Drug Interactions between ombitasvir / paritaprevir / ritonavir and silodosin

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.

Taking silodosin with food can reduce the risk and/or severity of side effects. Therefore, silodosin should be administered with or immediately after a meal.

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.

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 silodosin is contraindicated in patients with severe hepatic impairment. No dosage adjustment is needed in patients with mild or moderate hepatic impairment.

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 silodosin is contraindicated in patients with severe renal impairment (CrCl < 30 mL/min). Caution and regular monitoring is recommended in patients with moderate renal impairment as the plasma concentrations can increase three times higher when compared with subjects with normal renal function. Dose should be reduced to 4 mg/day in patients with moderate renal impairment.

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.

Intraoperative Floppy Iris Syndrome has been observed during cataract surgery in some patients on or previously treated with antiadrenergic agents. If a patient is undergoing cataract surgery, the ophthalmologist should be prepared for possible modifications of the surgical technique (iris hooks, iris dilator rings). There does not appear to be a benefit in stopping antiadrenergic agents therapy prior to the cataracts surgery.

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.

Peripheral alpha 1- adrenergic receptor blocking agents (aka alpha 1- blockers) cause vasodilation and can produce marked hypotension, especially orthostatic hypotension with syncope or other postural symptoms such as dizziness, lightheadedness, and palpitations. Orthostatic effects are most common during initiation of therapy and often occur within 90 minutes after the first dose. However, they can also occur following a dosage increase or resumption of therapy after an interruption of more than a few days. Agents with alpha 1a specificity, such as tamsulosin, act primarily on the prostate but are not devoid of hypotensive effects. Therapy with peripheral alpha-1 blockers should be administered cautiously in patients with or predisposed to hypotensive or syncopal episodes. Caution is also advised in patients who are dehydrated (e.g., due to severe or prolonged diarrhea or vomiting), since they may be more sensitive to the hypotensive effect of the drugs. Therapy should be initiated with the lowest dosage possible and titrated gradually based on patient response and tolerance in accordance with the individual product package labeling. During initiation or reinstitution of therapy and following an increase in dosage, patients should be advised not to rise abruptly from a sitting or recumbent position and to avoid situations where injury could result if syncope occur. Concomitant use of alcohol, extensive periods of standing, prolonged or intense exercise, and exposure to heat can also precipitate orthostatic hypotension and should be minimized. If dizziness, lightheadedness or palpitations occur, the patient should sit or lie down, and seek medical attention if symptoms are recurrent or bothersome.

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.

Peripheral alpha 1- adrenergic receptor blocking agents (aka alpha 1- blockers) cause vasodilation and can produce marked hypotension, especially orthostatic hypotension with syncope or other postural symptoms such as dizziness, lightheadedness, and palpitations. Orthostatic effects are most common during initiation of therapy and often occur within 90 minutes after the first dose. However, they can also occur following a dosage increase or resumption of therapy after an interruption of more than a few days. Agents with alpha 1a specificity, such as tamsulosin, act primarily on the prostate but are not devoid of hypotensive effects. Therapy with peripheral alpha-1 blockers should be administered cautiously in patients with or predisposed to hypotensive or syncopal episodes. Caution is also advised in patients who are dehydrated (e.g., due to severe or prolonged diarrhea or vomiting), since they may be more sensitive to the hypotensive effect of the drugs. Therapy should be initiated with the lowest dosage possible and titrated gradually based on patient response and tolerance in accordance with the individual product package labeling. During initiation or reinstitution of therapy and following an increase in dosage, patients should be advised not to rise abruptly from a sitting or recumbent position and to avoid situations where injury could result if syncope occur. Concomitant use of alcohol, extensive periods of standing, prolonged or intense exercise, and exposure to heat can also precipitate orthostatic hypotension and should be minimized. If dizziness, lightheadedness or palpitations occur, the patient should sit or lie down, and seek medical attention if symptoms are recurrent or bothersome.

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.

Peripheral alpha 1- adrenergic receptor blocking agents (aka alpha 1- blockers) cause vasodilation and can produce marked hypotension, especially orthostatic hypotension with syncope or other postural symptoms such as dizziness, lightheadedness, and palpitations. Orthostatic effects are most common during initiation of therapy and often occur within 90 minutes after the first dose. However, they can also occur following a dosage increase or resumption of therapy after an interruption of more than a few days. Agents with alpha 1a specificity, such as tamsulosin, act primarily on the prostate but are not devoid of hypotensive effects. Therapy with peripheral alpha-1 blockers should be administered cautiously in patients with or predisposed to hypotensive or syncopal episodes. Caution is also advised in patients who are dehydrated (e.g., due to severe or prolonged diarrhea or vomiting), since they may be more sensitive to the hypotensive effect of the drugs. Therapy should be initiated with the lowest dosage possible and titrated gradually based on patient response and tolerance in accordance with the individual product package labeling. During initiation or reinstitution of therapy and following an increase in dosage, patients should be advised not to rise abruptly from a sitting or recumbent position and to avoid situations where injury could result if syncope occur. Concomitant use of alcohol, extensive periods of standing, prolonged or intense exercise, and exposure to heat can also precipitate orthostatic hypotension and should be minimized. If dizziness, lightheadedness or palpitations occur, the patient should sit or lie down, and seek medical attention if symptoms are recurrent or bothersome.