Drug Interactions between methotrexate and ombitasvir / paritaprevir / ritonavir

Caffeine may reduce the effectiveness of methotrexate in the treatment of arthritis. If you are receiving methotrexate for arthritis, you may want to limit your intake of caffeine-containing foods and medications. Check with your doctor or pharmacist if you have concerns or are uncertain what products may contain caffeine.

Ritonavir should be taken with food to lessen gastrointestinal side effects. It is important that you take this medication exactly as prescribed by your doctor. Do not change your treatment or stop treatment without first talking to your doctor.

Food significantly increases the absorption of paritaprevir. You should take each dose of paritaprevir with a meal. Taking it on an empty stomach may lead to inadequate blood levels and reduced effectiveness of the medication.

Methotrexate may cause liver problems, and using it with other medications that can also affect the liver such as ethanol (alcohol) may increase that risk. You should avoid or limit the use of alcohol while being treated with these medications. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark urine, pale stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. Talk to your doctor or pharmacist if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Caffeine may reduce the effectiveness of methotrexate in the treatment of arthritis. If you are receiving methotrexate for arthritis, you may want to limit your intake of caffeine-containing foods and products. Contact your doctor if your symptoms worsen or your condition changes during treatment with these medications. Your doctor may be able to prescribe alternatives that do not interact. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

The use of methotrexate is contraindicated as treatment for psoriasis or rheumatoid arthritis in patients with alcoholism, alcoholic liver disease or other chronic liver diseases. Methotrexate causes hepatotoxicity, fibrosis and cirrhosis, usually after long-term therapy. Fibrosis and cirrhosis may not be preceded by symptoms or abnormal liver function tests. If methotrexate is used, patients should be instructed to immediately report any signs or symptoms suggestive of hepatic dysfunction such as jaundice, dark urine, right upper quadrant pain, or anorexia. Persistent liver function test abnormalities and/or depression of serum albumin may require evaluation, including a liver biopsy.

Methotrexate can induce myelosuppression causing leukopenia, thrombocytopenia, neutropenia, pancytopenia and anemia. Therapy with methotrexate is contraindicated as treatment of psoriasis in patients with bone marrow suppression or preexisting blood dyscrasias. Methotrexate should be discontinued immediately in patients with psoriasis or rheumatoid arthritis if there is a significant fall in blood cell counts. If need outweighs risk, therapy with methotrexate should be administered cautiously in patients with malignancy and hematopoietic impairment. Additionally, methotrexate should be used with extreme caution in patients with active infection, and it is usually contraindicated in patients with overt or laboratory evidence of immunodeficiency syndromes. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression or infection such as fever, sore throat, or bleeding. Clinical monitoring of hematopoietic function is recommended.

Methotrexate can induce myelosuppression causing leukopenia, thrombocytopenia, neutropenia, pancytopenia and anemia. Therapy with methotrexate is contraindicated as treatment of psoriasis in patients with bone marrow suppression or preexisting blood dyscrasias. Methotrexate should be discontinued immediately in patients with psoriasis or rheumatoid arthritis if there is a significant fall in blood cell counts. If need outweighs risk, therapy with methotrexate should be administered cautiously in patients with malignancy and hematopoietic impairment. Additionally, methotrexate should be used with extreme caution in patients with active infection, and it is usually contraindicated in patients with overt or laboratory evidence of immunodeficiency syndromes. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression or infection such as fever, sore throat, or bleeding. Clinical monitoring of hematopoietic function is recommended.

Methotrexate induces stomatitis within the oral mucosa and gastrointestinal tract. Therapy with methotrexate should be administered with extreme caution in patients with peptic ulcer disease or ulcerative colitis. If vomiting, diarrhea or ulcerative stomatitis occur, treatment should be discontinued until recovery to avoid the risk of hemorraghic enteritis or intestinal perforation which could be fatal.

