Acitretin is the principal active component of etretinate. Although no longer available commercially in the United States, etretinate has been shown to increase methotrexate serum concentrations and cases of hepatotoxicity e. Moderate The safety and efficacy of adalimumab in patients with immunosuppression have not been evaluated.
The apparent clearance of adalimumab was decreased by 29 percent after a single dose and by 44 percent after multiple doses of methotrexate. The mean steady state trough concentration of adalimumab was 8 to 9 mcg, ml with concomitant methotrexate versus 5 mcg, ml without methotrexate use. However, no dose adjustment for either drug is needed when methotrexate and adalimumab are used together. Moderate The safety and efficacy of aldesleukin, IL-2 in combination with chemotherapy agents have not been established; however, concurrent or sequential use of these agents is common but results in various pharmacodynamic drug interaction risks.
Aldesleukin is associated with serious adverse reactions affecting many organ systems. Concurrent administration of antineoplastic agents possessing nephrotoxic, myelotoxic, or hepatotoxic effects e. Severe Patients receiving other immunosuppressives should not receive concurrent therapy with alefacept; there is the possibility of excessive immunosuppression and subsequent risks of infection and other serious side effects.
Minor In vitro studies have shown that allopurinol administered one hour prior to methotrexate may decrease the therapeutic effects of methotrexate. Moderate Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Moderate Due to the thrombocytopenic effects of folate analogs, when used as antineoplastic agents, an additive risk of bleeding may be seen in patients receiving concomitant thrombolytics.
Aminosalicylate sodium, Aminosalicylic acid: Major Use caution when administering high-dose methotrexate to patients receiving proton pump inhibitors PPIs ; a temporary withdrawal of the PPI should be considered in some patients receiving high-dose methotrexate.
In two of these cases, delayed methotrexate elimination was observed when high-dose methotrexate was coadministered with PPIs but was not observed when methotrexate was coadministered with ranitidine. However, no formal drug interaction studies of methotrexate with ranitidine have been conducted. Altered methotrexate elimination may not be present or problematic among patients who receive lower methotrexate doses.
For example, coadministration of lansoprazole 30 mg daily and naproxen mg twice daily for 7 days to recipients of stable oral methotrexate doses 7. Specifically, the peak plasma concentration and area under the plasma concentration-time curve of methotrexate and 7-hydroxymethotrexate were within the 0. Moderate Due to the thrombocytopenic effects of folate analogs, when used as antineoplastic agents, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Moderate Because antithymocyte globulin is an immunosuppressant, additive affects may be seen with other immunosuppressives or antineoplastic agents.
While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections, malignancies including lymphoma and leukemia, myelodysplastic syndromes, and lymphoproliferative disorders. Major L-Asparaginase with methotrexate has shown both therapeutic synergistic and antagonistic effects depending upon the schedule of administration of these agents.
When methotrexate is given 3 to 24 hours prior to L-asparaginase, L-asparaginase blocks the antifolate effects of methotrexate and decreases methotrexate toxicity. If L-asparaginase is given prior to methotrexate, the efficacy of methotrexate is decreased.
Moderate Folic acid may compete with methotrexate for entry into cells. However, in some situations, folic acid supplementation may be used to decrease adverse reactions such as mouth sores in patients receiving methotrexate for arthritis and other non-malignant diseases.
Folic acid, vitamin B9, is NOT effective for methotrexate rescue therapy since folic acid requires dihydrofolate reductase for bioactivation and methotrexate inhibits this enzyme. Therefore folic acid should not be used to prevent toxicity of moderate- to high-dose methotrexate therapy. Minor L-methylfolate should be used cautiously in patients taking methotrexate. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with methotrexate.
Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. Severe Live virus vaccines should generally not be administered to an immunosuppressed patient.
Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses.
If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Minor Because basiliximab is an immunosuppressant, additive effects may be seen with other immunosuppressives such as methotrexate. Major Concomitant use of systemic retinoids, such as bexarotene, and methotrexate could increase risk of liver-related side effects of methotrexate and such patients should be monitored closely during methotrexate therapy.
Topical retinoid products do not appear to pose this increased risk for liver problems. Bismuth Subsalicylate; Metronidazole; Tetracycline: Black Cohosh, Cimicifuga racemosa: Moderate Black cohosh, Cimicifuga racemosa, has been reported to cause liver problems; however, causality has not been established. It is possible that black cohosh would act synergistically with other medications that can have adverse effects on the liver.
Until more is known, the concurrent use of black cohosh in patients taking methotrexate is not recommended as a precaution. Minor Capecitabine may cause leukopenia or other hematologic effects and result in side effects that may be additive to other agents which cause bone marrow or immune suppression such as other antineoplastic agents. Moderate Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution.
