HCPCS
Q5134
1 mg = 1 unit
Phase 1
Identify what you're billing
Confirm the right code, dose, and REMS program before building the claim.
Tyruko vs. Tysabri — Q5134 vs. J2323 FDA verified Oct 2025
Same molecule, same dose, same indications — different HCPCS, different NDC, different REMS.
Tyruko is the first FDA-approved biosimilar to Tysabri (natalizumab). The molecule, dose, and indications are identical — but the billing code, NDC, and REMS program are separate. A site that administers both products must enroll in both REMS independently and submit claims under the correct HCPCS code per dose.
| Tyruko (biosimilar) | Tysabri (reference) | |
|---|---|---|
| HCPCS | Q5134 | J2323 |
| Generic | natalizumab-sztn | natalizumab |
| NDC (300 mg vial) | 61314-0543-94 | 59075-0730-15 |
| Manufacturer | Sandoz (Novartis) | Biogen |
| FDA approval | August 24, 2023 (BLA 761322) | November 2004 |
| Vial | 300 mg / 15 mL SDV (identical) | 300 mg / 15 mL SDV |
| Dose | 300 mg IV q4wk (identical) | 300 mg IV q4wk |
| Indications | RRMS + Crohn's (identical) | RRMS + Crohn's |
| REMS program | TYRUKO REMS (Sandoz, 800-489-7856) | TOUCH (Biogen, 800-456-2255) |
| Q2 2026 ASP+6% | $24.321/mg | $24.321/mg (currently identical) |
Pricing parity: as of Q2 2026, CMS reports identical ASP+6% rates for Tyruko ($24.321/mg)
and Tysabri ($24.321/mg). This is unusual for biosimilars, which typically launch at a discount; expect
Tyruko's per-mg rate to drift below Tysabri's as biosimilar uptake matures. Many commercial payers list
both as preferred MS alternatives in 2026 (Aetna confirmed).
Different REMS, mandatory enrollment: a clinician who has Tysabri TOUCH certification
cannot prescribe Tyruko without separate TYRUKO REMS enrollment. Same for the infusion site and the
patient. This is a common operational gotcha for sites that previously only carried Tysabri.
Dosing & unit math FDA label Oct 2025
From FDA prescribing information, label revised October 2025 (BLA 761322).
FDA-labeled dose schedule (verbatim):
"300 mg infused intravenously over one hour, every four weeks."
- Frequency: every 4 weeks (q4wk), no loading
- Per dose: 1 vial (300 mg / 15 mL) diluted in 100 mL 0.9% NaCl
- Infusion rate: ~5 mg/min, ~1 hour total
- Post-infusion observation: 1 hour for the first 12 infusions; clinical judgment thereafter
- 1 mg = 1 unit: bill 300 units of Q5134 per dose
- No premedication routinely required (different from anti-CD20 MS DMTs)
Worked example — first-year billing
# Every 4 weeks — 300 mg infusion (1 hour)
Drug units billed: 300
HCPCS: Q5134 · Modifier: verify JZ per CMS list · Vials: 1 × 300 mg
Admin: 96365 (1 hour, therapeutic IV)
# Year-1 dose count: 13 doses (q4wk for 52 weeks)
# Total year-1 drug units billed: 3,900 (13 × 300)
Drug units billed: 300
HCPCS: Q5134 · Modifier: verify JZ per CMS list · Vials: 1 × 300 mg
Admin: 96365 (1 hour, therapeutic IV)
# Year-1 dose count: 13 doses (q4wk for 52 weeks)
# Total year-1 drug units billed: 3,900 (13 × 300)
Required pre-infusion checks (per TYRUKO REMS)
- PML symptom screening (cognitive, motor, visual changes)
- Confirm patient is enrolled in TYRUKO REMS and current on monitoring
- Anti-JCV antibody status documented (drives PML risk stratification)
- For long-term users (>2 yr): heightened MRI vigilance
- No active infection
NDC reference FDA NDC Directory verified May 2026
| NDC (10-digit) | NDC (11-digit, claim form) | Package | Manufacturer |
|---|---|---|---|
61314-543-94 |
61314-0543-94 |
300 mg natalizumab-sztn in 15 mL (20 mg/mL), single-dose vial — only SKU | Sandoz Inc. |
11-digit NDC required on most claim forms. Pad the middle segment with a leading zero:
61314-0543-94. Use the
N4 qualifier in CMS-1500 Box 24A and UB-04 Box 43.
