METHOTREXATE UNITREXATE UNITREXATE UNITREXATE UNITREXATE MELADININE MTX MTX CYTOTREXATE CYTOTREXATE CYTOTREXATE PHARMATREXATE PHARMATREXATE METHOTREXATE METHOTREXATE METOTREXATO METOTREXATO METHOTREXATE METHOTREXATE METHOTREXATE METHOTREXATE METHOTREXATE EMTHEXATE PF EMTHEXATE PF EMTHEXATE EMTHEXATE DMARD METHOTREXATE METHOTREXATE METHOTREXATE METHOTREXATE

Dose: 12 mg/sq.meter
Single Dose: 22 (22)
Frequency: As recommended.
Route: Intra Thecal
Instructions: Once a week

Dose: 5 to 15 mg/sq.meter
Single Dose: 10 (10)
Frequency: As recommended.
Route: Intra Muscular
Instructions: Per Week for Rheum. Arthritis

Methotrexate also known as Amethopterin. . It is of Synthetic origin and belongs to Benzoyl Glutamic Acid. It belongs to Dihydrofolate reductase inhibitor pharmacological group on the basis of mechanism of action and also classified in Antineoplastic Agnet, Antimetabolite pharmacological group.The Molecular Weight of Methotrexate is 454.50. Its pKa is 4.8, 5.5.

Methotrexate is contraindicated in conditions like Neutropenia,Ulcerative colitis,Thrombocytopenia,Renal failure,Bone marrow depression,Pulmonary disease.

The severe or irreversible adverse effects of Methotrexate, which give rise to further complications include Hepatotoxicity, Coma, Seizures, Neurotoxicity, Hepatotoxicity, Eelvated hepatic enzymes, Chemical arachnoiditis, Motor paralysis of extremities, Cranial nerve palsy, Dementia, Dementia, Nuchal rigidity.Methotrexate produces potentially life-threatening effects which include Myelosuppression, Nephrotoxicity, GI mucositis. which are responsible for the discontinuation of Methotrexate therapy.The signs and symptoms that are produced after the acute overdosage of Methotrexate include Myelosuppression, Motor paralysis of extremities.The symptomatic adverse reactions produced by Methotrexate are more or less tolerable and if they become severe, they can be treated symptomatically, these include Nausea, Vomiting, Fever, Erythema, Cough, Ocular irritation, Desquamation, Pneumonitis, Vasculitis, Pleuritis, Intestitial pulmonary infitterate.

'Methotrexate is primarily indicated in conditions like Adjunct in epilepsy, Bone marrow transplantation, Breast cancer, Choriocarcinoma, Endometriosis, Gastric cancer, Graft rejection, Graft versus host disease, Granulomatous disease, Head and neck cancer, Juvenile rheumatoid arthritis, Leukaemia, Lymphocytic leukaemia, Lymphoma, Medulloblastoma, Mycoses, Non-hodgkin''s lymphoma, Osteosarcoma, Ovarian cancer, Pityriasis, Premedication, Psoriasis, Rheumatoid arthritis, Status epilepticus; seizures in neurosurgery, Wegeners granulomatosis, and can also be given in adjunctive therapy as an alternative drug of choice in Crohn''s disease, Dermatomyositis, Hydatidiform mole, Systemic lupus erythematosus.'

