
For new prophy starts, several major commercial payers now require documented Takhzyro (J0593) or Haegarda (J0599) failure or intolerance before approving Cinryze. Established Cinryze patients are typically grandfathered. Verify per-payer current step policy — this evolves rapidly as SC alternatives gain market share.
Specialist requirement
All major payers require consultation with an allergist or immunologist (or hematologist with HAE expertise) for Cinryze approval. PA submissions from PCPs without specialist documentation typically deny.
Medicare reimbursement CMS Q2 2026 (live)
Quarterly ASP from CMS Part B Drug Pricing File. Refreshes automatically each quarter.
Q2 2026 payment snapshot — J0598
Effective April 1 – June 30, 2026 · Based on 4Q25 ASP submissions · Unit basis: 10 IU
ASP + 6%
$65.501
per 10 IU billing unit
1,000 IU dose
$6,550.10
100 units × ASP+6%
500 IU pediatric dose
$3,275.05
50 units × ASP+6%
Annualized cost: 1,000 IU q3.5d ≈ 104 doses/year × $6,550.10 = ~$681,210/year
(Medicare ASP+6%). After ~2% sequestration: ~$663,000/year actual paid. Pediatric 500 IU q3.5d
≈ ~$340,600/year.
Per-IU equivalent: $65.501 / 10 IU = approximately $6.55 per IU. If you see a per-IU
rate quoted, multiply by 10 to compare against the per-billing-unit ASP figure.
Coverage
No NCD specific to C1 esterase inhibitors. Coverage falls under MAC LCDs for biologics + generic Part B drug coverage framework. UnitedHealthcare publishes a public HAE LCD; other MACs cover J0598 for FDA-approved on-label prophylaxis with appropriate ICD-10 (D84.1) and HAE Type I/II lab confirmation.
Code history
- J0598 — permanent code, "Injection, C-1 esterase inhibitor (human), Cinryze, 10 units" — brand-specific HCPCS
- Originally approved as Cinryze under ViroPharma (Oct 2008), acquired by Shire (2014), then Takeda (2019)
Patient assistance — Takeda OnePath Takeda verified May 2026
- Takeda OnePath: 1-866-861-1750 (HAE patient support hub) — benefits investigation, prior authorization assistance, appeal support, nurse education for self-/home-administration
- Cinryze Co-Pay Program: commercial copay support; eligible commercially-insured patients receive first dose free + ongoing copay assistance up to program annual cap (excludes Medicare, Medicaid, federal program patients)
- Takeda Patient Assistance Foundation: free product for uninsured / underinsured patients meeting income requirements
- Bridge supply: Takeda OnePath provides interim doses while PA / appeals are pending, on a case-by-case basis
- Foundations: for Medicare patients, refer to PAN Foundation, HealthWell Foundation, US HAEA Patient Assistance — verify open HAE-funded charity programs quarterly
- Web: cinryze.com / Takeda OnePath HAE support
Need to model what a specific patient will actually pay for Cinryze prophy after copay assistance, deductible,
coinsurance, and OOP max across an entire year? Run a CareCost Estimate — J0598
pre-loaded with Q2 2026 ASP and Takeda OnePath logic.
Phase 4
Fix problems
10x unit overbilling, prophy/acute mis-mapping, and missing JZ are the top three.
