HCPCS
J0223
0.5 mg = 1 unit (UNUSUAL)
Phase 1
Identify what you're billing
Confirm AHP diagnosis (genetic + biochemical), document attack history, line up monitoring before billing.
Acute hepatic porphyria (AHP) treatment landscape Verified May 2026
AHP is a rare set of inherited disorders of heme biosynthesis. Modern care has two pillars: acute attack treatment (IV hemin) and chronic attack prevention (Givlaari).
Acute hepatic porphyria comprises four inherited enzyme deficiencies in the heme biosynthetic pathway: acute intermittent porphyria (AIP, HMBS gene — ~80% of AHP), hereditary coproporphyria (HCP, CPOX), variegate porphyria (VP, PPOX), and δ-aminolevulinic acid dehydratase deficiency porphyria (ADP, ALAD — ultra-rare). Patients present with neurovisceral attacks: severe abdominal pain, autonomic dysfunction, peripheral neuropathy, psychiatric symptoms, and seizures. Attacks are precipitated by drugs, hormones, fasting, alcohol, and stress.
| Therapy | HCPCS | Mechanism | Use case | Manufacturer |
|---|---|---|---|---|
| Givlaari (givosiran) | J0223 |
siRNA targeting ALAS1 (GalNAc-conj.) | Chronic attack prevention — standard of care for recurrent AHP attacks | Alnylam |
| Panhematin (hemin) | J1640 |
Heme replacement (downregulates ALAS1) | Acute attack treatment — IV daily × 4 days | Recordati |
| Normosang (heme arginate) | Not US-approved | Heme replacement | Acute attack (Europe) | Recordati (EU) |
| Liver transplant | Surgical | Removes hepatic source of porphyrin precursors | Refractory severe AHP (rare; pre-Givlaari standard) | n/a |
| Glucose / IV dextrose | Supportive | Suppresses ALAS1 induction (weak) | Mild attacks; bridge to hemin | n/a |
Why Givlaari changed the standard of care: Before Givlaari, patients with recurrent AHP
attacks (≥4/year) often required prophylactic weekly hemin infusions, accepting major complications
(iron overload, central line infections, vascular access loss). The ENVISION trial (NEJM 2020) showed
givosiran reduced annualized attack rate by ~74% vs placebo. Givlaari is now the established first-line
therapy for chronic attack prevention.
Alnylam siRNA portfolio — Givlaari in context Verified May 2026
Givlaari shares Alnylam's GalNAc-conjugated siRNA platform with Amvuttra, Oxlumo, and Leqvio. Same delivery technology, four different J-codes, four different unit bases.
All four Alnylam SC siRNAs use the same N-acetylgalactosamine (GalNAc) conjugate strategy: the siRNA is linked to triantennary GalNAc, which binds the asialoglycoprotein receptor (ASGPR) on hepatocytes, enabling efficient liver-specific delivery. Each siRNA targets a different gene, supports a different disease, and carries a different J-code with a different unit basis — pay attention to the per-code descriptor.
| Drug | HCPCS | Unit basis | Target | Indication | Route / interval | Q2 2026 ASP+6% |
|---|---|---|---|---|---|---|
| Givlaari (givosiran) | J0223 |
0.5 mg = 1 unit | ALAS1 | AHP (acute hepatic porphyria) | SC monthly | $120.983 / 0.5 mg |
| Onpattro (patisiran) | J0222 |
0.1 mg = 1 unit | TTR (LNP delivery) | hATTR-PN | IV q3wk (~17/yr) | ~$100.896 / 0.1 mg |
| Amvuttra (vutrisiran) | J0225 |
1 mg = 1 unit | TTR (GalNAc) | hATTR-PN + ATTR-CM | SC q3mo (4/yr) | $5,019.273 / mg |
| Oxlumo (lumasiran) | J0224 |
0.5 mg = 1 unit | HAO1 (glycolate oxidase) | Primary hyperoxaluria type 1 (PH1) | SC monthly × 3, then q3mo | Verify CMS file |
| Leqvio (inclisiran) | J1306 |
1 mg = 1 unit | PCSK9 | ASCVD / heFH (LDL-C lowering) | SC day 0, day 90, then q6mo | (Pharmacy benefit common) |
Givlaari (J0223) and Oxlumo (J0224) both use the unusual 0.5 mg = 1 unit basis. Amvuttra
(J0225) and Leqvio (J1306) use the standard 1 mg = 1 unit basis. When a practice mixes Alnylam products,
the most common error is reusing the unit math from one product on another. Always read the J-code
descriptor literally before computing units.