TYRUKO REMS — mandatory enrollment Sandoz verified May 2026
Tyruko is available only through TYRUKO REMS — a Sandoz program separate from Tysabri's TOUCH.
Because of natalizumab's PML risk, FDA requires both products to operate under restricted-distribution Risk Evaluation and Mitigation Strategy programs. Tyruko's REMS is operated by Sandoz; Tysabri's TOUCH is operated by Biogen. The programs do not interoperate.
Who must enroll
- Prescribers: certified through TYRUKO REMS; cannot use TOUCH certification interchangeably
- Pharmacies: only TYRUKO REMS-certified specialty pharmacies may dispense Q5134
- Infusion centers: must complete TYRUKO REMS site enrollment before administering
- Patients: enrolled with prescriber, sign Patient Enrollment Form, receive Medication Guide
Required monitoring
- Baseline MRI within 3 months prior to first dose
- Anti-JCV antibody testing at baseline + every 6 months
- Clinical assessment at 3 months, 6 months, then every 6 months while on therapy
- Post-discontinuation surveillance for 6 months after last dose
- Status reporting to TYRUKO REMS at each milestone
Billing implications
There is no separate REMS HCPCS code — REMS enrollment is not billable. However, documentation of REMS enrollment is a frequent payer audit target. Notes should reference TYRUKO REMS enrollment number on each infusion encounter. Most payers' Tyruko PA criteria require attestation that the patient is enrolled and current on REMS monitoring.
Contact: TYRUKO REMS Coordinating Center, 800-489-7856. Web: tyrukorems.com.
Common error: Site administers Tyruko based on existing TOUCH certification (for Tysabri).
TYRUKO REMS is independent — this is a hard violation that triggers REMS audit and potential payer
recoupment. Confirm separate TYRUKO REMS enrollment for the prescriber, site, and patient before any
Tyruko dose.
Phase 2
Code the claim
Build the line items: admin code, modifiers, ICD-10, site of care.
Administration codes CPT verified May 2026
Tyruko is non-chemotherapeutic — use therapeutic infusion codes, not chemo.
| Code | Description | When to use |
|---|---|---|
96365 |
IV infusion, for therapy/prophylaxis/diagnosis; initial, up to 1 hour | Primary code. Tyruko infuses over ~1 hour at ~5 mg/min. |
96366 |
IV infusion, for therapy/prophylaxis/diagnosis; each additional hour | Typically NOT billed — infusion fits within the first hour. |
96413 / 96415 |
Chemotherapy IV administration codes | Not appropriate. Natalizumab is non-chemotherapeutic. |
S9329 + 99601 / 99602 |
Home infusion HCPCS + administration CPT | Home infusion supported via home-infusion vendor; verify payer coverage. |
Why not chemo: some payers historically denied 96413 for non-chemotherapeutic monoclonal
antibodies. Tyruko (and Tysabri reference) have always billed under 96365. Don't be tempted to bill chemo
admin codes for the higher reimbursement — the documentation won't support it.
Modifiers CMS verified May 2026 — verify JZ list
JZ/JW caveat unique to Tyruko: Per BuyAndBill's interpretation of CMS guidance,
"CMS does not include TYRUKO (Q5134) on its list of HCPCS pertaining to single-dose containers, and per
CMS guidelines, the JZ/JW wastage modifiers may not apply." This is unusual — the vial IS single-dose
by FDA labeling. Verify against the current CMS single-dose container list at billing time.
When in doubt, follow MAC-specific guidance; some MACs may still expect JZ on every claim.
JZ — possibly required
Effective July 1, 2023, CMS requires JZ on all claims for single-dose container drugs when no drug is discarded — but only for codes on the CMS single-dose container list. Q5134's inclusion on that list has been inconsistent. Default behavior: include JZ when no drug is wasted; be prepared for some MACs to either ignore the modifier or pay without it.
JW — rarely applies
The 300 mg dose uses one full vial; no drug is discarded. JW is not applicable in routine use.
Modifier 25 — situational
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. Routine pre-infusion REMS check is bundled.
340B modifiers (JG, TB)
For 340B-acquired Tyruko, follow your MAC's current 340B modifier policy. Sandoz's billing guide does not provide 340B-specific instructions for Tyruko.
ICD-10-CM diagnosis codes FY2026 verified May 2026
Tyruko inherits Tysabri's full diagnosis space — MS family AND Crohn's family.
