Methotrexate 2.5mg Tablet (Emthexate)

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METHOTREXATE 2.5 MG TAB

  • Details of drug:
    • Drug Name
      • Brand : Emthexate 2.5
      • Generic : Methotrexate 2.5 mg
    • Strength : 2.5 mg
    • Dosage form : tablet
    • Drug classification : immunosuppressant, cytotoxic chemotherapy, DMARD [1]
    • Formulary class : SDL1
    • Regulatory Class : POM
    • Cost : $0.13
    • Manufacturer: Pharmachemie [1]
    • Distributer : Dynamed [1]
    • Recommended dosing

Others

  • Acute lymphoid leukemia
  • Juvenile rheumatoid arthritis, Polyarticular course [2]
  • Adult :
  •  Mycosis fungoides, Advanced
  •  Recommended : 5 to 50 mg orally once weekly
  •  Poor response to TX : 15 to 37.5 mg IM twice weekly
  •  Dose adjusted according to patient response and hematologic monitoring
  •  When used as a single agent to TX disease, 50% patient respond to therapy [2]
  •  2.5-10 mg a day orally for several weeks or months. Initial dose and follow-up doses are determined by patient response and haematological monitoring. Methotrexate 50 mg once a week or 25 mg twice a week IM has been employed as well. [3]
  •  Non-Hodgkin’s lymphoma, Advanced
  •  Recommended
  •  (Burkitt lymphoma- stage 1 & 2) : 10 to 25 mg/day orally for 4 to 8 days  [ TX may consist of several courses separated by rest periods of 7 to 10 days
  •  Stage 3 lymphosarcoma : Methotrexate 0.625 to 2.5 mg/kg/day with combination of antineoplastic agent [2]
  •  Psoriasis (Severe)
  •  Recommended : 10 to 25 mg/wk OR
  •                              Every 2.5 mg every 12 hours for 3 dose
  •  Once optimal response achieved, decrease the dose and increase the rest period
  •  CANNOT USE : dose above 30 mg/wk

 

——————————————————————————-

  •  Single weekly dose of 7.5 to 30 mg orally
  •  3 doses (2.5 to 5 mg) at 12-hours interval
  •  Test dose of 5 to 10 mg given to detect any unusual sensitivity to adverse effects, regular dosing initiated 1 week after lab result is normal
  •  Dose can gradually increase by 2.5 to 5 mg/wk
  •  Maximum doses should not exceed 20 mg/wk with divided schedule, OR 37.5 and 75 mg/wk with single oral use [2]
  •  The treatment of psoriasis in women should start immediately after the menstruation. One week prior to initiation of Emthexate therapy, a test dose of 5-10 mg is given parenterally to detect idiosyncratic reactions of the patient. [3]

Adults: 5-10mg PO given 1 week prior to initiation to detect reactions followed by:

  •  (A) 2.5 to 5 mg PO q12h for 3 doses weekly or q8h for 4 doses weekly. Increase dose by 2.5 mg/week but do not exceed 30 mg/week; OR
  •  (B) 10 to 25 mg PO/IM/IV once weekly. Increase dose by 2.5 to 5 mg weekly but do not exceed 50 mg/wk; OR
  •  (C) 2.5 mg PO daily for 5 days then 2 days rest. Daily dose should not exceed 6.25 mg. There may be more hepatotoxicity with this regimen. [4]

Others

  • Renal failure

Adult

  •  GFR 10 to 50 mL/min : receive 50% of the usual dose given at normal dose interval
  •  GFR less than 10 mL/min : avoid methotrexate
  •  GFR greater than 50 mL/min : no dose adjustment necessary
  •  Methotrexate 80% to 90% cleared unchanged by kidney
  •  Methotrexate clearance is 72% of CrCl [2]

