Nelfinavir

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Structural formula
Structure of nelfinavir
General
Non-proprietary name Nelfinavir
Molecular formula C 32 H 45 N 3 O 4 S
External identifiers / databases
CAS number 159989-64-7
PubChem 64143
ChemSpider 57718
DrugBank DB00220
Wikidata Q423366
Drug information
ATC code

J05 AE04

Drug class

HIV protease inhibitor

properties
Molar mass 567.78 g · mol -1
pK s value

6.0; 11.6

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Nelfinavir (NLV, trade name: Viracept , manufacturer: Hoffmann-La Roche ) is a drug from the group of HIV protease inhibitors and indicated for the anti- retroviral treatment of HIV-1 infected patients. HIV protease inhibitors are combined with other antiviral agents ( NRTI , NNRTI ) as part of a so-called "highly active antiretroviral therapy" ( HAART ) .

When the European approval expired in January 2013, Roche discontinued the production of Viracept due to falling demand worldwide.

history

Nelfinavir was developed by Agouron Pharmaceuticals (now: Pfizer ) and patented in 1995. First nelfinavir formulations were approved by the American FDA in March 1997 and by the European authorities in January 1998.

indication

Nelfinavir is indicated for combination antiviral therapy in HIV infection. For this purpose, the combination with two active substances from the group of nucleoside analogues is recommended. It can be used in adults, adolescents and children over three years of age.

pharmacology

The mechanism of action is similar to that of other HIV protease inhibitors, i.e. an enzyme that is necessary for virus replication , the HIV protease , is inhibited. However, the binding mechanism between enzyme and active ingredient is unique, so that there is no cross-resistance with other HIV protease inhibitors. In contrast to these, nelfinavir is able to inhibit HIV-1 and HIV-2 proteases equally. As already recognized in the laboratory experiment, a certain development of resistance of the viruses to the active substance also occurred during therapy . In accordance with the practice with other HIV protease inhibitors, however, this reduction in sensitivity can be significantly reduced by using the drug in combination with other antiviral agents. An advantage over previous representatives of the same group is the fact that the absorption of nelfinavir is significantly improved by simultaneous food intake. Almost all of the substance is bound to plasma proteins in the blood and metabolized in the liver . The cytochrome P450 system plays a key role here, which leads to multiple interactions with other drugs. The metabolites are excreted in the stool. The plasma half-life of nelfinavir is approximately 3.5 to 5 hours.

Side effects and contraindications

The most common side effects affect the gastrointestinal tract ( flatulence , diarrhea ) , as with similar active substances, although it has been found that these symptoms occurred more frequently with triple medication than with treatment with stavudine or zidovudine / lamivudine. Headache and skin reactions, rarely tiredness and hepatitis, are also observed . Nelfinavir inhibits hepatic monooxygenases (cytochrome P450) and through this mechanism can lead to several complications with other drugs (e.g. astemizole , cisapride , various benzodiazepines , ergotoxins and some antiarrhythmics ).

Pharmaceutical information

Nelfinavir is used pharmaceutically as the salt of methanesulfonic acid ( INN: nelfinavir mesilat ). In the case of drug syntheses in which a reaction with a sulfonic acid takes place, mutagenic and carcinogenic impurities can arise under unfavorable manufacturing conditions . In 2007 Roche temporarily withdrew all formulations from the market in European countries and some other regions after an impurity, ethyl methanesulfonate (EMS), appeared in certain lots of nelfinavir . By introducing appropriate measures in the manufacturing process, the contamination can be kept below a critical limit value.

Web links

Individual evidence

  1. ↑ a b c d Entry on nelfinavir. In: Römpp Online . Georg Thieme Verlag, accessed on July 17, 2019.
  2. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  3. ↑ Non-renewal of the marketing authorization in the European Union (PDF; 49 kB), January 24, 2013.
  4. ↑ Pharmazeutische Zeitung 4/2013, p. 101.
  5. ↑ Questions and Answers on the Recall of Viracept. (PDF; 39 kB) EMA , June 6, 2007, accessed on November 1, 2017 (English).
  6. ^ European Medicines Agency recommends lifting of suspension for Viracept. (PDF; 29 kB) EMA , September 20, 2007, accessed on November 1, 2017 (English).
  7. ↑ Reintroduction of the HIV drug Viracept film-coated tablets 250 mg from Roche in Switzerland ( Memento of March 4, 2016 in the Internet Archive ).