Methotrexate Pharmacology


About Methotrexate
Antimetabolite ,antifolate, Immunosuppressant, Antineoplastic, Antirheumatic.
Mechanism of Action of Methotrexate
Drug inhibits the enzyme dihydrofolate reductase (DHFR), which catalyses the conversion of dihydrofolate to active tetrahydrofolate.It is an important step in the folic acid synthesis. Folic acid is needed for the de novo nucleoside thymidine, required for DNA synthesis. Drug therefore, inhibit the synthesis of DNA, RNA and protein. In lower doses it inhibit the enzyme involved in purine metabolism, leading to accumulation of adenosine, or the inhibition of T-cell activation and suppression of intercellular adhesion molecule expression by T-cells.
Pharmacokinets of Methotrexate
Absorption-Absorption after oral administration depends upon the doses. At lower doses there is complete absorption and at larger doses incomplete absorption.
Completely absorbed, after intramuscular and intravenous administration
Distribution- Widely distributed in the body.50% bound to the plasma proteins. It crosses the blood brain barrier and enters to the cerebrospinal fluid.
Metabolism- Metabolized into its metabolites in the liver.
Excretion-Excreted through urine
Onset of Action for Methotrexate
Duration of Action for Methotrexate
Half Life of Methotrexate
Its plasma half life is 3-15hrs
Side Effects of Methotrexate
1. Nausea
2. Vomiting
3. Difficulty in breathing
4. Closing of the throat
5. Bone marrow suppression
6. Bruising or unusual bleeding
7. Tarry stools
8. Fever
9. Chills
10. Congestive heart failure
11. Diarrhea
12. Loss of appetite
13. Facial flushing
14. Darkening of skin and nails
15. Alopecia
16. Red urine
17. Hepatotoxicity
18. Hyperurecemia
19. Pancreatitis
20. GI ulceration
21. Jaundice
22. Thrombocytopenia
23. Leucopenia
24. Arachnoiditis
25. Neurotoxicity
26. Necrotizing demyelinating leukoencephalopathy
27. Pharyngitis
28. Gingivitis

Contra-indications of Methotrexate
1. Hypersensitivity to the drug
2. Haematological failure
3. Immunodeficiency
4. Treatment of rheumatoid arthritis or psoriasis
5. Blood dyscriasis
6. Liver disease
7. Abnormal liver function test
8. Renal failure
Special Precautions while taking Methotrexate
1. Renal impairment
2. Hepatic impairment
3. Bone marrow depression
4. Ulcerative disorders of the GIT
5. CNS disturbances
6. Folate deficiency
7. Infection
8. Monitor patient`s haematological, hepatic and renal function regularly.
Pregnancy Related Information
Old Age Related Information
Use with caution
Breast Feeding Related Information
Children Related Information
Use with caution
Indications for Methotrexate
1. Acute lymphoblastic leukemia
2. Choriocarcinoma
3. Burkitt`s lymphoma
4. Meningeal leukemia
5. Lymphosarcoma
6. Hydatidiform mole
7. Psoriasis
8. Rheumatoid arthritis
9. Corticosteroid dependant asthma
10. Non metastatic osteosarcoma
11. Mycosis fungoides
12. Carcinoma of neck
13. Carcinoma of head
14. Crohn`s disease
Interactions for Methotrexate
Aminoglycosides: Decrease absorption and AUC of oral methotrexate.
Charcoal: Decreases serum level of both oral and IV methotrexate.
Etretinate: Hepatotoxicity.
Folic acid or its derivatives: Decrease response to methotexate.
NSAIDs: Increase plasma levels of methotrexate which may be fatal.
Phenytoin: Serum concentation of phenytoin decreased.
Probenecid, Salicylates & Sulfonamides (including Phenylbutazone, Tetracyclines, Chloramphenicol, PABA & TMP-SMZ): Increase in efficacy as well as toxic effects of methrotrexate.
Procarbazine: Increases nephrotoxicity of methotrexate.
Thiopurines: Increase AUC and plasma levels of thiopurines.
Asparaginase: Reduces toxicity.
Food: Reduction in plasma concentration of methotrexate.
Typical Dosage for Methotrexate
For acute lymphoblastic leukemia: 15mg/metre square once or twice weekly
For choriocarcinoma: 15 to 30 mg/day for 5 days at intervals of 1-2weeks, for 3-5 cycles
For Burkitt`s lymphoma:10 to15 mg/day for 4-8 days, repeated after 7-10 days
For mycosis fungoides:2.5 to 10mg/day
For psoriasis: 10 to 25mg/day
For rheumatoid arthritis:7.5mg weekly
For choriocarcinoma:15-30mg/metre square for 5 days at intervals of 1-2 weeks; 3-5 such cycle
For Burkitt`s lymphoma:50mg as a single dose or in 2 divided doses weekly
For adjunct treatment in osteocarcinoma:12mg/metre square for 4 hour
For head and neck carcinoma: 40-60mg/metre square /week
Schedule of Methotrexate
Storage Requirements for Methotrexate
Stored at room temperature away from light and moisture
Effects of Missed Dosage of Methotrexate
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.
Effects of Overdose of Methotrexate
Give symptomatic and supportive treatment. Administer an antagonist (calcium leucoverin) for hematopoetic toxicity, within one hour after methotrexate intake.

Home Delivery for Methotrexate in Your City

Medicine India is just a publishing medium for medicine related information and does not provide services or sales of medicines including methotrexate.

However, we do publish a comprehensive directory of Pharmacies, Chemists and Druggists in cities all over India. You can use this directory to find the medicine stores in your city (or area) that provide home delivery services for methotrexate and other medicines and health products. Home delivery services for methotrexate may be free or they may cost you depending on the pharmacy and the minimum order requirements. It would be best to get this clarified while placing the order.

Please be aware that you should take methotrexate only if a doctor has recommended or prescribed it. Some or all pharmacies who provide a home delivery service for medicines might insist on a prescription for methotrexate before they complete the sale. You can get this information while placing the order for methotrexate with the pharmacy.

Methotrexate is a generic medicine name and there are several brands available for it. Some of the brands for methotrexate might be better known than methotrexate itself. If the pharmacy that's willing to deliver medicines to your home doesn't have methotrexate in stock, you can ask for one of the branded alternatives for methotrexate.