Drug Interactions between ombitasvir / paritaprevir / ritonavir and ospemifene

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 ospemifene. You should take ospemifene with a meal, preferably at the same time each day. Taking it on an empty stomach may lead to inadequate blood levels and reduced effectiveness of the medication.

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.

The use of ospemifene is contraindicated in women with any undiagnosed abnormal genital bleeding. There is an increased risk of endometrial hyperplasia and endometrial cancer in patients using estrogens. Adequate diagnostic measures should be undertaken to rule out malignancy in any postmenopausal woman with undiagnosed persistent or recurring abnormal genital bleeding.

There is a reported increase of stroke and deep vein thrombosis (DVT) in postmenopausal women receiving oral conjugated estrogens. Ospemifene should be prescribed for the shortest duration consistent with treatment goals, weighting risks and benefits for each woman. Ospemifene is contraindicated in women with active DVT, pulmonary embolism, active arterial thromboembolic disease (such as stroke or myocardial infarctions), or a history of any of these conditions. Other risk factors for cardiovascular disorders and/or venous thromboembolism such as hypertension, diabetes, smoking, hypercholesterolemia, obesity, lupus erythematosus (in personal or family history), should be evaluated and managed appropriately.

There is a reported increase of stroke and deep vein thrombosis (DVT) in postmenopausal women receiving oral conjugated estrogens. Ospemifene should be prescribed for the shortest duration consistent with treatment goals, weighting risks and benefits for each woman. Ospemifene is contraindicated in women with active DVT, pulmonary embolism, active arterial thromboembolic disease (such as stroke or myocardial infarctions), or a history of any of these conditions. Other risk factors for cardiovascular disorders and/or venous thromboembolism such as hypertension, diabetes, smoking, hypercholesterolemia, obesity, lupus erythematosus (in personal or family history), should be evaluated and managed appropriately.

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.

Ospemifene should not be used in women with severe hepatic impairment, as the pharmacokinetics have not been studied in these patients. No clinically important differences were observed in women with mild to moderate hepatic impairment when compared to healthy women, therefore no dose adjustment is needed in these patients.

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).

There is a reported increase of stroke and deep vein thrombosis (DVT) in postmenopausal women receiving oral conjugated estrogens. Ospemifene should be prescribed for the shortest duration consistent with treatment goals, weighting risks and benefits for each woman. Ospemifene is contraindicated in women with active DVT, pulmonary embolism, active arterial thromboembolic disease (such as stroke or myocardial infarctions), or a history of any of these conditions. Other risk factors for cardiovascular disorders and/or venous thromboembolism such as hypertension, diabetes, smoking, hypercholesterolemia, obesity, lupus erythematosus (in personal or family history), should be evaluated and managed appropriately.

Ospemifene has not been adequately studied in women with breast cancer, therefore should not be used in women with known, suspected or with a history of breast cancer. Additionally, ospemifene is contraindicated in the presence of any known or suspected estrogen-dependent neoplasia.

There is a reported increase of stroke and deep vein thrombosis (DVT) in postmenopausal women receiving oral conjugated estrogens. Ospemifene should be prescribed for the shortest duration consistent with treatment goals, weighting risks and benefits for each woman. Ospemifene is contraindicated in women with active DVT, pulmonary embolism, active arterial thromboembolic disease (such as stroke or myocardial infarctions), or a history of any of these conditions. Other risk factors for cardiovascular disorders and/or venous thromboembolism such as hypertension, diabetes, smoking, hypercholesterolemia, obesity, lupus erythematosus (in personal or family history), should be evaluated and managed appropriately.

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.