Common denials & how to fix them
| Denial reason | Common cause | Fix |
|---|---|---|
| Unit count anomaly / overpayment audit | Billed 1,000 units instead of 100 units for 1,000 IU dose (10x error) | Resubmit corrected claim — J0598 unit basis is 10 IU. 1,000 IU = 100 units. Add this to your billing software's J0598 alert rules. |
| Wrong indication (acute attack billed) | Cinryze (J0598) submitted for acute HAE attack treatment | Cinryze is prophylaxis-only. Re-bill acute attacks under Berinert (J0597) or Ruconest (J0596). Confirm encounter ICD-10 supports prophylaxis (D84.1). |
| JZ missing on single-dose vial claim | Submitted J0598 without JZ or JW modifier | Resubmit with JZ. Required since 7/1/2023 on every claim with no waste. Cinryze 1,000 IU prophy uses two whole 500 IU vials — add JZ. |
| HAE Type I/II not confirmed | PA submitted without C4, C1-INH antigen, C1-INH function lab values | Submit confirmatory labs + HAE specialist note; resubmit PA. Most major payers require all three lab values. |
| Step therapy not met | Cinryze approved as new prophy start without Takhzyro / Haegarda trial | Document SC therapy failure or contraindication; submit appeal with HAE specialist letter. Some payers grandfather established patients. |
| Wrong admin code (96413) | Chemo IV billed instead of non-chemo IV | Resubmit with 96365. Cinryze is a plasma-derived protein replacement, not chemotherapy. |
| Site of care (HOPD) | HOPD administration on commercial plan with home-infusion site-of-care steering | Move to home infusion (POS 12) via specialty home infusion vendor or AIC (POS 49). Submit medical necessity letter if HOPD required. |
| Specialist consultation missing | PA from PCP without allergist/immunologist documentation | Add HAE specialist consult note to PA; resubmit. All major payers require specialist sign-off. |
Frequently asked questions
What is the HCPCS code for Cinryze?
Cinryze is billed under HCPCS J0598 — "Injection, C-1 esterase inhibitor (human), Cinryze,
10 units." One billable unit equals 10 IU, NOT 1 IU. This unusual unit basis is the most common
biller error on J0598 claims. A standard 1,000 IU prophylaxis dose is billed as 100 units
(1,000 IU ÷ 10 IU/unit), not 1,000 units.
How many units do I bill for a 1,000 IU Cinryze dose?
Bill 100 units of J0598 per 1,000 IU dose. Cinryze's billing unit is 10 IU, so
divide the IU dose by 10 to get billable units. Each 500 IU vial = 50 billable units; a typical 1,000 IU prophy
dose uses two 500 IU vials = 100 units. Billing 1,000 units instead of 100 will overpay by 10x and trigger payer
recoupment audits.
Is Cinryze for HAE acute attacks or prophylaxis?
Prophylaxis only. Cinryze is FDA-approved for routine prophylaxis against angioedema attacks in adolescent and adult patients with hereditary angioedema (HAE Type I and Type II). It is NOT indicated for acute HAE attack treatment. For on-demand (acute) treatment, use Berinert (J0597) — plasma-derived C1-INH, the same molecule as Cinryze, different indication — or Ruconest (J0596) recombinant C1-INH IV. Submitting Cinryze claims with acute-attack ICD-10 documentation typically triggers denial.
What administration CPT do I use for Cinryze?
CPT 96365 — "IV infusion, for therapy/prophylaxis/diagnosis; initial, up to 1 hour." Cinryze is
non-chemotherapy (do NOT use 96413). The standard infusion runs ~10 minutes (1 mL/min for 10 mL
reconstituted volume), comfortably inside the 96365 1-hour window. Add 96366 for each additional hour only if
extended for combo or reaction management.
Do I bill JZ or JW for Cinryze?
Bill JZ on virtually every Cinryze claim. Each 500 IU vial is single-dose, and standard prophy dosing
is the fixed weight-independent 1,000 IU q3-4d, which uses exactly two 500 IU vials with zero waste. JW
only applies if the prescriber orders an unusual fractional dose that produces partial-vial waste (rare for Cinryze).
One of JZ or JW must be on every J0598 claim per CMS's July 2023 single-dose container policy.
What is the Medicare reimbursement for J0598?
For Q2 2026, the Medicare Part B payment limit for J0598 is $65.501 per 10 IU billing unit (ASP + 6%) — equivalent to roughly $6.55 per IU. The standard 1,000 IU prophy dose reimburses at approximately $6,550.10 per infusion (100 units × ASP+6%). Annualized cost (q3.5d average): ~104 doses/year = ~$681,200/year drug cost (Medicare ASP+6%). Sequestration (~2%) reduces actual paid to roughly ASP + 4.3%.