Multiple sclerosis
| ICD-10 | Description | Tyruko-eligible? |
|---|---|---|
G35 | Multiple sclerosis (parent) | Many payers reject parent — use specific G35.x |
G35.A | Relapsing-remitting MS | Yes (primary indication) |
G35.C0 | Secondary progressive MS, unspecified | Use if active relapses present |
G35.C1 | Active SPMS | Yes (covered indication) |
G35.D | MS, unspecified | Acceptable |
G35.B0–B2 | Primary progressive MS family | NO — not approved for PPMS |
G37.9 | CNS demyelinating, NOS | Acceptable for CIS |
Crohn's disease
| ICD-10 | Description | Tyruko-eligible? |
|---|---|---|
K50.00 / K50.01x | Crohn's of small intestine (without/with complications) | Yes |
K50.10 / K50.11x | Crohn's of large intestine (without/with complications) | Yes |
K50.80 / K50.81x | Crohn's of both small + large intestine | Yes |
K50.90 / K50.91x | Crohn's, unspecified | Yes |
Tyruko covers BOTH MS and Crohn's. Different from many MS-specific DMTs that only carry MS
indications. When billing for Crohn's, use K50.x family codes; the MS DMT step-therapy rules don't apply.
Site of care & place of service Verified May 2026
Tyruko's 1-hour infusion + 1-hour observation (first 12 doses) fits ambulatory infusion settings cleanly. UHC and Aetna both run site-of-care UM programs that steer natalizumab away from hospital outpatient toward non-hospital sites and home infusion.
| Setting | POS | Claim form | Electronic |
|---|---|---|---|
| Physician office | 11 | CMS-1500 | 837P |
| Ambulatory infusion suite | 49 | CMS-1500 | 837P |
| Hospital outpatient | 19 or 22 | UB-04 / CMS-1450 | 837I |
| Patient home | 12 | CMS-1500 (with home-infusion HCPCS) | 837P |
REMS site requirement: regardless of POS, the site must be enrolled in TYRUKO REMS. Home
infusion vendors must be REMS-certified to administer Tyruko. Confirm vendor REMS status before scheduling
a home dose.
Claim form field mapping Sandoz Nov 2024
CMS-1500 / 837P (physician office, AIC; POS 11/49).
| Information | CMS-1500 box | Notes |
|---|---|---|
| NPI | 17b | Rendering provider |
| NDC qualifier + 11-digit NDC + UoM + qty | 24A shaded area | Format: N461314054394ML15 |
| HCPCS Q5134 + admin CPT 96365 | 24D | Each on its own line |
| Drug units | 24G | 300 (mg) |
| ICD-10 | 21 | G35.A / G35.C1 / G35.D / G37.9 (MS) or K50.x (Crohn's) |
| PA number | 23 | Required by UHC, Aetna, most BCBS |
| REMS reference (encouraged) | Box 19 / NTE segment | TYRUKO REMS enrollment number for audit-readiness |
Form references: NUCC (CMS-1500).
Phase 3
Get paid
Combined natalizumab policies; biosimilar preference at parity with reference at most payers.
Payer policy snapshot Reviewed May 2026
Most major payers cover Tyruko + Tysabri under combined natalizumab-agents policies.
| Payer | PA? | Biosimilar preference | MS + Crohn's? | Re-auth |
|---|---|---|---|---|
| UnitedHealthcare Combined natalizumab policy |
Yes | Tyruko + Tysabri at parity | Both covered | 12 mo |
| Aetna CPB 0751 + 2025 Clinical Program Summary |
Yes | Tyruko listed alongside Ocrevus + Tysabri as preferred MS alternatives | Both covered | w/ documented response |
| Anthem / Carelon PAM-077 (combined) |
Yes | Combined policy treats both as therapeutically interchangeable | Both covered | w/ disease stability |
| BCBS FEP 5.60.013 (combined natalizumab) |
Yes | Combined policy effective Jan 2025 | Both covered | w/ documented response |
Key finding: No major commercial payer requires step therapy through other MS DMTs before
approving Tyruko. As a biosimilar, it's typically covered at parity with the reference product. PA criteria
focus on appropriate diagnosis (MS or Crohn's), anti-JCV antibody testing, and TYRUKO REMS enrollment.
What to document for approval
- Confirmed diagnosis (MS or moderately-to-severely active Crohn's)
- Anti-JCV antibody status (baseline + ongoing)
- TYRUKO REMS enrollment confirmation (prescriber, site, patient)
- For MS: documented relapse activity; baseline MRI
- For Crohn's: documented inadequate response or intolerance to TNF inhibitors (per most payer policies)
- No active infection, no PML history, no serious immunocompromise
Medicare reimbursement CMS Q2 2026 (live)
Quarterly ASP from CMS Part B Drug Pricing File. Refreshes automatically each quarter.
