Drug Interactions between ombitasvir / paritaprevir / ritonavir and toremifene

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.

You should avoid drinking grapefruit juice during treatment with toremifene. Grapefruit juice may increase the blood levels of toremifene. This can make you more likely to develop side effects such as vaginal bleeding, blood clots, or an irregular heart rhythm that may be serious or life-threatening. Contact your doctor if you experience potential signs and symptoms of blood clots such as chest pain, shortness of breath, sudden loss of vision, and pain, redness or swelling your arms or legs. You should also seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, or fast or pounding heartbeats during treatment with toremifene.

Talk to your doctor before using toremifene with soy products. There is some evidence that substances present in soy may stimulate breast tumor growth and interfere with the action of toremifene, although this has not been proven. Whether soy products are effective for hot flashes is also uncertain. 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.

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.

Toremifene has shown to prolong the QTc interval in a dose and concentration related manner, which can result in Torsade de Pointes (ventricular tachycardia), syncope, seizure, and/or death. Toremifene should not be prescribed to patients with congenital or acquired QT prolongation, uncorrected hypokalemia or uncorrected hypomagnesemia. Caution is advised in patients with congestive heart failure, and patients taking other drugs that can prolong the QT interval.

Toremifene has shown to prolong the QTc interval in a dose and concentration related manner, which can result in Torsade de Pointes (ventricular tachycardia), syncope, seizure, and/or death. Toremifene should not be prescribed to patients with congenital or acquired QT prolongation, uncorrected hypokalemia or uncorrected hypomagnesemia. Caution is advised in patients with congestive heart failure, and patients taking other drugs that can prolong the QT interval.

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).

Toremifene has shown to prolong the QTc interval in a dose and concentration related manner, which can result in Torsade de Pointes (ventricular tachycardia), syncope, seizure, and/or death. Toremifene should not be prescribed to patients with congenital or acquired QT prolongation, uncorrected hypokalemia or uncorrected hypomagnesemia. Caution is advised in patients with congestive heart failure, and patients taking other drugs that can prolong the QT interval.

Toremifene has shown to prolong the QTc interval in a dose and concentration related manner, which can result in Torsade de Pointes (ventricular tachycardia), syncope, seizure, and/or death. Toremifene should not be prescribed to patients with congenital or acquired QT prolongation, uncorrected hypokalemia or uncorrected hypomagnesemia. Caution is advised in patients with congestive heart failure, and patients taking other drugs that can prolong the QT interval.

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.

Endometrial cancer, endometrial hyperplasia, hypertrophy, and uterine polyps have been reported in some patients treated with toremifene. Long-term use of toremifene has not been established in patients with preexisting endometrial hyperplasia. All patients should have baseline and annual gynecological examinations. In particular, patients at high risk of endometrial cancer should be closely monitored.

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.

Thromboembolic events such as thrombophlebitis and pulmonary embolism have been noted during toremifene therapy. Patients with an active or past history of thromboembolic events should generally not be administered toremifene.

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, hepatitis, and non-alcoholic fatty liver disease have been reported in clinical trials and postmarketing with toremifene. Liver function tests should be performed periodically. Caution is advised in patients with any hepatic impairment.

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.

Thromboembolic events such as thrombophlebitis and pulmonary embolism have been noted during toremifene therapy. Patients with an active or past history of thromboembolic events should generally not be administered toremifene.