CurrentViva HealthPolicy IC-0007

Pemetrexed (Alimta, Pemfexy, Pemrydi) — Intravenous Clinical Coverage and Prior Authorization Criteria

Clinical coverage and prior authorization criteria for intravenous pemetrexed formulations for oncology indications, including dosing, renewal, and authorization length rules for Viva Health members.

Policy Summary

PayerViva Health

PolicyPemetrexed (Alimta, Pemfexy, Pemrydi) — Intravenous

Policy CodePolicy IC-0007

Change TypeNo material changes

Effective DateSep 4, 2025

Next Review DateSep 4, 2025

Key ActionObtain prior authorization; initial approvals are typically valid for 6 months and renewals may be requested every 6 months unless otherwise specified.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

6 monthsinitial PA validity

500 mg/m2common dose

J9305, J9322, J9324HCPCS examples

Multiplecovered diagnosis codes

N/AMedicare Part B

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Primary CNS Lymphoma

Covered when ALL of the following are met

Age: Patient is at least 18 years of age

Diagnosis: Primary Central Nervous System (CNS) Lymphoma (including vitreoretinal lymphoma/PCNSL ocular variant without other CNS involvement)

Use setting: Used as a single agent; AND used as induction therapy in patients unsuitable for or intolerant to high-dose methotrexate OR used for relapsed or refractory disease

Non-Squamous NSCLC

Covered when ANY of the following apply

Combination with platinum: Used in combination with a carboplatin- or cisplatin-containing regimen

Maintenance: Used in combination with bevacizumab, pembrolizumab, cemiplimab, or durvalumab for continuation maintenance if previously used first-line and patient achieved tumor response or stable disease

Single agent recurrent/metastatic: Used as a single agent for recurrent, advanced, or metastatic disease (excluding locoregional recurrence or symptomatic local disease without evidence of disseminated disease) or mediastinal lymph node recurrence after prior radiation

First-line for biomarker-negative tumors: Used as first-line therapy for tumors that are negative for actionable molecular genomic biomarkers

Actionable biomarkers include EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, NRG1, and ERBB2 (HER2)

First-line for specific mutations: Used as first-line therapy for tumors with EGFR exon 20 insertion, BRAF V600E, NTRK1/2/3 fusion, MET exon 14 skipping, NRG1 fusion, or ERBB2 (HER2) mutation

Peritoneal and Pleural Mesothelioma (including PeM, PM, pericardial, tunica vaginalis)

Covered when ANY of the following indication-specific pathways are met

Adjuvant after CRS+HIPEC: Used as adjuvant therapy following cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) when patient has surgical/pathologic high-risk features

High-risk features include Ki-67 >9%, PCI >17, CC score >1, nodal metastasis, thrombocytosis, PS=2, biphasic/sarcomatoid histology, or bicavitary disease

First-line: Used as first-line therapy for medically inoperable disease, when complete cytoreduction is not achievable, presence of high-risk features, or disease progressed after CRS+HIPEC with no prior adjuvant systemic therapy

May be single agent or combined with platinum with or without bevacizumab or pembrolizumab

Subsequent therapy: Used as subsequent therapy as single agent or with platinum +/- bevacizumab when immunotherapy was given first-line or as rechallenge after prior pemetrexed-based first-line with good response

Thymomas and Thymic Carcinomas

Covered when ALL of the following are met

Single agent: Used as a single agent

Intolerance or sequencing: Patient unable to tolerate first-line combination regimens; used preoperatively if R0 resection is considered uncertain, postoperatively after R1/R2 resection (applies to thymic carcinoma), or as first-line for recurrent/advanced/metastatic disease

Second-line: Used as second-line therapy for unresectable or metastatic disease

Ovarian, Fallopian Tube, Primary Peritoneal, and Related Tumors

Covered when ALL of the following are met

Histology: Patient has recurrent or persistent Grade 1 Endometrioid Carcinoma, Carcinosarcoma (malignant mixed Müllerian tumor), Mucinous neoplasm of the ovary, Epithelial ovarian/fallopian tube/primary peritoneal cancer, or Clear cell carcinoma of the ovary

