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Pemetrexed – Uses, Dosage, Side Effects, Interactions

Dr. Harun Ar Rashid, MD - Arthritis, Bones, Joints Pain, Trauma, and Internal Medicine Specialist Dr. Harun Ar Rashid, MD - Arthritis, Bones, Joints Pain, Trauma, and Internal Medicine Specialist
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Drugs (A - Z)

Pemetrexed is a parenterally administered folate antagonist and antineoplastic agent, used in the treatment of non-small cell lung cancer and malignant mesothelioma. Pemetrexed therapy has been associated with moderate rates of serum enzyme elevations during therapy but has not been convincingly linked to instances of acute, clinically apparent liver injury. Pemetrexed Disodium is the disodium salt of a synthetic pyrimidine-based antifolate. Pemetrexed binds to and inhibits the enzyme thymidylate synthase (TS) which catalyzes the methylation of 2′-deoxyuridine-5′-monophosphate (dUMP) to 2′-deoxythymidine-5′-monophosphate (dTMP), an essential precursor in DNA synthesis.

Pemetrexed Disodium is the disodium salt of a synthetic pyrimidine-based antifolate. Pemetrexed binds to and inhibits the enzyme thymidylate synthase (TS) which catalyzes the methylation of 2′-deoxyuridine-5′-monophosphate (dUMP) to 2′-deoxythymidine-5′-monophosphate (dTMP), an essential precursor in DNA synthesis.

Pemetrexed is an N-acylglutamic acid in which the N-acyl group is specified as 4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl. Inhibits thymidylate synthase (TS), 421 dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). It has a role as an antineoplastic agent, an antimetabolite, an EC 2.1.1.45 (thymidylate synthase) inhibitor, an EC 1.5.1.3 (dihydrofolate reductase) inhibitor, and an EC 2.1.2.2 (phosphoribosylglycinamide formyltransferase) inhibitor. It is a pyrrolopyrimidine and an N-acyl-L-glutamic acid. It is the conjugate acid of pemetrexed(2-).

Mechanism of Action

Pemetrexed is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. 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 TS and GARFT. 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.

or

Pemetrexed is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. 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 folyl polyglutamate synthase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. 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.

Indications

  • Carcinoma of the head and neck (Covered by class waiver: oropharyngeal epithelial carcinoma, excluding nasopharyngeal carcinoma), Malignant pleural mesothelioma
  • Malignant Pleural Mesothelioma (MPM)
  • Metastatic Cervical Cancer
  • Metastatic Non-squamous Non-Small Cell Lung Cancer
  • Metastatic Ureter Urothelial Carcinoma
  • Ovarian Cancer
  • Pleural Mesotheliomas
  • Locally advanced nonsquamous non-small cell lung cancer
  • Recurrent, metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
  • Unresectable Thymoma
  • Used in combination with cisplatin for the treatment of malignant pleural mesothelioma in adults whose disease is unresectable or who otherwise are not candidates for potentially curative surgery. Also used as a monotherapy for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy
  • For malignant pleural mesothelioma, Pemetrexed in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma. Non-small cell lung cancer, Pemetrexed in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Pemetrexed is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Pemetrexed is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.,
  • Malignant pleural mesotheliomaPemetrexed Pfizer in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma. Non-small cell lung cancerPemetrexed Pfizer in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Pemetrexed Pfizer is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Pemetrexed Pfizer is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.
  • For malignant pleural mesothelioma, Pemetrexed Krka in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma. Non-small cell lung cancer, Pemetrexed Krka in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Pemetrexed Krka is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Pemetrexed Krka is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.,
  • Malignant pleural mesothelioma Pemetrexed medac in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma. Non-small cell lung cancer Pemetrexed medac in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Pemetrexed medac is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Pemetrexed medac is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.
  • Malignant pleural mesotheliomaPemetrexed Fresenius Kabi in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma. Non-small cell lung cancerPemetrexed Fresenius Kabi in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Pemetrexed Fresenius Kabi is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Pemetrexed Fresenius Kabi is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.
  • For malignant pleural mesothelioma, Pemetrexed Accord in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma. Non-small cell lung cancer, Pemetrexed Accord in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Pemetrexed Accord is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Pemetrexed Accord is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.,
  • Malignant pleural mesothelioma Pemetrexed Hospira UK Limited in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma. Non-small cell lung cancerPemetrexed Hospira UK Limited in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Pemetrexed Hospira UK Limited is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Pemetrexed Hospira UK Limited is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology
  • For malignant pleural mesothelioma, Ciambra in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma. Non-small cell lung cancer, Ciambra in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Ciambra is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Ciambra is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.,
  • Malignant pleural mesothelioma. Pemetrexed Sandoz in combination with cisplatin is indicated for the treatment of chemotherapy-naive patients with unresectable malignant pleural mesothelioma. Non-small cell lung cancer, Pemetrexed Sandoz in combination with cisplatin is indicated for first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Pemetrexed Sandoz is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Pemetrexed Sandoz is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.
  • Malignant pleural mesotheliomaAlimta in combination with cisplatin is indicated for the treatment of chemotherapy-naïve patients with unresectable malignant pleural mesothelioma. Non-small-cell lung cancerAlimta in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small-cell lung cancer other than predominantly squamous cell histology. Alimta is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small-cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Alimta is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small-cell lung cancer other than predominantly squamous cell histology
  • Malignant pleural mesotheliomaPemetrexed Lilly in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma. Non-small cell lung cancerPemetrexed Lilly in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Pemetrexed Lilly is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Pemetrexed Lilly is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.
  • Carcinoma of the head and neck (Covered by class waiver: oropharyngeal epithelial carcinoma, excluding nasopharyngeal carcinoma), Malignant pleural mesothelioma

