Telmisartan

Telmisartan, sold under the trade name Micardis among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease.[1] It is a reasonable initial treatment for high blood pressure.[1] It is taken by mouth.[1] Versions are available as the combination telmisartan/hydrochlorothiazide and telmisartan/amlodipine.[1]

Telmisartan
Clinical data
Pronunciation/tɛlmɪˈsɑːrtən/
Trade namesMicardis, Actavis, others
AHFS/Drugs.comMonograph
MedlinePlusa601249
License data
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
    Routes of
    administration    		By mouth
    Drug classAngiotensin II receptor antagonist
    ATC code
    Legal status
    Legal status
    • AU: S4 (Prescription only)
    • UK: POM (Prescription only)
    • US: ℞-only
    Pharmacokinetic data
    Bioavailability42–100%
    Protein binding>99.5%
    MetabolismMinimal hepatic (glucuronidation)
    Elimination half-life24 hours
    ExcretionFaecal 97%
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.149.347
    Chemical and physical data
    FormulaC33H30N4O2
    Molar mass514.617 g/mol g·mol−1
    3D model (JSmol)
      (verify)

    Common side effects include upper respiratory tract infections, diarrhea, and back pain.[1] Serious side effects may include kidney problems, low blood pressure, and angioedema.[1] Use in pregnancy may harm the baby and use when breastfeeding is not recommended.[2] It is an angiotensin II receptor antagonist and works by blocking the effects of angiotensin II.[1]

    Telmisartan was patented in 1991 and came into medical use in 1999.[3] It is available as a generic medication.[4] A month supply in the United Kingdom costs the NHS less than £2 as of 2019.[4] In the United States the wholesale cost of this amount is about US$10.[5] In 2016, it was the 246th most prescribed medication in the United States, with more than 1.9 million prescriptions.[6]

    Medical uses

    Telmisartan is used to treat high blood pressure, heart failure, and diabetic kidney disease.[1] It is a reasonable initial treatment for high blood pressure.[1][7]

    Contraindications

    Telmisartan is contraindicated during pregnancy. Like other drugs affecting the renin–angiotensin system (RAS), telmisartan can cause birth defects, stillbirths, and neonatal deaths. It is not known whether the drug passes into the breast milk.[8] Also it is contraindicated in bilateral renal artery stenosis in which it can cause renal failure.

    Side effects

    Side effects are similar to other angiotensin II receptor antagonists and include tachycardia and bradycardia (fast or slow heartbeat), hypotension (low blood pressure) and edema (swelling of arms, legs, lips, tongue, or throat, the latter leading to breathing problems). Allergic reactions may also occur.[8]

    Interactions

    Due to its mechanism of action, telmisartan increases blood potassium levels. Combination with potassium preparations or potassium-sparing diuretics could cause hyperkalaemia (excessive potassium levels). Combination with NSAIDs, especially in patients with impaired kidney function, has a risk of causing (usually reversible) kidney failure.[9]

    Pharmacology

    Mechanism of action

    Telmisartan is an angiotensin II receptor blocker that shows high affinity for the angiotensin II receptor type 1 (AT1), with a binding affinity 3000 times greater for AT1 than AT2.

    In addition to blocking the RAS, telmisartan acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPAR-γ), a central regulator of insulin and glucose metabolism. It is believed that telmisartan's dual mode of action may provide protective benefits against the vascular and renal damage caused by diabetes and cardiovascular disease (CVD).[10]

    Telmisartan's activity at the peroxisome proliferator-activated receptor delta (PPAR-δ) receptor has prompted speculation around its potential as a sport doping agent as an alternative to GW 501516.[11] Telmisartan activates PPAR-δ receptors in several tissues.[12][13][14][15]

    Also, Telmisartan has a PPARγ agonist activity.[16]

    Pharmacokinetics

    The substance is quickly but to varying degrees absorbed from the gut. The average bioavailability is about 50% (42–100%). Food intake has no clinically relevant influence on the kinetics of telmisartan. Plasma protein binding is over 99.5%, mainly to albumin and alpha-1-acid glycoprotein.[9] It has the longest half-life of any ARB (24 hours)[17][10] and the largest volume of distribution among ARBs (500 liters).[18][19] Less than 3% of telmisartan is inactivated by glucuronidation in the liver, and over 97% is eliminated in unchanged form via bile and faeces.[20][9]

