Lopinavir/ritonavir
Lopinavir/ritonavir, sold under the brand name Kaletra among others, is a fixed-dose combination antiretroviral medication for the treatment and prevention of HIV/AIDS. It combines lopinavir with a low dose of ritonavir. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth as a tablet, capsule, or solution.
Common side effects include diarrhea, vomiting, feeling tired, headaches, and muscle pains. Severe side effects may include pancreatitis, liver problems, and high blood sugar. It is commonly used in pregnancy and it appears to be safe. Both medications are HIV protease inhibitors. Ritonavir functions by slowing down the breakdown of lopinavir.
Lopinavir/ritonavir as a combination medication was approved for use in the United States in 2000. It is on the World Health Organization's List of Essential Medicines.
Medical uses
Lopinavir/ritonavir was once a preferred combination for HIV first-line therapy in the United States. But due to its higher pill burden compared to other protease inhibitor-based regimens and increased gastrointestinal intolerance, it is no longer recommended to treatment-naive patients.Adverse effects
The most common adverse effects observed with lopinavir/ritonavir are diarrhea and nausea. In key clinical trials, moderate or severe diarrhea occurred in up to 27% of patients, and moderate/severe nausea in up to 16%. Other common adverse effects include abdominal pain, asthenia, headache, vomiting and, particularly in children, rash.Lopinavir/ritonavir is anticipated to have varying degrees of interaction with other medications that are also CYP3A and/or P-gp substrates.
People with a structural heart disease, preexisting conduction system abnormalities, ischaemic heart disease, or cardiomyopathies should use lopinavir/ritonavir with caution.
In March 2011, the US Food and Drug Administration notified healthcare professionals of serious health problems that have been reported in premature babies receiving lopinavir/ritonavir oral solution, probably because of its propylene glycol content. They recommend the use should be avoided in premature babies.
History
Abbott Laboratories was one of the earliest users of the Advanced Photon Source, a national synchrotron-radiation light source at Argonne National Laboratory. One of the early research projects undertaken at the APS focused on proteins from the human immunodeficiency virus. Using the APS beam line for X-ray crystallography, researchers determined viral protein structures that allowed them to determine their approach to the development of HIV protease inhibitors, a key enzyme target that processes HIV polyproteins after infection, the function of which allows the lifecycle of the virus to proceed. As a result of this structure-based drug design approach using the Argonne APS, Abbott was able to develop new products that inhibit the protease, and therefore stop virus replication.Lopinavir was developed by Abbott in an attempt to improve upon the company's earlier protease inhibitor, ritonavir, specifically with regard to its serum protein-binding properties and its HIV resistance profile. Administered alone, lopinavir has insufficient bioavailability; however, like several HIV protease inhibitors, its blood levels are greatly increased by low doses of ritonavir, a potent inhibitor of intestinal and hepatic cytochrome P450 3A4, which would otherwise reduce drug levels through catabolism.
Lopinavir/ritonavir was approved by the US Food and Drug Administration in September 2000, and in the European Union in March 2001.
In March 2020, during the COVID-19 pandemic, the Israeli government announced that it would force AbbVie to license its patents for lopinavir/ritonavir. In response, AbbVie announced that it would cease enforcing its patents on the drug entirely.