Pitavastatin

Pitavastatin
Names
Trade namesLivalo, Livazo, Zypitamag, others
IUPAC name
  • (3R,5S,6E)-7-[2-Cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid
Clinical data
Drug classStatin[1]
Main usesAbnormal lipid levels, high risk of heart disease[1]
Side effectsMuscle pain, diarrhea[1]
Pregnancy
category
  • AU: D
  • US: X (Contraindicated)
    Routes of
    use    		By mouth (tablets)
    Typical dose1 to 4 mg OD[1]
    External links
    AHFS/Drugs.comMonograph
    US NLMPitavastatin
    MedlinePlusa610018
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • CA: ℞-only
    • UK: POM (Prescription only)
    • US: ℞-only
    • In general: ℞ (Prescription only)
    Pharmacokinetics
    Bioavailability60%
    Protein binding96%
    MetabolismLiver (CYP2C9, minimally)
    Elimination half-life11 hours
    ExcretionFaeces
    Chemical and physical data
    FormulaC25H24FNO4
    Molar mass421.461 g·mol−1
    3D model (JSmol)
    SMILES
    • O=C(O)C[C@H](O)C[C@H](O)/C=C/c1c(c3ccccc3nc1C2CC2)c4ccc(F)cc4
    InChI
    • InChI=1S/C25H24FNO4/c26-17-9-7-15(8-10-17)24-20-3-1-2-4-22(20)27-25(16-5-6-16)21(24)12-11-18(28)13-19(29)14-23(30)31/h1-4,7-12,16,18-19,28-29H,5-6,13-14H2,(H,30,31)/b12-11+/t18-,19-/m1/s1 checkY
    • Key:VGYFMXBACGZSIL-MCBHFWOFSA-N checkY

    Pitavastatin, sold under the brand name Livalo among others is a medication used to treat abnormal lipid levels and reduce the risk of heart disease.[1] It is taken by mouth.[1]

    Common side effects include muscle pain and diarrhea.[1] Other side effects may include muscle breakdown with kidney problems, liver problems, diabetes, allergic reactions, and memory problems.[1] Use in pregnancy may harm the baby.[1] It is a statin and works by blocking HMG-CoA reductase.[1]

    Pitavastatin was patented in 1987 and approved for medical use in 2003.[2] It was approved in the United States in 2009.[1] It is available in a number of countries in Europe.[3] In the United States 3 month of medication costs about 1,000 USD as of 2021.[4]

    Medical uses

    Like the other statins, pitavastatin is indicated for hypercholesterolaemia (elevated cholesterol) and for the prevention of cardiovascular disease.

    A 2009 study found pitavastatin increased HDL cholesterol, especially in patients with HDL lower than 40 mg/dL, who had a 25% rise, in addition to reducing LDL cholesterol 31%.[5] HDL improved in patients who switched from other statins and rose over time. In the 70-month CIRCLE observational study, pitavastatin increased HDL similar or more than atorvastatin.[6]

    Dosage

    It is taken at a dose of 1 to 4 mg per day.[1]

    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).[8][9]

    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.[10]

    Hyperuricemia or increased levels of serum uric acid have been reported with pitavastatin.[11]

    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,[12] 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.[8]

    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.[8] 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.

    It is available in Japan, South Korea and in India.[13] In the US, it received FDA approval in 2009.[14]

    Names

    The drug is marketed in the United States under the trade names Livalo and Zypitamag, and in the European Union and Russia under the trade name Livazo.

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 12 "Pitavastatin Monograph for Professionals". Drugs.com. Archived from the original on 24 January 2021. Retrieved 28 October 2021.
    2. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 473. ISBN 9783527607495. Archived from the original on 16 May 2021. Retrieved 18 October 2021.
    3. ↑ "List of nationally authorised medicinal products" (PDF). Archived (PDF) from the original on 28 October 2021. Retrieved 28 October 2021.
    4. ↑ "Livalo Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 10 May 2016. Retrieved 28 October 2021.
    5. ↑ Teramoto T, Shimano H, Yokote K, Urashima M (October 2009). "Effects of pitavastatin (LIVALO Tablet) on high density lipoprotein cholesterol (HDL-C) in hypercholesterolemia". Journal of Atherosclerosis and Thrombosis. 16 (5): 654–61. doi:10.5551/jat.1719. PMID 19907105.
    6. ↑ Masana L (30 May 2013). "Pitavastatin in cardiometabolic disease: therapeutic profile". Cardiovascular Diabetology. 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. Archived from the original on 20 August 2019. Retrieved 18 October 2021.
    8. 1 2 3 Mukhtar RY, Reid J, Reckless JP (February 2005). "Pitavastatin". International Journal of Clinical Practice. 59 (2): 239–52. doi:10.1111/j.1742-1241.2005.00461.x. PMID 15854203.
    9. ↑ Kawashiri MA, Nohara A, Tada H, Mori M, Tsuchida M, Katsuda S, et al. (May 2008). "Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia: results from a crossover study". Clinical Pharmacology and Therapeutics. 83 (5): 731–9. doi:10.1038/sj.clpt.6100396. PMID 17957184. S2CID 20956339.
    10. ↑ 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 the Carotid Intima-Media Thickness in Patients with Dyslipidemia". Journal of Atherosclerosis and Thrombosis. 22 (11): 1158–71. doi:10.5551/jat.29520. PMID 26084792.
    11. ↑ Ogata N, Fujimori S, Oka Y, Kaneko K (June 2010). "Effects of three strong statins (atorvastatin, pitavastatin, and rosuvastatin) on serum uric acid levels in dyslipidemic patients". Nucleosides, Nucleotides & Nucleic Acids. 29 (4–6): 321–4. doi:10.1080/15257771003741323. PMID 20544514. S2CID 30650248.
    12. ↑ Drugs.com: Livalo Monograph.
    13. ↑ "Zydus Cadila launches pitavastatin in India". Archived from the original on 26 September 2017. Retrieved 28 May 2006.
    14. ↑ "The Seventh Statin; Pitavastatin". Archived from the original on 20 October 2021. Retrieved 18 October 2021.
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