Drug Interactions between ombitasvir / paritaprevir / ritonavir and trazodone

Alcohol can increase the nervous system side effects of traZODone such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with traZODone. Do not use more than the recommended dose of traZODone, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. Talk to your doctor or pharmacist if you have any questions or concerns.

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.

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).

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.

Although less cardiotoxic than the tricyclic antidepressants, trazodone may be arrhythmogenic in some patients with cardiac disease. The use of trazodone has been associated with the occurrence of arrhythmias, including PVCs, ventricular couplets, ventricular tachycardia, atrial fibrillation, and heart block. Myocardial infarction has been reported. Trazodone should not be used during the acute recovery phase following myocardial infarction, and should be administered only with extreme caution in patients with hyperthyroidism and/or cardiovascular disease. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. Many of the newer antidepressants, including bupropion and the selective serotonin reuptake inhibitors (SSRIs), are considerably less or minimally cardiotoxic and may be appropriate alternatives.

Adults, young adults and children patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. Phenylpiperazine antidepressants are not approved for use in pediatric patients.

All antidepressants may occasionally cause mania or hypomania, particularly in patients with bipolar disorder. Therapy with antidepressants should be administered cautiously in patients with a history of mania/hypomania.

Although less cardiotoxic than the tricyclic antidepressants, trazodone may be arrhythmogenic in some patients with cardiac disease. The use of trazodone has been associated with the occurrence of arrhythmias, including PVCs, ventricular couplets, ventricular tachycardia, atrial fibrillation, and heart block. Myocardial infarction has been reported. Trazodone should not be used during the acute recovery phase following myocardial infarction, and should be administered only with extreme caution in patients with hyperthyroidism and/or cardiovascular disease. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. Many of the newer antidepressants, including bupropion and the selective serotonin reuptake inhibitors (SSRIs), are considerably less or minimally cardiotoxic and may be appropriate alternatives.

Trazodone has alpha-1 adrenergic blocking activity and may cause hypotension (including orthostatic hypotension) in approximately 5% of patients. Therapy with trazodone should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with trazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

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.

Trazodone has alpha-1 adrenergic blocking activity and may cause hypotension (including orthostatic hypotension) in approximately 5% of patients. Therapy with trazodone should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with trazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Treatment with trazodone may cause hyponatremia, in many cases secondary to development of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Caution should be used when treating patients at greater risk of developing hyponatremia such as elderly patients, patients taking diuretics or those who are volume-depleted. Discontinuation of trazodone should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted.

Adults, young adults and children patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. Phenylpiperazine antidepressants are not approved for use in pediatric patients.

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.

Trazodone has alpha-1 adrenergic blocking activity and may cause hypotension (including orthostatic hypotension) in approximately 5% of patients. Therapy with trazodone should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with trazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Some antidepressants exert mydriatic activity that can induce increased intraocular pressure and result in angle-closure (narrow-angle) glaucoma in a patient with anatomically narrow angles who does not have a patent iridectomy. Prior to initiating therapy with these agents, patients should be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible. The use of these drugs in patients with untreated anatomically narrow angles should be avoided.

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.

Trazodone has alpha-1 adrenergic blocking activity and may cause hypotension (including orthostatic hypotension) in approximately 5% of patients. Therapy with trazodone should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with trazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Trazodone has alpha-1 adrenergic blocking activity and may cause hypotension (including orthostatic hypotension) in approximately 5% of patients. Therapy with trazodone should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with trazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

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.

Although less cardiotoxic than the tricyclic antidepressants, trazodone may be arrhythmogenic in some patients with cardiac disease. The use of trazodone has been associated with the occurrence of arrhythmias, including PVCs, ventricular couplets, ventricular tachycardia, atrial fibrillation, and heart block. Myocardial infarction has been reported. Trazodone should not be used during the acute recovery phase following myocardial infarction, and should be administered only with extreme caution in patients with hyperthyroidism and/or cardiovascular disease. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. Many of the newer antidepressants, including bupropion and the selective serotonin reuptake inhibitors (SSRIs), are considerably less or minimally cardiotoxic and may be appropriate alternatives.

Treatment with trazodone may cause hyponatremia, in many cases secondary to development of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Caution should be used when treating patients at greater risk of developing hyponatremia such as elderly patients, patients taking diuretics or those who are volume-depleted. Discontinuation of trazodone should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted.

Trazodone has alpha-1 adrenergic blocking activity and may cause hypotension (including orthostatic hypotension) in approximately 5% of patients. Therapy with trazodone should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with trazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Trazodone has alpha-1 adrenergic blocking activity and may cause hypotension (including orthostatic hypotension) in approximately 5% of patients. Therapy with trazodone should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with trazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Trazodone undergoes metabolism in the liver. The metabolites, at least one of which is pharmacologically active, are excreted by the kidney. There are no data available concerning the pharmacokinetic disposition of trazodone or its metabolites in patients with renal and/or liver disease. Therapy with trazodone should be administered cautiously in patients with significantly impaired renal or hepatic function. Dosage adjustments may be necessary.

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.

All antidepressants may occasionally cause mania or hypomania, particularly in patients with bipolar disorder. Therapy with antidepressants should be administered cautiously in patients with a history of mania/hypomania.

Trazodone undergoes metabolism in the liver. The metabolites, at least one of which is pharmacologically active, are excreted by the kidney. There are no data available concerning the pharmacokinetic disposition of trazodone or its metabolites in patients with renal and/or liver disease. Therapy with trazodone should be administered cautiously in patients with significantly impaired renal or hepatic function. Dosage adjustments may be necessary.

The use of most antidepressants is associated with a risk of seizures. There have been only rare reports of convulsions, including grand mal seizures, following the administration of nefazodone or trazodone. Although a causal relationship has not been established, therapy with these agents should be administered cautiously in patients with a history of seizures.

Treatment with trazodone may cause hyponatremia, in many cases secondary to development of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Caution should be used when treating patients at greater risk of developing hyponatremia such as elderly patients, patients taking diuretics or those who are volume-depleted. Discontinuation of trazodone should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted.

Trazodone has alpha-1 adrenergic blocking activity and may cause hypotension (including orthostatic hypotension) in approximately 5% of patients. Therapy with trazodone should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with trazodone. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.