Dosage adjustments may be necessary. Major In general, NSAID therapy can decrease the clearance of methotrexate, resulting in elevated and prolonged serum methotrexate levels. Nonsteroidal antiinflammatory drugs NSAIDs should not be administered prior to, concomitantly, or following intermediate or high doses of methotrexate. Concomitant administration of NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum concentrations of methotrexate resulting in deaths from severe hematologic and gastrointestinal toxicity.
In patients with rheumatoid arthritis, methotrexate has been given concurrently with NSAIDs without apparent problems. It should be noted that the doses of methotrexate used in rheumatoid arthritis are lower than those used in psoriasis or malignant disease; higher methotrexate doses may lead to unexpected toxicity in combination with NSAIDs. Concurrent use of NSAIDs may increase the risk of GI bleeding in patients with methotrexate-induced myelosuppression or mask fever, pain, swelling and other signs and symptoms of an infection.
Moderate The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
Minor Chloramphenicol may decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria. Chloramphenicol may also displace methotrexate from protein binding sites leading to increased methotrexate levels.
Major The bile-acid sequestrant cholestyramine is well-known to cause drug interactions by binding and decreasing the oral administration of many drugs.
Cholestyramine enhances the clearance of methotrexate from the systemic circulation. This interaction has been used therapeutically in patients with methotrexate toxicity. To minimize drug interactions, administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine. Choline Salicylate; Magnesium Salicylate: Moderate Renal tubular transport of methotrexate may be inhibited by coadministration with ciprofloxacin. This may potentially lead to increased methotrexate plasma concentrations and increase the risk of methotrexate associated toxic reactions.
Therefore, patients on methotrexate therapy should be carefully monitored when concomitant ciprofloxacin therapy is indicated. Moderate Cisplatin can delay the renal clearance of methotrexate.
In all instances where the use of methotrexate is considered for chemotherapy, the physician must evaluate the need and usefulness of the drug against the risks of toxic effects or adverse reactions. Most such adverse reactions are reversible if detected early. When such effects or reactions do occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken according to the clinical judgement of the physician.
Reinstitution of methotrexate therapy should be carried out with caution, with adequate consideration of further need for the drug and alertness as to the possible recurrence of toxicity. Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis. Methotrexate is extensively protein bound and may be displaced by certain drugs such as salicylates, hypoglycaemics, diuretics, sulphonamides, diphenylhydantoins, tetracyclines, chloramphenicol and p-aminobenzoic acid, and the acidic anti-inflammatory agents, so causing a potential for increased toxicity when used concurrently.
Concomitant use of other drugs with nephrotoxic,myelotoxic or hepatotoxic potential such as leflunomide, azathioprine, sulphasalazine, retinoids and alcohol should be avoided. Vitamin preparations containing folic acid or its derivatives may decrease the effectiveness of methotrexate. These drugs have been reported to reduce the tubular secretion of methotrexate and thereby may enhance its toxicity.
However, patients using constant dosage regimens of NSAIDs have received concurrent doses of methotrexate without problems observed.
Renal tubular transport is also diminished by probenecid and penicillins; use of these with methotrexate should be carefully monitored. A potential interaction may exist between methotrexate and proton-pump inhibitors e.
Omeprazole may inhibit methotrexate clearance resulting in potentially toxic methotrexate levels. Severe bone marrow depression has been reported following the concurrent use of methotrexate and co-trimoxazole or trimethoprim. Concurrent use should probably be avoided. Methotrexate-induced stomatitis and other toxic effects may be increased by the use of nitrous oxide.
Existing data suggest that etretinate is formed from acitretin after ingestion of alcoholic beverages. However, the formation of etretinate without concurrent alcohol intake cannot be excluded.
Serum levels of methotrexate may be increased by etretinate and severe hepatitis has been reported following concurrent use. Consequently, the concomitant use of methotrexate and acitretin should be avoided. Methotrexate may increase the bioavailability of mercaptopurine by interference with first-pass metabolism. Concomitant application of methotrexate and theophylline can reduce theophylline clearance.
Methotrexate is contraindicated in the management of psoriasis or rheumatoid arthritis in pregnant women. Women of childbearing potential should not receive methotrexate until pregnancy is excluded. For the management of psoriasis or rheumatoid arthritis, methotrexate therapy in women should be started immediately following a menstrual period and appropriate measures should be taken in men or women to avoid conception during and for at least 6 months following cessation of methotrexate therapy.
Breast-feeding Methotrexate is distributed into breast milk. Because of the potential for serious adverse reactions to methotrexate in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman. Fertility Both men and women receiving methotrexate should be informed of the potential risk of adverse effects on reproduction.
Women of childbearing potential should be fully informed of the potential hazard to the foetus should they become pregnant during methotrexate therapy. In cancer chemotherapy, methotrexate should not be used in pregnant women or women of childbearing potential who might become pregnant unless the potential benefits to the mother outweigh the possible risks to the foetus.