Pemetrexed is a parenterally administered folate antagonist and antineoplastic agent, used in the treatment of non-small cell lung cancer and malignant mesothelioma. Pemetrexed therapy has been associated with moderate rates of serum enzyme elevations during therapy, but has not been convincingly linked to instances of acute, clinically apparent liver injury.

Use in Cancer

Pemetrexed disodium is approved to be used alone or with other drugs to treat:

  • Malignant pleural mesothelioma in patients who cannot be treated with surgery.
  • Nonsquamous non-small cell lung cancer in certain patients whose disease is recurrent, locally advanced or has metastasized (spread to other parts of the body).
  • Antineoplastic Agents – Substances that inhibit or prevent the proliferation of NEOPLASMS.
  • Enzyme Inhibitors – Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
  • Folic Acid Antagonists – Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy.
  • Nucleic Acid Synthesis Inhibitors – Compounds that inhibit cell production of DNA or RNA

Pemetrexed disodium is also being studied in the treatment of other types of cancer.

Contraindications

The following conditions are contraindicated with this drug. Check with your physician if you have any of the following:

  • are allergic or any ingredients of the medication
  • are infected with Human Immunodeficiency Virus (HIV)
  • have or have had tuberculosis
  • currently, have any severe infection
  • have active cancer
  • are taking medications to treat cancer or medications that weaken your immune system
  • have a history of progressive multifocal leukoencephalopathy (PML)
  • have high blood pressure that is not controlled
  • have a history of stroke or arterial dissection
  • have a history of angina or heart attack
  • have a clotting disorder or are taking anticoagulants
  • In patients who are infected with Human Immunodeficiency Virus (HIV-None) because it causes prolonged reductions of CD4+ lymphocyte counts

Dosage

Strengths: 500 mg; 100 mg; 25 mg/mL; 1 g; 750 mg

Malignant Pleural Mesothelioma

  • COMBINATION USE WITH CISPLATIN in patients with a CrCl of 45 mL/min or greater: 500 mg/m2 as IV over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity

PREMEDICATION REGIMEN AND CONCURRENT MEDICATIONS:

  • Vitamin Supplementation: Patients should initiate folic acid 400 to 1000 mcg orally once daily beginning 7 days before the first dose of chemotherapy. Folic acid should be continued during the full course of therapy and for 21 days after the last dose.
  • Vitamin B12 1 mg should be administered IM 1 week prior to the first dose of chemotherapy and every 3 cycles thereafter.
  • Subsequent vitamin B12 injections may be given the same day as therapy.
  • Corticosteroids: Dexamethasone 4 mg orally 2 times a day the day before, the day of, and the day after chemotherapy administration.

