Méthotrexate : interactions médicamenteuses

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

An increased risk of hepatitis has been reported to result from combined use of methotrexate and etretinate. (notice Acitrétine, Contre-indications)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (notice Adalimumab, Mise en garde encadrée)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Most patients with rheumatoid arthritis who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (notice Baricitinib, Mise en garde encadrée)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

About 13 percent of the cases of neutropenia have ended fatally, but almost all fatalities were in patients with serious illness, having collagen vascular disease, renal failure, heart failure or immunosuppressant therapy, or a combination of these complicating factors. (notice Captopril, Mises en garde)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

In kidney, liver, and heart transplant patients Neoral may be administered with other immunosuppressive agents. (notice Ciclosporine, Mise en garde encadrée)

Prevention or Management Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. (notice Cladribine, Interactions médicamenteuses)

Immunosuppressant/neoplastic: everolimus Co-administration of everolimus and PREZISTA/ritonavir is not recommended. irinotecan Discontinue PREZISTA/ritonavir at least 1 week prior to starting irinotecan therapy. (notice Darunavir, Interactions médicamenteuses)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Use of KEVEYIS with drugs that are sensitive to OAT1 inhibition (e.g., methotrexate, famotidine, oseltamivir) is not recommended [see Clinical Pharmacology (12.3) ]. (notice Diclofénamide, Interactions médicamenteuses)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (notice Étanercept, Mise en garde encadrée)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Chicken pox and measles, for example, can have a more serious or even fatal course in children on immunosuppressant corticosteroids. (notice Fludrocortisone, Mises en garde)

Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles. (notice Flunisolide, Précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Because of foscarnet's tendency to cause renal impairment, the use of FOSCAVIR should be avoided in combination with potentially nephrotoxic drugs such as aminoglycosides, amphotericin B, cyclosporine, acyclovir, methotrexate, tacrolimus and intravenous pentamidine (see above) unless the potential benefits outweigh the risks to the patient. (notice Foscarnet, Interactions médicamenteuses)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (notice Infliximab, Mise en garde encadrée)

Immunosuppressants Everolimus Sirolimus Temsirolimus (IV) Not recommended during and 2 weeks after TOLSURA treatment. (notice Itraconazole, Interactions médicamenteuses)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

…methylergonovine • HMG-CoA reductase inhibitors: lovastatin, simvastatin (these drugs can be temporarily discontinued to allow PAXLOVID use [see Table 2 , Drug Interactions (7.3) ] ) • Immunosuppressants: voclosporin • Microsomal triglyceride transfer protein inhibitor: lomitapide • Migraine medications: eletriptan, ubrogepant • Mineralocorticoid receptor antagonists:… (notice Nirmatrelvir et ritonavir, Contre-indications)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

…Prevention or Management: Phenytoin and antacids should not be taken at the same time of day Antineoplastic agents (usually in combination) Bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate Antiviral agents Fosamprenavir, nelfinavir, ritonavir Antiepileptic drugs Carbamazepine, vigabatrin Other Chronic alcohol abuse, diazepam, diazoxide, folic acid, reserpine,… (notice Phénytoïne, Interactions médicamenteuses)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Dihydrofolate Reductase (DHFR) Inhibitors : Avoid concomitant use (e.g., trimethoprim, methotrexate, trimetrexate, pemetrexed, pralatrexate, raltitrexed, or piritrexim). (notice Sépiaptérine, Interactions médicamenteuses)

Coadministration of VOSEVI with BCRP substrates (e.g., methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan) is not recommended [see Clinical Pharmacology (12.3) ]. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (notice Tocilizumab, Mise en garde encadrée)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (notice Tofacitinib, Mise en garde encadrée)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (notice Méthotrexate, Mises en garde et précautions)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (notice Upadacitinib, Mise en garde encadrée)

Frequent PT/INR determinations are advisable until it has been definitely determined that the PT/INR has stabilized Immunosuppressants Clinical Impact: Immunosuppressants such as cyclosporine and tacrolimus can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route… (notice Acide fénofibrique, Interactions médicamenteuses)

