SUSTIVAÒ
(efavirenz) capsules and tablets
DESCRIPTION
SUSTIVA Ò; (efavirenz) is a human immunodeficiency virus type 1 (HIV-1) specific, non-nucleoside, reverse transcriptase inhibitor (NNRTI).
Capsules: SUSTIVA is available as capsules for oral administration containing either 50 mg, 100 mg, or 200 mg of efavirenz and the following inactive ingredients: lactose monohydrate, magnesium stearate, sodium lauryl sulfate, and sodium starch glycolate. The capsule shell contains the following inactive ingredients and dyes: gelatin, sodium lauryl sulfate, titanium dioxide, and/or yellow iron oxide. The capsule shells may also contain silicon dioxide. The capsules are printed with ink containing carmine 40 blue, FD&C Blue No. 2, and titanium dioxide.
Tablets: SUSTIVA is available as film-coated tablets for oral administration containing 600 mg of efavirenz and the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. The film coating contains Opadry Ò; Yellow and OpadryÒ; Clear. The tablets are polished with carnauba wax and printed with purple ink, OpacodeÒ; WB.
Efavirenz is chemically described as (S)-6-chloro-4 (cyclopropylethynyl)-1,4-dihydro-4-( trifluoromethyl)-2H-3,1-benzoxazin-2-one.
Its empirical formula is C14H9ClF3NO2 and its structural formula is:
Efavirenz is a white to slightly pink crystalline powder with a molecular mass of 315.68. It is practically insoluble in water (<10 mg/mL).
CLINICAL STUDIES
Clinical isolates with reduced susceptibility in vitro to EFV have been obtained. One or more RT substitutions at amino acid positions 98, 100, 101, 103, 106, 108, 188, 190, 225, and 227 were observed in patients failing treatment with EFV in combination with IDV, or with ZDV plus LAM. The mutation K103N was the most frequently observed. Long-term resistance surveillance (average 52 weeks, range 4-106 weeks) analyzed 28 matching baseline and virologic failure isolates. Sixty-one percent (17/28) of these failure isolates had decreased EFV susceptibility in vitro with a median 88-fold change in EFV susceptibility (IC50 value) from reference. The most frequent NNRTI mutation to develop in these patient isolates was K103N (54%). Other NNRTI mutations that developed included L100I (7%), K101E/Q/R (14%), V108I (11%), G190S/T/A (7%), P225H (18%), and M230I/L (11%).
Cross-Resistance
Cross-resistance among NNRTIs has been observed. Clinical isolates previously characterized as EFV-resistant were also phenotypically resistant in vitro to DLV and NVP compared to baseline. DLV- and/or NVP-resistant clinical viral isolates with NNRTI resistance-associated substitutions (A98G, L100I, K101E/P, K103N/S, V106A, Y181X, Y188X, G190X, P225H, F227L, or M230L) showed reduced susceptibility to EFV in vitro. Greater than 90% of NRTI-resistant clinical isolates tested in vitro retained susceptibility to EFV.
