Efavirenz: Effects, Uses & Risks

Efavirenz is the name given to a non-nucleoside reverse transcriptase inhibitor. The drug is used to treat HIV infection.

What is efavirenz?

The active ingredient efavirenz (EFV) belongs to the group of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The drug is used as a pure enantiomer and is used to treat HIV infections such as AIDS. It is part of a combination antiretroviral treatment. Efavirenz was approved as a drug in Europe by the EMEA (European Medicines Agency) in 1999. However, because resistance to the active ingredient quickly develops during monotherapy, the non-nucleoside reverse transcriptase inhibitor must always be taken together with another antiretroviral substance that the patient has never received before. Efavirenz was already on the market in North America before it was approved in Europe. Efavirenz is available in Germany as a monopreparation under the trade name Sustiva. There is also a combination preparation called Atripla.

Pharmacologic action

Viruses are not able to provide for their reproduction independently. Thus, for this purpose, they need the multiplication apparatus of the cells they infect. To achieve this, the viruses insert the genetic material of the cells into their own genetic material. In the process, the cells receive blueprints according to which they produce the viruses. This process is more difficult in the case of HI viruses, since their genome is shaped differently from that of mammals and humans. In order for the genetic material of HI viruses to enter human cells, it is necessary to “rewrite” it. The enzyme reverse transcriptase is responsible for this change. In this way, the HI virus can rearrange its genetic material in such a way that it can be introduced into the human genetic material without difficulty. Since Efavirenz belongs to the group of reverse transcriptase inhibitors, it has the ability to block the active site of reverse transcriptase. As a result, the enzyme is no longer able to rewrite the genetic material of the viruses. The information is classified as foreign by the body’s cells and is therefore no longer reproduced. This counteracts the production of new HI viruses. This process reduces the viral load, which delays the onset of AIDS. In addition, the symptoms of HIV infection are reduced, which in turn improves the patient’s quality of life. Efavirenz binds 99 percent to plasma proteins in the blood. Its concentration in cerebrospinal fluid is three times higher than in blood plasma. The half-life of the active substance is about 50 hours. One third of efavirenz is excreted in metabolite form in the urine. The remainder of the substance passes out of the organism via stool without changes.

Medical application and use

The sole field of application of Efavirenz is HIV infections in which the human body is immunodeficient. The drug can be used in adult and adolescent patients, as well as in children aged three years and older. As a drug for viral inhibition, Efavirenz acts directly against the HI viruses. However, it can also be used to counteract or slow down the onset of AIDS. The intake of high-fat foods can affect the absorption of efavirenz. It increases by about 50 percent. The drug is usually taken in the evening on an empty stomach before bedtime. Since the half-life of efavirenz is high, a single dose of the drug per day is sufficient. Efavirenz can be taken as a solution or in the form of film-coated tablets.

Risks and side effects

The use of efavirenz poses a risk of side effects that primarily affect the central nervous system (CNS). For example, affected patients often suffer from fatigue, drowsiness, sleep problems, nightmares, and dizziness. Particularly in the initial phase of efavirenz treatment, up to 50 percent of all patients are affected by these undesirable side effects. Other side effects may include difficulty concentrating, anxiety, depression, headache, abdominal pain, diarrhea, nausea, rashes on the skin, and itching. In most cases, these side effects improve after one to four weeks. However, in 10 to 20 percent of all those affected, symptoms persist, so it is then advisable to switch to another preparation.Other side effects may also occur, such as acute inflammation of the liver (hepatitis), acute inflammation of the pancreas (pancreatitis), mood swings, euphoria, aggression, paranoia, delusions, restlessness, memory problems, movement disorders, balance disorders, convulsions, visual disturbances, confusion and suicidal thoughts, which may even lead to a suicide attempt. If skin blisters, mucosal changes, skin peeling, and fever occur on the skin during treatment, urgent consultation with the physician should be made and therapy may need to be discontinued. Since the side effects are not infrequently associated with meal ingestion, it is recommended that Efavirenz be administered on an empty stomach. In some cases, the drug causes disturbances in the distribution of body fat. In this case, the fat on the body and face decreases, while it increases in the abdomen. There are also some contraindications to taking Efavirenz. Thus, its use must not take place if the patient suffers from hypersensitivity to the active substance or pronounced liver damage. Strict medical control is necessary in case of renal dysfunction, liver disease, epilepsy, psychiatric disorders in advance or resistance to other HIV drugs. In pregnancy, efavirenz should be taken only if there are no other treatment options. Animal studies showed adverse effects on the child from the drug.