Children

  •  GFR 10 to 50 mL/min : receive 50% of the usual dose given at normal dose interval
  •  GFR less than 10 mL/min : avoid methotrexate
  •  GFR greater than 50 mL/min : no dose adjustment necessary
  •  Methotrexate 80% to 90% cleared unchanged by kidney
  •  Methotrexate clearance is 72% of CrCl
  •  Full dose should be used if CrCl is greater than 60 mL/min
  •  High-dose methotrexate should not be used if the CrCl is less than 60 mL/min
  •  Reduce the dosage by 25% if CrCl is 10 mL/min to 60 mL/min and less, and by 50% if it is less than 10 mL/min [2]
  • Hepatic failure

Adult

  •  Bilirubin less than 3 mg/dL, AST less than 180 international unit : 100% dose may be administered
  •  Bilirubin 3.1 to 5 mg/dL, AST greater than 180 international unit : 75% dose may be administered
  •  Bilirubin more  than 5 mg/dL : dose omitted [2]

Children

  •  Bilirubin less than 3 mg%, AST less than 180 international unit : 100% dose may be administered
  •  Bilirubin 3.1 to 5 mg%, AST greater than 180 international unit : 75% dose may be administered
  •  Bilirubin more  than 5 mg% : dose omitted [2]
  •  Chemotherapeutic agent act by inhibiting dihydrofolate reductase (enzyme that reduces folic acid to tetrahydrofolic acid, which helps in the synthesis of nucleotide and thymidylate) Dihydrofolate reductase interferes with DNA synthesis, repair and cellular reproduction.
  •  breastfeeding; risk of serious adverse reactions in breast fed infant
  •  known hypersensitivity to methotrexate
  •  males, sexually active; avoid impregnating female during and for a minimum of 3 months after therapy
  •  patients with psoriasis who have preexisting blood dyscrasias (such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia), overt or laboratory evidence of immunodeficiency syndromes, and/or alcoholism, alcoholic liver disease, or other chronic liver disease
  •  pregnant women with psoriasis or rheumatoid arthritis; may cause fetal death or teratogenic effects; avoid pregnancy during and for at least 1 ovulatory cycle after therapy [2]
  •  Contraindicated in pregnancy & lactation and in the treatment of psoriasis of patients in a poor state of nutrition, serious renal or liver disorders, bone marrow hypoplasia, leucopenia, thrombocytopenia or anaemia.
  •  Should not be used in infectious disease (ie, tuberculosis, pyelonephritis, etc). [3]
  • Indication
    • Palliative treatment of acute lymphoblastic leukaemia (CNS, leukaemia and maintenance therapy). In combination with corticosteroids, Emthexate is commonly used to maintain remissions. It can also be used in treating osteosarcoma, non-Hodgkin’s lymphoma, advanced cancer at the head and neck, invasive tumours at the bladder, Burkitt’s lymphoma, advanced stages of lymphosarcoma especially in children in combination with other drugs, and in advanced stages of mycosis fungoides. It has also been used in treating serious cases of psoriasis in adults, but regarding the serious risks, only in severe cases, resistant to other forms of therapy and only if the diagnosis has been made by biopsy and/or dermatological examination.[3]
  • MOA
    • Tissues with high rates of cellular proliferation such as neoplasms, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are generally more sensitive to the effects of methotrexate than most normal tissues [2]
  • Instruction to patient
    • Counselling point
      • Should not be used if allergy to methotrexate or breastfeeding
      • Should not be used for psoriasis if pregnant, or liver disease or certain problem with blood or immune system
      • Ask If patient drink alcohol and on a regular basis
      • Medication have many side effects, make sure patient understand all the risk and benefits before receiving TX
