Drug Interactions between cefotetan and ombitasvir / paritaprevir / ritonavir

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.

Ask your doctor before using cefoTEtan together with ethanol (alcohol). Do not drink alcohol while you are taking cefoTEtan. You may have unpleasant side effects such as fast heartbeats, warmth or redness under your skin, tingly feeling, nausea, and vomiting. Check your food and medicine labels to be sure these products do not contain alcohol. 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.

Hypoprothrombinemia, with or without bleeding, has been reported rarely with various cephalosporins, particularly those containing an N-methylthiotetrazole (NMTT) side chain (cefamandole, cefmetazole, cefoperazone, cefotetan). The sulfhydryl group of this side chain is suspected of interfering with the hepatic synthesis of prothrombin. Risk factors include advanced age, debility, vitamin K deficiency, malnutrition, malabsorption, and severe renal or hepatobiliary impairment. Therapy with cephalosporins containing the NMTT side chain should be administered cautiously in patients with any of these risk factors and/or significant active bleeding or a hemorrhagic diathesis. Prophylactic administration of vitamin K may be indicated in some patients, especially when intestinal sterilization and surgical procedures are performed.

Hypoprothrombinemia, with or without bleeding, has been reported rarely with various cephalosporins, particularly those containing an N-methylthiotetrazole (NMTT) side chain (cefamandole, cefmetazole, cefoperazone, cefotetan). The sulfhydryl group of this side chain is suspected of interfering with the hepatic synthesis of prothrombin. Risk factors include advanced age, debility, vitamin K deficiency, malnutrition, malabsorption, and severe renal or hepatobiliary impairment. Therapy with cephalosporins containing the NMTT side chain should be administered cautiously in patients with any of these risk factors and/or significant active bleeding or a hemorrhagic diathesis. Prophylactic administration of vitamin K may be indicated in some patients, especially when intestinal sterilization and surgical procedures are performed.

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation 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.

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).

Hypoprothrombinemia, with or without bleeding, has been reported rarely with various cephalosporins, particularly those containing an N-methylthiotetrazole (NMTT) side chain (cefamandole, cefmetazole, cefoperazone, cefotetan). The sulfhydryl group of this side chain is suspected of interfering with the hepatic synthesis of prothrombin. Risk factors include advanced age, debility, vitamin K deficiency, malnutrition, malabsorption, and severe renal or hepatobiliary impairment. Therapy with cephalosporins containing the NMTT side chain should be administered cautiously in patients with any of these risk factors and/or significant active bleeding or a hemorrhagic diathesis. Prophylactic administration of vitamin K may be indicated in some patients, especially when intestinal sterilization and surgical procedures are performed.

Hypoprothrombinemia, with or without bleeding, has been reported rarely with various cephalosporins, particularly those containing an N-methylthiotetrazole (NMTT) side chain (cefamandole, cefmetazole, cefoperazone, cefotetan). The sulfhydryl group of this side chain is suspected of interfering with the hepatic synthesis of prothrombin. Risk factors include advanced age, debility, vitamin K deficiency, malnutrition, malabsorption, and severe renal or hepatobiliary impairment. Therapy with cephalosporins containing the NMTT side chain should be administered cautiously in patients with any of these risk factors and/or significant active bleeding or a hemorrhagic diathesis. Prophylactic administration of vitamin K may be indicated in some patients, especially when intestinal sterilization and surgical procedures are performed.

Hypoprothrombinemia, with or without bleeding, has been reported rarely with various cephalosporins, particularly those containing an N-methylthiotetrazole (NMTT) side chain (cefamandole, cefmetazole, cefoperazone, cefotetan). The sulfhydryl group of this side chain is suspected of interfering with the hepatic synthesis of prothrombin. Risk factors include advanced age, debility, vitamin K deficiency, malnutrition, malabsorption, and severe renal or hepatobiliary impairment. Therapy with cephalosporins containing the NMTT side chain should be administered cautiously in patients with any of these risk factors and/or significant active bleeding or a hemorrhagic diathesis. Prophylactic administration of vitamin K may be indicated in some patients, especially when intestinal sterilization and surgical procedures are performed.

Hypoprothrombinemia, with or without bleeding, has been reported rarely with various cephalosporins, particularly those containing an N-methylthiotetrazole (NMTT) side chain (cefamandole, cefmetazole, cefoperazone, cefotetan). The sulfhydryl group of this side chain is suspected of interfering with the hepatic synthesis of prothrombin. Risk factors include advanced age, debility, vitamin K deficiency, malnutrition, malabsorption, and severe renal or hepatobiliary impairment. Therapy with cephalosporins containing the NMTT side chain should be administered cautiously in patients with any of these risk factors and/or significant active bleeding or a hemorrhagic diathesis. Prophylactic administration of vitamin K may be indicated in some patients, especially when intestinal sterilization and surgical procedures are performed.