Non-Small Cell Lung Cancer

  • COMBINATION USE WITH CISPLATIN for initial treatment of nonsquamous non-small cell lung cancer in patients with a CrCl of 45 mL/min or greater: 500 mg/m2 IV over 10 minutes administered prior to cisplatin on Day 1 of each 21-day cycle for up to 6 cycles in the absence of disease progression or unacceptable toxicity
  • FOR MAINTENANCE TREATMENT of NSCLC in patients with a CrCl of 45 mL/min or greater: 500 mg/m2 as IV over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity after 4 cycles of platinum-based first-line chemotherapy
  • FOR TREATMENT OF RECURRENT NSCLC in patients with a CrCl of 45 mL/min or greater: 500 mg/m2 IV over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity
  • COMBINATION USE CARBOPLATIN AND PEMBROLIZUMAB for the initial treatment of NSCLC in patients with a CrCl of 45 mL/min or greater: 500 mg/m2 IV over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity after 4 cycles. Following completion of platinum-based therapy, this drug may be administered as maintenance therapy, alone or with pembrolizumab, until disease progression or unacceptable toxicity. Pembrolizumab should be administered prior to this drug when given on the same day. Please refer to the full prescribing information for pembrolizumab and for carboplatin.

PREMEDICATION REGIMEN AND CONCURRENT MEDICATIONS:

  • Vitamin Supplementation: Patients should initiate folic acid 400 to 1000 mcg orally once daily beginning 7 days before the first dose of chemotherapy. Folic acid should be continued during the full course of therapy and for 21 days after the last dose.
  • Vitamin B12 1 mg should be administered IM 1 week prior to the first dose of chemotherapy and every 3 cycles thereafter.
  • Subsequent vitamin B12 injections may be given on the same day as therapy.
  • Corticosteroids: Dexamethasone 4 mg orally 2 times a day the day before, the day of, and the day after chemotherapy administration.

Side Effects

The Most Common

  • Pemetrexed can suppress bone marrow function manifested by neutropenia,
  • thrombocytopenia, and anemia; myelosuppression
  • nausea, vomiting
  • diarrhea
  • constipation
  • loss of appetite
  • weight loss
  • tiredness
  • difficulty falling asleep or staying asleep
  • joint pain
  • blisters, skin sores, skin peeling, or painful ulcers in your mouth, lips, nose, throat, or genital area
  • swelling, blistering, or rash that looks like a sunburn in an area previously treated with radiation
  • unusual bleeding or bruising
  • sore throat, fever, chills, cough or other signs of infection
  • chest pain
  • fast heartbeat
  • difficulty breathing or swallowing
  • slow or difficult speech
  • extreme tiredness or weakness
  • dizziness or faintness
  • weakness or numbness of an arm or leg
  • pain, burning, numbness, or tingling in the hands or feet
  • pale skin
  • headache
  • hives
  • itching
  • decreased urination

More Common

  • symptoms of anemia (low red blood cell count) such as tiredness, paleness, or shortness of breath
  • unusual bleeding or bruising
  • constipation
  • diarrhea
  • loss of appetite
  • mild skin rash, redness, or itching
  • nausea and vomiting
  • numbness, burning or tingling in hands or feet
  • redness, heat, irritation or pain, swelling, or lump at the site of injection
  • temporary hair loss
  • tiredness
  • weight loss

Rare

  • black, tarry stools or blood in the urine
  • dehydration
  • fever and chills
  • mood changes and depression
  • mouth, throat, or lip sores
  • pinpoint-sized red spots on the skin
  • severe red, scaly, swollen, or peeling areas of skin
  • sore throat
  • unusual tiredness or weakness
  • vomiting (severe)
  • chest pain
  • difficulty swallowing
  • severe shortness of breath
  • severe skin reaction
  • signs of a severe allergic reaction (e.g., hives; difficulty breathing; or swelling of the face, throat, or tongue)

Drug Interaction

Food Interactions

  • Administer folic acid supplement. Folic acid supplement of 400 to 1000 mcg daily should be given 7 days before treatment with pemetrexed and continued until 21 days after discontinuation of pemetrexed to reduce the risk of hematologic and gastrointestinal toxicities.
  • Administer vitamin supplements. Administration of vitamin B12 intramuscular supplement one week before treatment with pemetrexed and every three cycles will reduce the risk of hematological and gastrointestinal toxicities.