      • Ask healthcare professionals on the best way to dispose unwanted medicine
      • Harmful if you are pregnant, can harm unborn baby.
        • Cause birth defect when father is using it when his sexual partner becomes pregnant
        • Man : continue birth control for at least 3 months after stopping treatment
        • Woman : continue birth control until you have had two menstrual periods after stopping treatment
      • May make skin more sensitive to sunlight. Wear sunscreen. Do not use sunlamps or tanning bed. Tell doctor if increased skin redness or other problem
      • May get infections more easily. Wash hands frequently [2]
    • How to use it
      • Take medication for psoriasis only once a week, best to take it on the same day each week
      • Ask doctor if unsure when or how often to take the medication
      • If miss a dose, take it as soon as you remember.
        • If it is almost time for your next dose, wait until then and take a regular dose
        • Do not take extra medicine to make up for a missed dose (If you use this medicine only once a week and you miss a dose or forget to use your medicine, skip the missed dose and use your medicine as soon as possible. Return to your regular schedule the following week. Do not use extra medicine to make up for a missed dose.) [2]
  • Side effect
    • Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing
    • Blistering, peeling, red skin rash
    • Cough, fever, chest pain, trouble breathing, blue lips or fingers
    • Eyes or skin turn yellow, or dark-colored urine or pale stools
    • Fever
    • Nausea, vomiting, diarrhea, loss of appetite, stomach pain
    • Sores or white patches on your lips, mouth, or throat
    • Unusual bleeding, bruising, or weakness [2]
    • Interference with the rapidly dividing cells of healthy organs ( bone marrow, epithelium of mouth and throat, mucosa of the gastrointestinal tract, bladder and gonads)
    • Bone marrow depression
    • Haematotoxicity: Leucopenia, thrombocytopenia and anaemia
    • Gastrointestinal System: stomatitis ulcerosa = toxicity
    • Liver: Atrophy, necrosis, fatty degeneration, fibrosis and cirrhosis.
    • Skin: Erythematosus rashes, alopecia, irregular formation of the nails, pigmentation, pruritus, urticaria, folliculitis, vasculitis and acne.
    • Weakened Resistance: Increasing chance of infection by involution of spleen, lymph glands and thymus and lack of granulocytes. Fungi that are generally non-pathogenic can affect the body. Chills and fever, pneumonia, cystitis.
    • Other Side Effects: Headache, sleepiness, tiredness and dizziness. Aphasia, hemiparesis, convulsions, hypogammaglobulinemia, defective oogenesis or spermatogenesis, transient oligospermia, menstrual dysfunction and sterility. [3]
  • ADR
    • Common
      • Dermatologic: Alopecia (0.5% to 10% ), Photosensitivity (3% to 10% ), Rash, Sensation of burning of skin (3% to 10% )
      • Gastrointestinal: Abdominal pain, Diarrhea (1% to 3% ), Indigestion, Nausea, Stomatitis (2% to 10% ), Vomiting
      • Hematologic: Thrombocytopenia (3% to 10% )
      • Hepatic: Increased liver enzymes (14% to 15% )
      • Neurologic: Dizziness (0.2% to 3% ), Headache (1.2%)
      • Respiratory: Bronchitis, Nasopharyngitis
    • Serious
      • Cardiovascular: Thromboembolic disorder
      • Dermatologic: Erythema multiforme, Stevens-Johnson syndrome, Toxic epidermal necrolysis
      • Hematologic: Agranulocytosis, Aplastic anemia, Leukopenia (1% to 3% ), Pancytopenia (1% to 3% )
      • Hepatic: Cirrhosis of liver (0.1% ), Hepatic fibrosis (7% ), Hepatotoxicity
      • Immunologic: Opportunistic infection
      • Renal: Renal failure [2]

