HCPCS
J9271
1 mg = 1 unit
Phase 1
Identify what you're billing
Confirm the right code, dose, and biomarker requirements before billing.
Keytruda IV vs. Keytruda Qlex SC FDA verified Apr 2026
Same molecule, very different billing. Qlex was approved September 2025 and is still ramping up payer coverage.
Merck offers Keytruda in two formulations: the original intravenous Keytruda (J9271, since 2014) and the subcutaneous Keytruda Qlex (BLA 761467, approved September 19, 2025). Same active ingredient, different billing infrastructure entirely.
| Keytruda (IV) | Keytruda Qlex (SC) | |
|---|---|---|
| HCPCS | J9271 | None yet — bills via J3490 / J9999 |
| Generic | pembrolizumab | pembrolizumab + berahyaluronidase alfa-pmph |
| NDC (carton) | 00006-3026-02 (single) / 00006-3026-04 (dual) | 00006-3083-01 (395 mg) / 00006-5083-01 (790 mg) |
| Manufacturer | Merck Sharp & Dohme | Merck Sharp & Dohme |
| FDA approval | September 2014 (BLA 125514) | September 19, 2025 (BLA 761467) |
| Adult dose | 200 mg q3w / 400 mg q6w | 395 mg q3w / 790 mg q6w |
| Administration time | 30 minutes (IV infusion) | 1–2 minutes (SC injection) |
| Admin CPT | 96413 (chemo IV) | 96401 (chemo SC) |
| Pediatric approved? | Yes (cHL, MSI-H/dMMR) | No |
| Indications coverage | 21+ approved | Most adult solid-tumor indications |
Why Qlex matters for billing: SC administration takes 1–2 minutes vs IV's 30
minutes. Major site-of-care implications — SC enables office and ASC administration without
infusion-suite chair time. Many payers will steer toward Qlex once permanent codes and policies catch up.
Cannot substitute Qlex for IV without payer authorization. Qlex is a different BLA, with
different NDCs and different billing pathway. Submit a separate PA for Qlex if switching from IV.
Dosing & unit math FDA label Apr 2026
From FDA prescribing information, label revised April 2026 (BLA 125514).
Adult monotherapy
- 200 mg IV every 3 weeks (most common; 17 doses/year)
- 400 mg IV every 6 weeks (extended interval; 8–9 doses/year)
- Same total annual drug volume; payer choice often driven by chair-time logistics
- 1 mg = 1 unit — bill 200 or 400 units per dose
Pediatric (specific indications)
- cHL pediatric: 2 mg/kg IV q3w, max 200 mg/dose
- MSI-H/dMMR pediatric solid tumors: 2 mg/kg IV q3w, max 200 mg/dose
- Bill the actual mg administered (not rounded)
- Pediatric patients <100 kg will produce partial-vial waste — JW modifier applies (see Modifiers)
Combination regimens (verify per indication)
- NSCLC + chemo (KEYNOTE-189): 200 mg q3w + carboplatin/pemetrexed
- RCC + axitinib or + lenvatinib: 200 mg q3w + oral TKI
- HER2+ gastric + trastuzumab + chemo: 200 mg q3w + standard CAP regimen
- Urothelial + Padcev (enfortumab vedotin): 200 mg q3w + Padcev
- Ovarian + paclitaxel ± bevacizumab (Feb 2026): 200 mg q3w + chemo
Worked example — first-year billing for a 1L NSCLC patient (200 mg q3w mono)
# 17 doses/year (200 mg q3w schedule)
Drug units billed per dose: 200 (J9271)
HCPCS: J9271 · Modifier: JZ · Vials: 2 × 100 mg
Admin: 96413 (30-min chemo IV)
# Year-1 totals
Total doses: 17
Total drug units billed: 3,400 (17 × 200)
Total drug cost (Q2 2026 ASP+6%): ~$208,253 before sequestration
Drug units billed per dose: 200 (J9271)
HCPCS: J9271 · Modifier: JZ · Vials: 2 × 100 mg
Admin: 96413 (30-min chemo IV)
# Year-1 totals
Total doses: 17
Total drug units billed: 3,400 (17 × 200)
Total drug cost (Q2 2026 ASP+6%): ~$208,253 before sequestration
No premedication routinely required
Unlike anti-CD20 mAbs (Ocrevus, Briumvi, Tyruko), Keytruda does NOT require pre-infusion methylprednisolone or antihistamine. Manage infusion reactions per FDA label if they occur.
