Methotrexate interactions

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 )] . (Methotrexate label, Warnings and precautions)

An increased risk of hepatitis has been reported to result from combined use of methotrexate and etretinate. (Acitretin label, Contraindications)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Adalimumab label, Boxed warning)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

Most patients with rheumatoid arthritis who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Baricitinib label, Boxed warning)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

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. (Captopril label, Warnings)

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 )] . (Methotrexate label, Warnings and precautions)

Prevention or Management Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. (Cladribine label, Drug interactions)

In kidney, liver, and heart transplant patients Neoral may be administered with other immunosuppressive agents. (Cyclosporine label, Boxed warning)

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. (Darunavir label, Drug interactions)

Use of KEVEYIS with drugs that are sensitive to OAT1 inhibition (e.g., methotrexate, famotidine, oseltamivir) is not recommended [see Clinical Pharmacology (12.3) ]. (Dichlorphenamide label, Drug interactions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Etanercept label, Boxed warning)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

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

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

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 )] . (Methotrexate label, Warnings and precautions)

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. (Foscarnet label, Drug interactions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Infliximab label, Boxed warning)

Immunosuppressants Everolimus Sirolimus Temsirolimus (IV) Not recommended during and 2 weeks after TOLSURA treatment. (Itraconazole label, Drug interactions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

…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:… (Nirmatrelvir and ritonavir label, Contraindications)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

…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,… (Phenytoin label, Drug interactions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

Dihydrofolate Reductase (DHFR) Inhibitors : Avoid concomitant use (e.g., trimethoprim, methotrexate, trimetrexate, pemetrexed, pralatrexate, raltitrexed, or piritrexim). (Sepiapterin label, Drug interactions)

Coadministration of VOSEVI with BCRP substrates (e.g., methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan) is not recommended [see Clinical Pharmacology (12.3) ]. (Sofosbuvir and velpatasvir label, Drug interactions)

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 )] . (Methotrexate label, Warnings and precautions)

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 )] . (Methotrexate label, Warnings and precautions)

…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. (Tacrolimus label, Boxed warning)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Tocilizumab label, Boxed warning)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Tofacitinib label, Boxed warning)

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 )] . (Methotrexate label, Warnings and precautions)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Upadacitinib label, Boxed warning)

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (Methotrexate label, Drug interactions)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (Methotrexate label, Drug interactions)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (Methotrexate label, Drug interactions)

Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (Amlodipine label, Drug interactions)

Impact of Amlodipine on Other Drugs Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (Amlodipine and atorvastatin label, Drug interactions)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (Amlodipine and olmesartan label, Drug interactions)

Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when coadministered. (Amlodipine and valsartan label, Drug interactions)

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. (Methotrexate label, Drug interactions)

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. (Methotrexate label, Drug interactions)

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. (Methotrexate label, Drug interactions)

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. (Methotrexate label, Drug interactions)

Immunosuppressants: cyclosporine, sirolimus, tacrolimus ↑ immunosuppressants Therapeutic concentration monitoring is recommended for these immunosuppressants when coadministered with REYATAZ. (Atazanavir label, Drug interactions)

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including XATMEP. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

Antineoplastic agents (e.g., cyclophosphamide, methotrexate) : Concomitant use of thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance their myelosuppressive effects. (Benazepril and hydrochlorothiazide label, Drug interactions)

Consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. (Bendamustine label, Warnings and precautions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (Methotrexate label, Drug interactions)

Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including XATMEP. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (Methotrexate label, Drug interactions)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (Methotrexate label, Drug interactions)

Cytotoxic products – Thiazides may reduce the renal excretion of cytotoxic medicinal products (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects. (Candesartan and hydrochlorothiazide label, Drug interactions)

Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs (e.g. platinum salts, irinotecan, methotrexate, intravenous bisphosphonates). (Capecitabine label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

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. (Ciprofloxacin label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

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. (Darunavir and cobicistat label, Drug interactions)

Hepatotoxic medications, such as high-dose methotrexate, may impair liver function and increase the risk of toxicity. (Daunorubicin label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections. (Denosumab label, Warnings and precautions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (Dexlansoprazole label, Warnings and precautions)

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. (Methotrexate label, Drug interactions)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives, methotrexate: Monitoring of valproate concentrations is recommended ( 7.1 ) (Divalproex (valproate) label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

…(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). (Eltrombopag label, Drug interactions)

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. (Elvitegravir, cobicistat, emtricitabine, and tenofovir label, Drug interactions)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (Methotrexate label, Drug interactions)

• Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (Esomeprazole label, Warnings and precautions)

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. (Etravirine label, Drug interactions)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (Methotrexate label, Drug interactions)

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… (Fenofibrate label, Drug interactions)

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… (Fenofibric acid label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

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. (Methotrexate label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus ↑ Immunosuppressants Therapeutic concentration monitoring is recommended for immunosuppressant agents. (Fosamprenavir label, Drug interactions)

…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,… (Fosphenytoin label, Drug interactions)

Methotrexate and other drugs undergoing renal tubular secretion Furosemide may decrease renal elimination of other drugs that undergo tubular secretion. (Furosemide label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

