II. Indications

  1. FDA Approved (in combination regimens)
    1. Mesothelioma (malignant, pleural)
    2. Non-Small Cell Lung Cancer (non-squamous cell)
  2. Off-Label Use
    1. Bladder Cancer (metastatic)
    2. Cervical Cancer
    3. Ovarian Cancer (resistant)
    4. Thymic Cancer

III. Contraindications

  1. Children
  2. Creatinine Clearance <45 ml/min

IV. Mechanism

  1. Pemetrexed is a synthetic Pyrimidine-based antifolate agent, similar to Methotrexate
  2. Pemetrexed binds the enzyme thymidylate synthase (TS), blocking its activity
    1. Inhibits methylation of dUMP to dTMP
    2. Inhibits DNA synthesis

V. Medications

  1. Pemetrexed powder for IV Solution: Available in 100 mg and 500 mg vials

VI. Dosing

  1. See other references for disease specific dosing protocols
  2. Coadministered agents to reduce adverse effects
    1. Folic Acid 400 to 1000 mcg orally daily for 21 days (after last dose)
    2. Vitamin B12 1000 mcg IM every 3 Pemetrexed cycles
    3. Dexamethasone 4 mg orally twice daily for 3 days starting on the day prior to treatment

VII. Adverse Effects

  1. Myelosuppression
  2. Rash
    1. Decreased with Dexamethasone (see dosing above)

VIII. Safety

  1. Avoid in Pregnancy (any trimester)
    1. Use reliable Contraception
  2. Avoid in Lactation
  3. Monitoring
    1. Complete Blood Count
    2. Renal Function Tests

IX. Drug Interactions

  1. NSAIDs
    1. Avoid coadministering at time of Pemetrexed infusion

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