    History

    Society and culture

    Telmisartan is available as a generic medication.[4] A month supply in the United Kingdom costs the NHS less than £2 as of 2019.[4] In the United States the National Average Drug Acquisition Cost of this amount is about US$10 as of 2019.[5]

    References
    1. "Telmisartan Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 3 March 2019.
    2. "Telmisartan Pregnancy and Breastfeeding Warnings". Drugs.com. Retrieved 3 March 2019.
    3. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 471. ISBN 9783527607495.
    4. British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 178. ISBN 9780857113382.
    5. "NADAC as of 2019-02-27". Centers for Medicare and Medicaid Services. Retrieved 3 March 2019.
    6. "The Top 300 of 2019". clincalc.com. Retrieved 26 February 2019.
    7. Opie & Gersh 2009, p. 146.
    8. Drugs.com: Micardis
    9. Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
    10. Benson, S. C.; Pershadsingh, H.; Ho, C.; Chittiboyina, A.; Desai, P.; Pravenec, M.; Qi, N.; Wang, J.; Avery, M.; Kurtz, T. W. (2004). "Identification of Telmisartan as a Unique Angiotensin II Receptor Antagonist with Selective PPAR -Modulating Activity". Hypertension. 43 (5): 993–1002. doi:10.1161/01.HYP.0000123072.34629.57. PMID 15007034.
    11. Sanchis-Gomar, F.; Lippi, G. (2011). "Telmisartan as metabolic modulator: A new perspective in sports doping?". Journal of Strength and Conditioning Research. 26 (3): 608–10. doi:10.1519/JSC.0b013e31824301b6. PMID 22130396.
    12. Cytoplasmic and Nuclear Receptors: Advances in Research and Application: 2011 Edition. ScholarlyEditions. 2012. pp. 21–. ISBN 978-1-464-93110-9. Retrieved 2 April 2013.
    13. Feng, X.; Luo, Z.; Ma, L.; Ma, S.; Yang, D.; Zhao, Z.; Yan, Z.; He, H.; Cao, T.; Liu, D.; Zhu, Z. (2011). "Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway". Journal of Cellular and Molecular Medicine. 15 (7): 1572–1581. doi:10.1111/j.1582-4934.2010.01085.x. PMC 3823201. PMID 20477906.
    14. He, H.; Yang, D.; Ma, L.; Luo, Z.; Ma, S.; Feng, X.; Cao, T.; Yan, Z.; Liu, D.; Tepel, M.; Zhu, Z. (2010). "Telmisartan Prevents Weight Gain and Obesity Through Activation of Peroxisome Proliferator-Activated Receptor- -Dependent Pathways". Hypertension. 55 (4): 869–879. doi:10.1161/HYPERTENSIONAHA.109.143958. PMID 20176998.
    15. Li, L.; Luo, Z.; Yu, H.; Feng, X.; Wang, P.; Chen, J.; Pu, Y.; Zhao, Y.; He, H.; Zhong, J.; Liu, D.; Zhu, Z. (2012). "Telmisartan Improves Insulin Resistance of Skeletal Muscle Through Peroxisome Proliferator-Activated Receptor- Activation". Diabetes. 62 (3): 762–774. doi:10.2337/db12-0570. PMC 3581229. PMID 23238297.
    16. Opie 2013, p. 171.
    17. Pritor prescribing information
    18. Department of Pharmacokinetics and Drug Metabolism, Biberach an der Riss, Boehringer Ingelheim Pharma KG, Biberach, Germany (July 2000). "Pharmacokinetics of orally and intravenously administered telmisartan in healthy young and elderly volunteers and in hypertensive patients" (PDF). Journal of International Medical Research. Retrieved 18 January 2014.CS1 maint: multiple names: authors list (link)
    19. Philippe Gosse (September 2006). "A Review of Telmisartan in the Treatment of Hypertension: Blood Pressure Control in the Early Morning Hours". Vasc Health Risk Manag. 2 (3): 195–201. doi:10.2147/vhrm.2006.2.3.195. PMC 1993985. PMID 17326326.
    20. Drugs.com: Telmisartan

    Sources
    • Opie, Lionel H.; Gersh, Bernard J. (2009). Drugs for the heart (seventh ed.). Saunders. ISBN 978-1-4160-6158-8.
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