Methotrexate is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementAceclofenacAceclofenac increases plasma concentration of lithium, methotrexate and cardiac glycosides.Acetazolamide (Na)Acetazolamide potentiate effect of phenytoinAlcoholAmoxicillinLarge doses of amoxicillin elevate the serum concentration of methotrexate by competitively inhibiting its renal tubular secretion results in serious hematologic effects.MajorClosely monitor the serum concentration of methotrexate. Dose of methotrexate should be reduce if necessary.Leucovorin rescue should be available.AspirinAspirin reduces the renal elimination of methotrexate and may displace it from binding site, thus increase the pharmacological effect and toxicity of methotrexate.MajorClosely monitor the sign and symptoms of bone marrow suppression and nephrotoxicity.AzapropazoneBenorylateCarbenicillin (Na)Coadministration of large doses carbenicillin increases the serum level of methotrexate by competitive inhibition of renal tubular secretion of methotrexate.Hematological effects observed due to reduction in clearance of methotrexate upto 35%.MajorSerum concentration levels must be closely monitored and dose adjustment of methotrexate is necessary.CarmustineCelecoxibCholine Magnesium TrisalicylateCiprofloxacinCiprofloxacin increases the plasma concentration of methotrexate by competitively inhibiting renal tubular secretion of methotrexate result in severe toxicity.ModerateConcomitant use of these drugs considered contraindicated. Closely monitor for altered pharmacologic effects. Adjust the dose if necessary.Cop-FluampicilCo-TrimoxazoleCrisantaspaseDeflazacortDexibuprofenMethotrexate used at doses of 15 mg/week or more: If NSAIDs and methotrexate are given within 24 hours of each other plasma levels of methotrexate may increase, via a reduction in its renal clearance thus increasing the potential for methotrexate toxicity. The concomitant use of Dexibuprofen with methotrexate is not recommended.DexketoprofenDiclofenac (Na)Diclofenac increases the plasma concentration of methotrexate by interfering with renal elimination results in increased toxicity and pharmacological effects.MajorClosely monitor for signs of bone marrow suppression and nephrotoxicity. Avoid any other over-the-counter NSAID product.Doxorubicin (HCl)EnfluraneEtretinateEtretinate potentiate the risk of hepatitis when it is given with methotrexate.MajorCombination is considered contraindicated.FluorouracilFlurbiprofenFlurbiprofen increases the plasma concentration of methotrexate by interfering with renal elimination results in increased toxicity and pharmacological effects.MajorClosely monitor for signs of bone marrow suppression and nephrotoxicity. Avoid any other over-the-counter NSAID product.Folic AcidFolinic AcidIbuprofenIbuprofen increases the plasma concentration of methotrexate by interfering with renal elimination results in increased toxicity and pharmacological effects.MajorClosely monitor for signs of bone marrow suppression and nephrotoxicity. Avoid any other over-the-counter NSAID product.IndomethacinIndomethacin interfere with the renal excretion of methotrexate thus increases its pharmacological effects and toxicity.MajorClosely monitor for sign and symptoms of of bone marrow suppression and nephrotoxicity.KetoprofenExcretion of methotrexate is reduced by ketoprofen thus increase toxicity.MajorLow dose of methotrexate should be used and closely monitor thesign and symptoms of bone marrow suppression and nephrotoxicity.Ketorolac (Tromethamine)Ketorolac reduces the renal elimination of methotrexate result in increased toxicity and pharmacological effect.MajorClosely monitor for sign and symptoms of bone marrow suppression and nephrotoxicity.LornoxicamIncreased serum concentration of methotrexate and cyclosporinMedroxyprogesterone (Acetate)MethyltestosteroneCoadministration of methotrexate with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Methotrexate, especially at higher doses or with prolonged treatment, has been associated with hepatotoxicity including acute hepatitis, chronic fibrosis, necrosis, cirrhosis, and liver enzyme elevations.ModerateConcomitant use is generally not recommended unless the potential benefit outweighs the risk of hepatotoxicity. Baseline and regular monitoring of hepatic function is recommended.NabumetoneConcurrent use may enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.Caution should be used when NSAIDs are administered concomitantly with methotrexate.NaproxenExcretion of methotrexate is reduced by naproxen thus increase toxicity.MajorLow dose of methotrexate should be used. Closely monitor the sign and symptoms of bone marrow suppression and nephrotoxicity.NeomycinNeomycin decreases the GI absorption of methotrexate result in reduced efficacy of methotrexate.ModerateClosely monitor the altered efficacy and safety of methotrexate. Use intravenous route of administration for methotrexate to avoid interaction.Nitrous OxideOmeprazoleOmeprazole increases the serum concentration of methotrexate by inhibiting its active tubular secretion through renal H+/K+ ATPase pumps.ModerateOmeprazole therapy should discontinue several days before administration of methotrexate. Closely monitor the serum level and toxicity of methotrexate. Use H2 antagonist as an alternative.OxandroloneCoadministration of methotrexate with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Methotrexate, especially at higher doses or with prolonged treatment, has been associated with hepatotoxicity including acute hepatitis, chronic fibrosis, necrosis, cirrhosis, and liver enzyme elevations.ModerateConcomitant use is generally not recommended unless the potential benefit outweighs the risk of hepatotoxicity. Baseline and regular monitoring of hepatic function is recommended.OxymetholoneCoadministration of methotrexate with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Methotrexate, especially at higher doses or with prolonged treatment, has been associated with hepatotoxicity including acute hepatitis, chronic fibrosis, necrosis, cirrhosis, and liver enzyme elevations.ModerateCoadministration of methotrexate with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Methotrexate, especially at higher doses or with prolonged treatment, has been associated with hepatotoxicity including acute hepatitis, chronic fibrosis, necrosis, cirrhosis, and liver enzyme elevations.Paromomycin (Sulphate)The combined use of methotrexate and paromomycin decreases the GI absorption of methotrexate result in reduced efficacy of methotrexate.ModerateClosely monitor for altered efficacy and safety of