Elvitegravir (EVG) is an integrase inhibitor used to treat HIV infection. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Administration on August 27, 2012 for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild. On September 24, 2014 the FDA approved Elvitegravir as a single pill formulation under the trade name Vitekta. On November 5, 2015 the FDA approved the drug for use in patients affected with HIV-1 as a part of a second fixed dose combination pill known as

Genvoya Tenofovir alafenamide, sold under the brand name Vemlidy, is a hepatitis B virus (HBV) nucleotide reverse transcriptase inhibitor medication for the treatment of Hepatitis B, chronic hepatitis B virus (HBV) infection in adults with Liver diseas ...

. According to the results of the phase II clinical trial, patients taking once-daily elvitegravir boosted by ritonavir had greater reductions in viral load after 24 weeks compared to individuals randomized to receive a ritonavir-boosted protease inhibitor.

Medical uses

In the United States, elvitegravir can be obtained either as part of the combination pills Stribild or

, or as the single pill formulation Vitekta. Vitekta is FDA approved to be used for the treatment of HIV-1 infection in adults who have previous treatment experience with antiretroviral therapy. It must be used in combination with a protease inhibitor that is coadministered with ritonavir as well as additional antiretroviral drug(s)."Vitekta Package Insert"
Foster City, CA: Gilead Sciences, Inc.; 2014. Accessed November 1, 2014

Adverse effects

The most common side effects of taking elvitegravir are diarrhea (in 7% of patients) and nausea (4%). Other side effects that occurred in more than 1% of people are

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

tiredness Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, rashes, and vomiting.

Interactions and contraindications

Elvitegravir is metabolised via the liver enzyme CYP3A. Substances that induce this enzyme can reduce elvitegravir concentrations in the body, potentially triggering the development of resistant virus strains. Consequently, co-administration of strong CYP3A inducers is contraindicated; examples are

rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), mycobacterium avium complex, ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. ...

, the anticonvulsants carbamazepine, phenobarbital and phenytoin, as well as St John's wort. Glucuronidation of elvitegravir is facilitated by the enzymes UGT1A1 and 3, resulting in increased blood plasma levels when taken together with strong UGT1A inhibitors such as ritonavir and other HIV protease inhibitors. (But ritonavir also increases elvitegravir levels by inhibiting CYP3A.) Furthermore, elvitegravir is a weak to medium inducer of CYP1A2, CYP2C19, CYP2C9, CYP3A, and a number of UGTs; the clinical relevance of these findings is however unclear.

Pharmacology

Mechanism of action

Elvitegravir inhibits the enzyme

integrase Retroviral integrase (IN) is an enzyme produced by a retrovirus (such as HIV) that integrates—forms covalent links between—its genetic information into that of the host cell it infects. Retroviral INs are not to be confused with phage int ...

of HIV-1, and of HIV-2 to a lesser extent. The virus needs this enzyme to integrate its genetic code into the host's DNA.

Pharmacokinetics

The drug is taken by mouth. When taken together with ritonavir and a meal, it reaches highest blood plasma concentrations after four hours. Bioavailability is better with fatty meals. In the bloodstream, 98–99% of the substance are bound to plasma proteins. It is metabolized mainly by CYP3A oxidation, and secondly by UGT1A1 and 3 glucuronidation. Nearly 95% are excreted via the feces, and the rest via urine. Plasma half-life when combined with ritonavir is 8.7 to 13.7 hours.

References

External links

* {{Portal bar , Medicine , Viruses Integrase inhibitors Quinolines Chloroarenes Fluoroarenes Japan Tobacco