Same Alnylam Assist patient support program covers all four medical-benefit Alnylam siRNAs
(Givlaari, Onpattro, Amvuttra, Oxlumo). One enrollment phone line: 1-833-256-2748.
Leqvio uses a different Novartis/Alnylam co-promotion support pathway.
Dosing & unit math FDA label 2019
Weight-based monthly SC. Watch the 0.5 mg unit basis — the single biggest J0223 billing error.
Adult dosing
- 2.5 mg/kg subcutaneously once monthly (every 4 weeks) — weight-based, lifelong therapy
- 189 mg/mL single-dose vial; partial-vial use creates real waste
- Administered by HCP in clinic; abdomen, thigh, or upper arm; rotate sites
- 1 unit = 0.5 mg (NOT 1 mg) — double total mg to derive units
- ~13 doses per year (every 4 weeks × 52 weeks)
- If a dose is missed, administer as soon as possible and resume on the original monthly schedule
- Dose modification (reduce to 1.25 mg/kg) for grade ≥3 transaminase elevation; permanent discontinuation for severe drug-induced liver injury
Worked example — 70 kg adult
# Compute monthly dose
Weight: 70 kg · Dose: 2.5 mg/kg
Total mg per dose = 70 × 2.5 = 175 mg
# Convert mg to J0223 units (1 unit = 0.5 mg)
Units = 175 mg ÷ 0.5 mg/unit = 350 units
HCPCS: J0223 · Modifier: JZ (full vial, no waste) · Admin: 96372
# Reimbursement at Q2 2026 ASP+6%
Per dose = 350 units × $120.983 = $42,344.05
Annual (~13 doses) = ~$550,469 before sequestration
Weight: 70 kg · Dose: 2.5 mg/kg
Total mg per dose = 70 × 2.5 = 175 mg
# Convert mg to J0223 units (1 unit = 0.5 mg)
Units = 175 mg ÷ 0.5 mg/unit = 350 units
HCPCS: J0223 · Modifier: JZ (full vial, no waste) · Admin: 96372
# Reimbursement at Q2 2026 ASP+6%
Per dose = 350 units × $120.983 = $42,344.05
Annual (~13 doses) = ~$550,469 before sequestration
Worked example — 60 kg adult (partial vial — JW applies)
# Compute monthly dose
Weight: 60 kg · Dose: 2.5 mg/kg
Total mg administered = 60 × 2.5 = 150 mg
Units administered = 150 ÷ 0.5 = 300 units (J0223 + JZ)
# Vial size: 189 mg/mL single-dose vial
Vial nominal content used: ~150 mg / ~189 mg
Discarded: ~39 mg = 78 units
Bill discard separately: J0223 + JW · Document waste in chart
# Total units billed for this dose
300 (administered, JZ) + 78 (waste, JW) = 378 units
Weight: 60 kg · Dose: 2.5 mg/kg
Total mg administered = 60 × 2.5 = 150 mg
Units administered = 150 ÷ 0.5 = 300 units (J0223 + JZ)
# Vial size: 189 mg/mL single-dose vial
Vial nominal content used: ~150 mg / ~189 mg
Discarded: ~39 mg = 78 units
Bill discard separately: J0223 + JW · Document waste in chart
# Total units billed for this dose
300 (administered, JZ) + 78 (waste, JW) = 378 units
The 50% under-billing trap. A practice accustomed to "1 mg = 1 unit" J-codes will
instinctively bill 175 units instead of 350 units for a 175 mg dose. This UNDER-bills by exactly
50% — about $21,000 missed per dose, $275,000+ per patient per year. The fix: always read the
descriptor ("Injection, givosiran, 0.5 mg") and double total mg to derive units.
Pre-treatment testing & AHP confirmation Verified May 2026
Givlaari PA universally requires biochemical + genetic confirmation of AHP plus documented attack history.
