New Data Showed Minimal Potential for Drug Interaction Between Cholesterol Drug LIVAZO and a Common Antiretroviral Therapy
By Kowa Pharmaceutical Europe kpe Co. Ltd, PRNESunday, July 17, 2011
WOKINGHAM, England, July 18, 2011 -
- Study Demonstrated no Significant Impact on Blood Levels
When LIVAZO (pitavastatin) was Taken With HIV
Protease Inhibitor Combination lopinavir/ritonavir in Healthy
Volunteers
Kowa Pharmaceuticals America, Inc. and Eli Lilly and Company
(NYSE: LLY) today released new study results that investigated the
potential interaction of cholesterol drug LIVALO (pitavastatin,
known as LIVAZO in the EU) 4 mg in healthy volunteers taking the
protease inhibitor (PI) combination lopinavir/ritonavir, a fixed
dose combination drug for the treatment of HIV
infection.[1] Protease inhibitors are commonly used
antiretroviral HIV medications.[2] 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
LIVAZO or each of the PIs was minimally affected. Based on the 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
PIs” 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 LIVAZO, and
secondarily any potential PK effect of LIVAZO on lopinavir and
ritonavir.[3] LIVAZO (4mg) and lopinavir/ritonavir
(800mg/200mg) 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 Cmax was not affected by
co-administration of lopinavir/ritonavir. Total exposure of
pitavastatin at steady state as measured by AUC0-tau was
weakly affected by co-administration of lopinavir/ritonavir
(decrease of approximately 20%). Cmax and
AUC0-tau of lopinavir and ritonavir at steady state were
marginally affected by co-administration of pitavastatin. These
effects were not considered to be clinically
significant.[4]
A second objective of the study was to investigate any potential
effect on the safety of LIVAZO 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 AE of
diarrhoea during treatment with lopinavir/ritonavir only. There
were no severe AEs, SAEs, or deaths.[5]
“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 Center 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.[6],[7] 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.[8]
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.
About LIVAZO
LIVAZO 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),
low-density lipoprotein cholestrerol (LDL-C), apolipoprotein B (Apo
B), triglycerides (TG), and to increase high-density lipoprotein
cholesterol (HDL-C) LIVAZO 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 U.S. June 2010, LIVAZO is
also approved in Japan (2003), South Korea (2005), Thailand (2007),
China (2008), European Union (2010), Taiwan (2011) and Lebanon
(2011.)
About Kowa
Kowa Company, Ltd. (KCL) is a privately held multinational
company headquartered in Nagoya, Japan. Established in 1894, KCL is
actively engaged in various manufacturing and commercial activities
in the fields of pharmaceutical, life science, information
technology, textiles, machinery and various consumer products.
KCL’s pharmaceutical division was founded in 1947, and is focused
on cardiovascular therapeutics, with sales of the company’s
flagship product, LIVALO, totalling $520 million (14.3% market
share) in Japan during 2010 and expected to exceed $700 million in
the near future.
Kowa Research Europe Ltd. (KRE), established in 1999 in the
United Kingdom, is responsible for European clinical trials for
Kowa’s strategic global pharmaceutical development.
Kowa Pharmaceutical Europe (KPE) Co. Ltd, established in 2000,
is a specialty pharmaceutical company located in Wokingham, UK,
focused primarily on cardiometabolic therapeutics. Working in
harmony with KRE, these European pharmaceutical divisions of
Japanese Kowa Company, Ltd. are committed to ground-breaking
research, development and marketing to ensure quality products are
made available to people around the world, enabling them to enjoy a
better standard of health and a more comfortable life.
Visit our New Website:
References
[1] Sponseller, C. Effects of Steady State
Lopinavir/Ritonavir on the Pharmacokinetics of Pitavastatin in
Healthy Adult Volunteers. 6th International AIDS
Society (IAS) Conference on HIV Pathogenesis, Treatment and
Prevention. Rome, Italy. July 17-20, 2011.
[2] Sponseller, C. Effects of Steady State
Lopinavir/Ritonavir on the Pharmacokinetics of Pitavastatin in
Healthy Adult Volunteers. 6th International AIDS
Society (IAS) Conference on HIV Pathogenesis, Treatment and
Prevention. Rome, Italy. July 17-20, 2011.
[3] Sponseller, C. Effects of Steady State
Lopinavir/Ritonavir on the Pharmacokinetics of Pitavastatin in
Healthy Adult Volunteers. 6th International AIDS
Society (IAS) Conference on HIV Pathogenesis, Treatment and
Prevention. Rome, Italy. July 17-20, 2011.
[4] Sponseller, C. Effects of Steady State
Lopinavir/Ritonavir on the Pharmacokinetics of Pitavastatin in
Healthy Adult Volunteers. 6th International AIDS
Society (IAS) Conference on HIV Pathogenesis, Treatment and
Prevention. Rome, Italy. July 17-20, 2011.
[5] Sponseller, C. Effects of Steady State
Lopinavir/Ritonavir on the Pharmacokinetics of Pitavastatin in
Healthy Adult Volunteers. 6th International AIDS
Society (IAS) Conference on HIV Pathogenesis, Treatment and
Prevention. Rome, Italy. July 17-20, 2011.
[6] Calza L, Manfredi R, Pocaterra D, Chiodo F. Risk
of premature atherosclerosis and ischemic heart disease associated
with HIV infection and antiretroviral therapy. J Infect
2008; 57:16-32.
[7] Echevarria KL, Hardin TC, Smith JA.
Hyperlipidemia associated with protease inhibitor therapy. Ann
Pharmacother. 1999; 33:859-63.
[8] Kaul DR, CintiSK, Carver PL et al. HIV protease
inhibitors: advances in therapy and adverse reactions, including
metabolic complications. Pharmacotherapy. 1999;
19:281-98.
[9] Guengerich FP. Chem Res Toxicol.
2008;21(1):70-83; Jayakanthan M et al. Analysis of CYP3A4-HIV-1
protease drugs interactions by computational methods for Highly
Active Antiretroviral Therapy in HIV/AIDS Mol Graph Model. 2010
Jan;28(5):455-63.
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Tags: England, July 18, Kowa Pharmaceutical Europe (kpe) Co. Ltd, United Kingdom, Wokingham