 

  • CI
  • Interaction
    • Drug Drug

Aceclofenac

Acemetacin

Acitretin

Adapalene

Adenovirus Vaccine Type 4, Live

Adenovirus Vaccine Type 7, Live

Alitretinoin

Amiodarone

Amoxicillin

Amtolmetin Guacil

Asparaginase

Aspirin

Azathioprine

Bacillus of Calmette and Guerin Vaccine, Live

Bentiromide

Bexarotene

Bromfenac

Bufexamac

Celecoxib

Chloral Hydrate

Chloramphenicol

Cholestyramine

Choline Salicylate

Ciprofloxacin

Clonixin

Cobicistat

Cyclosporine

Dantrolene

Dexibuprofen

Dexketoprofen

Dexlansoprazole

Diclofenac

Dicloxacillin

Diflunisal

Dipyrone

Doxycycline

Eltrombopag

Esomeprazole

Etodolac

Etofenamate

Etoricoxib

Etretinate

Felbinac

Fenbufen

Fenoprofen

Fenretinide

Fepradinol

Feprazone

Floctafenine

Floxacillin

Flufenamic Acid

Flurbiprofen

Folic Acid

Fosphenytoin

Hydrochlorothiazide

Ibuprofen

Ibuprofen Lysine

Indomethacin

Influenza Virus Vaccine, Live

Isotretinoin

Ketoprofen

Ketorolac

Leflunomide

L-Methylfolate

Lornoxicam

Loxoprofen

Lumiracoxib

Measles Virus Vaccine, Live

Meclofenamate

Mefenamic Acid

Meloxicam

Mercaptopurine

Mezlocillin

Morniflumate

Mumps Virus Vaccine, Live

Nabumetone

Naproxen

Neomycin

Nepafenac

Niflumic Acid

Nimesulide

Omeprazole

Oxaprozin

Oxyphenbutazone

Pantoprazole

Parecoxib

Penicillin G

Penicillin V

Phenylbutazone

Phenytoin

Piketoprofen

Piperacillin

Piroxicam

Pirprofen

Pranoprofen

Pristinamycin

Probenecid

Procarbazine

Proglumetacin

Propyphenazone

Proquazone

Pyrimethamine

Rabeprazole

Rofecoxib

Rotavirus Vaccine, Live

Rubella Virus Vaccine, Live

Salicylic Acid

Salsalate

Sapropterin

Smallpox Vaccine

Sodium Salicylate

Sulfamethizole

Sulfamethoxazole

Sulfapyridine

Sulfasalazine

Sulfisoxazole

Sulindac

Tamoxifen

Tazarotene

Tegafur

Tenoxicam

Tetracycline

Theophylline

Tiaprofenic Acid

Ticarcillin

Tolfenamic Acid

Tolmetin

Tretinoin

Triamterene

Trimethoprim

Typhoid Vaccine

Valdecoxib

Varicella Virus Vaccine

Warfarin

Yellow Fever Vaccine[2]

 

Since methotrexate is partially bound to serum proteins, its effect may be increased by preparations eg, salicylates, sulfonamides, phenytoin, tetracyclines, chloramphenicol and p-aminobenzoic acid, sulfisoxazole, adriamycin, bleomycin, cyclophosphamide, NSAIDs, aminoglycosides, allopurinol, vincristine, hydrocortisone, prednisone, asparaginase and cytosine arabinoside by displacement, thereby increasing the fraction of free methotrexate in plasma. Weak organic acids, like probenecid and salicylic acid can delay renal excretion of methotrexate. Both interactions increase the therapeutic activity and toxicity of methotrexate.

No vaccination with live virus vaccines should be performed in patients receiving methotrexate. Partial or total protection can be attained by means of killed vaccines. Folic acid preparations can decrease the effectiveness of methotrexate therapy. Antibiotics may influence intestinal flora and impede methotrexate re-absorption.

Interaction with therapeutic radiation may occur. In combination with other cytostatic drugs, pharmacologic interactions may occur; resulting in increased therapeutic activity and increased toxicity. [3]

  • Drug food
    • Ethanol
  • Drug Lab
    • Folic acid
    • Vitamin B12
  • IV admixture
    • Methotrexate
    • Aluminum
    • Aztreonam
    • Bleomycin
    • Cephalothin
    • Cisplatin
    • Cyclophosphamide
    • Cytarabine
    • Dacarbazine
    • Doxapram
    • Doxorubicin
    • Droperidol
    • Filgrastim
    • Fludarabine
    • Fluorouracil
    • Furosemide
    • Heparin
    • Heparin Sodium

Hydrocortisone Sodium Succinate

Hydroxyzine

Idarubicin

Leucovorin

Mercaptopurine

Metoclopramide

Mitomycin

Ondansetron

Paclitaxel

Prednisolone

Propofol

Ranitidine

Sargramostim

Sodium Bicarbonate

Vancomycin

Vinblastine

Vincristine [2]

  • Pregnancy class

FDA Pregnancy Rating Category X

  • Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant. [2]

 

Australian Pregnancy Rating Rating D

  • Drugs which have caused, are suspected to have caused, or may be expected to cause an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. [2]

 Source

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