Most payers will not approve Givlaari without both biochemical (urine PBG/ALA elevation, ideally during or shortly after an attack) and genetic (pathogenic variant in HMBS, CPOX, PPOX, or ALAD) confirmation. A documented history of recurrent attacks — typically ≥2 attacks per year requiring hospitalization, IV hemin (Panhematin), or urgent care contact — is also standard.
| Test | CPT / HCPCS | Use case |
|---|---|---|
| Urine porphobilinogen (PBG), quantitative | 84110 | Biochemical confirmation of acute attack — elevated PBG is hallmark of AIP |
| Urine δ-aminolevulinic acid (ALA), quantitative | 82135 | Elevated in all AHPs except ADP-only patients |
| Urine total porphyrins (with fractionation) | 84120 / 84126 | Differentiate AIP vs HCP vs VP — coproporphyrin and uroporphyrin patterns |
| Plasma porphyrin scan (fluorescence) | 84120 | VP-specific peak at 624–626 nm |
| Fecal porphyrins | 84126 | HCP / VP differentiation |
| HMBS gene sequencing (AIP) | 81406 Tier 2 Level 7 | Genetic confirmation of AIP — most common AHP (~80%) |
| CPOX gene sequencing (HCP) | 81479 unlisted molecular | Genetic confirmation of HCP |
| PPOX gene sequencing (VP) | 81479 unlisted molecular | Genetic confirmation of VP |
| ALAD gene sequencing (ADP) | 81479 unlisted molecular | Genetic confirmation of ADP (ultra-rare) |
| AHP gene panel (multi-gene) | 81479 or panel CPT | Single-test confirmation when porphyria type uncertain |
| Family cascade testing | Variant-specific (81403) | First-degree relatives of AHP patients |
Submit attack history with PA. Itemize each attack with date, hospitalization or urgent
care contact, IV hemin (Panhematin) doses, and triggering factor when known. Most payers expect ≥2
documented attacks per year over the prior 6–12 months. ER/hospital records, infusion logs, and
outpatient clinic notes are all acceptable.
Specialist consultation: Most payers require prescription by or consultation with a
hepatologist, clinical geneticist, hematologist, or porphyria specialist. The American Porphyria
Foundation maintains a directory of porphyria centers; payers may accept consultation notes from one
of those centers as the specialist requirement.
Monitoring protocol — LFTs + SCr FDA label 2019
Required by FDA label for safety. Document monitoring in chart and PA continuation-of-therapy submissions.
| Monitor | Cadence | Action threshold |
|---|---|---|
| Hepatic transaminases (ALT, AST) | Baseline, then monthly × 6 months, then as clinically indicated | Increase >3× ULN → consider dose interruption / reduction; severe DILI → discontinue |
| Total bilirubin, alkaline phosphatase | Baseline + with LFTs | Hyperbilirubinemia or ALP elevation triggers further hepatic workup |
| Serum creatinine / eGFR | Baseline + every 6 months | Decreased eGFR observed in clinical trials; monitor for renal trends |
| Urine PBG, ALA | Periodic (e.g., quarterly during year 1, then annually) | Disease activity monitoring (not a stop-rule but supports continuation-of-therapy PA) |
| Anaphylaxis observation | Each injection visit (clinic observation) | Anaphylaxis is rare but reported; observe for ~30–60 min post-injection per practice protocol |
| Injection-site reactions | Each visit; chart photos as needed | Erythema, pain, pruritus typical; rotate sites |
LFT monitoring is non-negotiable. The FDA label specifically calls out hepatic
transaminase elevations — including elevations >3× ULN — observed in clinical
trials. Some patients required dose interruption or discontinuation. Continuation-of-therapy PA
submissions should include the most recent LFT panel. Without documented monitoring, payer audits
may recoup paid claims.
Bill the labs: ALT (
84460), AST (84450), bilirubin total
(82247), ALP (84075), creatinine (82565), eGFR (calculated, no
separate code). Urine PBG (84110), ALA (82135). These are routine and
usually adjudicate without issue, but document the linkage to J0223 monitoring in the encounter note.