Exclusion of biochemical-only relapse: Patient is not experiencing an immediate biochemical relapse (e.g., rising CA-125 without radiographic evidence of disease) OR has recurrent Low-Grade Serous Carcinoma

Cervical and Vaginal Cancer

Covered when ALL of the following are met

Cervical histology: Used as subsequent therapy for recurrent or metastatic cervical cancer with squamous, adenocarcinoma, or adenosquamous histology; used as a single agent

Vaginal cancer: Used as a single agent for subsequent therapy for recurrent or metastatic vaginal cancer

Thyroid Carcinoma

Covered when ANY of the following indication-specific pathways are met

Combination with carboplatin: Used in combination with carboplatin for follicular or papillary thyroid carcinoma with unresectable locoregional recurrent/persistent or metastatic disease refractory to radioactive iodine (RAI)

Oncocytic carcinoma: Used for unresectable locoregional recurrent/persistent or metastatic oncocytic (Hürthle cell) carcinoma that has progressed after prior treatment

Anaplastic carcinoma: Used as second-line therapy for stage IVC (metastatic) anaplastic carcinoma

Do not administer pemetrexed to patients with creatinine clearance (CrCl) less than 45 mL/min. This renal function threshold is an absolute administration exclusion and applies across indications; dosing guidance and precautions for decreased renal function (for example, avoiding ibuprofen around administration when CrCl <80 mL/min) are provided elsewhere in the policy.

Some pemetrexed products are approved as 505(b)(2) NDAs (designated Ψ) and are FDA‑approved but are not rated therapeutically equivalent to the innovator product in the FDA Orange Book. Therapeutic equivalence status is listed by product/HCPCS in the policy; specific product equivalence considerations may affect substitution or coverage decisions and should be reviewed against the Orange Book and the listed HCPCS/NDC mapping.

The preceding information in this appendix is intended for non‑Medicare coverage determinations. Medicare rules, including the Medicare Benefit Policy Manual and any applicable National Coverage Determinations (NCDs), Local Coverage Determinations (LCDs), or Local Coverage Articles (LCAs), may apply and must be followed where relevant to a claim or member. The CMS Medicare Coverage Database may be used to locate current NCD/LCD/LCA guidance.

Use of pemetrexed as first‑line therapy for non‑small cell lung cancer is limited by tumor biomarker status: the policy specifies pemetrexed as first‑line when tumors are negative for actionable molecular genomic biomarkers. If testing identifies a clinically actionable molecular marker (for example EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, NRG1, ERBB2, or others listed), treatment should be guided by that marker rather than defaulting to pemetrexed as first‑line therapy.

Billing, HCPCS, NDC and Diagnosis Codes

Billing and HCPCS/NDC codesmixed

J9305	Pemetrexed Disodium Lyophilisate for injection (Alimta) HCPCS code
J9322	Pemetrexed Disodium Lyophilisate for injection (BluePoint) HCPCS code
J9324	Pemetrexed Disodium Hemipentahydrate Solution for injection (Pemrydi RTU/Pemfexy) HCPCS code
NDC 70121-2453-xx	Pemrydi RTU 100 mg/10 mL SDV
NDC 70121-2461-xx	Pemrydi RTU 500 mg/50 mL SDV
NDC 70121-2462-xx	Pemrydi RTU 1000 mg/100 mL SDV
NDC 00002-7640-xx	Alimta 100 mg powder for injection

Covered HCPCS Codes for pemetrexed (documented group)HCPCSCovered

J9292	Injection, pemetrexed dipotassium, 10 mg
J9294	Injection, pemetrexed (hospira), not therapeutically equivalent to J9305, 10 mg
J9296	Injection, pemetrexed (accord), not therapeutically equivalent to J9305, 10 mg
J9297	Injection, pemetrexed (sandoz), not therapeutically equivalent to J9305, 10 mg
J9304	Injection, pemetrexed (pemfexy), 10 mg
J9305	Injection, pemetrexed, not otherwise specified, 10 mg
J9314	Injection, pemetrexed (teva), not therapeutically equivalent to J9305, 10 mg
J9322	Injection, pemetrexed (bluepoint), not therapeutically equivalent to J9305, 10 mg
J9323	Injection, pemetrexed ditromethamine, 10 mg
J9324	Injection, pemetrexed (pemrydi rtu), 10 mg