Nitrous Oxide The use of nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, resulting in the potential for increase toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (notice Méthotrexate, Interactions médicamenteuses)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (notice Méthotrexate, Interactions médicamenteuses)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (notice Méthotrexate, Interactions médicamenteuses)

Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (notice Amlodipine, Interactions médicamenteuses)

Impact of Amlodipine on Other Drugs Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (notice Amlodipine et atorvastatine, Interactions médicamenteuses)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (notice Amlodipine et olmésartan, Interactions médicamenteuses)

Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when coadministered. (notice Amlodipine et valsartan, Interactions médicamenteuses)

Effect of Other Drugs on XATMEP Oral Antibiotics Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

Effect of Other Drugs on XATMEP Oral Antibiotics Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

Effect of Other Drugs on XATMEP Oral Antibiotics Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

Effect of Other Drugs on XATMEP Oral Antibiotics Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

Immunosuppressants: cyclosporine, sirolimus, tacrolimus ↑ immunosuppressants Therapeutic concentration monitoring is recommended for these immunosuppressants when coadministered with REYATAZ. (notice Atazanavir, Interactions médicamenteuses)

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including XATMEP. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Antineoplastic agents (e.g., cyclophosphamide, methotrexate) : Concomitant use of thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance their myelosuppressive effects. (notice Bénazépril et hydrochlorothiazide, Interactions médicamenteuses)

Consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. (notice Bendamustine, Mises en garde et précautions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (notice Méthotrexate, Interactions médicamenteuses)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (notice Méthotrexate, Interactions médicamenteuses)

Cytotoxic products – Thiazides may reduce the renal excretion of cytotoxic medicinal products (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects. (notice Candésartan et hydrochlorothiazide, Interactions médicamenteuses)

Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs (e.g. platinum salts, irinotecan, methotrexate, intravenous bisphosphonates). (notice Capécitabine, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Methotrexate Use with caution Inhibition of methotrexate renal tubular transport potentially leading to increased methotrexate plasma levels Potential increase in the risk of methotrexate associated toxic reactions. (notice Ciprofloxacine, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Therapeutic drug monitoring is recommended with concomitant use Immunosuppressant /neoplastic: everolimus ↑ immunosuppressants Co-administration of everolimus and PREZCOBIX or PREZCOBIX PED is not recommended. irinotecan Discontinue PREZCOBIX or PREZCOBIX PED at least 1 week prior to starting irinotecan therapy. (notice Darunavir et cobicistat, Interactions médicamenteuses)

Hepatotoxic medications, such as high-dose methotrexate, may impair liver function and increase the risk of toxicity. (notice Daunorubicine, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections. (notice Dénosumab, Mises en garde et précautions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (notice Dexlansoprazole, Mises en garde et précautions)

Effect of Other Drugs on XATMEP Oral Antibiotics Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives, methotrexate: Monitoring of valproate concentrations is recommended ( 7.1 ) (notice Divalproate de sodium (valproate), Interactions médicamenteuses)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (notice Éfavirenz, Interactions médicamenteuses)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (notice Éfavirenz, lamivudine et ténofovir, Interactions médicamenteuses)

…(e.g., atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, olmesartan, pitavastatin, pravastatin, rosuvastatin, repaglinide, rifampin, simvastatin acid, SN-38 [active metabolite of irinotecan], valsartan) or breast cancer resistance protein (BCRP) (e.g., imatinib, irinotecan, lapatinib, methotrexate, mitoxantrone, rosuvastatin, sulfasalazine, topotecan). (notice Eltrombopag, Interactions médicamenteuses)

Immuno-suppressants: e.g., cyclosporine (CsA) sirolimus tacrolimus ↑ immuno-suppressants ↑ elvitegravir (with CsA) ↑ cobicistat (with CsA) Therapeutic monitoring of the immunosuppressive agents is recommended upon coadministration with GENVOYA. (notice Elvitégravir, cobicistat, emtricitabine et ténofovir, Interactions médicamenteuses)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (notice Méthotrexate, Interactions médicamenteuses)

• Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (notice Ésoméprazole, Mises en garde et précautions)

Immunosuppressants : cyclosporine sirolimus tacrolimus ↓ immunosuppressant Etravirine and systemic immunosuppressants should be co-administered with caution because plasma concentrations of cyclosporine, sirolimus, or tacrolimus may be affected. (notice Étravirine, Interactions médicamenteuses)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (notice Méthotrexate, Interactions médicamenteuses)

