Medical Drug Criteria (MDC)

Policy Num:       P1.002.028
Policy Name:     Pemetrexed (Alimta®, Axtle™, Pemfexy™, Pemrydi RTU®) IV
Policy ID:          [P1.002.028][Ac L M+ P+ ][09-J1000-01]

Last Review:       September 22, 2025
Next Review:      September 20, 2026
 

Related Policies: None

Pemetrexed (Alimta®, Axtle™, Pemfexy™, Pemrydi RTU®) IV

Summary

Policy Statements

1. Malignant Pleural Mesothelioma
   1. Member meets one of the following:
      1. Pemetrexed is used alone
      2. Pemetrexed is used in combination with cisplatin or carboplatin
      3. Pemetrexed is used in combination with bevacizumab and cisplatin
      4. Pemetrexed is used in combination with bevacizumab and carboplatin
      5. Pemetrexed is used in combination with bevacizumab for maintenance therapy
   2. Pemetrexed dose does not exceed 500 mg/m2 every 21 days
   3. Axtle, Pemfexy, Pemrydi RTU only: Pemetrexed (Alimta) is unavailable due to national drug shortage
2. Non-Small Cell Lung Cancer
   1. Member meets one of the following:
      1. Pemetrexed is used alone
      2. Pemetrexed is used in combination with cisplatin or carboplatin
      3. Pemetrexed is used in combination with bevacizumab
      4. Pemetrexed is used in combination with pembrolizumab for maintenance therapy
      5. Pemetrexed is used in combination with bevacizumab and either cisplatin or carboplatin
      6. Pemetrexed is used in combination with pembrolizumab and either cisplatin or carboplatin
   2. Pemetrexed dose does not exceed 500 mg/m2 every 21 days
   3. Axtle, Pemfexy, Pemrydi RTU only: Pemetrexed (Alimta) is unavailable due to national drug shortage
3. Ovarian Cancer (including Fallopian Tube Cancer and Primary Peritoneal Cancer)
   1. Member is diagnosed with persistent or recurrent disease
   2. Pemetrexed is used alone
   3. Pemetrexed dose does not exceed 500 mg/m2 every 21 days
   4. Axtle, Pemfexy, Pemrydi RTU only: Pemetrexed (Alimta) is unavailable due to national drug shortage
4. Thymoma or Thymic Carcinoma
   1. Pemetrexed is used as second-line therapy or as first-line therapy in members who cannot tolerate first-line combination regimens
   2. Pemetrexed is used alone
   3. Pemetrexed dose does not exceed 500 mg/m2 every 21 days
   4. Axtle, Pemfexy, Pemrydi RTU only: Pemetrexed (Alimta) is unavailable due to national drug shortage
5. Primary Central Nervous System Lymphoma
   1. Member is diagnosed with relapsed or refractory disease or pemetrexed is used as an induction therapy if member is unsuitable for or intolerant to high-dose methotrexate
   2. Pemetrexed is used alone
   3. Pemetrexed dose does not exceed 500 mg/m2 every 21 days
   4. Axtle, Pemfexy, Pemrydi RTU only: Pemetrexed (Alimta) is unavailable due to national drug shortage
6. Other FDA-approved or NCCN supported diagnosis (not previously listed above)
   1. Member meets one of the following:
      1. Member is diagnosed with a condition that is consistent with an indication listed in the product’s FDA-approved prescribing information (or package insert) AND member meets any additional requirements listed in the “Indications and Usage” section of the FDA-approved prescribing information (or package insert)
      2. Indication AND usage is recognized in NCCN Treatment Guidelines/NCCN  Drugs and Biologics Compendium  as a Category 1, 2A or 2B recommendation
      3. Pemetrexed dose does not exceed 500 mg/m2 every 21 days
      4. Axtle, Pemfexy, Pemrydi RTU only: Pemetrexed (Alimta) is unavailable due to national drug shortage