Q2 2026 payment snapshot — Q5134
Effective April 1 – June 30, 2026 · Based on 4Q25 ASP submissions
ASP + 6%
$24.321
per mg / per unit
300 mg dose
$7,296.30
300 units × ASP+6%
After sequestration
~$7,150
~2% reduction (actual paid)
Annualized cost: 13 doses/year × $7,296.30 = ~$94,852/year per patient
before sequestration and copay assistance. Tyruko's biosimilar discount has not yet emerged in the ASP file
— pricing is currently at parity with Tysabri reference.
Coverage
No NCD or LCD specific to natalizumab. Coverage falls under the generic drug-coverage LCD framework (e.g., LCD L33394). All MACs cover Q5134 for FDA-approved on-label indications. Bill with G35.x for MS or K50.x for Crohn's.
Code history
- Aug 2023 – Mar 2024 — billed under unclassified
J3490/J3590 - Q5134 — permanent code, effective April 1, 2024
Patient assistance — Sandoz One Source Sandoz verified May 2026
- Sandoz One Source: 1-844-726-3691, M–F
- Tyruko Commercial Co-pay Program: covers eligible commercially insured patients up to $10,000/year out-of-pocket (excludes Medicare, Medicaid, federal program patients)
- Patient Assistance Program (PAP): free drug for uninsured / underinsured eligible patients
- Product Replacement Program: for spoiled / damaged / contaminated product
- In-home training: coordination with home infusion vendors
- TYRUKO REMS Coordinating Center: 800-489-7856 (separate from copay support)
- Web: tyruko.com/tyruko-patient-support/sandoz-one-source/
Need to model what a specific patient will actually pay after copay assistance, deductible, coinsurance,
and OOP max? Run a CareCost Estimate — Q5134 pre-loaded.
Phase 4
Fix problems
REMS confusion, JZ/JW ambiguity, and Q5134 vs J2323 mix-ups are the top three.
Common denials & how to fix them
| Denial reason | Common cause | Fix |
|---|---|---|
| REMS not on file | Site administered Tyruko based on existing TOUCH (Tysabri) certification | Enroll in TYRUKO REMS independently. Re-submit with REMS enrollment number documented. Be prepared for REMS audit + recoupment risk. |
| Wrong J-code (J2323 instead of Q5134) | Tyruko billed under Tysabri reference J-code | Resubmit under Q5134. Confirm vial NDC matches: 61314-0543-94 = Tyruko, 59075-0730-15 = Tysabri. |
| Wrong admin code (96413) | Chemo admin code billed for non-chemo natalizumab | Resubmit with 96365 (therapeutic IV, 1 hour). Always 96365 for natalizumab. |
| JZ/JW modifier dispute | MAC interpretation of single-dose container list inconsistent | Verify CMS list at billing time. Some MACs accept claim without JZ; some require it. Default: include JZ when no waste; document if rejected. |
| Wrong ICD-10 (PPMS for MS) | G35.B0/B1/B2 used — natalizumab not approved for PPMS | If patient has PPMS, switch to Ocrevus (J2350). Use G35.A (RRMS) or G35.C1 (active SPMS) for Tyruko MS billing. |
| NDC format | 10-digit NDC submitted; payer requires 11-digit | Use 11-digit form: 61314-0543-94 with N4 qualifier. |
| PA not on file | Initial dose given before authorization confirmed | Submit with appeal + clinical documentation including REMS confirmation. |
| Anti-JCV not documented | Payer requires anti-JCV antibody status for PA | Submit anti-JCV antibody result. If positive, include risk-benefit discussion documentation. |
Frequently asked questions
What is the HCPCS code for Tyruko?
Tyruko (natalizumab-sztn) is billed under HCPCS Q5134 — "Injection, natalizumab-sztn
(tyruko), biosimilar, 1 mg." Each milligram equals one billable unit, so the standard 300 mg IV dose is
billed as 300 units. The reference product Tysabri uses HCPCS J2323. Q5134 became effective
April 1, 2024; before that Tyruko was billed under unclassified codes J3490 / J3590.
How is Tyruko dosed?
300 mg IV infusion over approximately 1 hour, every 4 weeks. Identical dosing to the reference product Tysabri. Each dose uses one full 300 mg / 15 mL single-dose vial.