NDC reference FDA NDC Directory verified May 2026
| NDC (10/11-digit) | Package | Use |
|---|---|---|
0006-3026-02 / 00006-3026-02 |
100 mg / 4 mL single-dose vial — 1 vial per carton | Pediatric weight-based dosing; some adult scenarios |
0006-3026-04 / 00006-3026-04 |
100 mg / 4 mL single-dose vial — 2 vials per carton (200 mg total) | Standard 200 mg adult dose — one carton per dose |
Use carton-level NDC, not vial-level. Payers expect the carton NDC on the claim form.
Vial-level NDC will trigger denial. Use the dual-vial carton (00006-3026-04) for 200 mg doses to bundle
cleanly; 400 mg doses use two dual-vial cartons.
Keytruda Qlex SC NDCs (separate billing):
00006-3083-01 (395 mg / 2.4 mL,
q3w dose) and 00006-5083-01 (790 mg / 4.8 mL, q6w dose). Bill via unclassified J3490 or J9999
with NDC and dose documentation until permanent code is assigned.
Phase 2
Code the claim
Chemotherapy admin codes apply (despite immunotherapy classification clinically).
Administration codes CPT verified May 2026
Pembrolizumab is billed as chemotherapy administration despite being immunotherapy.
| Code | Description | When to use |
|---|---|---|
96413 |
Chemotherapy administration, IV infusion technique; up to 1 hour, single or initial substance/drug | Primary code for Keytruda IV. 30-min standard infusion fits within 1-hour window. |
96415 |
Chemotherapy administration, IV infusion; each additional hour | Rarely needed for monotherapy. Pair with 96413 for combo regimens that extend chair time beyond 1 hour. |
96365 / 96366 |
Therapeutic IV infusion (non-chemo) | NOT appropriate. CPT classifies pembrolizumab admin under chemo codes per AMA guidelines for monoclonal antibody immunotherapy. |
96401 |
Chemotherapy administration, SC/IM; non-hormonal anti-neoplastic | For Keytruda Qlex SC formulation only (not IV). |
Why chemo admin for immunotherapy: CPT chemotherapy administration codes (96409–96425) apply to
complex monoclonal antibody administration regardless of mechanism of action. Pembrolizumab (and other immune
checkpoint inhibitors) are billed under chemo admin codes per AMA classification. This pays materially more
than 96365 therapeutic infusion.
Modifiers CMS verified May 2026
JZ — required on virtually every adult claim
Effective July 1, 2023, CMS requires the JZ modifier on all single-dose container claims when no drug is discarded. The Keytruda 200 mg adult dose uses two 100 mg vials with zero waste; the 400 mg dose uses four vials with zero waste. JZ applies to virtually every adult Keytruda claim.
JW — pediatric weight-based dosing only
JW reports the discarded portion of a single-dose vial. For Keytruda, JW only applies to pediatric weight-based dosing where partial-vial waste occurs. Example: a 25 kg child receiving 50 mg (2 mg/kg) uses one 100 mg vial and discards 50 mg — bill JW with 50 units of waste on a separate claim line. One of JZ or JW must be on every J9271 claim.
Common error: Forgetting to bill the discarded portion on pediatric claims. CMS audits
often catch this — bill the JW line with the actual discarded units alongside the JZ-style admin
line for the units administered. Wasted drug is reimbursable but must be reported.
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. Routine pre-infusion clinical assessment is bundled.
