pemetrexed

pemetrexed

PEMETREXED

Complete information including dosage, side effects, interactions and pregnancy & breast feeding warnings for patient and professional use

Indication (uses)

  • Nonsquamous Non-Small Cell Lung Cancer – Combination with Cisplatin 
    • Pemetrexed is indicated in combination with cisplatin therapy for the initial treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer.
  • Nonsquamous Non-Small Cell Lung Cancer – Maintenance
    • Pemetrexed is indicated for the maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
  • Nonsquamous Non-Small Cell Lung Cancer – After Prior Chemotherapy
    • Pemetrexed is indicated as a single-agent for the treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer after prior chemotherapy.
  • Mesothelioma
    • ALIMTA (Pemetrexed) in combination with cisplatin is indicated for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery.
  • Limitations of Use
    • ALIMTA (Pemetrexed) is not indicated for the treatment of patients with squamous cell non-small cell lung cancer.

Pharmacological classification

  • Anti-cancer (folate metabolic inhibitor) drug used for the treatment of cancer.

Brand names

ALIMTA

Dosage form

  • Available as injection in single use vials with each vial containing 100 mg or 500 mg of Pemetrexed.

Mechanism of action

Pemetrexed is a folate analog metabolic inhibitor that exerts its action by disrupting folatedependent 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), which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is taken into cells by membrane carriers such as 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, is thought to occur to a lesser extent, in normal tissues. Polyglutamated metabolites are thought to have an increased intracellular half-life resulting in prolonged drug action in malignant cells

Dosage

Combination Use with Cisplatin for Nonsquamous Non-Small Cell Lung Cancer or Malignant Pleural Mesothelioma

  • The recommended dose of ALIMTA is 500 mg/m2 administered as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle. The recommended dose of cisplatin is 75 mg/m2 infused over 2 hours beginning approximately 30 minutes after the end of ALIMTA administration.

Single-Agent Use as Maintenance Following First-Line Therapy, or as a Second-Line Therapy

  • The recommended dose of ALIMTA is 500 mg/m2 administered as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle.

Premedication Regimen and Concurrent Medications

  • Vitamin Supplementation : Instruct patients to initiate folic acid 400 mcg to 1000 mcg orally once daily beginning 7 days before the first dose of ALIMTA. Continue folic acid during the full course of therapy and for 21 days after the last dose of ALIMTA.
  • Administer vitamin B12 1 mg intramuscularly 1 week prior to the first dose of ALIMTA and every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as treatment with ALIMTA.
  • Corticosteroids : Administer dexamethasone 4 mg by mouth twice daily the day before, the day of, and the day after ALIMTA administration.

Renal dose adjustments

  • ALIMTA is known to be primarily excreted by the kidneys. Decreased renal function will result in reduced clearance and greater exposure (AUC) to ALIMTA compared with patients with normal renal function.
  • Cisplatin coadministration with ALIMTA has not been studied in patients with moderate renal impairment.

Hepatic dose adjustments

  • There was no effect of elevated AST, ALT, or total bilirubin on the pharmacokinetics of Pemetrexed. However, no formal studies have been conducted to examine the pharmacokinetics of Pemetrexed in patients with hepatic impairment.

Geriatric dose adjustments

  • No dose adjustments is required if renal function is normal.

Pediatric use

  • Safety and effectiveness of Pemetrexed in pediatric patients have not been established.

Overdosage

  • Symptoms of overdose include neutropenia, anemia, thrombocytopenia, mucositis, and rash.
  • Anticipated complications of overdose include bone marrow suppression as manifested by neutropenia, thrombocytopenia, and anemia.
  • In addition, infection with or without fever, diarrhea, and mucositis may be seen.
  • No specific antidote is known.
  • It is not known whether Pemetrexed can be dialyzed or not.
  • Seek immediate medical attention.
  • Treatment of overdosage involves
  • General supportive measures.

Side effects or adverse effects

Side effects specific to Pemetrexed for injection

  • Bone Marrow Suppression
    • ALIMTA can suppress bone marrow function, as manifested by neutropenia, thrombocytopenia, and anemia (or pancytopenia); myelosuppression is usually the dose-limiting toxicity.
    • Dose reductions for subsequent cycles are based on nadir ANC, platelet count, and maximum nonhematologic toxicity seen in the previous cycle.
    • Bone marrow depression is the most serious side effect/toxicity. It is also a limiting factor for the dose. Infections and bleeding are the common complications.
    • Bone marrow depression results in granulocytopenia, agranulocytosis, thrombocytopenia and aplastic anemia.
    • Consult your doctor as soon as possible if you observe any of the below mentioned symptoms:
      • Sore throat
      • Chills
      • Sudden fever
      • Weakness in limbs
      • Mouth ulcers
      • Bleeding gums
      • Sore mouth
      • Fast heart rate
      • Low blood pressure
      • Sore gums
      • Skin abscesses
      • Rapid breathing
      • Rapid progression of infection of any organ
      • Rapid progression of Septicemia
    • Gastrointestinal side effects
      • Nausea and vomiting are commonly observed with anti-cancer medicines.
      • Mucositis – painful inflammation and ulceration of mucus membrane lining the digestive tract.
      • Diarrhea, shredding of mucosa and haemorrhage due to decreased rate of renewal of gastrointestinal mucosa lining.
    • Skin
      • Alopecia or hair loss.
      • Dermatitis
    • Oral side effects
      • Breaches during chewing.
      • Depression of immunity due to reduction in number of WBCs largely increases the risk of oral infections.
      • Bleeding gums
      • Rapid progression of dental caries.
    • Gonadal side effects
      • Infertility due to Oligozoospermia in males.
      • Impotence in males.
      • Loss or reduces sex drive.
      • Inhibition of ovulation in females
      • Amenorrhea in females.
      • Damage to germinal cells may lead to mutagenesis.
    • Lymphoreticular tissue
      • Lymphocytopenia (reduced number of lymphocytes)
      • Inhibition of lymphocyte function.
      • Suppression of immunity due to bone marrow depression and reduced lymphocyte function highly increases the risk of opportunistic infections like:
        • Candida and other infections causing deep mycosis.
        • Cytomegalo virus
        • Herpes zoster
        • Pneumocystis jiroveci
        • Toxoplasma
      • Fetal side effects
        • Use of anti-cancer medicines in pregnant women may cause fetal damage leading to:
          • Fetal death
          • Abortion
          • Teratogenesis
        • Renal side effects
          • Renal failure, Gout and Urate stones may develop in urinary tract.
        • Hyperuricemia
          • An elevated level of uric acid is common in leukemia and bulky lymphomas.

