Trade names Livalo, Livazo MedlinePlus a610018 Routes of
administration By mouth (tablets) Bioavailability 60% | AHFS/Drugs.com Monograph License data US FDA: Pitavastatin CAS ID 147511-69-1 Protein binding 96% | |
 | ||
Pregnancy
category AU: D
US: X (Contraindicated) | ||
Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol lowering medication class of statins, marketed in the United States under the trade name Livalo, and in European Union and Russia under the trade name Livazo. Like other statins, it is an inhibitor of HMG-CoA reductase, the enzyme that catalyses the first step of cholesterol synthesis.
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It has been available in Japan since 2003, and is being marketed in South Korea and in India. It is expected that pitavastatin will be approved outside Southeast Asia as well. In the US, it received FDA approval in 2009. Kowa Pharmaceuticals is the owner of the American patent to pitavastatin.
Uses
Like the other statins, pitavastatin is indicated for hypercholesterolaemia (elevated cholesterol) and for the prevention of cardiovascular disease.
A 2009 study of the 104 week LIVES trial found pitavastatin increased HDL cholesterol, especially in patients with HDL lower than 40 mg/dL, who had a 24.6% rise, in addition to greatly reducing LDL cholesterol 31.3%. HDL improved in patients who switched from other statins and rose over time. In the 70-month CIRCLE observational study, pitavastatin increased HDL more than atorvastatin.
It has neutral or possibly beneficial effects on glucose control. As a consequence, pitavastatin is likely to be appropriate for patients with metabolic syndrome plus high LDL, low HDL and diabetes mellitus.
Side effects
Common statin-related side effects (headaches, stomach upset, abnormal liver function tests and muscle cramps) were similar to other statins. However, pitavastatin seems to lead to fewer muscle side effects than certain statins that are lipid-soluble, as a result of the fact that pitavastatin is water-soluble (as is pravastatin, for example). One study found that coenzyme Q10 was not reduced as much as with certain other statins (though this is unlikely given the inherent chemistry of the HMG-CoA reductase pathway that all statin drugs inhibit).
Pitavastatin appears to have improved tolerably in its metabolic profile, with a neutral effect on glucose regulation, as opposed to many statins.
As opposed to other statins, there is evidence that pitavastatin improves insulin resistance in humans, with insulin resistance assessed by the homeostatic model assessment (HOMA-IR) method.
Hyperuricemia or increased levels of serum uric acid have been reported with pitavastatin.
Metabolism and interactions
Most statins are metabolised in part by one or more hepatic cytochrome P450 enzymes, leading to an increased potential for drug interactions and problems with certain foods (such as grapefruit juice). Pitavastatin appears to be a substrate of CYP2C9, and not CYP3A4 (which is a common source of interactions in other statins). As a result, pitavastatin is less likely to interact with drugs that are metabolized via CYP3A4, which might be important for elderly patients who need to take multiple medicines.
History
Pitavastatin (previously known as itavastatin, itabavastin, nisvastatin, NK-104 or NKS-104) was discovered in Japan by Nissan Chemical Industries and developed further by Kowa Pharmaceuticals, Tokyo. Pitavastatin was approved for use in the United States by the FDA on 08/03/2009 under the trade name Livalo. Pitavastatin has been also approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in UK on 17 August 2010.