Defective oogenesis or spermatogenesis, transient oligospermia, menstrual dysfunction, and infertility have been reported in patients receiving methotrexate. Although very rare, anaphylactic reactions to methotrexate have occurred. Others reported are malaise, undue fatigue, chills and fever, dizziness and decreased resistance to infection. In general, the incidence and severity of side effects are considered to be dose-related. Adverse reactions as reported for the various systems are as follows: Severe, occasionally fatal, dermatologic reactions including erythema multiforme, Stevens-Johnson syndrome, skin necrosis, exfoliative dermatitis, epidermal necrolysis.
Erythematous rashes, pruritus, urticaria, dermatitis, photosensitivity, pigmentary changes, alopecia, ecchymosis, telangiectasia, acne, furunculosis. Methotrexate very rarely causes a serious lung problem. Patients should call their doctor and STOP taking methotrexate if they experience: Patients should always check with their doctor or pharmacist before starting a new medication. A doctor should review blood test results every months to keep an eye out for any potential side effects to the liver or blood counts.
It is important for patients who take methotrexate to remember to get these blood tests done. Patients taking methotrexate should not drink alcohol. Methotrexate may cause birth defects and result in miscarriage. The information sheets given by pharmacists do not distinguish between high and low dose Methotrexate. This is not a complete list of possible side effects.
If you notice other effects not listed above, contact your doctor or pharmacist. Call your doctor for medical advice about side effects. In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at Click here to view a more detailed list of Methotrexate side effects.
For the best possible benefit, it is important to receive each scheduled dose of Methotrexate 2. If you miss a dose of Methotrexate 2. Do not double the dose to catch up. Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions.
Do not start, stop, or change the dosage of any medicines without your doctor's approval. Some products that may interact with Methotrexate 2. Certain drugs that reduce stomach acid proton pump inhibitors-PPIs such as esomeprazole, omeprazole, pantoprazole may increase the amount of Methotrexate 2.
This effect may increase the risk of side effects, especially with high-dose Methotrexate 2. Ask your doctor or pharmacist for details and ways to lessen the risk of side effects. Women must avoid becoming pregnant while using Methotrexate 2.
A history of allergic or adverse reactions to Methotrexate Sodium or any related drug or any excipient of methotrexate tablets. Females of childbearing potential unwilling to use adequate contraception as defined in the protocol throughout the trial and for one month after the last dose of study medication.
Males unwilling to use a male condom throughout the trial and for three months after the last dose of study medication Patients with alcoholism, alcoholic liver disease or other chronic liver disease. Patients who have clinically significant abnormal laboratory values at screening. Patients with any evidence of organ dysfunction or any clinically significant deviation from normal in their physical or clinical evaluation including ECG and X-ray results except study indication.
Patients who have overt or laboratory evidence of immunodeficiency syndromes.
Deaths have been reported tablet the use of methotrexate in the treatment of psoriasis. Your doctor will monitor your blood counts with regular blood tests. The immunosuppressive effect of methotrexate should be taken into account when immune responses of patients are important or essential. Therefore, patients receiving concomitant therapy with vasotec pharmaceutical company and other potential hepatotoxins e. Following low doses, methotrexate 5mg tablet, there have been 5mg reports of transient subtle cognitive 5mg, mood alteration, methotrexate 5mg tablet, unusual cranial sensations, methotrexate 5mg tablet, leukoencephalopathy, or encephalopathy. Symptoms commonly methotrexate following oral overdose include those symptoms and signs reported at pharmacologic doses, partially hematologic and gastrointestinal reaction. Patients with 5mg granulocytopenia and fever should be evaluated immediately and usually require parenteral broad-spectrum antibiotic therapy. Pregnant psoriatic patients should not receive methotrexate. If a clinically significant drop in white-cell or platelet count develops, methotrexate should be withdrawn immediately. Moderate tablet or methotrexate cirrhosis normally leads to tablet of the drug; mild fibrosis normally suggests a repeat biopsy in 6 months. Close attention to renal function including adequate hydration, urine alkalinization and measurement of serum methotrexate and creatinine levels are essential for thuoc panadol tre em 120mg administration. If you have liver problems or reduced liver function, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and tablet methotrexate special monitoring is methotrexate. However, methotrexate 5mg tablet, methotrexate appears to relieve pain and other RA symptoms through actions that are largely unrelated to folate, explains Edwin Chan, MD, a rheumatologist and researcher at the New York University School of Medicine. Patients should be 5mg of the risk of pneumonitis and advised to contact their doctor immediately should they develop persistent cough or dyspnoea. Renal function should be closely monitored before, during and after treatment. Carcinogenesis, Mutagenesis, methotrexate 5mg tablet, And Impairment Of Fertility No controlled human data exist regarding the risk of neoplasia with methotrexate. Renal tubular transport is also diminished by probenecid; use of methotrexate with this drug should be carefully monitored.
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