NDC reference FDA NDC Directory verified May 2026
| NDC (10/11-digit) | Package | Use |
|---|---|---|
71336-1001-1 / 71336-1001-01 |
189 mg/mL single-dose vial — 1 vial per carton | Standard adult dose (volume drawn per weight-based calculation) |
Use carton-level NDC. Payers expect the carton NDC on the claim form; product-level NDC
will trigger denial. NDC unit of measure = ML (milliliters). Always verify the most current NDC against
Alnylam's billing guide and the FDA NDC Directory at billing time.
Phase 2
Code the claim
96372 SC admin (NOT IV/chemo). JZ on full-vial claims; JW for documented partial-vial waste.
Administration codes CPT verified May 2026
Givosiran is a non-chemotherapy subcutaneous injection by HCP — 96372 is the correct admin code.
| Code | Description | When to use |
|---|---|---|
96372 |
Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular | Primary code for Givlaari. SC injection by HCP; non-chemotherapy. |
96365 |
Therapeutic IV infusion; up to 1 hour | NOT appropriate for Givlaari. Wrong route — givosiran is SC, not IV. |
96413 |
Chemotherapy administration, IV infusion technique | NOT appropriate for Givlaari. Wrong drug class (siRNA is not chemo) and wrong route (SC, not IV). |
96401 |
Chemotherapy administration, SC/IM; non-hormonal anti-neoplastic | NOT appropriate for Givlaari. Wrong drug class — givosiran is not anti-neoplastic chemotherapy. |
Why 96372 (not 96365 or 96413): CPT 96372 is the correct code for clinic-administered
therapeutic SC/IM injections of non-chemotherapy drugs. Givosiran is administered SC by HCP (not
self-injected at home), is not anti-neoplastic, and is not infused IV. 96372 pays appropriately for the
~5–10 minute injection encounter plus the brief observation period.
Modifiers CMS verified May 2026
JZ — full-vial claims (no waste)
Effective July 1, 2023, CMS requires the JZ modifier on all single-dose container claims when no drug is discarded. JZ applies on Givlaari claims when the patient's calculated dose consumes the full 189 mg vial volume with no residual.
JW — partial-vial waste (weight-based dosing)
Givlaari is dosed at 2.5 mg/kg from a 189 mg/mL single-dose vial — partial-vial use is common for patients whose calculated dose is less than the full vial content. Bill the discarded volume separately on its own claim line with the JW modifier and document the discarded amount in the chart (date, time, witness, calculated discard in mg and units). JW is required by CMS for documented single-dose container waste.
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 injection (e.g., monthly LFT review with dose adjustment decision, attack-trigger counseling).
340B modifiers (JG, TB)
For 340B-acquired Givlaari, follow your MAC's current 340B modifier policy. Alnylam's billing guide does not provide 340B-specific instructions for J0223.
JZ vs JW worked example: 70 kg patient, 175 mg dose from a 189 mg vial. ~14 mg
discarded (= 28 units). Bill: line 1 J0223 350 units JZ (administered)? — no, this is single-dose
container with documented waste, so use JW for the discarded portion. Many MACs accept:
line 1 J0223 350 units (administered, no modifier or JZ if entire vial accounted), line 2 J0223 28 units
JW (waste). When in doubt, read your MAC's current discarded-drug billing instructions before splitting.
ICD-10-CM by porphyria type FY2026 verified May 2026
Most AHP patients code to E80.21 (acute intermittent porphyria) or E80.20 (porphyria, unspecified). Attack-related codes are supplementary, not primary, for chronic Givlaari therapy.
| Indication / scenario | ICD-10 | Notes |
|---|---|---|
| Acute intermittent porphyria (AIP) — most common AHP | E80.21 | Primary for the majority of Givlaari patients (HMBS gene) |
| Porphyria, unspecified (general AHP not yet typed) | E80.20 | Acceptable when biochemical AHP confirmed but genetic typing pending |
| Other porphyria (HCP, VP, ADP) | E80.29 | For hereditary coproporphyria, variegate porphyria, δ-ALAD deficiency |
| Acute encephalopathy (during attack only, supplementary) | G93.49 | NOT primary for chronic Givlaari therapy — supplementary if attack-related encephalopathy documented |
| Abdominal pain (during attack only, supplementary) | R10.x | NOT primary for chronic prevention — only relevant during acute attack visits |
| Polyneuropathy in AHP attack | G62.81 + E80.2x | Supplementary if attack-related neuropathy documented |
| Family history of porphyria | Z83.49 | For family cascade screening encounters |
| Long-term use of biologic (drug surveillance) | Z79.899 | Supplementary for chronic siRNA therapy |
Don't use attack symptom codes as primary for chronic Givlaari claims. Givlaari is
attack-prevention therapy, not attack treatment. Primary diagnosis on every J0223 claim should be the
underlying AHP type (E80.21 for AIP, E80.20 unspecified, or E80.29 for HCP/VP/ADP). G93.49 acute
encephalopathy and R10.x abdominal pain are appropriate during acute attack visits but not as the
primary Dx for the chronic Givlaari injection encounter.