methotrexate. Consider intravenous route of administration (for methotrexate) to avoid interaction.Phenylbutazone Phenytoin (Na)Methotrexate markedly decrease plasma phenytoin concentration, absorption and seizures but increases its metabolism.ModeratePhenytoin dosage must be increased during therapy and to decreased after therapy.Careful monitoring of seizures activity is recommended.Piperacillin (Na)Large doses of piperacillin elevate the serum concentration of methotrexate by competitively inhibiting its renal tubular secretion results in serious hematologic effects.MajorClosely monitor the serum concentration of methotrexate. Dose of methotrexate should be reduce if necessary.Leucovorin rescue should be available.Pivmecillinam (HCl)Clearance of methotrexate from the body can be reduced by concurrent use of Pivmecillinam (HCl). The methotrexate dose may need to be adjusted.ProbenecidProbenecid reduced excretion of methotrexate (increase toxicity).MajorLow doses of methotrexate should be given and patient monitor for symptoms of bone marrow suppression,hepatotoxicity and nephrotoxicity.ProcarbazineCoadministration results renal impairment because procabazine have transient effect on kidneys which alter the excreation of methotrexate.ModerateAn interval of 72 hours is recommended between administration of final dose of procarbazine.PyrimethamineThis combination will increase the risk of bone marrow depression.ModeratePeriodic monitoring for folic acid deficiency and bone marrow depression is recommended.Riboflavin (Vitamin B2)Methotrexate, a medication used to treat cancer and autoimmune diseases such as rheumatoid arthritis, can inhibit the body from using riboflavin.Salicylic AcidSalsalateWhen Salsalate are combined with methotrexate the blood levels of methotrexate may increase, presumably because the elimination of methotrexate is reduced. This may lead to side effects from methotrexate.Sodium AcetateAlkalinization of the urine can increase the renal elimination of methotrexate. The pharmacologic effects of methotrexate may be decreased. No special clinical interventions appear to be necessary. In some cases of methotrexate toxicity, this interaction may prove beneficial.MinorSodium CitrateSodium Citrate may increase the excretion and decrease the serum levels of Methotrexate, possibly decreasing their pharmacologic effects.Sodium SalicylateSalicylates interfere with the excretion of methotrexate and may displace it from binding site result in increased toxicity.MajorMonitor patient for signs and symptoms of bone marrow suppression and nephrotoxicity.Sodium ValproateSulfadimidine Concurrent use increases the toxicity of methotrexate.SulfametopyrazineSulfametopyrazine may potentiate effects of methotrexate.SulfapyridineThe effects of Methotrexate may be potentiated during concurrent use with sulfonamides because of displacement from plasma protein-binding sites.SulfisoxazoleSulfisoxazole decrease renal clearance of methotrexate and increase risk of bone marrow suppression.Sulfisoxazole may also displace methotrexate from plasma protein binding site.MajorComplete blood count should be monitored periodically for signs and symptoms of anemia,leukopenia, megaloblastosis and pancytopenia.SulfisoxazoleSulphadiazineSulphafurazole DiethanolamineSulphafurazole diethanolamine increases the effect of Methotrexate.SulphamethizoleThe effects of methotrexate may be potentiated during concurrent use with sulfonamides because of displacement from plasma protein binding sites.SultamicillinConcurrent use with penicillins has resulted in decreased clearance of methotrexate and a corresponding increase in methotrexate toxicity. Patients should be closely monitored.TeniposideConcurrent use may increase the plasma clearance of methotrexate.TenoxicamMethotrexate toxicity due to decreased elimination of methotrexate.Tetracycline (HCl)Tetracycline increases serum concentration of methotrexate by displacing it from the site of plasma protein binding.MajorThis combination should be avoided. An alternate anti-infective is recommended but if these drugs must be used together, closely monitor the serious methotrexate toxicity.TheophyllineMethotrexate reduces oral theophylline clearance.ModerateClose monitoring of theophylline serum level and signs of toxicity.Tiaprofenic AcidSevere bone marrow suppression, aplastic anemia, and GI toxicity have been reported with concomitant NSAID therapy. Avoid use during moderate or high-dose methotrexate.Tice-BCGMethotrexate may increase the risk of serious, life-threatening infections when given concurrently with Tice-BCG.TocilizumabThere is possibility of increase immunosuppression , risk of infection and marked elevation in liver enzyme when toclizumab is administered with DMARDs ( e.g Methotrexate)Reduce the dose of methotrexate i.e 10-25 mg once weeklyTolmetin (Na)Tolmetin increases the plasma concentration of methotrexate by interfering with renal elimination results in increased toxicity and pharmacological effects.MajorClosely monitor for signs of bone marrow suppression and nephrotoxicity. Avoid any other over-the-counter NSAID product.TrimethoprimCoadministration enhance thre risk of severe myelosuppression and megoblastic anemia due to synergistic effect involving folate antagonism.MajorCoadministration generally be avoided. If given then close monitoring for hematologic toxicity is recommended.Vidarabine (Monohydrate) These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.

False +ve result of protein in CSF

Drug should not be given to Pregnant Mothers, patients suffering from Kidney dysfunction, and Neonates.If prescribing authority justifies the benefits of the drug against the possible damages he/she should reevaluate them and consult the reference material and previous studies.

Tab, Inj Store in a well closed container, Below 40°C. Protect from Sunlight.

Methotrexate should be used with caution in patients with history of kidney, liver, lungs or intestinal diseases, chickenpox (or recent exposure to it), alcohol use and of any allergy, especially drug allergies. As this may cause sensitivity to the effects of the sun, so avoid prolonged exposure to sunlight or sunlamps. Avoid touching eyes or inside nose without first washing hands to prevent eye infections. Do not have immunizations or vaccinations without consent of doctor and avoid contact with people who have recently received oral polio vaccine. Avoid alcohol use. Males should ensure that effective contraceptive measures are used during and for 3 months after methotrexate treatment. Methotrexate should not be used during pregnancy or lactation.