340B modifiers (JG, TB)
For 340B-acquired Keytruda, follow your MAC's current 340B modifier policy. Merck's billing guide does not provide 340B-specific instructions.
ICD-10-CM by indication group FY2026 verified May 2026
21+ approved indications. Use the most specific code supported by encounter documentation.
| Indication | ICD-10 family | Notes |
|---|---|---|
| Melanoma (advanced/metastatic) | C43.x | Adult + pediatric ≥12; adjuvant + metastatic |
| NSCLC | C34.x | Histology-specific 4th character; PD-L1 testing required for 1L mono |
| Mesothelioma | C45.0 | Combo with platinum/pemetrexed |
| HNSCC (head & neck SCC) | C00–C14, C32 | Site-specific; PD-L1 CPS testing |
| Classical Hodgkin Lymphoma (cHL) | C81.x | Adult + pediatric |
| PMBCL | C85.2 | Primary mediastinal large B-cell lymphoma |
| Urothelial carcinoma | C67.x | + Padcev combo recently expanded |
| MSI-H / dMMR (tissue-agnostic) | Any C-code + biomarker confirmation | Requires MSI/dMMR evidence in PA |
| MSI-H / dMMR CRC | C18–C20 + biomarker | 1L mono or combo |
| Gastric / GEJ (HER2+ or HER2-) | C16.x | HER2+ uses + trastuzumab combo; HER2- uses + chemo |
| Esophageal SCC / adenoCa | C15.x | + chemo regimens |
| Cervical (CPS ≥1) | C53.x | + chemo ± bevacizumab |
| HCC (hepatocellular) | C22.0 | 2L+ post-sorafenib |
| Biliary tract | C22.1, C23, C24.x | + gem/cis combo |
| Merkel cell | C44.x | Recurrent locally advanced or metastatic |
| RCC | C64–C66 | + axitinib or + lenvatinib |
| Endometrial | C54.x | + Lenvima for advanced; mono for MSI-H/dMMR |
| TMB-H tissue-agnostic | Any C-code + TMB ≥10 mut/Mb (FoundationOne CDx) | Requires TMB documentation in PA |
| cSCC (cutaneous squamous) | C44.x | Recurrent locally advanced or metastatic |
| TNBC (triple-negative breast) | C50.x | + chemo; PD-L1 CPS ≥10 for some lines |
| Ovarian (Feb 2026 addition) | C56.x | + paclitaxel ± bevacizumab; CPS ≥1 platinum-resistant |
Indication-specific PA criteria are the norm. Most payers require ICD-10 code, prior
therapies, line of therapy, AND biomarker results. The ICD-10 code alone is not sufficient for approval.
Site of care & place of service Verified May 2026
UnitedHealthcare, Aetna, and most major BCBS plans run aggressive site-of-care UM for immune checkpoint inhibitors. Aetna CPB 0892 explicitly steers ICIs out of HOPD after the first 3 months unless on combo chemo or active toxicity management.
| Setting | POS | Claim form | Payer steering |
|---|---|---|---|
| Physician oncology office | 11 | CMS-1500 / 837P | Preferred by commercial UM |
| Ambulatory infusion suite (AIC) | 49 | CMS-1500 / 837P | Preferred by commercial UM |
| Oncology ASC | 24 | CMS-1500 / 837P | Acceptable |
| Hospital outpatient (on-campus) | 22 | UB-04 / 837I | Disfavored after first 3 months |
| Hospital outpatient (off-campus PBD) | 19 | UB-04 / 837I | Disfavored after first 3 months |
| Patient home | 12 | CMS-1500 (with home infusion) | Possible but rare for IV oncology IO |
Site-of-care opportunity with Qlex: Once Keytruda Qlex (SC) gets a permanent code and
broader payer coverage, the 1–2 minute SC injection enables office-only administration without ASC
chair time. This will be a major site-of-care shift in 2026–2027.
