Efavirenz

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of efavirenz
General
Non-proprietary name Efavirenz
other names

(4 S ) -6-Chloro-4- (2-cyclopropylethynyl) -4- (trifluoromethyl) -1 H -3,1-benzoxazin-2-one

Molecular formula C 14 H 9 ClF 3 NO 2
External identifiers / databases
CAS number 154598-52-4
EC number 620-492-6
ECHA InfoCard 100.149.346
PubChem 64139
DrugBank DB00625
Wikidata Q422645
Drug information
ATC code

J05 AG03

Drug class

Antivirals , non-nucleoside reverse transcriptase inhibitors

Mechanism of action

non-competitive inhibition of reverse transcriptase

properties
Molar mass 315.67 g · mol -1
Physical state

firmly

Melting point

139-141 ° C

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
09 - Dangerous for the environment 08 - Dangerous to health 07 - Warning

danger

H and P phrases H: 302-319-360-372-410
P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Efavirenz (EFV, trade names Sustiva ® , Stocrin ® ; manufacturer: Bristol-Myers Squibb ) is a chiral drug for the treatment of HIV-1 infected patients as part of a combination antiretroviral therapy .

Efavirenz belongs to the group of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and is used as a pure enantiomer .

history

Efavirenz was approved by the American Food and Drug Administration in September 1998; in Germany, efavirenz has been marketed by Bristol-Myers Squibb since 1999. At the end of October 2015, the company announced that it would no longer market the dissolved version of Sustiva ® .

Mode of action

Efavirenz belongs to the class of non-nucleoside reverse transcriptase inhibitors . The active ingredient binds non-competitively to the reverse transcriptase of HIV-I , near the substrate binding site for nucleosides . This blocks the catalytically active binding site. Only a few nucleosides can bind and the polymerization is slowed down significantly.

Pharmacokinetics

The maximum plasma concentration is reached after about 5 hours. Food intake usually has no effect on absorption . The exception are very high-fat meals, which increase absorption by an average of 50%. Plasma protein binding of> 99%. The CSF concentration is about three times as high as the free efavirenz concentration in the plasma. The half-life is between 40 and 55 hours. 14–34% is excreted in the urine in the form of metabolites and 16–61% in the stool as unchanged substance.

Contraindications

Efavirenz should not be used for therapy during pregnancy or if the patient wishes to have children, as it is teratogenic .

Side effects

Efavirenz can cause central nervous system symptoms such as drowsiness, headache, poor concentration, difficulty sleeping, or unusual dreams, especially in the first few days of treatment. In most cases, the CNS symptoms are only mild or moderate and resolve after two to four weeks without interruption of therapy or dose reduction.

The antiviral can, among other things, cause a rapid cannabinoid test to accidentally fail.

Individual evidence

  1. ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 698, ISBN 978-0-911910-00-1 .
  2. ↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of 153789 in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), which was accessed on January 16, 2020, is reproduced from a self-classification by the distributor .
  3. ↑ a b Efavirenz: HIV patients benefit from once daily intake. November 22, 1998, accessed August 8, 2020 .

Trade names

Monopreparations

Stocrin (A, CH), Sustiva (D, A)

Combination preparations

Atripla (D, A)

Web links

literature

  • Cozzi-Lepri, A. et al. (2002): Virologic and immunologic response to regimens containing nevirapine or efavirenz in combination with 2 nucleoside analogues in the (I.Co.NA) study. J Infect Dis 185 (8); 1062-9; PMID 11930316 .
  • Fisac, C. et al. (2005): Metabolic benefits 24 months after replacing a protease inhibitor with abacavir, efavirenz or nevirapine. AIDS . 19 (9); 917-25; PMID 15905672 .
  • Fumaz, CR. et al. (2002): Quality of life, emotional status, and adherence of HIV-1 infected patients treated with efavirenz versus PI-containing regimens. J Acquir Immune Defic Syndr. 29 (3); 244-53; PMID 11873073 .
  • Gallego, L. et al. (2004): Analyzing sleep abnormalities in HIV-infected patients treated with efavirenz. Clin Infect Dis . 38 (3); 430-2; PMID 14727217 .
  • Haas, DW. et al. (2004): Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS. 18 (18); 2391-2400. PMID 15622315 .
  • Lochet, P. et al. (2003): Long-term assessment of neuropsychiatric adverse reactions associated with efavirenz. HIV Medicine 4 (1); 62-6. PMID 12534961 ; doi : 10.1046 / j.1468-1293.2003.00136 (free full text access , English).
  • Martinez, E. et al. (2003): Substitution of nevirapine, efavirenz or abacavir for protease inhibitors in patients with HIV infection. N Engl J Med . 349 (11); 1036-46; PMID 12968087 ; PDF (free full text access).
  • Marzolini, C. et al. (2001): Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1 infected patients. AIDS. 15 (1); 71-5; PMID 11192870 .
  • Sheran, M. The NNRTIs efavirenz and nevirapine in the treatment of HIV. HIV Clin Trials . 6 (3); 158-68; PMID 16192249 .
  • Squires, K. et al. (2004): Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV. J Acquir Immune Defic Syndr. 36 (5); 1011-1019; PMID 15247553 .
  • Staszewski, S. et al. (1999): Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. N Engl J Med. 341 (25); 1865-73; PMID 10601505 ; PDF (free full text access).
  • Sulkowski, MS. et al. (2002): Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections. Hepatology 35 (1); 182-9; PMID 11786975 ; doi : 10.1053 / jhep.2002.30319 (free full text access , English).
  • Sütterlin, S., Vögele, C., & Gauggel, S. (2010). Neuropsychiatric complications of Efavirenz therapy: suggestions for a new research paradigm. The Journal of Neuropsychiatry and Clinical Neurosciences, 22 (4), 361-369. PMID 21037119 .
  • Torre, D. et al. (2001): Nevirapine or efavirenz combined with two nucleoside reverse transcriptase inhibitors compared to HAART: a meta-analysis of randomized clinical trials. HIV Clin Trials. 2 (2); 113-21; PMID 11590519 .
  • van Leth, F. et al. (2004): Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomized open-label trial, the 2NN Study. Lancet 363 (9417); 1253-63; PMID 15094269 .
  • Winston, A. et al. (2004): Dose escalation or immediate full dose when switching from efavirenz to nevirapine-based highly active antiretroviral therapy in HIV-1 infected individuals? AIDS 18 (3); 572-4; PMID 15090815 .
  1. ↑ Rote Liste Service GmbH (Ed.): Rote Liste 2017 - drug directory for Germany (including EU approvals and certain medical devices) , Rote Liste Service GmbH, Frankfurt / Main, 2017, edition 57, ISBN 978-3-946057-10 -9 , p. 179.