Please note: The side effects mentioned above are from the reported cases. However, side effects are not limited to above mentioned conditions and symptoms. Consult your doctor as soon as possible if you feel or observe any symptoms that you relate to your treatment.

Warnings & Precautions

  • Vitamin supplement and corticosteroids should be co-administered with Pemetrexed.
  • Pemetrexed is primarily eliminated by kidneys. Renal function of the patient should be considered.
  • Caution should be exercised while co-administering Pemetrexed with NSAID.

Contraindications

  • Contraindicated in patients allergic to Pemetrexed.

Pregnancy & breast feeding warnings

  • Pregnancy

Category D, which means there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

  • Nursing:
  • It is not known whether Pemetrexed is excreted in human breast milk or not.
  • Since many drugs are excreted in milk and because of the potential for side effects in nursing infants, a decision should be made whether to discontinue drug or to discontinue nursing.

Interactions

Drug – drug interactions

  • Caution should be exercised when co-administering Pemetrexed with NSAID. Renal function of the patient should be considered.
  • Concomitant administration of Pemetrexed with nephrotoxic drugs may delay the clearance of Pemetrexed.
  • Concomitant use of Pemetrexed with following drugs/medicines should be strictly avoided.
    • Adefovir, Deferasirox, diatrizoate, Tenofovir, ioxilan, ioxagalate, ioversol, iothalamate, iopromide, iopalmidol, iohexol, iodixanol, iodipamide, iodamide, sirolimus, tacrolimus and Cidofovir may increase the risk of renal problems.
    • Clozapine and topotecan as it may lower the WBC count.
    • Deferiprone as it increases the risk of infections and affect bone marrow suppression.
    • Aldesleukin may cause tumor lysis syndrome.
    • Amiodarone, dronedarone, droperidol, pimozide, ziprasidone and Dofetilide may increase the risk of irregular heart rate.
    • Leflunomide as it increases the risk of infections.
    • Thalidomaide as it increases the risk of dangerous blood clots.
    • Adalimumab as it increases the risk of infections.
    • Natalizumab as it increases the risk of infections.
    • Talimogene laherparepvec may increase the risk of potentially life threatening herpes infection.
    • Teriflunomide as it increases the risk of infections.
    • Certolizumab as it increases the risk of infections.
    • Alemtuzumab as it increases the risk of serious infections.
    • Influenza virus vaccine (live, trivalent) as it increases the risk of infections.
    • Small pox vaccine as it increases the risk of infections.
    • Measles virus vaccine as it increases the risk of infections.
    • Mumps virus vaccine as it increases the risk of infections.
    • Polio virus vaccine (live, trivalent) as it increases the risk of infections.
    • Varicella virus vaccine as it increases the risk of infections.
    • Typhoid vaccine (live) as it increases the risk of infections.
    • BCG vaccine as it increases the risk of infections.
    • Yellow fever vaccine as it increases the risk of infections.
    • Zoster vaccine (live) as it increases the risk of infections.
    • Tofacitinib as it increases the risk of infections.
    • Etelcalcetide as it increases the risk of hypocalcemia.
    • Etanercept as it increases the risk of infections.
    • Fingolimod as it increases the risk of infections.
    • Golimumab as it increases the risk of infections.
    • Infliximab as it increases the risk of infections.
    • Alefacept as it increases the risk of infections.
    • Alemtuzumab as it increases the risk of infections.
    • Azathioprine as it increases the risk of infections.
    • Canakinumab as it increases the risk of infections.
    • Cladribine as it increases the risk of infections.
    • Denosumab as it increases the risk of infections.
    • Efalizumab as it increases the risk of infections.
    • Ocrelizumab as it increases the risk of infections.
    • Omacetaxine as it increases the risk of infections.
    • Ustekinumab as it increases the risk of infections.
    • Cefalosporins as it may increase the risk of serious side effects such as anemia, bleeding problems, infections and nerve damage.

Click here to go to Pemetrexed forums.

By | 2017-12-28T12:42:46+00:00 September 2nd, 2017|medicines|0 Comments

About the Author:

B. Pharm (K.L.E. society's S.V.V. Patil College of Pharmacy, Bengaluru) M. Pharm (Maharishi Arvind Institute of Pharmacy, Jaipur)

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