Site of care & place of service Verified May 2026
Because Givlaari is a quick SC injection with a brief in-clinic observation period for anaphylaxis, it is well-suited to physician office and clinic settings. Hospital outpatient is generally not necessary and may be disfavored by commercial site-of-care UM. Home administration is uncommon and not preferred due to anaphylaxis risk and the need for monthly LFT monitoring at the same encounter.
| Setting | POS | Claim form | Payer steering |
|---|---|---|---|
| Hepatology / hematology / specialist office | 11 | CMS-1500 / 837P | Preferred by commercial UM |
| Ambulatory infusion suite (AIC) | 49 | CMS-1500 / 837P | Preferred |
| Hospital outpatient (on-campus) | 22 | UB-04 / 837I | Disfavored after first dose |
| Hospital outpatient (off-campus PBD) | 19 | UB-04 / 837I | Disfavored |
| Patient home | 12 | CMS-1500 (with home infusion vendor) | Allowed by some payers; uncommon — LFT/SCr lab access at same encounter typically preferred in clinic |
Site-of-care opportunity: Pair the monthly Givlaari injection visit with the
first-6-months LFT panel at the same encounter. After month 6, dosing visits can shift to a longer
interval between full lab visits, but anaphylaxis observation continues every dose.
Claim form field mapping Alnylam Mar 2026
From Alnylam Assist HCP coding & reimbursement materials.
| Information | CMS-1500 box | Notes |
|---|---|---|
| NPI | 17b | Rendering provider (hepatology, hematology, or porphyria specialist) |
| NDC qualifier + 11-digit NDC + UoM + qty | 24A shaded area | N4 + carton NDC + ML + volume drawn (e.g., 0.93 mL for 175 mg from 189 mg/mL vial) |
| HCPCS J0223 + JZ | 24D (drug line, administered) | JZ if no waste; otherwise see JW row below |
| Drug units (administered) | 24G | Total mg administered ÷ 0.5. e.g., 175 mg = 350 units |
| HCPCS J0223 + JW (separate line) | 24D (drug line, waste) | For documented partial-vial discard. e.g., 14 mg discarded = 28 units JW |
| CPT 96372 (admin line) | 24D (admin line) | Therapeutic SC injection, non-chemo |
| ICD-10 (primary) | 21 | E80.21 AIP (most common); E80.20 if type unspecified; E80.29 for HCP/VP/ADP |
| ICD-10 (supplementary) | 21 | Z79.899 long-term biologic; G62.81 if neuropathy documented |
| PA number | 23 | Required by all major payers |
Phase 3
Get paid
PA always required. Genetic + biochemical confirmation + attack history must be in the package up front.
Payer policy snapshot Reviewed May 2026
All major payers require PA. Workup completeness drives approval speed.