1–10 of 11

1/2

Covered ICD-10 Diagnosis CodesICD-10Covered

C33	Malignant neoplasm of trachea
C34.00	Malignant neoplasm of unspecified main bronchus
C34.01	Malignant neoplasm of right main bronchus
C34.02	Malignant neoplasm of left main bronchus
C34.10	Malignant neoplasm of upper lobe, unspecified bronchus or lung
C34.11	Malignant neoplasm of upper lobe, right bronchus or lung
C34.12	Malignant neoplasm of upper lobe, left bronchus or lung
C34.2	Malignant neoplasm of middle lobe, bronchus or lung
C34.30	Malignant neoplasm of lower lobe, unspecified bronchus or lung
C34.31	Malignant neoplasm of lower lobe, right bronchus or lung

1–10 of 68

1/7

Creatinine clearance — Renal function thresholds for pemetrexed

ThresholdDo not administer pemetrexed if creatinine clearance (CrCl) is < 45 mL/min.

Renal precautionsAvoid ibuprofen for 2 days before, the day of, and 2 days after administration in patients with CrCl < 80 mL/min.

SupplementationSupplement with oral folic acid and intramuscular vitamin B12 per dosing guidance.

Medicare Part B Covered Diagnosis Codes

Medicare Part B covered diagnosesN/A

NoteMedicare NCDs/LCDs/LCAs may apply and must be followed where applicable; see CMS Medicare Coverage Database.

Prior Authorization and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for pemetrexed in many indications. Initial authorizations are typically valid for 6 months unless an indication-specific duration is specified (for example, thymomas/thymic carcinomas: 6 cycles; mesothelioma in specified combinations: 6 cycles or 6 doses as noted). Authorizations may be renewed every 6 months unless renewal is specifically disallowed for the indication (see renewal criteria).

Initial authorization: typically 6 months (some indications specify 6 cycles or 6 doses).
Renewal: may be renewed every 6 months unless the indication disallows renewal (refer to Renewal Criteria).

Note

PA Consideration Based on Cost and NQTL

Prior authorization may be considered for pemetrexed primarily due to the drug cost and because the NQTL assessment identified the drug's indication and cost as considerations for utilization management. The plan applied utilization review/PA comparably across MH/SUD and M/S benefits.

NQTL checklist identified: Indication = Yes (Consider for PA); Cost of drug = Yes (Consider for PA).
Safety/efficacy and potential for misuse/abuse were not flagged as primary PA considerations.

Documentation Required

Documentation Required for Prior Authorization

Documentation supporting prior authorization must demonstrate the medical necessity and indication for use. Provide clinical records that confirm diagnosis, relevant molecular testing (e.g., EGFR and other actionable biomarkers where specified), disease stage, performance status, prior therapies and responses, and any concomitant therapy requirements.

Include diagnostic documentation (pathology, staging) and results of FDA-approved or CLIA-compliant molecular testing when applicable (e.g., EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, NRG1, ERBB2).
Document prior lines of therapy, dates, responses, and rationale for current regimen (e.g., intolerance to first-line combination).
Support for dosing regimen and combination therapy (e.g., use with platinum agents, bevacizumab, pembrolizumab) when required by indication.

Step Therapy

Therapy Sequencing and Regimen Notes

Therapy sequencing and agent selection must follow the indication-specific guidance. Pemetrexed may be used as a single agent when patients are unsuitable for standard first-line regimens, as subsequent therapy after prior platinum or immunotherapy regimens where indicated, or as continuation/switch maintenance after response to first-line therapy per the clinical criteria.

