Pemetrexed

PEMETREXED (PEMTORI IV) — CLINICIAN SUMMARY

🔴 RED FLAG (IMPORTANT) INFORMATION

(Main things to consider when using this drug)

• Renal function is critical — contraindicated if CrCl <45 mL/min; check renal function before every cycle.

• Folic acid + vitamin B12 supplementation is mandatory — omission significantly increases toxicity and mortality.

• Myelosuppression common — check FBC before each cycle; infection and bleeding risk.

• NSAIDs increase toxicity — withhold NSAIDs around dosing, especially in renal impairment.

• Serious skin reactions possible (including Stevens–Johnson syndrome and radiation recall).

• Pulmonary toxicity (interstitial pneumonitis) — investigate new cough or dyspnoea.

• Avoid live vaccines (e.g. yellow fever).

1. BASIC INFORMATION

Generic name: Pemetrexed (as pemetrexed disodium)
Brand name: PEMTORI IV
Drug class: Antimetabolite antifolate chemotherapy
Formulation: Powder for solution for IV infusion
Strengths: 100 mg vial, 500 mg vial
Mechanism of action:
Inhibits multiple folate-dependent enzymes (thymidylate synthase, DHFR, GARFT) → impaired DNA and RNA synthesis → cytotoxicity in rapidly dividing tumour cells.

2. INDICATIONS

• Malignant pleural mesothelioma — in combination with cisplatin

• Advanced or metastatic non-small cell lung cancer (NSCLC):

  • First-line (with cisplatin)

  • Maintenance therapy after response or stable disease

  • Second-line monotherapy after prior chemotherapy

(Use restricted to non-squamous histology.)

3. DOSING & ADMINISTRATION

Standard dose:

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

Administration:

• IV infusion over 10 minutes

• When combined with cisplatin: cisplatin given ~30 minutes after pemetrexed

Premedication and supplements (MANDATORY):

• Folic acid: 350–1000 micrograms orally daily

  • Start ≥7 days before first dose

  • Continue during treatment and for 21 days after last dose

• Vitamin B12: 1000 micrograms IM

  • 1 week before first dose

  • Then every 9 weeks

• Dexamethasone: 4 mg orally twice daily

  • Day before, day of, and day after pemetrexed

  • Reduces skin toxicity

4. DOSE MODIFICATIONS

Renal impairment:

• CrCl ≥45 mL/min: no dose adjustment

• CrCl <45 mL/min: DO NOT ADMINISTER

Hematologic toxicity:

• Delay treatment if neutrophils, platelets, or haemoglobin are below acceptable limits

• Resume at reduced dose or discontinue based on severity and recurrence

Non-haematologic toxicity:

• Grade ≥3 toxicity → withhold until recovery

• Permanently discontinue for severe or life-threatening reactions

5. CO-MEDICATIONS / INTERACTIONS

Avoid or use caution with:

• NSAIDs (ibuprofen, aspirin, piroxicam) — increased renal and hematologic toxicity

• Nephrotoxic drugs (aminoglycosides, loop diuretics, ciclosporin, platinum agents)

• Probenecid, penicillins — delayed pemetrexed clearance

• Oral anticoagulants — increased bleeding risk with cytopenias

• Live vaccines (yellow fever contraindicated)

Ensure adequate hydration when used with cisplatin.

6. CONTRAINDICATIONS

• Hypersensitivity to pemetrexed or excipients

• Severe renal impairment (CrCl <45 mL/min)

• Pregnancy and breastfeeding

• Concomitant yellow fever vaccination

• Paediatric patients (<18 years)

7. MONITORING REQUIREMENTS

Baseline and before each cycle:

• FBC

• Renal function (creatinine, CrCl)

• Liver function tests

• Performance status

• Signs of infection or bleeding

Ongoing:

• Monitor for skin reactions

• Monitor respiratory symptoms (pneumonitis)

• Monitor for cumulative fatigue and GI toxicity

8. SIDE EFFECTS & MANAGEMENT

Very common / Common:

• Anaemia, neutropenia, thrombocytopenia

• Fatigue

• Nausea, vomiting, diarrhoea, constipation

• Mucositis

• Rash, pruritus

• Elevated liver enzymes

• Renal impairment

Serious / Uncommon:

• Febrile neutropenia

• Severe infections and sepsis

• Stevens–Johnson syndrome / severe skin reactions

• Interstitial pneumonitis

• Hepatitis

• Thromboembolic events

• Radiation recall dermatitis

9. USE IN SPECIAL POPULATIONS

Renal impairment: Contraindicated if CrCl <45 mL/min
Hepatic impairment: Use with caution; monitor LFTs
Elderly: No dose adjustment, but higher toxicity risk
Pregnancy: Contraindicated (teratogenic)
Breastfeeding: Contraindicated
Fertility: May cause permanent infertility; fertility preservation should be discussed

10. DURATION OF USE / WHEN TO STOP

Continue until:

• Disease progression, or

• Unacceptable toxicity

Permanently discontinue for:

• Severe renal dysfunction

• Life-threatening hematologic or skin toxicity

• Recurrent severe adverse events despite dose modification

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2025/04/pil-approved-4.pdf