Claim form field mapping Merck Aug 2025
From Merck Access Program HCP coding & coverage page (US-PDS-00587 03/26).
| Information | CMS-1500 box | Notes |
|---|---|---|
| NPI | 17b | Rendering provider |
| NDC qualifier + 11-digit NDC + UoM + qty | 24A shaded area | N4 + carton NDC + ML + total volume (8 mL for 200 mg, 16 mL for 400 mg) |
| HCPCS J9271 + JZ (or JW for pediatric waste) | 24D (drug line) | Mark JZ on virtually every adult claim |
| Drug units | 24G | 200, 400, or actual mg for pediatric |
| CPT 96413 (admin line) | 24D (admin line) | 30-min infusion fits within 1-hour window |
| ICD-10 | 21 | Indication-specific (see ICD-10 table) |
| Biomarker test claim line (separate) | 24D | CPT 88360 (PD-L1 IHC), 88342 (MMR), 81301 (MSI), etc. |
| PA number | 23 | Required by all major payers |
Phase 3
Get paid
Biomarker testing is a hard prerequisite for many indications. Get it done first.
Payer policy snapshot + biomarker requirements Reviewed May 2026
All major payers require biomarker testing for many Keytruda indications. Get the test results in hand before submitting PA.
| Payer | PA? | Biomarker enforcement | Site-of-care UM |
|---|---|---|---|
| UnitedHealthcare Oncology Med Coverage Policy |
Yes | Strict for NSCLC 1L mono (PD-L1 TPS), HNSCC, gastric (HER2 + PD-L1), CRC (MSI-H/dMMR) | Aggressive: ICI steering away from HOPD via Optum-managed program |
| Aetna CPB + Medical Drug policies |
Yes | PD-L1 required for relevant indications; MSI-H/dMMR for tissue-agnostic & CRC | Yes (separate Site-of-Care policy; ICIs steered out of HOPD after 3 months) |
| BCBS plans Vary by plan |
Yes | Generally aligned with NCCN guidelines + FDA label biomarker requirements | Plan-specific; most have ICI site-of-care steering |
Biomarker test billing (separate from drug claim)
| Test | CPT | For Keytruda indications |
|---|---|---|
| PD-L1 IHC 22C3 pharmDx | 88360 (manual) / 88361 (computer-assisted) | NSCLC, HNSCC, gastric/GEJ, esophageal, cervical, TNBC, ovarian |
| MMR IHC (4 proteins) | 88342 × 4 | Tissue-agnostic, CRC, endometrial |
| MSI by PCR | 81301 | Tissue-agnostic, CRC |
| TMB by NGS | 0037U / 0250U or large-panel 81455 | Tissue-agnostic TMB-H ≥10 mut/Mb |
| FoundationOne CDx (large NGS panel) | 0244U | Multi-biomarker for tissue-agnostic indications |
Step therapy
Generally NOT required for FDA-labeled 1L indications. Some payers require prior platinum chemotherapy failure before pembrolizumab monotherapy in 2L+ settings (e.g., urothelial post-platinum, NSCLC PD-L1 TPS <1%). Verify per-payer.
Medicare reimbursement CMS Q2 2026 (live)
Quarterly ASP from CMS Part B Drug Pricing File. Refreshes automatically each quarter.
Q2 2026 payment snapshot — J9271
Effective April 1 – June 30, 2026 · Based on 4Q25 ASP submissions
ASP + 6%
$61.251
per mg / per unit
200 mg dose (q3w)
$12,250.20
200 units × ASP+6%
400 mg dose (q6w)
$24,500.40
400 units × ASP+6%
Annualized cost: 200 mg q3w × 17 doses = ~$208,253/year (Medicare ASP+6%).
400 mg q6w × 8–9 doses = ~$208,253/year (same total drug volume).
After ~2% sequestration: ~$204,000/year actual paid.
Coverage
No NCD specific to pembrolizumab. Coverage falls under MAC LCDs for biologics + the generic drug-coverage framework. All MACs cover J9271 for FDA-approved on-label indications with appropriate ICD-10 and biomarker documentation.