Immunosuppressants Clinical Impact: Immunosuppressants such as cyclosporine and tacrolimus can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route of fibrate drugs including fenofibrate, there is a risk that an interaction will lead to deterioration of renal… (notice Fénofibrate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus ↑ Immunosuppressants Therapeutic concentration monitoring is recommended for immunosuppressant agents. (notice Fosamprénavir, Interactions médicamenteuses)

…ticlopidine, tolbutamide, trazodone, warfarin Drugs that may decrease phenytoin serum levels Antineoplastic agents usually in combination Bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate Antiviral agents Fosamprenavir, nelfinavir, ritonavir Antiepileptic drugs Carbamazepine, vigabatrin Other Chronic alcohol abuse, diazepam, diazoxide, folic acid, reserpine,… (notice Fosphénytoïne, Interactions médicamenteuses)

Methotrexate and other drugs undergoing renal tubular secretion Furosemide may decrease renal elimination of other drugs that undergo tubular secretion. (notice Furosémide, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Methotrexate Concomitant use of PLAQUENIL and methotrexate may increase the incidence of adverse reactions. (notice Hydroxychloroquine, Interactions médicamenteuses)

Gleevec may delay the clearance of methotrexate when methotrexate is used at high doses (> 500 mg/m 2 ). (notice Imatinib, Interactions médicamenteuses)

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (notice Méthotrexate, Interactions médicamenteuses)

Immunosuppressants everolimus, rapamycin (also known as sirolimus), temsirolimus budesonide, ciclesonide, cyclosporine, dexamethasone, fluticasone, methylprednisolone, tacrolimus Rapamycin (sirolimus): Ketoconazole tablets 200 mg daily for 10 days increased the C max and AUC of a single 5 mg dose of sirolimus by 4.3 fold and 10.9 fold, respectively in 23 healthy… (notice Kétoconazole, Interactions médicamenteuses)

Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (notice Lansoprazole, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressants or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Lédipasvir et sofosbuvir, Mises en garde et précautions)

If ARAVA and methotrexate are given concomitantly, follow the American College of Rheumatology (ACR) guidelines for monitoring methotrexate liver toxicity with ALT, AST, and serum albumin testing. (notice Léflunomide, Mises en garde et précautions)

Caution should be exercised when JUXTAPID is used with other medications known to have potential for hepatotoxicity, such as isotretinoin, amiodarone, acetaminophen (>4 g/day for ≥3 days/week), methotrexate, tetracyclines, and tamoxifen. (notice Lomitapide, Mises en garde et précautions)

Immunosuppressants: e.g. cyclosporine, tacrolimus, sirolimus ↑ immunosuppressants Therapeutic concentration monitoring is recommended for immunosuppressant agents when co-administered with KALETRA. (notice Lopinavir et ritonavir, Interactions médicamenteuses)

Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including XATMEP. (notice Méthotrexate, Interactions médicamenteuses)

A treatment regimen containing multiple immunosuppressants (including thiopurines) should therefore be used with caution as this could lead to lymphoproliferative disorders, some with reported fatalities. (notice Mercaptopurine, Mises en garde et précautions)

Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including XATMEP. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Lymphoma and Other Malignancies Patients receiving immunosuppressants, including mycophenolate mofetil, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions ( 6.1 )]. (notice Mycophénolate, Mises en garde et précautions)

Effect of Other Drugs on XATMEP Oral Antibiotics Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

…infections, Crohn’s disease patients receiving natalizumab products should not be treated with concomitant immunosuppressants (e.g., 6‑ mercaptopurine, azathioprine, cyclosporine, or methotrexate) or inhibitors of TNF-α, and corticosteroids should be tapered in those patients with Crohn’s disease who are on chronic corticosteroids when they start TYRUKO therapy… (notice Natalizumab, Interactions médicamenteuses)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (notice Néfazodone, Interactions médicamenteuses)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus Plasma concentrations may be decreased. (notice Névirapine, Interactions médicamenteuses)

