Drug Interactions between gadobenate dimeglumine and ombitasvir / paritaprevir / ritonavir

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.

Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Gadobenate ion is eliminated predominately via the kidneys. The risk for NSF appears highest among patients with chronic, severe kidney disease (GFR <30 mL/min/1.73m2), or acute kidney injury. It is recommended to avoid the use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other processes. NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle and internal organs. Consider screening patients for acute kidney injury and other conditions that may reduce renal function and for patients at risk for chronically reduced renal function (e.g., age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. For patients receiving hemodialysis, physicians may consider the prompt initiation of hemodialysis following the administration of a GBCA to enhance the contrast agent's elimination. The usefulness of hemodialysis in the prevention of NSF is unknown.

Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Gadobenate ion is eliminated predominately via the kidneys. The risk for NSF appears highest among patients with chronic, severe kidney disease (GFR <30 mL/min/1.73m2), or acute kidney injury. It is recommended to avoid the use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other processes. NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle and internal organs. Consider screening patients for acute kidney injury and other conditions that may reduce renal function and for patients at risk for chronically reduced renal function (e.g., age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. For patients receiving hemodialysis, physicians may consider the prompt initiation of hemodialysis following the administration of a GBCA to enhance the contrast agent's elimination. The usefulness of hemodialysis in the prevention of NSF is unknown.

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.

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.

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).

Gadolinium based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Use of these agents should be avoided in these patients unless the diagnostic information is essential and unavailable with non- contrasted MRI or other diagnostic modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. The risk of NSF appears to be higher in patients with chronic severe renal disease and patients with acute kidney injury. Patients should be screened for acute renal injury and other conditions that might affect renal function such as age >60 years old, hypertension, and diabetes.

Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Gadobenate ion is eliminated predominately via the kidneys. The risk for NSF appears highest among patients with chronic, severe kidney disease (GFR <30 mL/min/1.73m2), or acute kidney injury. It is recommended to avoid the use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other processes. NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle and internal organs. Consider screening patients for acute kidney injury and other conditions that may reduce renal function and for patients at risk for chronically reduced renal function (e.g., age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. For patients receiving hemodialysis, physicians may consider the prompt initiation of hemodialysis following the administration of a GBCA to enhance the contrast agent's elimination. The usefulness of hemodialysis in the prevention of NSF is unknown.

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.

Patients with history of bronchial asthma might have an increased risk for a hypersensitivity reaction to gadolinium-based contrast agents. Patients should always be assessed for any history of a reaction to contrast media, asthma or other allergic disorders before the administration of these agents.

The use of gadobenate may cause cardiac arrhythmias. It is recommended to assess patients for underlying conditions or medications that predispose to arrhythmias.

Patients with history of bronchial asthma might have an increased risk for a hypersensitivity reaction to gadolinium-based contrast agents. Patients should always be assessed for any history of a reaction to contrast media, asthma or other allergic disorders before the administration of these agents.

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.

The use of certain Gadolinium-based contrast agents (GBCAs) in patients with severe renal or hepatic impairment may impair imaging performance. If GBCAs are used in these patients, complete MRI no later than 60 minutes after GBCAs administration and use a paired non-contrast and contrast MRI set for diagnosis. It is recommended to exercise caution when interpreting contrast MR images in the absence of companion non-contrast MR images

The use of certain Gadolinium-based contrast agents (GBCAs) in patients with severe renal or hepatic impairment may impair imaging performance. If GBCAs are used in these patients, complete MRI no later than 60 minutes after GBCAs administration and use a paired non-contrast and contrast MRI set for diagnosis. It is recommended to exercise caution when interpreting contrast MR images in the absence of companion non-contrast MR images