Drug Interactions between ombitasvir / paritaprevir / ritonavir and quazepam

Grapefruit and grapefruit juice may interact with quazepam and lead to potentially dangerous side effects. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor. Do not drink alcohol while taking quazepam. This medication can increase the effects of alcohol. You may feel more drowsy, dizzy, or tired if you take quazepam with alcohol. 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.

The use of benzodiazepines with alcohol is not recommended. Patients with acute alcohol intoxication exhibit depressed vital signs. The central nervous system depressant effects of benzodiazepines may be additive with those of alcohol, and severe respiratory depression and death may occur. Therapy with benzodiazepines should be administered cautiously in patients who might be prone to acute alcohol intake.

Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.

Benzodiazepines have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use and/or excessive dosages. However, abrupt cessation following continual use of as few as 6 weeks at therapeutic levels has occasionally precipitated withdrawal symptoms. Addiction- prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance when treated with benzodiazepines. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of benzodiazepine therapy should be undertaken gradually using a dosage- tapering schedule. If withdrawal symptoms occur, temporary reinstitution of benzodiazepines may be necessary.

The manufacturers consider the use of benzodiazepines to be contraindicated in patients with acute angle-closure glaucoma or untreated open-angle glaucoma. These agents do not possess anticholinergic activity but have very rarely been associated with increased intraocular pressure.

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.

Benzodiazepines are metabolized by the liver, and the metabolites are excreted in the urine. Chlordiazepoxide, clorazepate, diazepam, flurazepam and quazepam undergo oxidative N-dealkylation to active metabolites that are substantially longer-acting than the parent compound. These metabolites then undergo further biotransformation to pharmacologically inactive products before excretion by the kidney. Therapy with benzodiazepines should be administered cautiously at lower initial dosages in patients with impaired renal and/or hepatic function. Agents that are converted to weakly active, short-acting, or inactive metabolites may be preferable in hepatic impairment. Lorazepam, oxazepam and temazepam are conjugated to inactive metabolites, while alprazolam, estazolam and triazolam undergo hydroxylation to weakly active or inactive metabolites.

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).

Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.

Benzodiazepines are metabolized by the liver, and the metabolites are excreted in the urine. Chlordiazepoxide, clorazepate, diazepam, flurazepam and quazepam undergo oxidative N-dealkylation to active metabolites that are substantially longer-acting than the parent compound. These metabolites then undergo further biotransformation to pharmacologically inactive products before excretion by the kidney. Therapy with benzodiazepines should be administered cautiously at lower initial dosages in patients with impaired renal and/or hepatic function. Agents that are converted to weakly active, short-acting, or inactive metabolites may be preferable in hepatic impairment. Lorazepam, oxazepam and temazepam are conjugated to inactive metabolites, while alprazolam, estazolam and triazolam undergo hydroxylation to weakly active or inactive metabolites.

Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.

The use of benzodiazepines in patients with seizure disorders may increase the incidence or precipitate the onset of generalized tonic-clonic seizures (grand mal). Appropriate anticonvulsant medication might need to be initiated or the dosage increased. Abrupt cessation of benzodiazepine therapy may precipitate seizures and other withdrawal symptoms, particularly after prolonged use and/or excessive dosages. Status epilepticus may occur in patients with a history of seizures withdrawn rapidly from benzodiazepine therapy. Following chronic administration, cessation of benzodiazepine therapy should occur gradually with incrementally reduced dosages. Patients should be advised not to discontinue medication without first consulting with the physician.

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.

Benzodiazepines depress the central nervous system and may cause or exacerbate mental depression and cause suicidal behavior and ideation. Episodes of mania and hypomania have also been reported in depressed patients treated with some of these agents. Therapy with benzodiazepines should be administered cautiously in patients with a history of depression or other psychiatric disorders. Patients should be monitored for any changes in mood or behavior. It may be prudent to refrain from dispensing large quantities of medication to these 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.

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.

Paradoxical reactions, including excitability, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares and vivid dreams, have been reported with the use of benzodiazepines in psychiatric patients and pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with benzodiazepines. The manufacturers do not recommend the use of benzodiazepines for the treatment of psychosis.

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 plasma half-lives of benzodiazepines may be prolonged in obese patients, presumably due to increased distribution into fat. Marked increases in distribution (> 100%) have been reported for diazepam and midazolam, and moderate increases (25% to 100%) for alprazolam, lorazepam, and oxazepam. Therapy with benzodiazepines should be administered cautiously in obese patients, with careful monitoring of CNS status. Longer dosing intervals may be appropriate. When dosing by weight, loading doses should be based on actual body weight, while maintenance dose should be based on ideal body weight to avoid toxicity.

Benzodiazepines depress the central nervous system and may cause or exacerbate mental depression and cause suicidal behavior and ideation. Episodes of mania and hypomania have also been reported in depressed patients treated with some of these agents. Therapy with benzodiazepines should be administered cautiously in patients with a history of depression or other psychiatric disorders. Patients should be monitored for any changes in mood or behavior. It may be prudent to refrain from dispensing large quantities of medication to these patients.

Paradoxical reactions, including excitability, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares and vivid dreams, have been reported with the use of benzodiazepines in psychiatric patients and pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with benzodiazepines. The manufacturers do not recommend the use of benzodiazepines for the treatment of psychosis.

Sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder. The symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric or medical illness that should be evaluated. Worsening of insomnia with the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized disorder.