Pemetrexed – Antifolate Antineoplastic Therapy

Pemetrexed is a modern cytotoxic anti-cancer medication belonging to the class of antimetabolites and is a multi-targeted antifolate agent. The drug plays a key role in the therapy of non-small cell lung cancer by interfering with the fundamental vital processes of tumor cells.

The mechanism of action involves the inhibition of three key enzymes involved in nucleotide biosynthesis: thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). By blocking these enzymes, the drug disrupts the synthesis of purine and pyrimidine nucleotides, which are the building blocks of DNA and RNA. Without the ability to synthesize new genetic material, the tumor cell loses its ability to divide and undergoes cell death. A vital feature of the therapy is the mandatory supplementation of vitamins (folic acid and vitamin B12) before and during treatment, which significantly reduces the overall toxicity to healthy tissues without compromising its anti-tumor efficacy.

The drug is administered intravenously as an infusion in a specialized clinical setting under the supervision of an oncologist.

Wikipedia page
Pemetrexed

Indications

Pemetrexed is indicated for the treatment of adult patients in the following clinical scenarios:

  • Malignant Pleural Mesothelioma: in combination with cisplatin for patients whose disease is not amenable to curative surgery.
  • Non-Small Cell Lung Cancer (NSCLC): as first-line therapy for locally advanced or metastatic non-squamous NSCLC in combination with chemotherapy or immunotherapy.
  • Maintenance Therapy: for patients with non-squamous NSCLC whose disease has not progressed after first-line platinum-based chemotherapy.
  • Second-line Therapy: as a single agent for patients with non-squamous NSCLC after prior chemotherapy.

Dosage and administration

The administration of pemetrexed requires strict adherence to a preparation protocol to minimize side effects.

  • Standard Dose: 500 mg/m² of the patient's body surface area.
  • Administration Regimen: intravenous infusion over 10 minutes on the first day of each 21-day cycle.
  • Vitamin Pretreatment: folic acid (350–1000 mcg daily) and vitamin B12 injections (1000 mcg every 3 cycles) are mandatory to reduce hematologic toxicity.
  • Dexamethasone: prescribed the day before, the day of, and the day after the infusion to prevent skin reactions.
  • Adjustments: blood counts are performed before each cycle; if leukocyte or platelet levels are insufficient, the infusion is delayed or the dose is reduced.

The use of pemetrexed is restricted in the following conditions:

  • Hypersensitivity: known allergy to pemetrexed or any of its excipients.
  • Vaccination: concomitant administration of live attenuated vaccines (e.g., yellow fever vaccine).
  • Renal Impairment: severe renal failure (creatinine clearance less than 45 mL/min).
  • Pregnancy and Lactation: the drug has teratogenic potential; breastfeeding must be discontinued during therapy.
  • Pediatric Use: the efficacy of the drug in children has not been established.

The most common adverse events associated with pemetrexed use include:

  • Hematologic: decreased white blood cell count (neutropenia), anemia, and thrombocytopenia (risk of bleeding).
  • Gastrointestinal: nausea, vomiting, stomatitis (inflammation of the oral mucosa), diarrhea, and loss of appetite.
  • General: significant fatigue, weakness, and fever.
  • Dermatologic: rash, skin peeling, and pruritus (usually prevented by steroid premedication).
  • Neurologic: sensory neuropathy (rarely) and taste disturbances.
  • Renal: increased blood creatinine levels.

Frequently Asked Questions

Pemetrexed is an antineoplastic agent classified as a multi-targeted antifolate. It works by inhibiting three key enzymes involved in nucleotide synthesis (thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase). By depriving the cell of the ability to synthesize DNA and RNA, the drug effectively halts cell division and leads to tumor cell death.
Pemetrexed is primarily indicated for the treatment of malignant pleural mesothelioma (in combination with cisplatin) and locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). It can be used as a first-line treatment or as maintenance therapy.
Supplementation with folic acid and vitamin B12 is a mandatory part of the treatment regimen. These vitamins significantly reduce the frequency and severity of hematological and gastrointestinal toxicities without compromising the drug's efficacy. Typically, supplementation begins at least one week prior to the first dose of pemetrexed.
To prevent or reduce the severity of skin reactions (rash) associated with pemetrexed, patients are typically prescribed dexamethasone or a similar steroid. This is usually taken the day before, the day of, and the day after the infusion.
Medications such as ibuprofen or naproxen can slow down the clearance of pemetrexed by the kidneys, significantly increasing the risk of toxicity. Patients are advised to stop taking long-acting NSAIDs at least 5 days before the infusion and refrain from taking them for 2 days after the procedure.

List of medicines by active substance

-10%
Pemnat 500 mg Natco
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Natco

Pemnat

Pemetrexed
500 mg 1 vial
8539₴ 9438₴
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