Methotrexate Concomitant use of PLAQUENIL and methotrexate may increase the incidence of adverse reactions. (Hydroxychloroquine label, Drug interactions)

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

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (Methotrexate label, Drug interactions)

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… (Ketoconazole label, Drug interactions)

Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (Lansoprazole label, Warnings and precautions)

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. (Ledipasvir and sofosbuvir label, Warnings and precautions)

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. (Leflunomide label, Warnings and precautions)

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. (Lomitapide label, Warnings and precautions)

Immunosuppressants: e.g. cyclosporine, tacrolimus, sirolimus ↑ immunosuppressants Therapeutic concentration monitoring is recommended for immunosuppressant agents when co-administered with KALETRA. (Lopinavir and ritonavir label, Drug interactions)

Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including XATMEP. (Methotrexate label, Drug interactions)

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. (Mercaptopurine label, Warnings and precautions)

Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including XATMEP. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

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 )]. (Mycophenolate label, Warnings and precautions)

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. (Methotrexate label, Drug interactions)

…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… (Natalizumab label, Drug interactions)

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. (Nefazodone label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus Plasma concentrations may be decreased. (Nevirapine label, Drug interactions)

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. (Nitisinone label, Drug interactions)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (Olmesartan, amlodipine, and hydrochlorothiazide label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

• Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (Omeprazole label, Warnings and precautions)

Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (Omeprazole and sodium bicarbonate label, Warnings and precautions)

In a crossover trial in 76 pediatric patients, intravenous ondansetron did not increase blood levels of high-dose methotrexate. (Ondansetron label, Drug interactions)

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. (Methotrexate label, Drug interactions)

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. (Pantoprazole label, Warnings and precautions)

Treatment has consisted of high doses of corticosteroids alone or, in some cases, concomitantly with an immunosuppressant. (Penicillamine label, Warnings)

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. (Methotrexate label, Drug interactions)

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. (Methotrexate label, Drug interactions)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (Methotrexate label, Drug interactions)

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. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

Probenecid Probenecid may reduce renal elimination of methotrexate. (Methotrexate label, Drug interactions)

Probenecid Probenecid may reduce renal elimination of methotrexate. (Methotrexate label, Drug interactions)

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. (Pyrimethamine label, Drug interactions)

Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. (Rabeprazole label, Warnings and precautions)

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. (Rifampin label, Drug interactions)

…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… (Rifapentine label, Drug interactions)

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

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) ]. (Rolapitant label, Drug interactions)

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. (Sapropterin label, Drug interactions)

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. (Sulfadiazine label, Drug interactions)

Trimethoprim/sulfamethoxazole has been reported to increase bone marrow suppression in patients receiving methotrexate. (Methotrexate label, Drug interactions)

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (Methotrexate label, Drug interactions)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (Telmisartan and amlodipine label, Drug interactions)

Prophylaxis of PJP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required. (Temsirolimus label, Warnings and precautions)

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. (Teriflunomide label, Drug interactions)

Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. (Methotrexate label, Drug interactions)

Cyclosporine, tacrolimus: Monitor for toxicities of these immunosuppressive drugs ( 7.1 ) (Tinidazole label, Drug interactions)

Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity. (Methotrexate label, Drug interactions)

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. (Methotrexate label, Drug interactions)

Trimethoprim/sulfamethoxazole has been reported to increase bone marrow suppression in patients receiving methotrexate. (Methotrexate label, Drug interactions)

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. (Voriconazole label, Warnings and precautions)

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. (Atorvastatin label, Warnings and precautions)

Thirty-four patients were treated with corticosteroids and one patient was treated with a non-steroidal immunosuppressant. (Axitinib label, Warnings and precautions)

…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). (Cidofovir label, Drug interactions)

Administer prophylaxis for PJP when concomitant use of corticosteroids or other immunosuppressive agents are required. (Everolimus label, Warnings and precautions)

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. (Ezetimibe and simvastatin label, Warnings and precautions)

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. (Fluvastatin label, Warnings and precautions)

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. (Lovastatin label, Warnings)

In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. (Methimazole label, Warnings)

Oral neomycin inhibits the gastrointestinal absorption of penicillin V, oral vitamin B-12, methotrexate and 5-fluorouracil. (Neomycin label, Drug interactions)

Immunosuppressive Drugs Tacrolimus: Tacrolimus has been shown to be metabolized via the CYP3A system. (Nifedipine label, Precautions)

…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. (Pilocarpine label, Drug interactions)

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. (Pitavastatin label, Warnings and precautions)

CYP3A Substrates Immunosuppressants that are CYP3A4 Substrates Mechanism and Clinical Effect(s) Posaconazole is a strong CYP3A4 inhibitor. (Posaconazole label, Drug interactions)

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. (Pravastatin label, Warnings and precautions)

In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. (Propylthiouracil label, Warnings)

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. (Rituximab label, Warnings and precautions)

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. (Rosuvastatin label, Warnings and precautions)

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. (Simvastatin label, Warnings and precautions)

…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. (Clarithromycin label, Drug interactions)