Used as single agent when unable to tolerate first-line combination regimens (e.g., thymomas/thymic carcinomas).
Used as subsequent therapy or rechallenge where prior pemetrexed-based therapy produced a good response (e.g., peritoneal mesothelioma).
Used in combination with platinum agents or with bevacizumab/pembrolizumab for specific mesothelioma and NSCLC indications; follow indication-specific sequencing rules.

Billing Rule

Billing Codes and NDC Mapping

Billing should use the appropriate HCPCS codes and corresponding NDCs where applicable. Use the listed HCPCS/J-codes for pemetrexed formulations and map to available NDCs when billing.

Examples of HCPCS codes: J9292, J9294, J9296, J9297, J9304, J9305, J9314, J9322, J9323, J9324, J9999 (as applicable to formulation/manufacturer).
Select the HCPCS code that matches the drug formulation and manufacturer and include the appropriate NDC when required for billing (see product-specific NDC ranges in the billing appendix).
NDC examples from source: 00002-7640-xx; 68001-0543-xx; 00781-3518-xx; 16729-0522-xx; 00409-1045-xx; 00480-4516-xx; 83831-0131-xx; 42367-0531-xx; 00409-1060-xx; etc.

Denial Risk

Renewal and Denial Triggers

Renewal may be denied if the duration of authorization has been exceeded, if there is unacceptable toxicity, or if there is lack of disease response. Ensure documentation of continued benefit, acceptable toxicity profile, and adherence to indication-specific criteria when requesting renewal.

Renewal requirements: patient continues to meet indication-specific criteria; duration of authorization not exceeded; absence of unacceptable toxicity (examples: myelosuppression, renal toxicity with CrCl <45 mL/min, severe dermatologic reactions, interstitial pneumonitis); and objective disease response or stabilization.
Some indications explicitly disallow renewal (see Section I for indication-specific renewal restrictions).

Definitions and Biomarker Notes

Actionable molecular genomic biomarkers — scope and testing

Included biomarkersEGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, NRG1, ERBB2 (HER2).

Testing recommendationsComplete genotyping via tissue biopsy and/or plasma (liquid) testing is recommended to identify actionable markers.

Clinical useIf a clinically actionable marker is found, therapy should be guided by the identified marker rather than default pemetrexed first-line use.

Good risk status for leptomeningeal metastases

Good risk definitionKarnofsky Performance Status (KPS) ≥ 60; no major neurologic deficits; minimal systemic disease; and reasonable systemic treatment options available if needed.

Context of useSpecifically referenced for primary treatment candidacy in leptomeningeal metastases from EGFR mutation–positive NSCLC when using intrathecal/intracerebrospinal fluid pemetrexed.

ImplicationPatients meeting good-risk status may be eligible for primary or maintenance intrathecal pemetrexed per policy criteria.

505(b)(2) products — regulatory and coverage note

DefinitionProducts approved as 505(b)(2) New Drug Applications (designated Ψ) are FDA‑approved but are not rated as therapeutically equivalent to the innovator in the FDA Orange Book and are considered single‑source under statute.

ReferenceSee FDA Orange Book and National Drug Code Directory for complete lists and equivalence status.

Coverage impactTherapeutic equivalence status may affect substitution and coverage decisions for specific HCPCS/NDC products.

Non‑Quantitative Treatment Limitations (NQTLs)

DefinitionNon‑Quantitative Treatment Limitations (NQTLs) are methods, guidelines, standards of evidence, or other conditions that can restrict the duration, scope, or setting of benefits (e.g., utilization review, prior authorization).

ExamplesMay include utilization management tools such as prior authorization or other clinical review processes applied to drug coverage.

Parity noteThe utilization management NQTLs are applied comparably across MH/SUD and M/S prescription drugs per the checklist.

OpenPayer

Pemetrexed (Alimta, Pemfexy, Pemrydi) — Intravenous Clinical Coverage and Prior Authorization Criteria

Coverage Criteria for Pemetrexed

Billing, HCPCS, NDC and Diagnosis Codes

Prior Authorization and Provider Requirements

Background

Definitions and Biomarker Notes

Line of Therapy Rules

Biomarker and Testing Requirements