How does Cinryze compare to Takhzyro, Haegarda, Berinert, and Ruconest?
All five are HAE drugs but split into prophylaxis vs on-demand and IV vs SC. Prophylaxis: Cinryze (J0598, plasma C1-INH IV q3-4d), Haegarda (J0599, plasma C1-INH SC q3-4d, also Takeda), Takhzyro (J0593, lanadelumab kallikrein mAb SC q2-4w). On-demand (acute attacks): Berinert (J0597, plasma C1-INH IV — same molecule as Cinryze, different indication), Ruconest (J0596, recombinant C1-INH IV). Cinryze and Haegarda are interchangeable in mechanism but Haegarda is SC (no infusion chair time). Many payers now prefer Takhzyro or Haegarda for new prophy starts.
Where do patients get Cinryze financial assistance?
Takeda OnePath at 1-866-861-1750 administers all Cinryze patient support. Programs include the Cinryze Co-Pay Program (commercial insurance — first dose free, ongoing copay assistance up to program cap, excludes Medicare/Medicaid/federal patients), the Takeda Patient Assistance Foundation (free product for uninsured/underinsured meeting income requirements), and bridge-supply programs while PA is pending. For Medicare patients, refer to PAN Foundation, HealthWell Foundation, and US HAEA Patient Assistance — verify open funds quarterly.
Reference
Sources & methodology
Every claim on this page is sourced. Methodology and review history below.
Source documents
- Cinryze (Takeda) HCP & Patient Site
- FDA — Cinryze (C1 esterase inhibitor [human]) Prescribing Information
- CMS — Medicare Part B Drug ASP Pricing File
- UnitedHealthcare — Hereditary Angioedema Medical Drug Policy / LCD
- Aetna CPB — Hereditary Angioedema
- US Hereditary Angioedema Association (HAEA)
- WAO/EAACI — HAE Management Guidelines
- FDA National Drug Code Directory
- HCPCS J0598 reference (CMS Quarterly HCPCS Update)
About this page
We maintain this page as a living reference. Medicare ASP pricing is bound to our underlying CareCost data layer and refreshes automatically when CMS publishes new quarterly files. Coding and policy content is reviewed at least quarterly and updated whenever a source document changes.
Found an error? Email hello@carecostestimate.com.
Refresh cadence
| Element | Cadence | How it's refreshed |
|---|---|---|
| Medicare ASP pricing | Quarterly | Auto-bound to CareCost ASP layer; updates on CMS file release. |
| Payer policies (UHC, Aetna, BCBS, Cigna) | Semi-annual | Manual review against published payer policy documents. |
| HCPCS / CPT / modifier rules | Annual | Reviewed against CMS HCPCS quarterly files and AMA CPT releases. |
| NDC, dosing, FDA label, HAE class lineup | Event-driven | Tied to manufacturer document version + FDA label revision date. HAE class evolves with new entrants (e.g., garadacimab). |
Reviewer
Pending SME review. This page is staff-authored from primary sources (FDA, CMS, manufacturer,
payer documents — all linked above). Editorial review in progress. Until
that review is complete, treat this as a draft reference and verify each cited source for high-stakes claims
— particularly the J0598 10 IU unit basis and prophylaxis-only indication.
Change log
- — Initial publication. ASP data: Q2 2026 ($65.501 / 10 IU billing unit). Takeda OnePath verified 2026. Class context: Cinryze (J0598) vs Haegarda (J0599) vs Takhzyro (J0593) prophy; Berinert (J0597) vs Ruconest (J0596) on-demand. Prominent biller-error callout for 10 IU unit basis.
Methodology
Every claim on this page is sourced inline. Pricing reflects the current CMS Part B Drug ASP Pricing File. Payer policies are read directly from each payer's published medical/pharmacy policy documents. HAE class lineup is verified against current FDA-approved labels and HCPCS quarterly updates. We do not paraphrase from billing-software vendor blogs.