Pregnancy and Lactation

FDA pregnancy category D

Pregnancy

This medication may harm a fetus or baby. Women who could become pregnant should have a negative blood pregnancy test before starting this medication and should use effective contraception to prevent pregnancy during treatment. If you become pregnant while receiving this medication, contact your doctor immediately.

Breast-feeding

It is not known if pemetrexed passes into breast milk. Women should not breastfeed while receiving this medication.

Allergic reactions: Allergic reactions, including difficulty breathing and swelling of the throat and mouth, can occur with this medication. If you experience these symptoms, get immediate medical attention.

Blood clotting: This medication can reduce the number of platelet cells in the blood. Platelets help the blood to clot, and a shortage could make you bleed more easily. Tell your doctor of any signs that your blood is not clotting as quickly. Such symptoms may include black and tarry stools, blood in the urine, easy bruising, or cuts that won’t stop bleeding.

Fertility: This medication may cause temporary or permanent fertility problems. Talk to your doctor about your concerns and options.

Infection: As well as killing cancer cells, this medication can reduce the number of cells that fight infection in the body (white blood cells). Avoid contact with people who have contagious infections (e.g., colds, flu), and tell your doctor if you begin to notice signs of an infection such as fever or chills.

Kidney disease: This medication may affect your kidneys. You doctor will monitor your kidney function through blood tests while you are receiving this medication. People with significantly decreased kidney function should not receive pemetrexed. People with diabetes, high blood pressure, or who are dehydrated should discuss with their doctor how this medication may affect their medical condition, how their medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Liver problems: People with impaired liver function or liver problems (e.g., liver disease, liver cancer) should discuss with their doctor how this medication may affect their medical condition, how their medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Lung problems: This medication can cause lung problems that can be severe. If you experience shortness of breath and cough while taking this medication, contact your doctor or get immediate medical attention.

Skin reactions: Because skin reactions are known to occur in people who receive treatment with pemetrexed, it is recommended that a corticosteroid be taken a day before scheduled treatment.

Vitamin supplementation: To avoid undesirable side effects, people using pemetrexed must take a low-dose folic acid supplement or a multivitamin containing folic acid once a day for the week before the start of treatment, and for the 3 weeks after the last dose of treatment. In addition, vitamin B12 injections must be given at least 1 week before the first day of treatment, and then continued every 9 weeks from the previous dose until 3 weeks after the last dose of pemetrexed.

Children: The safety and effectiveness of using this medication have not been established for children.

What special precautions should I follow?

Before receiving a pemetrexed injection,

  • tell your doctor and pharmacist if you are allergic to pemetrexed, mannitol (Osmitrol), any other medications, or any of the ingredients in pemetrexed injection. Ask your pharmacist or check the manufacturer’s patient information for a list of the ingredients.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention ibuprofen (Advil, Motrin). You should not take ibuprofen two days before, the day of, or for two days after you receive the pemetrexed injection. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have had radiation therapy or have or have ever had kidney disease.
  • tell your doctor if you are pregnant or plan to become pregnant, or if you plan to father a child. If you are female, you should use a reliable method of birth control while receiving pemetrexed injection and for at least 6 months after the final dose. If you are male, you and your female partner should use effective birth control while you are receiving a pemetrexed injection and for 3 months after the final dose. If you or your partner becomes pregnant while using this medication, call your doctor. Pemetrexed injection may harm the fetus.
  • tell your doctor if you are breastfeeding. You should not breastfeed during your treatment with pemetrexed injection and for 1 week after the final dose.
  • you should know that pemetrexed injection may cause fertility problems in males that may affect your ability to father a child. It is not known if these effects are reversible. Talk to your doctor about the risks of receiving a pemetrexed injection.

When to Contact Your Doctor or Health Care Provider

Contact your healthcare provider immediately, day or night, if you should experience any of the following symptoms:

  • Fever of 100.4° F (38° C) or higher, chills (possible signs of infection)

The following symptoms require medical attention but are not an emergency. Contact your healthcare provider within 24 hours of noticing any of the following:

  • Nausea (interferes with the ability to eat and is unrelieved with prescribed medication).
  • Vomiting (vomiting more than 4-5 times in a 24-hour period).
  • Unusual bleeding or bruising.
  • Black or tarry stools, or blood in your stools.
  • Blood in the urine.
  • Pain or burning with urination.
  • Extreme fatigue (unable to carry on self-care activities).
  • Constipation is unrelieved by laxative use.
  • Signs of infection such as redness or swelling, pain on swallowing, coughing up mucous, or painful urination.
  • Unable to eat or drink for 24 hours or have signs of dehydration: tiredness, thirst, dry mouth, dark and decreased amount of urine, or dizziness.
  • Depressed (interfering with your ability to carry on your regular activities).