OAT1/OAT3 Substrates (e.g., adefovir, ganciclovir, methotrexate) Clinical Impact Increased exposure of the interacting drug. [see Clinical Pharmacology ( 12.3 )] Prevention or Management Monitor for potential adverse reactions related to the co-administered drug. (notice Nitisinone, Interactions médicamenteuses)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (notice Olmésartan, amlodipine et hydrochlorothiazide, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

• Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (notice Oméprazole, Mises en garde et précautions)

Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (notice Oméprazole et bicarbonate de sodium, Mises en garde et précautions)

In a crossover trial in 76 pediatric patients, intravenous ondansetron did not increase blood levels of high-dose methotrexate. (notice Ondansétron, Interactions médicamenteuses)

Effect of Other Drugs on XATMEP Oral Antibiotics Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

Concomitant Use of PROTONIX I.V. with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. (notice Pantoprazole, Mises en garde et précautions)

Treatment has consisted of high doses of corticosteroids alone or, in some cases, concomitantly with an immunosuppressant. (notice Pénicillamine, Mises en garde)

Effect of Other Drugs on XATMEP Oral Antibiotics Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

Effect of Other Drugs on XATMEP Oral Antibiotics Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (notice Méthotrexate, Interactions médicamenteuses)

Effect of Other Drugs on XATMEP Oral Antibiotics Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Probenecid Probenecid may reduce renal elimination of methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

Probenecid Probenecid may reduce renal elimination of methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

However, the concomitant use of other antifolic drugs or agents associated with myelosuppression including sulfonamides or trimethoprim- sulfamethoxazole combinations, proguanil, zidovudine, or cytostatic agents (e.g., methotrexate), while the patient is receiving pyrimethamine, may increase the risk of bone marrow suppression. (notice Pyriméthamine, Interactions médicamenteuses)

Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (notice Rabéprazole, Mises en garde et précautions)

Glipizide Decrease exposure Immunosuppressive Agents Cyclosporine Decrease exposure Tacrolimus Prevention or Management: Monitoring of whole blood concentrations and appropriate dosage adjustments of tacrolimus are recommended when rifampin and tacrolimus are used concomitantly. (notice Rifampicine, Interactions médicamenteuses)

…Digoxin Corticosteroids Prednisone Fibrates Clofibrate Oral Hypoglycemics Sulfonylureas (e.g., glyburide, glipizide) Hormonal Contraceptives/Progestins Ethinyl estradiol, levonorgestrel Immunosuppressants Cyclosporine, tacrolimus Methylxanthines Theophylline Narcotic analgesics Methadone Phosphodiesterase-5 (PDE-5) Inhibitors Sildenafil Thyroid preparations Levothyroxine… (notice Rifapentine, Interactions médicamenteuses)

Immunosuppressants: cyclosporine, tacrolimus, sirolimus (rapamycin) ↑ immunosuppressants Therapeutic concentration monitoring is recommended for immunosuppressant agents when co-administered with ritonavir. (notice Ritonavir, Interactions médicamenteuses)

BCRP Substrates with a Narrow Therapeutic Index (e.g., methotrexate, topotecan, or irinotecan) Clinical Impact: Increased plasma concentrations of BCRP substrates (e.g., methotrexate, topotecan, or irinotecan) may result in potential adverse reactions [see Clinical Pharmacology (12.3) ]. (notice Rolapitant, Interactions médicamenteuses)

Inhibitors of Folate Synthesis (e.g., methotrexate, valproic acid, phenobarbital, trimethoprim) Clinical Impact In vitro and in vivo nonclinical data suggest that drugs that inhibit folate synthesis may decrease the bioavailability of endogenous BH4 by inhibiting the enzyme dihydrofolate reductase, which is involved in the recycling (regeneration) of BH4. (notice Saproptérine, Interactions médicamenteuses)

Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including XATMEP. (notice Méthotrexate, Interactions médicamenteuses)

Drug Interactions Administration of a sulfonamide may increase the effect of oral anticoagulants and methotrexate, probably by displacement of these drugs from binding sites on plasma albumin. (notice Sulfadiazine, Interactions médicamenteuses)

Trimethoprim/sulfamethoxazole has been reported to increase bone marrow suppression in patients receiving methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (notice Méthotrexate, Interactions médicamenteuses)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (notice Telmisartan et amlodipine, Interactions médicamenteuses)

