Dutrebis Disease Interactions

Severe acute exacerbations of HBV have been reported in HIV-1/HBV-coinfected patients who have discontinued products containing emtricitabine, lamivudine, and/or tenofovir disoproxil fumarate (DF) and may occur with discontinuation of tenofovir alafenamide-containing products. It is recommended that all patients with HIV-1 infection be tested for the presence of HBV before or when initiating products containing emtricitabine, lamivudine, tenofovir DF, or tenofovir alafenamide. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in HIV-1/HBV-coinfected patients who discontinue products (including fixed-dose combination products) that contain emtricitabine, lamivudine, tenofovir DF, or tenofovir alafenamide. If appropriate, initiation or resumption of antihepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.

Hepatotoxicity including lactic acidosis, severe hepatomegaly with steatosis, fulminant hepatitis, and hepatic failure has been associated with the use of some nucleoside reverse transcriptase inhibitors (NRTIs) alone or in combination with other antiretroviral agents. Therapy with NRTIs should be administered cautiously in patients with preexisting liver disease, a history of alcohol abuse, or hepatitis. Therapy should be suspended if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur. The use of abacavir is contraindicated in patients with moderate to severe liver dysfunction as its safety and efficacy have not been established in these patients.

The nucleoside reverse transcriptase inhibitors, didanosine, stavudine, and lamivudine, may cause pancreatitis. The incidence is generally low but is up to 7% with didanosine, and up to 18% in pediatric patients given lamivudine. Patients with a history of or known risk factors for pancreatitis (such as alcohol abuse or hypertriglyceridemia) should be monitored closely during therapy with these agents. Therapy should be discontinued at the first signs/symptoms suggestive of pancreatitis (e.g., nausea, vomiting, abdominal pain, hyperamylasemia with dysglycemia, rising triglycerides, decreasing serum calcium), and preferably permanently discontinued if clinical pancreatitis develops.

The apparent oral clearance of nucleoside reverse transcriptase inhibitors is decreased in patients with renal dysfunction. Dosage adjustments are recommended for lamivudine and stavudine in patients with CrCl less than 50 mL/min; zidovudine dosage should be reduced in patients with CrCl less than 15 mL/min. Fixed-dose combination products containing lamivudine are not recommended for patients with CrCl less than 30 or 50 mL/min; the manufacturer product information should be consulted.

There were no clinically important pharmacokinetic differences between subjects with severe renal impairment and healthy subjects. No dosage adjustment is necessary for these patients. Because the extent to which raltegravir may be dialyzable is unknown, dosing before a dialysis session should be avoided.

There were no clinically important pharmacokinetic differences between subjects with moderate hepatic impairment and healthy subjects. No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. Therapy with raltegravir should be administered with caution in patients with severe hepatic impairment, as the pharmacokinetics of raltegravir have not been studied in this population. Liver transaminases and bilirubin should regularly be monitored during therapy.

The use of raltegravir has been associated with creatine kinase elevations. There have been reports of myopathy and rhabdomyolysis in patients taking raltegravir. Therapy with raltegravir should be used with caution in patients at increased risk of myopathy or rhabdomyolysis, such as patients receiving concomitant medications known to cause these conditions or patients with a history of rhabdomyolysis, myopathy or increased serum creatine kinase levels.

Isentress (brand of raltegravir) chewable tablets contain phenylalanine. The 25 mg chewable tablet contains approximately 0.05 mg phenylalanine and the 100 mg contains approximately 0.10 mg phenylalanine. The phenylalanine content should be considered when this product is used in patients who must restrict their intake of phenylalanine (i.e. phenylketonuria).