Always inform your healthcare provider if you experience any unusual symptoms.

Precautions

  • Before starting pemetrexed treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.). Do not take aspirin, or products containing aspirin unless your doctor specifically permits this.
  • Do not take non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen unless your doctor specifically permits this.
  • Do not receive any kind of immunization or vaccination without your doctor’s approval while taking pemetrexed.
  • Inform your healthcare professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (pemetrexed may be hazardous to the fetus. Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus).
  • For both men and women: Do not conceive a child (get pregnant) while taking pemetrexed. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.
  • Do not breastfeed while taking this medication.

Self-Care Tips

  • Folic acid supplementation should be started before your first dose of pemetrexed, continued during your course of therapy, and should continue until 21 days after your last dose of pemetrexed. Vitamin B12 is to be given 1 week before your first dose of pemetrexed, with doses of vitamin B12 every 9 weeks thereafter. Folic acid and vitamin B12 are used to minimize some of the side effects of pemetrexed.
  • Drink at least two to three quarts of fluid every 24 hours, unless you are instructed otherwise.
  • You may be at risk of infection so try to avoid crowds or people with colds and those not feeling well, and report fever or any other signs of infection immediately to your healthcare provider.
  • Wash your hands often.
  • Use an electric razor and a soft toothbrush to minimize bleeding.
  • Avoid contact sports or activities that could cause injury.
  • To reduce nausea, take anti-nausea medications as prescribed by your doctor, and eat small, frequent meals.
  • Avoid sun exposure. Wear SPF 15 (or higher) sunblock and protective clothing.
  • In general, drinking alcoholic beverages should be kept to a minimum or avoided completely. You should discuss this with your doctor.
  • Get plenty of rest.
  • Maintain good nutrition.
  • Keep your bowels moving. Your healthcare provider may prescribe a stool softener to help prevent constipation that may be caused by this medicine.
  • For flu-like symptoms, keep warm with blankets and drink plenty of liquids. There are medications that can help reduce the discomfort caused by chills.
  • Acetaminophen may help relieve discomfort from fever, headache, and/or generalized aches and pains. However, be sure to talk with your doctor before taking it.
  • If you experience symptoms or side effects, be sure to discuss them with your healthcare team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Pemetrexed
  2. https://pubchem.ncbi.nlm.nih.gov/compound/Pemetrexed-disodium-heptahydrate
  3. https://pubchem.ncbi.nlm.nih.gov/compound/Pemetrexed-disodium-hemipentahydrate
  4. https://www.drugs.com/mtm/pemetrexed.html
  5. https://medlineplus.gov/druginfo/meds/a607043.html
  6. https://www.medbroadcast.com/drug/getdrug/alimta
  7. https://go.drugbank.com/drugs/DB00642
  8. ChemIDplus
    LICENSE
    https://www.nlm.nih.gov/copyright.html
    Pemetrexed [INN:BAN]
    https://chem.nlm.nih.gov/chemidplus/sid/0137281233
    ChemIDplus Chemical Information Classification
    https://chem.nlm.nih.gov/chemidplus/
  9. DrugBank
    LICENSE
    Creative Common’s Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
    Pemetrexed
    https://www.drugbank.ca/drugs/DB00642
  10. EPA DSSTox
    LICENSE
    https://www.epa.gov/privacy/privacy-act-laws-policies-and-resources
    Pemetrexed
    https://comptox.epa.gov/dashboard/DTXSID2048329
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  11. European Chemicals Agency (ECHA)