| Payer | PA? | Key criteria |
|---|---|---|
| UnitedHealthcare Medical Drug Coverage Policy |
Yes | AHP dx + genetic confirmation (HMBS/CPOX/PPOX/ALAD) + biochemical (urine PBG/ALA elevation) + documented attack history (typically ≥2 attacks/year requiring hospitalization, IV hemin, or urgent care) + specialist Rx |
| Aetna CPB / Medical Drug policy |
Yes | Confirmed AHP + recurrent attacks documented; continuation requires demonstrated reduction in attack frequency |
| BCBS plans Vary by plan |
Yes | Generally aligned with FDA label + American Porphyria Foundation / EHC guidance |
| Medicare (MAC LCDs) | Coverage criteria via MAC | FDA label-aligned; generally covered for AHP attack reduction with appropriate documentation |
Required PA documentation
- Genetic confirmation: HMBS (AIP), CPOX (HCP), PPOX (VP), or ALAD (ADP) variant report — the laboratory report itself, not just a clinician note stating "positive"
- Biochemical confirmation: Urine PBG and ALA quantitative results, ideally during or shortly after a documented attack
- Attack history: Itemized attack log with dates, hospitalization/UC contacts, IV hemin (Panhematin) doses, triggering factors. ER and hospital records, infusion logs, outpatient notes all acceptable
- Specialist consultation note (hepatology, hematology, clinical genetics, or porphyria center)
- Baseline LFTs + SCr documented before starting therapy
- Plan for monthly LFT monitoring × 6 months and SCr q6mo
Continuation of therapy
Most payers re-authorize annually. Continuation packages should include: most recent LFT and SCr results within payer-required windows, documented reduction in attack frequency vs pre-treatment baseline (often quantified as percent reduction), and ongoing specialist oversight. The ENVISION trial showed ~74% reduction in annualized attack rate — payer benchmarks for continuation often track this magnitude.
Medicare reimbursement CMS Q2 2026 (live)
Quarterly ASP from CMS Part B Drug Pricing File. Refreshes automatically each quarter. Note 0.5 mg unit basis for all calculations.
Q2 2026 payment snapshot — J0223
Effective April 1 – June 30, 2026 · Based on 4Q25 ASP submissions
ASP + 6%
$120.983
per 0.5 mg unit / per billed unit
175 mg dose (70 kg)
$42,344.05
350 units × ASP+6%
Annual cost (~13 doses, 70 kg)
$550,472.65
13 × 175 mg per year
Annualized cost: 70 kg patient at 2.5 mg/kg monthly × 13 doses =
~$550,000/year (Medicare ASP+6%). After ~2% sequestration: ~$536,500/year actual
paid. Costs scale linearly with weight: a 90 kg patient (225 mg/dose, 450 units) is
~$707,000/year. Among the higher annual per-patient drug costs in the Part B catalog due to weight-based
dosing and lifelong indication.
Per-mg vs per-unit math: J0223 is priced per 0.5 mg unit. To convert to a per-mg
figure for cross-product comparisons, multiply by 2: $120.983 × 2 =
~$241.97 per mg. Total mg billed per year is the same regardless of unit basis;
only the unit count differs.
Coverage
No NCD specific to givosiran. Coverage falls under MAC LCDs for biologics and the generic drug-coverage framework. All MACs cover J0223 for the FDA-approved AHP indication with appropriate ICD-10 (E80.21 AIP / E80.20 unspecified / E80.29 other AHP), genetic + biochemical confirmation, attack history, and ongoing monitoring documentation.
Code history
- J0223 — permanent code, "Injection, givosiran, 0.5 mg." Pre-permanent-code period used unclassified
J3490with manufacturer NDC.
Patient assistance — Alnylam Assist Alnylam verified May 2026
- Alnylam Assist: 1-833-256-2748 / alnylam.com/alnylam-assist — benefits investigation, prior authorization assistance, appeal support, dosing logistics
- Alnylam Assist Co-Pay Program: commercial copay support for eligible commercially-insured patients (excludes Medicare, Medicaid, federal program patients)
- Alnylam Patient Foundation: independent 501(c)(3) providing free product for uninsured / underinsured patients meeting income requirements
- Foundations: for Medicare patients, refer to PAN Foundation, HealthWell Foundation — verify open AHP / porphyria funds quarterly (these funds open and close based on grant cycles)
- American Porphyria Foundation (porphyriafoundation.org): patient education, attack-trigger drug database, porphyria specialist directory
- Same Alnylam Assist program covers Onpattro, Amvuttra, and Givlaari
Need to model what a specific patient will actually pay after copay assistance, deductible, coinsurance,
and OOP max? Run a CareCost Estimate — J0223 pre-loaded.
Phase 4
Fix problems
The 0.5 mg unit basis and incomplete AHP confirmation drive most J0223 problems.
