Kowa Pharmaceuticals America, Inc. and Eli Lilly and Company released new study results that investigated the potential interaction of cholesterol drug Livalo (pitavastatin) 4 mg in healthy volunteers taking the Protease Inhibitor (PI) combination lopinavir/ritonavir, a fixed dose combination drug for the treatment of HIV infection.
Protease Inhibitors are commonly used antiretroviral HIV medications. The study, presented at the 6th International AIDS Society (IAS) conference on HIV pathogenesis, treatment and prevention in Rome, Italy, found that when co-administered, the individual drug blood levels for Livalo or each of the PIs was minimally affected. Based on these data from this FDA-mandated phase IV study, the United States Food and Drug Administration recently approved a labelling change to delete the lopinavir/ritonavir limitation of use from the US Livalo labelling.
“HIV is a chronic illness today, as opposed to 30 years ago, and patients with HIV are faced with additional challenges concerning dyslipidemia, accentuated by both the disease process as well as antiretroviral therapies. Additionally, these patients are frequently on multiple medications and the management of dyslipidemia can be even more of a challenge. We are pleased with the results of this study and the absence of a significant drug interaction when Livalo is co-administered with this combination of protease inhibitors,” said Craig Sponseller, MD, vice president of Medical Affairs, Kowa Pharmaceuticals America, Inc.
The study was designed to assess the pharmacokinetic (PK) interaction, or effect on overall exposure in the body, of the combination lopinavir/ritonavir on the PK of Livalo, and secondarily any potential PK effect of Livalo on lopinavir and ritonavir. Livalo (4 mg) and lopinavir/ritonavir (800 mg/200 mg) were co-administered in 24 healthy, adult volunteers over a 24 day period. At study end, peak exposure of pitavastatin at steady state, as measured by C (max), was not affected by co-administration of lopinavir/ritonavir. Total exposure of pitavastatin at steady state, as measured by AUC(0-T), was weakly affected by co-administration of lopinavir/ritonavir (decrease of approximately 20%). C(max) and AUC(0-T) of lopinavir and ritonavir at steady state were marginally affected by co-administration of pitavastatin. These effects were not considered to be clinically significant.
A second objective of the study was to investigate any potential effect on the safety of Livalo by the addition of lopinavir/ritonavir. No significant safety issues were observed. Eighteen of 24 patients reported at least one Treatment Emergent Adverse Event (TEAE), with the highest percentage coming from subjects receiving lopinavir/ritonavir only. All TEAEs were mild in severity, except for four subjects who had TEAEs after lopinavir/ritonavir only that were moderate in severity. One subject was discontinued from the study because of an Adverse Event (AE) of diarrhoea during treatment with lopinavir/ritonavir only. There were no severe AEs, SAEs, or deaths.
“This study is important to caregivers and patients alike, as Livalo showed minimal drug-drug interactions with a common antiretroviral therapy HIV patients need to fight the disease. For a patient population that is taking multiple medications, this is exciting news,” said Dr Judith Aberg, director of Virology, Bellevue Hospital Centre and director, Division of Infectious Diseases and Immunology, NYU School of Medicine.
Elevated cholesterol, particularly the "bad" cholesterol, Low Density Lipoprotein Cholesterol (LDL-C), triglycerides (TG), or both, is a common complication associated with HIV infection as well as the use of antiretroviral therapies. The frequency of hyperlipidemia, elevation of fats in the blood, in HIV-infected patients taking protease inhibitors, including lopinavir/ritonavir, is up to 66 percent of the patient population.
Cholesterol-lowering drugs, particularly statins, are often used in patients with HIV; therefore it is important for physicians to understand the potential drug-drug interactions with antiretroviral therapies.
Livalo is a HMG-CoA reductase inhibitor indicated for patients with primary hyperlipidemia and mixed dyslipidemia as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), LDL-C, Apolipoprotein B (Apo B), triglycerides (TG), and to increase High-Density Lipoprotein Cholesterol (HDL-C). It is predominantly metabolized via glucuronidation and is only minimally metabolized by CYP system, which may help reduce its potential for CYP-mediated drug-drug interactions.
In addition to being launched in the US June 2010, Livalo is also approved in Japan (2003), South Korea (2005), Thailand (2007), China (2008), European Union (2010), Taiwan (2011) and Lebanon (2011).
Primary Hyperlipidemia is defined as an elevation of cholesterol, particularly "bad" cholesterol (LDL-C), triglycerides (TG), or both. Mixed dyslipidemia is usually characterized by an elevation of LDL-C, TG, and a decrease in the "good" cholesterol (HDL-C) in the blood.
Despite the availability of treatments in the US there is still a need for more options to help treat elevated cholesterol. According to the American Heart Association, approximately one out of every three American adults has an LDL-C level of 130 mg/dL or higher, which is a major health risk. In addition, less than half of patients who qualify for any kind of lipid-modifying treatment are receiving it, and only about one-third of patients who are on treatment are achieving their LDL-C goals.
Livalo is a prescription medicine that, along with diet, has been approved for the treatment of high cholesterol. It has not been studied to evaluate its effect on reducing heart-related disease or death. It is not right for everyone, including: those who have had an allergic reaction to Livalo, anyone with liver disease, patients with severe kidney disease not on haemodialysis, women who are nursing, pregnant, or who may become pregnant and anyone currently taking cyclosporine.
If Livalo is taken tell your doctor right away if you experience any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by fever or a general feeling of discomfort. This could be a sign of a rare but serious side effect. Your doctor should do blood tests to monitor your liver function before starting Livalo, and then at 12 weeks following the start of Livalo, after any increase in dose, and periodically (e.g., every 6 months) thereafter. Please talk to your doctor about your alcohol use. Tell your doctor about all the medications you take including non-prescription medicines, vitamins, or herbal supplements.
The most common side effects of Livalo in clinical studies were: back pain, constipation, diarrhoea, muscle pain, pain in the legs or arms.
Kowa Company, Ltd. (KCL) is engaged in various manufacturing and commercial activities in the fields of pharmaceutical, life science, information technology, textiles, machinery and various consumer products and is also specializing primarily in the area of cardiometabolic diseases.
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations.