Drug information of Pemetrexed
Mechanism of effect
Pemetrexed is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication.
Pemetrexed is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase.
The polyglutamate forms are retained in cells and are inhibitors of thymidylate synthase and and glycinamide ribonucleotide formyltransferase. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues.
Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
- Vd (ss): 16.1 L
- Protein bound: 81%
- Metabolites: polyglutamate forms
- Total body clearance: 91.8 mL/min
- Half-Life: 3.5 hr
- Excretion: Urine
Malignant Pleural Mesothelioma
In combination with cisplatin: 500 mg/m² IV over 10 min on Day 1 q21Days
Continue until disease progression or unacceptable toxicity
Nonsquamous Non-Small Cell Lung Carcinoma
- Indicated as a single agent for the maintenance treatment of patients with locally advanced or metastatic, nonsquamous, non-small cell lung cancer (NSCLC) whose disease has not progressed after 4 cycles of platinum-based first-line chemotherapy
- 500 mg/m² IV over 10 min on Day 1 of q21Day; continue until disease progression or unacceptable toxicity after 4 cycles of platinum-based first-line chemotherapy
- Also, indicated as a single agent for the treatment of patients with recurrent, metastatic non-squamous, NSCLC after prior chemotherapy
- 500 mg/m² IV over 10 min on Day 1 of q21Day; continue until disease progression or unacceptable toxicity
Combination initial therapy
- In combination with cisplatin
- Indicated, in combination with cisplatin, for the initial treatment of patients with locally advanced or metastatic, nonsquamous NSCLC
- 500 mg/m² IV over 10 min prior to cisplatin on Day 1 of q21Day for up to 6 cycles in the absence of disease progression or unacceptable toxicity
- In combination with carboplatin and pembrolizumab
- Indicated, in combination with carboplatin and pembrolizumab, for the initial treatment of patients with metastatic, nonsquamous NSCLC
- 500 mg/m² IV over 10 min prior to carboplatin on Day 1 of q21Day cycle for 4 cycles until disease progression or unacceptable toxicity
Safety and efficacy not established
Side effectsanemia , Infection , Insomnia , Diarrhea , Heartburn , nausea , constipation , vomiting , neuropathy , dyspepsia , Peripheral edema , fever , anorexia , Creatinine increased , dysphagia , tiredness , allergic reactions , thrombocytopenia , Rash , conjunctivitis , Febrile Neutropenia , impairment of renal function , Hypersensitivity , taste disturbance
InteractionsIbuprofen , Indomethacin , Piroxicam , pimecrolimus , Trastuzumab , Tenofovir , Nabumetone , Oxaprozin , etodolac , choline magnesium trisalicylate , fenoprofen , Salsalate , Diflunisal , Celecoxib , Sulindac , Glucarpidase , Altretamine , Tofacitinib , Palifermin , flurbiprofen , Bacitracin , Ketoprofen , Meloxicam , Natalizumab , Ketorolac , Clozapine , Aspirin , denosumab , Tolmetin , Deferiprone , Diclofenac , Sulfasalazine , Fingolimod , Mefenamic acid , Cefamandole , Meningococcal conjugate vaccine , Bacampicillin
Severe myelosuppression may occur resulting in a requirement for transfusions and which may lead to neutropenic infection; risk of myelosuppression is increased in patients who do not receive vitamin supplementation; initiate supplementation with oral folic acid and intramuscular vitamin B12 prior to first dose of therapy; continue vitamin supplementation during treatment and for 21 days after last dose to reduce severity of hematologic and gastrointestinal toxicity
Therapy can cause severe, and sometimes fatal, renal toxicity
Serious and sometimes fatal, bullous, blistering and exfoliative skin toxicity, including cases suggestive of Stevens-Johnson Syndrome/Toxic epidermal necrolysis can occur
Serious interstitial pneumonitis, can occur with treatment; withhold therapy for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, or fever pending diagnostic evaluation; if pneumonitis confirmed, permanently discontinue therapy
Points of recommendation
- You may have more of a chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Some infections have been very bad and even deadly.
- You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
- If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
- If loose stools (diarrhea) or throwing up happens, you will need to make sure to avoid dehydration and electrolyte problems. Talk with the doctor.
- Have blood work checked as you have been told by the doctor. Talk with the doctor.
- This medicine may affect being able to father a child. It is not known how long this effect lasts. Talk with the doctor.
- If you are a man and have sex with a female who could get pregnant, protect her from pregnancy during care and for 3 months after care ends. Use birth control that you can trust.
- If you are a man and your sex partner gets pregnant while you take pemetrexed or within 3 months after your last dose, call your doctor right away.
- This medicine may cause harm to the unborn baby if you take it while you are pregnant.
- Use birth control that you can trust to prevent pregnancy while taking pemetrexed and for 6 months after stopping pemetrexed.
- If you get pregnant while taking pemetrexed or within 6 months after your last dose, call your doctor right away.