Pemetor

• Malignant Pleural Mesothelioma:
  First-line treatment in combination with cisplatin for unresectable malignant pleural mesothelioma.
• Non-Small Cell Lung Cancer (NSCLC):
• First-line treatment of locally advanced or metastatic non-squamous NSCLC in combination with cisplatin.
• Maintenance treatment of non-squamous NSCLC in patients whose disease has not progressed after four cycles of platinum-based chemotherapy.
• Second-line treatment of locally advanced or metastatic non-squamous NSCLC after prior chemotherapy.
• Off-label / Investigational:
• Occasionally used in other cancers such as bladder cancer and thymoma in clinical trials or compassionate use.

• Route: Intravenous infusion.
• Adult dosing for Malignant Pleural Mesothelioma and NSCLC:
• 500 mg/m² IV over 10 minutes on Day 1 of each 21-day cycle.
• When used with cisplatin, cisplatin is administered typically on Day 1 following pemetrexed infusion.
• Maintenance Therapy:
• 500 mg/m² IV every 21 days as a single agent after completion of induction chemotherapy.
• Pediatrics:
• Safety and efficacy not established.
• Elderly:
• No dose adjustment solely for age; monitor renal function closely.
• Renal Impairment:
• Contraindicated if creatinine clearance <45 mL/min.
• No specific dose adjustment guidelines available for moderate impairment.
• Hepatic Impairment:
• No dose adjustment necessary for mild to moderate impairment.
• Use with caution in severe hepatic impairment.
• Premedication:
• Folic acid 350–1000 mcg daily starting 7 days before first dose and continuing until 21 days after last dose.
• Vitamin B12 1000 mcg intramuscularly every 9 weeks starting 1 week prior to first dose.
• Dexamethasone 4 mg orally twice daily the day before, day of, and day after pemetrexed administration to reduce skin rash.

Pemetrexed is a multi-targeted antifolate chemotherapeutic agent. It inhibits several key folate-dependent enzymes involved in purine and pyrimidine synthesis, including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. This inhibition disrupts DNA and RNA synthesis, leading to impaired tumor cell replication and apoptosis, particularly in rapidly dividing malignant cells.

• Absorption: Administered IV; 100% bioavailability.
• Distribution: Volume of distribution ~16 L/m²; binds minimally to plasma proteins (~81%).
• Metabolism: Minimal hepatic metabolism; primarily excreted unchanged.
• Half-life: Approximately 3.5 hours.
• Elimination: Primarily renal excretion (~70–90% unchanged in urine).
• Onset: Cytotoxic effects occur after incorporation into the DNA synthesis pathway during cell division.

• Pregnancy: Category D (FDA). Known teratogenic and embryotoxic effects in animal studies; contraindicated in pregnancy unless potential benefits outweigh risks. Effective contraception required during and after treatment.
• Lactation: Unknown if excreted in human milk. Breastfeeding not recommended during treatment and for 3 weeks after last dose.

• Antimetabolite chemotherapeutic agent
• Antifolate antineoplastic agent

• Hypersensitivity to pemetrexed or any excipients.
• Severe renal impairment (creatinine clearance <45 mL/min).
• Pregnancy unless benefits outweigh risks.

• Bone marrow suppression: Monitor CBC regularly; risk of neutropenia, anemia, thrombocytopenia.
• Renal toxicity: Avoid in severe renal impairment; monitor renal function.
• Hepatotoxicity: Monitor liver enzymes; use with caution in hepatic impairment.
• Severe skin reactions: Premedicate with corticosteroids; monitor for rash.
• Pulmonary toxicity: Rare cases of interstitial pneumonitis reported.
• Infections: Increased risk due to myelosuppression; monitor closely.
• Folate and B12 supplementation: Mandatory to reduce hematologic and gastrointestinal toxicity.

• Hematologic: Neutropenia, anemia, thrombocytopenia (dose-limiting).
• Gastrointestinal: Nausea, vomiting, diarrhea, mucositis, stomatitis.
• Dermatologic: Rash, alopecia, pruritus.
• Other: Fatigue, fever, elevated liver enzymes, peripheral edema.
• Serious but rare: Severe neutropenia with infection, interstitial pneumonitis, severe skin reactions.

• NSAIDs: May increase pemetrexed toxicity in renal impairment; avoid use 2 days before to 2 days after pemetrexed dose in patients with mild to moderate renal impairment.
• Radiotherapy: Increased risk of toxicity when combined; use cautiously.
• Other nephrotoxic drugs: Increased risk of renal impairment; monitor renal function.
• No significant CYP450 metabolism; low potential for CYP-mediated drug interactions.

• Continued emphasis on folic acid and vitamin B12 supplementation to reduce toxicity.
• Updated dosing regimens support maintenance therapy in NSCLC after initial response.
• EMA and FDA reinforce renal function monitoring guidelines.
• Research ongoing in combination therapies with immune checkpoint inhibitors.

• Store between 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Do not freeze.
• Reconstituted solution should be used immediately or stored refrigerated (2°C to 8°C) and used within 24 hours.
• Follow aseptic techniques for reconstitution and dilution.