Indinavir
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| Non-proprietary name | Indinavir | |||||||||||||||
| Molecular formula | C 36 H 47 N 5 O 4 | |||||||||||||||
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| Molar mass | 613.80 g · mol -1 | |||||||||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||
Indinavir (IDV, trade name: Crixivan ® ) is a drug from the group of HIV protease inhibitors and is used to treat HIV-1 infected patients . HIV protease inhibitors are combined with other antiretroviral agents ( NRTI , NNRTI ) as part of a so-called "highly active antiretroviral therapy" ( HAART ) .
history
Indinavir was developed by MSD Sharp & Dohme . In 1996, oral dosage forms of indinavir received approval from the American FDA and the European EMEA . At the time of its inception, indinavir was one of the most effective antiviral agents. Newer, better tolerated representatives of the HIV protease inhibitors are increasingly replacing indinavir. In late 2019, MSD took indinavir out of trade with reference to better alternative therapies. As there is no generic preparation available, indinavir will therefore disappear completely from the market.
indication
Indinavir is indicated for the treatment of HIV infections, but can also be used for post-exposure prophylaxis . In principle, it is not used as a single drug, as this would not make sense due to the development of resistance of the viruses. However, the combination of indinavir with two other antiviral agents, such as lamivudine and zidovudine, is used . The recommended dose of indinavir is 800 mg three times a day in the form of tablets . Lower doses result in a significant reduction in effectiveness.
pharmacology
As a representative of the HIV protease inhibitors, indinavir is able to inhibit the enzyme HIV protease , which is necessary for the virus to reproduce HIV . The substance has about ten times the selectivity for the protease from HIV-1 compared to that from HIV-2. The result is a strong reduction in the viral load, especially in connection with other antiviral agents. About 60% of indinavir is bound to plasma proteins in the bloodstream . Metabolism and elimination takes place in the liver . The half-life is 1.8 hours.
Side effects and contraindications
In around 6% of patients, therapy has to be discontinued because of undesirable effects. Disturbances of the gastrointestinal tract often occur (abdominal pain, nausea, diarrhea ). It is recommended to drink plenty of fluids to reduce the risk of crystalluria and the formation of kidney stones . Another, less common side effect is what is known as lipodystrophy , an abnormal redistribution of fat ( bull neck ). Undesired changes in laboratory values can include increases in transaminases or bilirubin and proteinuria . HIV protease inhibitors have numerous interactions with other common drugs (e.g. rifampicin , terfenadine , astemizole , cisapride and benzodiazepines ) due to their elimination by the liver . This leads to a variety of problems with multiple medication, which is not uncommon in the course of an AIDS disease.
disadvantage
Indinavir must be taken very precisely every 8 hours to ensure sufficient bioavailability . It should be taken 1 hour before or 2 hours after a meal. Meals rich in fat and protein reduce absorption considerably, while light meals hardly change. However, it is recommended to take the preparation on an empty stomach. Newer active ingredients from the same group prove to be better alternatives in this regard, which is why indinavir is no longer the drug of first choice.
Web links
Individual evidence
- ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
- ↑ Apotheke Adhoc: MSD is taking Crixivan off the market. Accessed January 30, 2020 (German).
literature
- JP Vacca, BD Dorsey, WA Schleif, RB Levin, SL McDaniel, PL Darke, J. Zugay, JC Quintero, OM Blahy, E. Roth and others: L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor. In: Proc Natl Acad Sci U.S.A. 91 (9), Apr 26, 1994, pp. 4096-4100. PMC 43730 (free full text)