Code history
- J9271 — permanent code, effective January 1, 2016 (initial FDA approval was September 2014; pre-permanent-code period used unclassified J3490)
Patient assistance — Merck Access Program Merck verified May 2026
- The Merck Access Program for KEYTRUDA: 1-855-257-3932 — benefits investigation, prior authorization assistance, appeal support
- The Merck Co-pay Assistance Program for KEYTRUDA / KEYTRUDA QLEX: commercial copay support; eligible commercially-insured patients (excludes Medicare, Medicaid, federal program patients)
- The Merck Patient Assistance Program: free product for uninsured / underinsured patients meeting income requirements (administered through the Merck Patient Assistance Program, Inc., a 501(c)(3))
- Foundations: for Medicare patients, refer to PAN, HealthWell, CancerCare — verify open oncology funds quarterly
- Web: merckaccessprogram-keytruda.com
Need to model what a specific patient will actually pay after copay assistance, deductible, coinsurance,
and OOP max? Run a CareCost Estimate — J9271 pre-loaded.
Phase 4
Fix problems
Biomarker omission, wrong admin code, and pediatric JW errors are the top three.
Common denials & how to fix them
| Denial reason | Common cause | Fix |
|---|---|---|
| Biomarker not documented | PA submitted without PD-L1 / MSI-H / TMB-H result | Submit biomarker test result + retroactive PA. Schedule biomarker testing FIRST for any indication that requires it. |
| Wrong admin code (96365) | Therapeutic IV billed instead of chemo IV | Resubmit with 96413. Pembrolizumab is chemo admin per CPT classification despite being immunotherapy. |
| Pediatric JW missing | Wasted drug not reported on pediatric weight-based dose | Add JW line for discarded units. JZ on the administered units; JW on the wasted units. |
| JZ missing on adult claim | Single-dose vial claim without JZ | Resubmit with JZ. Required since 7/1/2023 on every claim with no waste. |
| Wrong NDC format (vial-level) | Vial NDC submitted instead of carton NDC | Use carton NDC: 00006-3026-02 (single) or 00006-3026-04 (dual). |
| Site of care (HOPD) | HOPD administration after first 3 months on commercial plan with site-of-care UM | Move to office (POS 11) or AIC (POS 49). Submit medical necessity letter if HOPD required. |
| Indication-specific PA criteria not met | ICD-10 alone insufficient; line of therapy or combo regimen not documented | Submit complete clinical history including prior therapies, response, and current line of therapy. |
| Qlex billed as Keytruda IV | SC formulation billed under J9271 | Qlex bills under unclassified J3490/J9999 with NDC 0006-3083-01 or 0006-5083-01. Submit separate PA. |
Frequently asked questions
What is the HCPCS code for Keytruda?
Keytruda (pembrolizumab IV) is billed under HCPCS J9271 — "Injection, pembrolizumab,
1 mg." Each milligram equals one billable unit, so the standard 200 mg q3w dose is billed as 200 units,
and the 400 mg q6w alternative as 400 units. J9271 has been effective since January 1, 2016. The
subcutaneous formulation Keytruda Qlex (approved September 2025) does not yet have a permanent J/Q code
and bills under unclassified J3490 or J9999.
How many units do I bill for a 200 mg Keytruda dose?
Bill 200 units of J9271 per 200 mg dose; 400 units per
400 mg dose; for pediatric weight-based dosing, bill the actual mg administered (max 200 mg per dose).
Each 200 mg dose uses two 100 mg/4 mL single-dose vials with no waste.
What administration CPT do I use for Keytruda?
CPT 96413 — "Chemotherapy administration, IV infusion technique; up to 1 hour, single
or initial substance/drug." Despite being immunotherapy, Keytruda is classified for billing purposes as
a chemotherapy administration drug because it is a complex monoclonal antibody. Standard infusion is
30 minutes, fitting within the 1-hour 96413 window. Do NOT bill 96365.
Do I bill JZ or JW for Keytruda?