HBV reactivation has been reported during or after completion of HCV direct-acting antiviral therapy in HCV/HBV-coinfected patients who were not receiving HBV antiviral therapy; some cases resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in hepatitis B surface antigen (HBsAg)-positive patients and patients with serologic evidence of resolved HBV infection (i.e., HBsAg negative and hepatitis B core antibody [anti-HBc] positive). HBV reactivation has also been reported in patients using certain immunosuppressant or chemotherapeutic agents; risk of HBV reactivation associated with HCV direct-acting antiviral therapy may be increased in these patients. All patients should be tested for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before starting HCV direct-acting antiviral therapy. Patients with serologic evidence of current or prior HBV infection should be monitored for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV therapy and posttherapy follow-up; appropriate patient management for HBV infection should be started as clinically indicated.

Because of their cytotoxic effects on rapidly proliferating tissues, antineoplastic agents frequently can, to varying extent, induce myelosuppression. The use of these drugs may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during antineoplastic therapy. Close clinical monitoring of hematopoietic function is recommended.

Methotrexate can induce myelosuppression causing leukopenia, thrombocytopenia, neutropenia, pancytopenia and anemia. Therapy with methotrexate is contraindicated as treatment of psoriasis in patients with bone marrow suppression or preexisting blood dyscrasias. Methotrexate should be discontinued immediately in patients with psoriasis or rheumatoid arthritis if there is a significant fall in blood cell counts. If need outweighs risk, therapy with methotrexate should be administered cautiously in patients with malignancy and hematopoietic impairment. Additionally, methotrexate should be used with extreme caution in patients with active infection, and it is usually contraindicated in patients with overt or laboratory evidence of immunodeficiency syndromes. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression or infection such as fever, sore throat, or bleeding. Clinical monitoring of hematopoietic function is recommended.

HBV reactivation has been reported during or after completion of HCV direct-acting antiviral therapy in HCV/HBV-coinfected patients who were not receiving HBV antiviral therapy; some cases resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in hepatitis B surface antigen (HBsAg)-positive patients and patients with serologic evidence of resolved HBV infection (i.e., HBsAg negative and hepatitis B core antibody [anti-HBc] positive). HBV reactivation has also been reported in patients using certain immunosuppressant or chemotherapeutic agents; risk of HBV reactivation associated with HCV direct-acting antiviral therapy may be increased in these patients. All patients should be tested for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before starting HCV direct-acting antiviral therapy. Patients with serologic evidence of current or prior HBV infection should be monitored for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV therapy and posttherapy follow-up; appropriate patient management for HBV infection should be started as clinically indicated.

Methotrexate induces stomatitis within the oral mucosa and gastrointestinal tract. Therapy with methotrexate should be administered with extreme caution in patients with peptic ulcer disease or ulcerative colitis. If vomiting, diarrhea or ulcerative stomatitis occur, treatment should be discontinued until recovery to avoid the risk of hemorraghic enteritis or intestinal perforation which could be fatal.

The use of drugs containing paritaprevir in combination with ombitasvir and ritonavir is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B and C). No dosage adjustment is required in patients with mild hepatic impairment (Child-Pugh A).

The use of methotrexate is contraindicated as treatment for psoriasis or rheumatoid arthritis in patients with alcoholism, alcoholic liver disease or other chronic liver diseases. Methotrexate causes hepatotoxicity, fibrosis and cirrhosis, usually after long-term therapy. Fibrosis and cirrhosis may not be preceded by symptoms or abnormal liver function tests. If methotrexate is used, patients should be instructed to immediately report any signs or symptoms suggestive of hepatic dysfunction such as jaundice, dark urine, right upper quadrant pain, or anorexia. Persistent liver function test abnormalities and/or depression of serum albumin may require evaluation, including a liver biopsy.

Methotrexate induces stomatitis within the oral mucosa and gastrointestinal tract. Therapy with methotrexate should be administered with extreme caution in patients with peptic ulcer disease or ulcerative colitis. If vomiting, diarrhea or ulcerative stomatitis occur, treatment should be discontinued until recovery to avoid the risk of hemorraghic enteritis or intestinal perforation which could be fatal.

