Drug profile of methotrexate :Introduction, History, ROA, Dose, MOA, Pharmacokinetics, Drug interactions, Side effects, Contraindications, Uses, Monitoring.

Drug profile of methotrexate : Introduction, History, ROA, Dose, MOA, Pharmacokinetics, Drug interactions, Side effects, Contraindications, Uses, Monitoring.

1. DRUG PROFILE OF METHOTREXATE D.Nishika Pharm.D Geethanjali college of pharmacy

2. Introduction Methotrexate (Mtx) is one of the oldest and highly efficacious anti-cancer drug. Amethopterin is the old name of methotrexate. Mtx is invented by Yellapragada subba rao. Mtx is antimetabolite class of drug that is used in the treatment of cancer. Mtx is used as DMARD (Disease modifying anti-Rheumatic drug) in the treatment of Rheumatoid arthritis.

3. It also acts as anti-inflammatory drug in the treatment of psoriasis and crohn’s disease. It works by decreasing inflammation, which can reduce pain and prevent long-term injury to the joints and skin. It may also be used to treat some types of cancer. It works by slowing down the growth of cancer cells. Mtx is an FDA approved folic acid antagonist indicated for the treatment of R A because of its high potency and efficacy. It can also be useful in patients with juvenile idiopathic arthritis.

4. History Methotrexate was first made in 1947 and initially was used to treat cancer, as it was less toxic than the then-current treatments. In 1956 it provided the first cures of a metastatic cancer. It is on the WHO List of Essential Medicines. Mtx is available as a generic medication. In 2021, it was the 132nd most commonly prescribed medication in the United States, with more than 4 million prescriptions.

5. Routes of administration : Oral Parenteral : Intravenous Intramuscular Subcutaneous Intrathecal Intra-arterial

6. Dose : 10-25mg /week for psoriasis 7.5mg /week for Rheumatoid arthritis High doses daily for cancer patients Folic acid is commonly co-prescribed with methotrexate to minimise the risk of adverse effects - Megaloblastic anaemia

7. Mechanism of action Note : DHFA – Dihydro folic acid DHFAR – Dihydro folic acid reductase THFA - Tetrahydro folic acid (DHFR Blocks by Mtx) (TS Blocks by Mtx)

8. Pharmocokinetics Absorption : Mtx is rapidly absorbed through GIT. Concurrent food intake (Particularly milk-based) reduces bioavailability in children but not in adults. Peak level (oral route) occurs in 1 hour. Dose of 30mg is well absorbed. Distribution : Broad distribution. Mtx is widely distributed into the body tissues with highest concentrations in kidneys, spleen, liver & skin.

9. After absorption, undergoes triphasic reduction in the body : 1 st phase : Takes 0.75 hours and represents distribution in the body. 2 nd phase : Takes 2-4 hrs and represents renal excretion. 3 rd phase : Takes 10-27 hrs and represents terminal half-life. Metabolism : Metabolism of Mtx is by liver and intracellular. Excretion : 90% of Mtx is excreted unchanged in urine within 48 hrs by glomerular secretion and active tubular secretion.

10. Drug interactions Alcohol : Increases toxicity in liver. Dipyridamole : Increase intracellular accumulation of Mtx. Probenecid : Intracellular accumulation of Mtx and decreased renal tubular function. NSAID : Decreased renal excretion. Penicillins : Decrease elimination of Mtx and increase risk of toxicity. Amino glycosides : Reduce GI absorption of Mtx. Theophylline : Mtx decrease the clearance of theophylline.

11. Side effects The common side effects are : Nausea & vomiting Megaloblastic anaemia Gastric pain Loss of appetite Loss of hair Dizziness Difficulty in breathing The other side effects are : Blood in urine Dark stools Irregular heartbeat Bone marrow suppression Low white blood cells On high doses causes mucosal ulceration

12. Contraindications Hypersensitivity to methotrexate Pregnant or breastfeeding women Pre-existing blood disorders Bone marrow hypoplasia Significant anaemia Chronic liver disease Liver cirrhosis Chronic alcoholism Active TB or Hepatitis Renal dysfunction

13. Uses In the treatment of cancer Rheumatoid arthritis Psoriasis Inflammatory bowel disease Acute leukemia Non-Hodgkin lymphoma Ectopic pregnancy Crohn’s disease Rheumatoid arthritis Psoriasis

14. Monitoring Careful history and physical examination. Identify patients with increased risk of toxicity. Monitor CBC and Platelet count. Liver function test should be done. (Liver biopsy can be done in case of hepatotoxicity) Serolo gic tests for hepatitis B,C. Creatinine clearance to avoid possible nephrotoxicity. HIV testing in patients at risk for AIDS. Monitoring for pulmonary toxicity. Methotrexate may also cause reactivation of TB in endemic countries, so tests to eliminate the presence of TB are required.

15. Reference www.drugs.com/methotrexate.html www.mayoclinic.org www.medicalnewstoday.com www.sciencedirect.com www.healthline.com

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