Bill JZ on virtually every adult Keytruda claim. The 200 mg dose uses two 100 mg vials with
zero waste; the 400 mg dose uses four vials with zero waste. JW only applies to pediatric
weight-based dosing where partial-vial waste occurs. One of JZ or JW must be on every J9271 claim per
CMS's July 2023 single-dose container policy.
What is the Medicare reimbursement for J9271?
For Q2 2026, the Medicare Part B payment limit for J9271 is $61.251 per mg (ASP + 6%). The standard 200 mg q3w dose reimburses at approximately $12,250.20 per infusion; the 400 mg q6w dose at approximately $24,500.40. Annualized cost (Medicare ASP+6%) ~$208,000/year. Sequestration (~2%) reduces actual paid to roughly ASP + 4.3%.
How many indications does Keytruda have?
21+ distinct indications across solid tumors and hematologic malignancies as of the April 2026 label revision: melanoma, NSCLC, mesothelioma, HNSCC, classical Hodgkin lymphoma (cHL), PMBCL, urothelial carcinoma, MSI-H/dMMR (tissue-agnostic), gastric/GEJ, esophageal, cervical, HCC, biliary tract, Merkel cell, RCC, endometrial, TMB-H tissue-agnostic, cSCC, TNBC, and ovarian (added February 2026). Many indications further split by line of therapy and combo regimen, producing 30+ distinct billing scenarios.
Does Keytruda require biomarker testing for prior auth?
Yes for many indications. PD-L1 IHC 22C3 pharmDx is required for: NSCLC 1L monotherapy, HNSCC, gastric/GEJ, esophageal, cervical (CPS≥1), TNBC, ovarian (CPS≥1, added Feb 2026). MSI-H or dMMR confirmation required for tissue-agnostic indication and CRC. TMB-H ≥10 mut/Mb (FoundationOne CDx) for tissue-agnostic TMB-H indication. Bill biomarker tests separately under their own CPT codes.
What is Keytruda Qlex and how does it differ from Keytruda IV?
Keytruda Qlex (pembrolizumab + berahyaluronidase alfa-pmph) is the subcutaneous formulation, FDA-approved September 19, 2025 under separate BLA 761467. It's administered SC in 1–2 minutes (vs IV 30 minutes for Keytruda) at fixed doses: 395 mg q3w or 790 mg q6w. Qlex does not yet have a permanent J or Q-code — bill under unclassified J3490 or J9999 with NDC and dose documentation, and CPT 96401 (chemo SC). Approved across most adult solid-tumor Keytruda indications. Cannot be substituted for IV without payer authorization.
Reference
Sources & methodology
Every claim on this page is sourced. Methodology and review history below.
Source documents
- Merck Access Program — Keytruda Coding & Coverage HCP page
- DailyMed — KEYTRUDA (pembrolizumab) Prescribing Information
- DailyMed — KEYTRUDA QLEX (pembrolizumab + berahyaluronidase alfa-pmph)
- FDA Keytruda label PDF (s172, 2025)
- Merck press releases — Sept 2025 Qlex approval, Feb 2026 ovarian indication
- CMS — Medicare Part B Drug ASP Pricing File
- SEER CanMED — HCPCS J9271 reference
- UnitedHealthcare — Oncology Medication Clinical Coverage Policy
- Aetna CPB 0892 — Immune Checkpoint Inhibitors / ICI Site-of-Care
- KEYTRUDA HCP — Approved Indications page
- 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 + biomarker test codes | Annual | Reviewed against CMS HCPCS quarterly files, AMA CPT releases, and AMA Category III code updates. |
| NDC, dosing, FDA label, indication list | Event-driven | Tied to manufacturer document version + FDA label revision date. Keytruda gets new indications ~3-5x per year. |
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: Merck Aug 2025 (US-PDS-00587 03/26). FDA label: Apr 2026 revision (BLA 125514). 21+ indications including Feb 2026 ovarian addition. Keytruda Qlex SC (Sept 2025 approval) referenced as sister formulation.
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.