Methotrexate is primarily eliminated by the kidney via glomerular filtration and active secretion. Clearance rates for methotrexate vary and at higher doses are generally decreased due to saturation of renal tubular reabsorption. Renal impairment or third space effusion (ascites, pleural effusions), decrease elimination and increase methotrexate serum concentrations. Therapy with methotrexate should be administered cautiously and at reduced dosages in patients with compromised renal function. Administration of leucovorin reduces toxicity from high dose methotrexate regimens or delayed elimination. Clinical monitoring of renal function is recommended.

Methotrexate is primarily eliminated by the kidney via glomerular filtration and active secretion. Clearance rates for methotrexate vary and at higher doses are generally decreased due to saturation of renal tubular reabsorption. Renal impairment or third space effusion (ascites, pleural effusions), decrease elimination and increase methotrexate serum concentrations. Therapy with methotrexate should be administered cautiously and at reduced dosages in patients with compromised renal function. Administration of leucovorin reduces toxicity from high dose methotrexate regimens or delayed elimination. Clinical monitoring of renal function is recommended.

New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia, and some cases of diabetic ketoacidosis have been reported during postmarketing surveillance in HIV-infected patients treated with protease inhibitors. Some patients required either initiation or dosage adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, hyperglycemia persisted despite discontinuation of protease inhibitor therapy. A causal relationship has not been established between protease inhibitor therapy and these events. Monitoring patients for hyperglycemia, new onset diabetes mellitus, or exacerbation of diabetes mellitus should be considered during protease inhibitor therapy.

There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, in patients with hemophilia type A and B treated with protease inhibitors; however, a causal relationship has not been established. In some patients, additional factor VIII was given. In more than half of the reported cases, protease inhibitor therapy was continued or reintroduced. Patients with hemophilia or other coagulation defects should be monitored closely for bleeding during protease inhibitor therapy.

New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia, and some cases of diabetic ketoacidosis have been reported during postmarketing surveillance in HIV-infected patients treated with protease inhibitors. Some patients required either initiation or dosage adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, hyperglycemia persisted despite discontinuation of protease inhibitor therapy. A causal relationship has not been established between protease inhibitor therapy and these events. Monitoring patients for hyperglycemia, new onset diabetes mellitus, or exacerbation of diabetes mellitus should be considered during protease inhibitor therapy.

Ritonavir may prolong the PR interval in some patients. Postmarketing cases of second or third degree atrioventricular block have been reported. Ritonavir should be administered with caution in patients with underlying structural heart disease, preexisting conduction abnormalities, ischemic heart disease, and cardiomyopathies as these patients might be at increased risk for developing cardiac conduction abnormalities.

Treatment with ritonavir alone or in combination with other protease inhibitors (e.g., lopinavir, saquinavir, tipranavir, fosamprenavir) has resulted in substantial increases in the concentration of total cholesterol and triglycerides. These effects have also been reported with other protease inhibitors but may be the most dramatic with ritonavir. The clinical significance of these elevations is unclear. Marked elevation in triglyceride levels is a risk factor for development of pancreatitis. Triglyceride and cholesterol testing is recommended before starting ritonavir (with or without other protease inhibitors) and periodically during therapy. Lipid disorders should be managed as clinically appropriate.

Hepatotoxicity (including jaundice, clinical hepatitis, and hepatic transaminase elevations exceeding 5 times the upper limit of normal) has been reported in patients receiving ritonavir alone or in combination with other antiretroviral drugs. Ritonavir should be administered with caution in patients with preexisting liver diseases, liver enzyme abnormalities, or hepatitis; increased monitoring of AST/ALT should be considered in these patients, especially during the first 3 months of ritonavir therapy. Ritonavir is not recommended for use in patients with severe liver dysfunction.