    https://echa.europa.eu/web/guest/legal-notice
    (2S)-2-[[4-[2-(2-amino-4-oxo-4,7-dihydro-1Hpyrrolo[2,3-d]pyrimidin-5-yl) ethyl] benzoyl] amino]-pentanedioic acid
    https://echa.europa.eu/information-on-chemicals
    (2S)-2-[[4-[2-(2-amino-4-oxo-4,7-dihydro-1Hpyrrolo[2,3-d]pyrimidin-5-yl) ethyl] benzoyl] amino]-pentanedioic acid
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/210683
  12. Hazardous Substances Data Bank (HSDB)
    PEMETREXED
    https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7316
  13. ChEBI
    Pemetrexed
    http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63616
    ChEBI Ontology
    http://www.ebi.ac.uk/chebi/userManualForward.do#ChEBI%20Ontology
  14. FDA Pharm Classes
    https://www.fda.gov/about-fda/about-website/website-policies#linking
    PEMETREXED
    https://dailymed.nlm.nih.gov/dailymed/browse-drug-classes.cfm
    FDA Pharmacological Classification
    https://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162549.htm
  15. LiverTox
    LICENSE
    https://www.nlm.nih.gov/copyright.html
    Pemetrexed
    https://www.ncbi.nlm.nih.gov/books/n/livertox/Pemetrexed/
  16. NCI Thesaurus (NCIt)
    https://www.cancer.gov/policies/copyright-reuse
    https://ncithesaurus.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C61614
    NCI Thesaurus Tree
    https://ncit.nci.nih.gov
  17. ChEMBL
    http://www.ebi.ac.uk/Information/termsofuse.html
    https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2360464/
    ChEMBL Protein Target Tree
    https://www.ebi.ac.uk/chembl/g/#browse/targets
  18. Comparative Toxicogenomics Database (CTD)
    http://ctdbase.org/about/legal.jsp
    https://ctdbase.org/detail.go?type=chem&acc=D000068437
  19. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
    https://www.dgidb.org/drugs/PEMETREXED
  20. ClinicalTrials.gov
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
    https://clinicaltrials.gov/
  21. DailyMed
    LICENSE
    https://www.nlm.nih.gov/copyright.html
    PEMETREXED DISODIUM
    https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=PEMETREXED+DISODIUM
    PEMETREXED
    https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=PEMETREXED
  22. Drug Induced Liver Injury Rank (DILIrank) Dataset
    https://www.fda.gov/about-fda/about-website/website-policies#linking
    pemetrexed
    https://www.fda.gov/science-research/liver-toxicity-knowledge-base-ltkb/drug-induced-liver-injury-rank-dilirank-dataset
  23. Nature Chemical Biology
    https://pubchem.ncbi.nlm.nih.gov/substance/50100129
  24. European Medicines Agency (EMA)
    LICENSE
    Information on the European Medicines Agency’s (EMA) website is subject to a disclaimer and copyright and limited reproduction notices.
    https://www.ema.europa.eu/en/about-us/legal-notice
    Armisarte (previously Pemetrexed Actavis) (EMEA/H/C/004109)
    https://www.ema.europa.eu/en/medicines/human/EPAR/armisarte
    Pemetrexed Pfizer (previously Pemetrexed Hospira) (EMEA/H/C/003970)
    https://www.ema.europa.eu/en/medicines/human/EPAR/pemetrexed-pfizer-previously-pemetrexed-hospira
    Pemetrexed Krka (EMEA/H/C/003958)
    https://www.ema.europa.eu/en/medicines/human/EPAR/pemetrexed-krka
    Pemetrexed medac (EMEA/H/C/003905)
    https://www.ema.europa.eu/en/medicines/human/EPAR/pemetrexed-medac
    Pemetrexed Fresenius Kabi (EMEA/H/C/003895)
    https://www.ema.europa.eu/en/medicines/human/EPAR/pemetrexed-fresenius-kabi
    Pemetrexed Accord (EMEA/H/C/004072)
    https://www.ema.europa.eu/en/medicines/human/EPAR/pemetrexed-accord
    Pemetrexed Pfizer (previously known as Pemetrexed Hospira UK Limited) (EMEA/H/C/004488)
    https://www.ema.europa.eu/en/medicines/human/EPAR/pemetrexed-pfizer-previously-known-pemetrexed-hospira-uk-limited
    Ciambra (EMEA/H/C/003788)
    https://www.ema.europa.eu/en/medicines/human/EPAR/ciambra