1. Authorization/reauthorization for pemetrexed has been previously approved by Triple-S or another health plan in the past two years for the treatment of bladder cancer, malignant pleural mesothelioma, non-small cell lung cancer, ovarian cancer, thymoma or thymic carcinoma, or primary central nervous system lymphoma or other FDA-approved or NCCN supported diagnosis; OR the member currently meets all indication-specific initiation criteria
2. Member’s disease has not progressed during treatment with pemetrexed
3. Pemetrexed dose does not exceed 500 mg/m2 every 21 days
4. Axtle, Pemfexy, Pemrydi RTU only: Pemetrexed (Alimta) is unavailable due to national drug shortage

Policy Guidelines

Precautions/Warnings

• Premedication regimen: Prior to treatment with ALIMTA, initiate supplementation with oral folic acid and intramuscular vitamin B12 to reduce the severity of hematologic and gastrointestinal toxicity
• Bone marrow suppression: Reduce doses for subsequent cycles based on hematologic and nonhematologic toxicities
• Do not administer when CrCl <45 mL/min
• Do not initiate a cycle unless ANC ≥1500 cells/mm3, platelets ≥100,000 cells/mm3, and CrCl ≥45 mL/min
• Fetal harm can occur when administered to a pregnant woman

DOSAGE/ADMINISTRATION

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved

• 500 mg/m2 IV on Day 1 of each 21-day cycle

Dose Adjustments

Renal impairment

• CrCl < 45 mL/min: Not recommended

Drug Availability

• Alimta, generic pemetrexed: 100 mg or 500 mg lyophilized powder in single-dose vial
• Pemfexy: 500 mg/20 mL (25 mg/mL) in a single-dose vial

Usual Dosage: Pemetrexed disodium is administered 500mg/m2 every 21 days.

REQUIRED MEDICAL INFORMATION

See policy statement

EXCLUSION CRITERIA

None

BENEFIT APPLICATION

BlueCard/National Account Issues
State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration-approved devices, drugs, or biologics may not be considered investigational, and thus thesedevices may be assessed only by their medical necessity.

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

OTHER CRITERIA

None

Practice Guidelines and Position Statements

None

References

1. Central nervous system treatment guidelines [Internet]. Version 2.2021. Fort Washington (PA): National Comprehensive Cancer Network; 2022 [cited 1/1/22]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp/.
2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2022 [cited 1/1/22]. Available from: http://www.clinicalpharmacology.com/.
3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 1/1/22]. Available from: http://clinicaltrials.gov/.
4. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 1/1/22].
5. Eagle Pharms. Pemfexy (pemetrexed disodium) injection. 2020 [cited 5/1/20]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209472s000lbl.pdf.
6. Eli Lilly and Company. Alimta (pemetrexed disodium) injection. 2019 [cited 1/1/20]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f5a860f3-37ec-429c-ae04-9c88d7c55c08/.
7. Malignant Pleural Mesothelioma treatment guidelines [Internet]. Version 1.2022. Fort Washington (PA): National Comprehensive Cancer Network; 2022 [cited 1/1/22]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp/.
8. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2022 [cited 1/1/22]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
9. Non-small cell lung cancer treatment guidelines [Internet]. Version 1.2022. Fort Washington (PA): National Comprehensive Cancer Network; 2022 [cited 1/1/22]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp/.
10. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2019 [cited 1/1/20]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
11. Ovarian cancer treatment guidelines [Internet]. Version 3.2021. Fort Washington (PA): National Comprehensive Cancer Network; 2019 [cited 1/1/20]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp/.
12. Thymomas and thymic carcinomas treatment guidelines [Internet]. Version 1.2022. Fort Washington (PA): National Comprehensive Cancer Network; 2019 [cited 1/1/20]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp/.
13. Florida Blue Medical Coverage Guideline  09-J1000-01 https://mcgs.bcbsfl.com/MCG?activity=openSearchedDocMcg&imgId=76F0EDESO9N8Z2O3ZLL Accessed 09/12/2025

Codes

Policy History