The pharmacological substance nelfinavir is a drug that is counted among the so-called HIV protease inhibitors. It is available on the medical market under the trade name Viracept. The drug Nelfinavir is indicated for antiretroviral therapy of patients infected with HIV-1. The special protease inhibitors are used as part of a so-called ‘highly active antiretroviral therapy‘, whereby they are administered together with other antiviral substances.
What is nelfinavir?
Basically, nelfinavir is a protease inhibitor that plays an important role in drug therapy for human immunodeficiency virus (HIV) infections. In 2013, the approval of the drug nelfinavir for the European market ended. Due to the decreasing demand for the drug, its distribution by the manufacturer in this region was discontinued for the time being. The salt of methanesulfonic acid is used in pharmaceutical applications. It should be noted that under certain circumstances carcinogenic impurities are generated during the synthesis of certain drugs. This is particularly the case when certain sulfonic acids are reacted and the production conditions are not ideal. For this reason, the drug nelfinavir was temporarily withdrawn from the pharmaceutical market in 2007. This is because corresponding impurities were detected in some preparations containing nelfinavir. However, it is possible to ensure a relatively safe product by taking appropriate safety measures during manufacture. Here, care must be taken to ensure that the specified limits are not exceeded.
Pharmacological effect
The drug nelfinavir has a characteristic mechanism of action, making it suitable for the therapy of infections with HIV. After ingestion, the active ingredient nelfinavir binds almost completely to proteins found in the plasma of the blood. The drug is broken down via the so-called cytochrome system. This is a system of the liver. If a second HIV protease inhibitor is taken at the same time, it delays the breakdown of the drug nelfinavir in the liver. As a result, the duration of action of the drug nelfinavir is prolonged. If the drug is taken together with a meal, this has a positive effect on the absorption of the active substance. In principle, the half-life of the substance nelfinavir is approximately four hours. Subsequently, all metabolites are excreted from the organism in the stool. It may also be taken together with specific nucleoside reverse transcriptase inhibitors. The active ingredient nelfinavir binds to the so-called viral HIV protease. This plays an important role in viral replication. Central to this is the affinity that the substance has for the HIV-1 and HIV-2 protease. As a result, the viral enzyme is impaired, so that the viruses do not reproduce further. This reduces the viral load for the organism of the affected patient. In principle, the mode of action of the drug nelfinavir is similar to that of other types of HIV protease inhibitors. However, the mechanism of binding of nelfinavir to the corresponding enzyme is unique. As a result, no cross-resistance to other protease inhibitors occurs. This is because, unlike most other HIV protease inhibitors, the active ingredient nelfinavir is able to reduce the HIV-1 and HIV-2 proteases equally. The viruses develop only mild resistance to the drug. However, most of this resistance can be avoided by combining nelfinavir with other antiviral substances. It is also advantageous that the absorption of the active substance is considerably improved if nelfinavir is taken together with a meal. In this case, the drug binds almost completely to the proteins in the blood plasma. Metabolism of the substance takes place in the liver. The plasma half-life of the drug averages between three and a half and five hours.
Medical application and use
The drug nelfinavir is used in the majority of cases for the drug treatment of infections with HIV type 1. It is primarily used against a background of so-called ‘highly active antiretroviral therapy’. The drug is suitable for the treatment of adult patients and children older than three years.Basically, it is used for combination antiviral therapy of HIV-infected patients.
Risks and side effects
During treatment with the substance nelfinavir, undesirable side effects appear in some cases. However, these do not occur in all patients. Most often, side effects such as digestive disorders occur while taking the drug nelfinavir. These manifest themselves, for example, in vomiting or diarrhea. Pain in the abdominal area and nausea are also possible. Some people also experience headaches and skin reactions. Some patients develop hepatitis and suffer from severe fatigue. Various interactions of the drug nelfinavir with other medical substances should be noted. These include, for example, the preparations cisapride and astemizole, as well as benzodiazepines, antiarrhythmics and ergotoxins. If a patient is taking such drugs, the administration of nelfinavir is contraindicated. This is because it affects the cytochrome P450 system, which is responsible for the breakdown of nelfinavir. It is the patient’s responsibility to report any side effects or other complaints to the treating physician in order to find an alternative.
