Sustiva - Efavirenz

Droperidol (Inapsine) Econazole (Spectazole) Efavirenz (Sustiva)... 

Abacavir (Ziagen) Amprenavir (Agenerase) Delavirdine (Rescriptor) Didanosine [ddl] (Videx) Efavirenz (Sustiva) Efavirenz/Emtricitabine/ Tenofovir (Atripla) Fosamprenavir (Lexiva)... 

Efavirenz (Sustiva) [Antiretroviral/NNRTI] Uses Hiv infxns Action Antiretroviral nonnucleoside RTI Dose Adults. 600 mg/d PO qhs Feds. See package insert avoid high-fat meals Caution [D, ] CDC recommends HIV-infected mothers not breast-feed Contra Component sensitivity Disp Caps SE Somnolence, vivid dreams, dizziness, rash, N/V/D Interactions T Effects W/ ritonavir T effects OF CNS depressants, ergot derivatives, midazolam, ritonavir, simvastatin, triazolam, warfarin X effects W/ carbamazepine, phenobarbital, rifabutin, rifampin, saquinavir, St. John s wort i effects OF amprenavir, carbamazepine, clarithromycin, indinavir, phenobarbital, saquinavir, warfarin may alter effectiveness OF OCPs EMS Concurrent EtOH usage can t CNS d ression OD May cause muscle contractions and adverse CNS effects activated charcoal may be effective... 

Efavirenz (Sustiva) is approved for the therapy of HIV infection of adults and children and is also used for postexposure prophylaxis. It is the only NNRTI approved for once-daUy dosing. Rash, although rarely severe, is a common adverse effect of efavirenz. Elevated liver enzymes and serum cholesterol also may occur. Central nervous system (CNS) effects in approximately half of patients may include dizziness, headache, insomnia, drowsiness, euphoria, agitation, impaired cognition, nightmares, vivid dreams, and hallucinations. These effects often subside after several weeks to months of therapy. 

More recently, RTIs that are chemically distinct from zidovudine and other NRTIs have also been developed (see Table 34-3). These agents are known as nonnucleoside reverse transcriptase inhibitors (NNR-TIs), and include drugs such as delavirdine (Rescrip-tor), efavirenz (Sustiva), and nevirapine (Viramune).32 These drugs also inhibit the reverse transcriptase enzyme, but act at a different site on the enzyme than do their NRTI counterparts. 

The third strategy developed to inhibit HIV replication is the NNRTIs. These drugs include delavir-dine (Rescriptor), efavirenz (Sustiva), and nevirapine (Viramune). Fike their nucleoside counterparts, NNR-... 

Oral (Videx-EC) 125, 200, 250, 400 mg delayed release capsules Efavirenz(Sustiva)... 

Efavirenz/Sustiva Oral Solution/Bristol-Meyers Squibb/HIV... 

Efavirenz. Efavirenz (Sustiva)"" is also mandated for use with at least two other antiretroviral agents. The compound is more than 99% protein bound, and CSF concentrations exceed the free fraction in the scram. Metabolism occurs in the liver. The half-life of a single dose of efavirenz is 52 to 76 hours, and 40 to 55 after multiple doses (the drag induces its own mctaboli.sm). Peak concentration is achieved... 

Efavirenz/ Sustiva 30 mg/mL Oral Solution/ Bristol-Meyers Squibb/1999 FsC. II ° H FIIV antiviral Adults 600 mg q.d. (up to 20 mF) Pediatrics 270-600 mg (9-20 mF) Oral solution 30 mg/mF Medium-chain triglycerides Benzoic acid Strawberry and Mint flavor RT... 

NNRTIs bind to reverse transcriptase, a protein HIV needs to make more copies of itself. In doing so, reverse transcriptase becomes disabled. Drugs within this category include Delavirdine (Rescriptor, DLV), Efavirenz (Sustiva, EFV), and Neviapine (Viramune, NVP). 

The non-nucleoside reverse transcriptase inhibitor efavirenz (Sustiva). 

DPC 961 (134, Scheme 2.21) has shown activity against wild-type HIV-1 and various non-nucleoside reverse transcriptase inhibitor-resistant HIV strains, and with greater potency than the structurally related efavirenz (Sustiva Bristol-Myers Squibb), an approved drug for HIV treat-ment. ° To facilitate the development of DPC 961, researchers at DuPont Pharmaceuticals Company (Wilmington, DE) developed an asymmetric conjugate addition strategy to introduce the trifluoromethyl amine stereocenter. As depicted in Scheme 2.21, treatment of the known aniline 128 ° with two equivalents of (R)-(-l-)-a-methylbenzyl isocyanate 129 afforded the hemiami-nal 130, which was subsequently converted into the 2(3//)-quinazolinone 131 by reaction with thionyl chloride and triethylamine. Reaction of the quinazolinone 131 with excess cyclopropylacetylene magnesium chloride 132 provided the dihydroquinazolinone 133 in 86% yield and 92% diastereomeric excess. Conversion of the dihydroquinazolinone 133 into DPC 961 134 involved treatment with tri-fluoroacetic acid or warm formic acid. Overall, this process provided 16 kg of DPC 961 134 in >55% overall yield from aniline 128. 

Ort/zo-lithiation chemistry has also been applied in both the racemic and the stereoselective synthesis of the anti-HIV agent efavirenz (Sustiva) wherein the NHBoc group served as a DMG in the synthesis of a key tri-fluoromethyl ketone intermediate (Scheme 11.11). In the asymmetric synthesis, this ketone was subjected to an enantioselective allqmylation with a cyclopropyl acetylide in the presence of (lR,2S)-Ar-pyrrolidinylnorephedrine to obtain the desired framework of efavirenz. Notably, MTBE was used in place of THF as a solvent to avoid the competitive attack of n-butyllithium on THF at 0 °C in the DoM step. 

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