Common denials & how to fix them
| Denial / problem | Common cause | Fix |
|---|---|---|
| Under-payment of ~50% — not technically a denial | Practice billed total mg as units (e.g., 175 units instead of 350 units) | Resubmit corrected claim with units = mg ÷ 0.5. Self-audit all prior J0223 claims for the same error pattern. |
| Genetic testing not documented | PA submitted without HMBS/CPOX/PPOX/ALAD variant report | Order AHP gene panel or single-gene sequencing first (CPT 81406 HMBS, or 81479 unlisted molecular for HCP/VP/ADP); submit lab report with PA |
| Biochemical confirmation missing | Urine PBG / ALA results not in PA package | Order quantitative urine PBG (84110) and ALA (82135), ideally during or shortly after an attack; submit quantitative results |
| Attack history insufficient | Fewer than 2 documented attacks/year, or attacks not adequately documented | Compile itemized attack log with dates, hospitalization/UC records, hemin doses, triggers; obtain ER records as needed |
| Wrong admin code (96365) | IV admin code billed instead of SC | Resubmit with 96372. Givosiran is SC, not IV. |
| Wrong admin code (96413 / 96401) | Chemotherapy admin billed instead of non-chemo SC | Resubmit with 96372. Givosiran is not chemotherapy and not anti-neoplastic. |
| Wrong primary ICD-10 (R10.x or G93.49) | Attack symptom code used as primary for chronic prevention claim | Resubmit with E80.21 (AIP), E80.20 (unspecified), or E80.29 (HCP/VP/ADP) as primary; symptom codes are supplementary |
| JZ missing on full-vial claim | Single-dose vial claim without JZ | Resubmit with JZ. Required since 7/1/2023 on every claim with no waste. |
| JW missing on partial-vial discard | Discarded portion not billed separately | Add separate line with J0223 + JW + discarded units; document waste in chart |
| Continuation denied for insufficient response | Re-authorization without documented attack frequency reduction | Submit attack log showing reduction vs pre-treatment baseline; ENVISION-magnitude (~74% reduction) is a useful benchmark |
| Continuation denied for missing monitoring | LFT or SCr labs not within payer-required window | Order labs (ALT 84460, AST 84450, SCr 82565); submit results with continuation PA |
| Wrong NDC format (product-level) | Product NDC submitted instead of carton NDC | Use carton NDC: 71336-1001-1. |
| Specialist requirement not met | PCP or non-specialty provider as prescriber | Add hepatology, hematology, clinical genetics, or porphyria-center consult to PA |
Frequently asked questions
What is the HCPCS code for Givlaari?
Givlaari (givosiran) is billed under HCPCS J0223 — "Injection, givosiran, 0.5 mg."
This is an unusual unit basis: 1 unit = 0.5 mg, NOT 1 mg. For a 70 kg patient at
2.5 mg/kg, the dose is 175 mg, which equals 350 units of J0223. Givlaari is
administered subcutaneously by HCP once monthly for life in adults with acute hepatic porphyria (AHP).
How many units do I bill for a Givlaari dose?
Units = (patient weight in kg × 2.5 mg/kg) ÷ 0.5 mg per unit. For a 70 kg patient: 70 × 2.5 = 175 mg = 350 units. For a 60 kg patient: 60 × 2.5 = 150 mg = 300 units. The 0.5 mg per unit basis is the single biggest billing-error trap for J0223 — practices that mistakenly bill 1 unit per mg will UNDER-bill by 50% and miss substantial reimbursement. Always divide total mg by 0.5 to derive units.
What administration CPT do I use for Givlaari?
CPT 96372 — therapeutic SC/IM injection, non-chemo. Do NOT bill 96365 (therapeutic IV;
wrong route), 96413 (chemo IV; wrong drug class), or 96401 (chemo SC; givosiran is not anti-neoplastic).
Givosiran is a clinic-administered SC injection of a non-chemotherapy biologic, so 96372 is the correct code.
What is the dosing schedule for Givlaari?
2.5 mg/kg subcutaneously once monthly (every 4 weeks) — weight-based, lifelong therapy; approximately 13 doses per year. No premedication required. LFT monitoring is required at baseline, then monthly × 6 months, then as clinically indicated. Serum creatinine is monitored at baseline and every 6 months.
What is the FDA-approved indication for Givlaari?
