Pitavastatin

Pitavastatin
Clinical data
Trade names Livalo, Livazo
AHFS/Drugs.com Monograph
MedlinePlus a610018
License data
Pregnancy
category
  • AU: D
  • US: X (Contraindicated)
    Routes of
    administration    		 By mouth (tablets)
    ATC code
    Legal status
    Legal status
    • AU: S4 (Prescription only)
    • CA: ℞-only
    • UK: POM (Prescription only)
    • US: ℞-only
    • In general: ℞ (Prescription only)
    Pharmacokinetic data
    Bioavailability 60%
    Protein binding 96%
    Metabolism Liver (CYP2C9, minimally)
    Elimination half-life 11 hours
    Excretion Faeces
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    ChemSpider
    UNII
    ChEBI
    ChEMBL
    ECHA InfoCard 100.171.153 Edit this at Wikidata
    Chemical and physical data
    Formula C25H24FNO4
    Molar mass 421.461
    3D model (JSmol)
     ☒N☑Y (what is this?)  (verify)

    Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol lowering medication class of statins,[1] 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.

    It has been available in Japan since 2003, and is being marketed in South Korea and in India.[2] It is expected that pitavastatin will be approved outside Southeast Asia as well.[3] In the US, it received FDA approval in 2009.[4] 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%.[5] 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.[6]

    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).[7] 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).[3][8]

    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.[9]

    Hyperuricemia or increased levels of serum uric acid have been reported with pitavastatin.[10]

    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). The primary metabolism pathway of pitavastatin is glucuronidation. It is minimally metabolized by the CYP450 enzymes CYP2C9 and CYP2C8,[11] but not by CYP3A4 (which is a common source of interactions in other statins). As a result, it 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.[3]

    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.[3] 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.

    References

    1. ↑ Kajinami, K; Takekoshi, N; Saito, Y (2003). "Pitavastatin: efficacy and safety profiles of a novel synthetic HMG-CoA reductase inhibitor". Cardiovascular drug reviews. 21 (3): 199–215. PMID 12931254.
    2. ↑ Zydus Cadila launches pitavastatin in India
    3. 1 2 3 4 Mukhtar, R. Y. A.; Reid, J.; Reckless, J. P. D. (2005). "Pitavastatin". International Journal of Clinical Practice. 59 (2): 239–252. doi:10.1111/j.1742-1241.2005.00461.x. PMID 15854203.
    4. ↑ The Seventh Statin; Pitavastatin
    5. ↑ Teramoto, T; Shimano, H; Yokote, K; Urashima, M (Oct 2009). "Effects of pitavastatin (LIVALO Tablet) on high density lipoprotein cholesterol (HDL-C) in hypercholesterolemia". J Atheroscler Thromb. 16: 654–61. doi:10.5551/jat.1719. PMID 19907105.
    6. ↑ Masana, L (May 30, 2013). "Pitavastatin in cardiometabolic disease: therapeutic profile". Cardiovasc Diabetol. 12 Suppl 1: S2. doi:10.1186/1475-2840-12-S1-S2. PMC 3668168. PMID 23819752.
    7. ↑ ScienceDaily (11 May 2013). "Alternative Cholesterol-Lowering Drug for Patients Who Can't Tolerate Statins". ScienceDaily.
    8. ↑ Kawashiri, MA; Nohara, A; Tada, H; Mori, M; Tsuchida, M; Katsuda, S; Inazu, A; Kobayashi, J; Koizumi, J; Mabuchi, H; Yamagishi, M (May 2008). "Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia: results from a crossover study". Clin Pharmacol Ther. 83 (5): 731–9. doi:10.1038/sj.clpt.6100396. PMID 17957184.
    9. ↑ Nakagomi, A; Shibui, T; Kohashi, K; Kosugi, M; Kusama, Y; Atarashi, H; Shimizu, W (2015). "Differential Effects of Atorvastatin and Pitavastatin on Inflammation, Insulin Resistance, and Carotid Intima-Media Thickness in Patients with Dyslipidemia". Journal of Atherosclerosis and Thrombosis. 22: 1158–1171. doi:10.5551/jat.29520.
    10. ↑ Ogata, N.; Fujimori, S.; Oka, Y.; Kaneko, K. (2010). "Effects of Three Strong Statins (Atorvastatin, Pitavastatin, and Rosuvastatin) on Serum Uric Acid Levels in Dyslipidemic Patients". Nucleosides, Nucleotides and Nucleic Acids. 29 (4–6): 321–324. doi:10.1080/15257771003741323.
    11. ↑ Drugs.com: Livalo Monograph.

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