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FDA Approves New Single Efavirenz 600 mg Tablet, Taken Once Per Day
  Efavirenz is a potent non-nucleoside reverse transcriptase inhibitor (NNRTI) that is taken once per day. The FDA (Food and Drug Administration) just approved a single 600 mg tablet that can be taken once per day. Previously, efavirenz was taken as 3 200 mg tablets once per day. Since this new development reduces the number of pills a patient will have to take, this should improve convenience and adherence to taking medication.
The FDA approved on February 1, 2002, a new formulation of Sustiva (efavirenz), a non nucleoside reverse transcriptase inhibitor for the treatment of HIV infection. Sustiva will now be available as a 600 mg tablet to be taken once daily, in combination with a protease inhibitor and/or nucleoside analogue reverse transcriptase inhibitors (NRTIs). Sustiva, will continue to be available in the 50mg, 100, and 200 mg capsules in addition to the new 600 mg tablet.
In addition, the Sustiva label was revised to include new statements in the DOSAGE AND ADMINISTRATION section. The revised statements are shown within > < symbols, below.
"Adults: The recommended dosage of SUSTIVA is 600 mg orally, once daily, in combination with a protease inhibitor and/or nucleoside analogue reverse transcriptase inhibitors (NRTIs). >It is recommended that SUSTIVA be taken on an empty stomach, preferably at bedtime. The increased efavirenz concentrations observed following administration of SUSTIVA with food may lead to an increase in frequency of adverse events. Dosing at bedtime may improve the tolerability of nervous system symptoms.<"
In addition the CLINICAL PHARMAOLOGY and PRECAUTIONS sections have been updated to include drug interaction information on Sustiva with the following medications; St. John's wort, lorazepam, methadone, cetirizine and rifabutin. The ADVERSE REACTION section was also revised to update the incidences of adverse events and laboratory abnormalities seen in clinical trials.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The new FDA Package Insert recommends take efavirenz on empty stomach; eating food can raise levels of efavirenz in your body.
Effect of Food on Oral Absorption: Capsules - Administration of a single 600-mg dose of efavirenz capsules with a high fat/high caloric meal (894 kcal, 54 g fat, 54% calories from fat) or a reduced fat/normal caloric meal (440 kcal, 2 g fat, 4% calories from fat) was associated with a mean increase of 22% and 17% in efavirenz AUC and a mean increase of 39% and 51% in efavirenz Cmax, respectively, relative to the exposures achieved when given under fasted conditions.
Tablets - Administration of a single 600-mg efavirenz tablet with a high fat/high caloric meal (approximately 1000 kcal, 500-600 kcal from fat) was associated with a 28% increase in mean AUC of efavirenz and a 79% increase in mean Cmax of efavirenz relative to the exposures achieved under fasted conditions.
Package insert reports: Ritonavir can raise EFV levels 4-26% (Cmax-peak level 5 hrs after taking EFV), and 10-34% (AUC) overal amount of drug in blood over 24 hr dosing period). Fluconazole reported to raise AUC of EFV 6-26%; Clarithromycin reported to raise Cmax 3-19%.
Patients receiving SUSTIVA should be alerted to the potential for additive central nervous system effects when SUSTIVA is used concomitantly with alcohol or psychoactive drugs.
Patients who experience central nervous system symptoms such as dizziness, impaired concentration and/or drowsiness should avoid potentially hazardous tasks such as driving or operating machinery.
In patients with known or suspected history of Hepatitis B or C infection and in patients treated with other medications associated with liver toxicity, monitoring of liver enzymes is recommended. Liver function tests should be monitored in patients with a prior history of Hepatitis B and/or C. In 156 patients treated with 600 mg of SUSTIVA who were seropositive for Hepatitis B and/or C, 7% developed AST levels and 8% developed ALT levels greater than five times the upper limit of normal. In 91 patients seropositive for Hepatitis B and/or C treated with control regimens, 5% developed AST elevations and 4% developed ALT elevations to these levels.
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