Treatment of acute hepatic porphyria (AHP) in adults to reduce the frequency of porphyria attacks. AHP includes acute intermittent porphyria (AIP, the most common, ~80% of AHP), hereditary coproporphyria (HCP), variegate porphyria (VP), and δ-aminolevulinic acid dehydratase deficiency porphyria (ADP). FDA approved November 20, 2019 (NDA 212194). Givlaari is the first and only siRNA therapy for AHP.
Is genetic testing required for Givlaari?
Most payer PA criteria require both biochemical and genetic confirmation of AHP. Biochemical: documented elevation in urine porphobilinogen (PBG) and δ-aminolevulinic acid (ALA), typically during or shortly after an attack. Genetic: pathogenic variant in HMBS (AIP), CPOX (HCP), PPOX (VP), or ALAD (ADP). Documented attack history (typically ≥2 attacks/year requiring hospitalization, IV hemin, or urgent care) is also required. Specialist consultation is generally required.
What is the Medicare reimbursement for J0223?
For Q2 2026, the Medicare Part B payment limit for J0223 is $120.983 per 0.5 mg unit (ASP + 6%). On a per-mg basis this equals $241.97 per mg. For a 70 kg patient at 2.5 mg/kg (175 mg = 350 units) per dose, reimbursement is approximately $42,344.05. Annualized (13 doses/year): approximately $550,472.65. Sequestration (~2%) reduces actual paid to roughly ASP + 4.3%. ASP is updated quarterly by CMS.
What monitoring is required during Givlaari therapy?
FDA label requires: (1) hepatic transaminases (ALT, AST) at baseline, then monthly for the first 6 months, then as clinically indicated — elevations >3× ULN have been observed and may require dose interruption or discontinuation; (2) serum creatinine and eGFR at baseline and every 6 months — eGFR decreases observed in clinical trials; (3) periodic urine PBG and ALA to monitor disease activity (not strictly required but routinely done); (4) anaphylaxis monitoring at each injection visit (rare but reported).
Is Givlaari related to Onpattro and Amvuttra?
Yes — all three are Alnylam siRNA therapies using GalNAc-conjugated delivery to hepatocytes (well, Onpattro uses a lipid nanoparticle, but Givlaari and Amvuttra both use the GalNAc conjugate). They share the Alnylam Assist patient support program (1-833-256-2748). Different J-codes, different unit bases (J0223 = 0.5 mg/unit, J0222 = 0.1 mg/unit, J0225 = 1 mg/unit), different indications. Practices that bill multiple Alnylam siRNAs should always read the specific J-code descriptor before computing units. See the Alnylam siRNA portfolio table.
Reference
Sources & methodology
Every claim on this page is sourced. Methodology and review history below.
Source documents
- Alnylam Assist — Givlaari HCP coding & reimbursement
- DailyMed — GIVLAARI (givosiran) Prescribing Information
- FDA Givlaari label PDF (NDA 212194)
- ENVISION trial — Givosiran for Acute Intermittent Porphyria (NEJM 2020)
- CMS — Medicare Part B Drug ASP Pricing File
- SEER CanMED — HCPCS J0223 reference
- UnitedHealthcare — Medical Drug Coverage Policy (givosiran)
- Aetna — Clinical Policy Bulletins (acute hepatic porphyria treatments)
- American Porphyria Foundation — AHP patient + provider resources
- European Porphyria Network — AHP clinical guidance
- FDA National Drug Code Directory
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) | Semi-annual | Manual review against published payer policy documents. |
| HCPCS / CPT / modifier rules + diagnostic test codes | Annual | Reviewed against CMS HCPCS quarterly files, AMA CPT releases. |
| NDC, dosing, FDA label, indication list | Event-driven | Tied to manufacturer document version + FDA label revision date. Major events: FDA approval Nov 2019. |
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.
Change log
- — Initial publication. ASP data: Q2 2026. Manufacturer source: Alnylam Assist Mar 2026. FDA label: NDA 212194 (November 2019). 0.5 mg unit basis prominently flagged as primary biller error trap. Alnylam siRNA portfolio comparison (Givlaari / Onpattro / Amvuttra / Oxlumo / Leqvio). Monitoring protocol (LFT monthly × 6 + SCr q6mo) detailed.
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. Indication list is verified against the current FDA label revision. We do not paraphrase from billing-software vendor blogs.