    Pemetrexed Sandoz (EMEA/H/C/004011)
    https://www.ema.europa.eu/en/medicines/human/EPAR/pemetrexed-sandoz
    Alimta (EMEA/H/C/000564)
    https://www.ema.europa.eu/en/medicines/human/EPAR/alimta
    Pemetrexed Lilly (EMEA/H/C/004114)
    https://www.ema.europa.eu/en/medicines/human/EPAR/pemetrexed-lilly
    pemetrexed disodium (P/34/2009)
    https://www.ema.europa.eu/en/medicines/human/paediatric-investigation-plans/emea-000126-pip01-07
  25. DTP/NCI
    https://www.cancer.gov/policies/copyright-reuse
    Pemetrexed
    https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=698037
  26. EU Clinical Trials Register
    https://www.clinicaltrialsregister.eu/
  27. FDA Orange Book
    https://www.fda.gov/about-fda/about-website/website-policies#linking
    https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
  28. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  29. WHO Anatomical Therapeutic Chemical (ATC) Classification
    https://www.whocc.no/copyright_disclaimer/
    https://www.whocc.no/atc/
    ATC Code
    https://www.whocc.no/atc_ddd_index/
  30. FDA Global Substance Registration System (GSRS)
    https://www.fda.gov/about-fda/about-website/website-policies#linking
    04Q9AIZ7NO
    https://www.fda.gov/ForIndustry/DataStandards/SubstanceRegistrationSystem-UniqueIngredientIdentifierUNII/
  31. National Drug Code (NDC) Directory
    https://www.fda.gov/about-fda/about-website/website-policies#linking
    PEMETREXED
    https://www.fda.gov/drugs/drug-approvals-and-databases/national-drug-code-directory
  32. NCI Cancer Drugs
    LICENSE
    https://www.cancer.gov/policies/copyright-reuse
    Alimta (Pemetrexed Disodium)
    https://www.cancer.gov/about-cancer/treatment/drugs/pemetrexeddisodium
  33. NIPH Clinical Trials Search of Japan
    https://rctportal.niph.go.jp/en/
  34. NLM RxNorm Terminology
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
    https://rxnav.nlm.nih.gov/id/rxnorm/68446
  35. Protein Data Bank in Europe (PDBe)
    http://www.ebi.ac.uk/pdbe-srv/pdbechem/chemicalCompound/show/LYA
  36. PubChem
    https://pubchem.ncbi.nlm.nih.gov
  37. RCSB Protein Data Bank (RCSB PDB)
    https://www.rcsb.org/pages/policies
    https://www.rcsb.org/
  38. SpectraBase
    https://spectrabase.com/spectrum/B8moGiK2sCH
  39. Springer Nature
    https://pubchem.ncbi.nlm.nih.gov/substance/?source=15745&sourceid=31051842-854736995
  40. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
    https://pubchem.ncbi.nlm.nih.gov/substance/?source=22163&sourceid=31051842-854732663
  41. Wikidata
    LICENSE
    CCZero
    https://creativecommons.org/publicdomain/zero/1.0/
    Pemetrexed
    https://www.wikidata.org/wiki/Q415220
  42. Wiley
    https://pubchem.ncbi.nlm.nih.gov/substance/?source=wiley&sourceid=45288
  43. Medical Subject Headings (MeSH)
    https://www.nlm.nih.gov/copyright.html
    Pemetrexed
    https://www.ncbi.nlm.nih.gov/mesh/2009832
    MeSH Tree
    http://www.nlm.nih.gov/mesh/meshhome.html
    Antineoplastic Agents
    https://www.ncbi.nlm.nih.gov/mesh/68000970
    Enzyme Inhibitors
    https://www.ncbi.nlm.nih.gov/mesh/68004791
    Folic Acid Antagonists
    https://www.ncbi.nlm.nih.gov/mesh/68005493
    Nucleic Acid Synthesis Inhibitors
    https://www.ncbi.nlm.nih.gov/mesh/68019384
  44. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
    Drug Groups
    http://www.genome.jp/kegg-bin/get_htext?br08330.keg
    Drug Classes
    http://www.genome.jp/kegg-bin/get_htext?br08332.keg
  45. UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS)
    GHS Classification Tree
    http://www.unece.org/trans/danger/publi/ghs/ghs_welcome_e.html
  46. PATENTSCOPE (WIPO)
    SID 403704198
    https://pubchem.ncbi.nlm.nih.gov/substance/403704198

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