Does the JZ or JW modifier apply to Tyruko?
Possibly NOT. Per BuyAndBill's interpretation of CMS guidance, "CMS does not include TYRUKO (Q5134) on its list of HCPCS pertaining to single-dose containers, and per CMS guidelines, the JZ/JW wastage modifiers may not apply." This is unusual — the vial IS single-dose by FDA labeling. Verify against CMS's current single-dose container list at billing time. When in doubt, follow MAC-specific guidance; some MACs may still expect JZ on every claim.
What is the administration code for Tyruko?
CPT 96365 — "Intravenous infusion, for therapy, prophylaxis, or diagnosis; initial,
up to 1 hour." Natalizumab is non-chemotherapeutic, so 96413 (chemo administration) is NOT appropriate.
The FDA label specifies a 1-hour infusion, so 96366 (each additional hour) is typically not billed.
Does Tyruko share TOUCH REMS with Tysabri?
No. Tyruko has its own separate REMS program — TYRUKO REMS — operated by Sandoz, contact 800-489-7856. Tysabri uses the TOUCH Prescribing Program (800-456-2255) operated by Biogen. Sites administering both products must enroll in BOTH REMS independently. Prescribers, pharmacies, infusion centers, and patients all enroll separately. Documentation of REMS enrollment is a frequent payer audit target.
What is the boxed warning for Tyruko?
Progressive multifocal leukoencephalopathy (PML) — an opportunistic JC virus infection that usually leads to death or severe disability. Risk factors: anti-JCV antibody positivity, treatment duration over 2 years, prior immunosuppressant use. Anti-JCV antibody testing is required for risk stratification. MRI surveillance is required at baseline, 3 months, 6 months, then every 6 months on therapy and 6 months post-discontinuation.
Is Tyruko approved for both MS and Crohn's disease?
Yes. Tyruko inherits the full Tysabri reference indications: relapsing forms of multiple sclerosis (RRMS, active SPMS, CIS) in adults, AND moderately-to-severely active Crohn's disease in adults. Most major commercial payers cover both indications under combined natalizumab-agents policies.
What is the Medicare reimbursement for Q5134?
For Q2 2026, the Medicare Part B payment limit for Q5134 is $24.321 per mg (ASP + 6%) — currently identical to the Tysabri reference J2323 at $24.321/mg, indicating CMS pricing parity. The standard 300 mg dose reimburses at approximately $7,296.30 before sequestration. ASP is updated quarterly by CMS.
Reference
Sources & methodology
Every claim on this page is sourced. Methodology and review history below.
Source documents
- DailyMed — TYRUKO (natalizumab-sztn) Prescribing Information
- FDA — TYRUKO label PDF (BLA 761322s000)
- Sandoz — TYRUKO HCP FAQs
- Sandoz One Source — Tyruko patient support
- TYRUKO REMS Program (Sandoz)
- CMS — Medicare Part B Drug ASP Pricing File
- CMS — HCPCS quarterly update file (canonical Q-code source)
- BuyAndBill — Q5134 reference page
- AAPC — HCPCS Q5134
- Aetna Clinical Policy Bulletin 0751 — Natalizumab
- UnitedHealthcare — Natalizumab (Tyruko & Tysabri) policy
- Carelon / Anthem — Natalizumab Agents Clinical Criteria PAM-077
- Sandoz / Novartis — Tyruko FDA approval announcement (Aug 2023)
- 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, Carelon, BCBS) | Semi-annual | Manual review against published payer policy documents. |
| HCPCS / CPT / modifier rules + CMS single-dose container list | Quarterly | JZ/JW applicability for Q5134 specifically requires more frequent verification. |
| NDC, dosing, FDA label | Event-driven | Tied to manufacturer document version + FDA label revision date. |
| TYRUKO REMS requirements | Annual | Reviewed against Sandoz REMS program documentation. |
Reviewer
Pending SME review. This page is staff-authored from primary sources (FDA, CMS, manufacturer,
payer documents — all linked above). Final review by our SME, Catherine Rose (CPC), is 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: Sandoz HCP FAQ (Nov 2024). FDA label: Oct 2025 (BLA 761322). Payer policies: UHC combined natalizumab, Aetna CPB 0751, Carelon PAM-077, BCBS FEP 5.60.013.
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. We do not paraphrase from billing-software vendor blogs. When CMS guidance is ambiguous (as with Q5134 and the single-dose container list), we surface the ambiguity rather than asserting a definitive answer.