Hypoprothrombinemia, with or without bleeding, has been reported rarely with various cephalosporins, particularly those containing an N-methylthiotetrazole (NMTT) side chain (cefamandole, cefmetazole, cefoperazone, cefotetan). The sulfhydryl group of this side chain is suspected of interfering with the hepatic synthesis of prothrombin. Risk factors include advanced age, debility, vitamin K deficiency, malnutrition, malabsorption, and severe renal or hepatobiliary impairment. Therapy with cephalosporins containing the NMTT side chain should be administered cautiously in patients with any of these risk factors and/or significant active bleeding or a hemorrhagic diathesis. Prophylactic administration of vitamin K may be indicated in some patients, especially when intestinal sterilization and surgical procedures are performed.

Hypoprothrombinemia, with or without bleeding, has been reported rarely with various cephalosporins, particularly those containing an N-methylthiotetrazole (NMTT) side chain (cefamandole, cefmetazole, cefoperazone, cefotetan). The sulfhydryl group of this side chain is suspected of interfering with the hepatic synthesis of prothrombin. Risk factors include advanced age, debility, vitamin K deficiency, malnutrition, malabsorption, and severe renal or hepatobiliary impairment. Therapy with cephalosporins containing the NMTT side chain should be administered cautiously in patients with any of these risk factors and/or significant active bleeding or a hemorrhagic diathesis. Prophylactic administration of vitamin K may be indicated in some patients, especially when intestinal sterilization and surgical procedures are performed.

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.

Disulfiram-like reactions may occur in patients who consume alcohol within 72 hours after administration of a cephalosporin antibiotic that contains an N-methylthiotetrazole (NMTT) side chain (cefamandole, cefmetazole, cefoperazone, cefotetan). The reaction appears to result from accumulation of acetaldehyde due to inhibition of acetaldehyde dehydrogenase. Therapy with cephalosporins containing the NMTT side chain should be administered cautiously in patients with a history of alcoholism. Patients should be instructed to avoid alcohol-containing products during therapy and up to 72 hours after the last dose.

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.

Parenteral cefotetan disodium contains approximately 80 mg (3.5 mEq) of sodium per each gram of cefotetan activity. The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

Use of cephalosporins may result in a false-positive reaction for glucose in urine with certain methods (e.g., Clinitest tablets). Glucose tests based on enzymatic glucose oxidase reactions are recommended for patients receiving cephalosporins.

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.

Parenteral cefotetan disodium contains approximately 80 mg (3.5 mEq) of sodium per each gram of cefotetan activity. The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

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.

Most cephalosporin antibiotics are removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis. Cefonicid, cefixime, and ceftriaxone are not significantly removed by hemodialysis.

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.

Parenteral cefotetan disodium contains approximately 80 mg (3.5 mEq) of sodium per each gram of cefotetan activity. The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

Parenteral cefotetan disodium contains approximately 80 mg (3.5 mEq) of sodium per each gram of cefotetan activity. The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

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.

Cases of hepatitis have been reported with the use of certain cephalosporins. Transient rise in AST, ALT, and alkaline phosphatase levels have also been observed. Caution and monitoring are recommended when these agents are prescribed to patients with hepatic disorders.

Most beta-lactam antibacterial agents are eliminated by the kidney as unchanged drug and, in some cases, also as metabolites. The serum concentrations of beta-lactam antibacterial agents and their metabolites may be increased, and the half-lives prolonged, in patients with impaired renal function. Neurotoxic reactions (e.g., encephalopathy, aphasia, asterixis, myoclonus, seizures, nonconvulsive status epilepticus, coma) have been reported in such patients treated parenterally with these agents. Dosage adjustments may be necessary, and modifications should be based on the degree of renal dysfunction as well as severity of infection in accordance with the individual manufacturer product information. Renal function tests should be performed periodically during prolonged and/or high-dose therapy since nephrotoxicity and alterations in renal function have occasionally been associated with the use of these drugs.

Cephalosporins have been implicated in triggering seizures. Nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported with cephalosporins, particularly in patients with a history of epilepsy and/or when recommended dosages of cephalosporins were exceeded due to renal dysfunction. Dosage should be adjusted based on the degree of renal function. Anticonvulsant therapy should be continued in patients with known seizure disorders. If CNS adverse reactions including seizures occur, patients should undergo a neurological evaluation to determine whether treatment should be discontinued.