Prophylaxis of PJP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required. (notice Temsirolimus, Mises en garde et précautions)

In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. (notice Tériflunomide, Interactions médicamenteuses)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (notice Méthotrexate, Interactions médicamenteuses)

Cyclosporine, tacrolimus: Monitor for toxicities of these immunosuppressive drugs ( 7.1 ) (notice Tinidazole, Interactions médicamenteuses)

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (notice Méthotrexate, Interactions médicamenteuses)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (notice Méthotrexate, Interactions médicamenteuses)

Trimethoprim/sulfamethoxazole has been reported to increase bone marrow suppression in patients receiving methotrexate. (notice Méthotrexate, Interactions médicamenteuses)

In addition, voriconazole has been associated with photosensitivity related skin reactions such as pseudoporphyria, cheilitis, and cutaneous lupus erythematosus, as well as increased risk of skin toxicity with concomitant use of methotrexate, a drug associated with ultraviolet (UV) reactivation. (notice Voriconazole, Mises en garde et précautions)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persists despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (notice Atorvastatine, Mises en garde et précautions)

Thirty-four patients were treated with corticosteroids and one patient was treated with a non-steroidal immunosuppressant. (notice Axitinib, Mises en garde et précautions)

…Probenecid Probenecid is known to interact with the metabolism or renal tubular excretion of many drugs (e.g., acetaminophen, acyclovir, angiotensin-converting enzyme inhibitors, aminosalicylic acid, barbiturates, benzodiazepines, bumetanide, clofibrate, methotrexate, famotidine, furosemide, nonsteroidal anti-inflammatory agents, theophylline, and zidovudine). (notice Cidofovir, Interactions médicamenteuses)

Administer prophylaxis for PJP when concomitant use of corticosteroids or other immunosuppressive agents are required. (notice Évérolimus, Mises en garde et précautions)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy without significant inflammation; and improvement with immunosuppressive agents. (notice Ézétimibe et simvastatine, Mises en garde et précautions)

IMNM is characterized by proximal muscle weakness and elevated serum CK, which persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement with immunosuppressive agents. (notice Fluvastatine, Mises en garde et précautions)

IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (notice Lovastatine, Mises en garde)

Oral neomycin inhibits the gastrointestinal absorption of penicillin V, oral vitamin B-12, methotrexate and 5-fluorouracil. (notice Néomycine, Interactions médicamenteuses)

Immunosuppressive Drugs Tacrolimus: Tacrolimus has been shown to be metabolized via the CYP3A system. (notice Nifédipine, Précautions)

…performed, the following concomitant drugs were used in at least 10% of patients in either or both Sjogren's efficacy studies: acetylsalicylic acid, artificial tears, calcium, conjugated estrogens, hydroxychloroquine sulfate, ibuprofen, levothyroxine sodium, medroxyprogesterone acetate, methotrexate, multivitamins, naproxen, omeprazole, paracetamol, and prednisone. (notice Pilocarpine, Interactions médicamenteuses)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (notice Pitavastatine, Mises en garde et précautions)

CYP3A Substrates Immunosuppressants that are CYP3A4 Substrates Mechanism and Clinical Effect(s) Posaconazole is a strong CYP3A4 inhibitor. (notice Posaconazole, Interactions médicamenteuses)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (notice Pravastatine, Mises en garde et précautions)

In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. (notice Propylthiouracile, Mises en garde)

The effect of rituximab on immune responses was assessed in a randomized, controlled study in patients with RA treated with rituximab and methotrexate (MTX) compared to patients treated with MTX alone. (notice Rituximab, Mises en garde et précautions)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (notice Rosuvastatine, Mises en garde et précautions)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy without significant inflammation; and improvement with immunosuppressive agents. (notice Simvastatine, Mises en garde et précautions)

In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. (notice Thiamazole, Mises en garde)

…Repaglinide, Rosiglitazone: [See Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.2 )] Insulin Insulin: [See Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.2 )] Immunosuppressants: Cyclosporine Use With Caution Cyclosporine: There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with cyclosporine. (notice Clarithromycine, Interactions médicamenteuses)