Tesamorelin

Tesamorelin
Names
Trade namesEgrifta
Clinical data
Drug classGrowth-hormone-releasing hormone (GHRH)[1]
Main usesHIV-associated lipodystrophy[1]
Side effectsJoint pain, redness at the site of injection, leg swelling[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • US: X (Contraindicated)
    Routes of
    use    		Subcutaneous injection
    Typical dose2mg OD[1]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa611035
    Legal
    Legal status
    • US: ℞-only
    • In general: ℞ (Prescription only)
    Pharmacokinetics
    Bioavailability≤4%[2]
    MetabolismProteolysis
    Elimination half-life26–38 min
    ExcretionKidney
    Chemical and physical data
    FormulaC221H366N72O67S
    Molar mass5135.86 g·mol−1
    3D model (JSmol)
    SMILES
    • CCC[C@@H](C(=O)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(cc1)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](Cc3ccc(cc3)O)NC(=O)C/C=C/CC
    InChI
    • InChI=1S/C220H364N72O67S/c1-24-28-30-54-162(307)259-144(92-119-55-59-121(298)60-56-119)197(342)254-115(20)178(323)275-149(96-168(315)316)198(343)255-116(21)179(324)290-171(110(15)26-3)213(358)283-146(91-118-44-31-29-32-45-118)205(350)292-173(117(22)297)214(359)284-148(95-161(229)306)204(349)288-154(104-296)209(354)279-145(93-120-57-61-122(299)62-58-120)202(347)267-130(52-41-84-247-219(239)240)186(331)266-126(47-34-36-79-222)196(341)289-170(109(13)14)211(356)282-140(87-105(5)6)182(327)251-100-165(310)257-133(64-71-156(224)301)189(334)277-143(90-108(11)12)201(346)287-151(101-293)207(352)256-114(19)177(322)263-129(51-40-83-246-218(237)238)185(330)265-125(46-33-35-78-221)188(333)276-142(89-107(9)10)200(345)278-141(88-106(7)8)199(344)272-137(67-74-159(227)304)194(339)281-150(97-169(317)318)206(351)291-172(111(16)27-4)212(357)274-139(77-86-360-23)195(340)286-152(102-294)208(353)268-131(53-42-85-248-220(241)242)187(332)270-135(65-72-157(225)302)191(336)269-132(63-70-155(223)300)181(326)250-99-164(309)258-134(68-75-166(311)312)190(335)285-153(103-295)210(355)280-147(94-160(228)305)203(348)273-136(66-73-158(226)303)192(337)271-138(69-76-167(313)314)193(338)264-124(48-37-80-243-215(231)232)180(325)249-98-163(308)252-112(17)175(320)261-127(49-38-81-244-216(233)234)183(328)253-113(18)176(321)262-128(50-39-82-245-217(235)236)184(329)260-123(43-25-2)174(230)319/h28-32,44-45,55-62,105-117,123-154,170-173,293-299H,24-27,33-43,46-54,63-104,221-222H2,1-23H3,(H2,223,300)(H2,224,301)(H2,225,302)(H2,226,303)(H2,227,304)(H2,228,305)(H2,229,306)(H2,230,319)(H,249,325)(H,250,326)(H,251,327)(H,252,308)(H,253,328)(H,254,342)(H,255,343)(H,256,352)(H,257,310)(H,258,309)(H,259,307)(H,260,329)(H,261,320)(H,262,321)(H,263,322)(H,264,338)(H,265,330)(H,266,331)(H,267,347)(H,268,353)(H,269,336)(H,270,332)(H,271,337)(H,272,344)(H,273,348)(H,274,357)(H,275,323)(H,276,333)(H,277,334)(H,278,345)(H,279,354)(H,280,355)(H,281,339)(H,282,356)(H,283,358)(H,284,359)(H,285,335)(H,286,340)(H,287,346)(H,288,349)(H,289,341)(H,290,324)(H,291,351)(H,292,350)(H,311,312)(H,313,314)(H,315,316)(H,317,318)(H4,231,232,243)(H4,233,234,244)(H4,235,236,245)(H4,237,238,246)(H4,239,240,247)(H4,241,242,248)/b30-28+/t110-,111-,112-,113-,114-,115-,116-,117+,123-,124-,125-,126-,127+,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,138-,139-,140-,141-,142-,143-,144-,145-,146-,147-,148-,149-,150-,151-,152-,153-,154-,170-,171-,172-,173-/m0/s1
    • Key:VQFDKKWXORFBDI-VAVVJCQZSA-N

    Tesamorelin, sold under the brand name Egrifta, is a medication used to treat HIV-associated lipodystrophy.[1] Specifically it is used for excess abdominal fat.[3] It is given by injection under the skin.[1]

    Common side effects include joint pain, redness at the site of injection, and leg swelling.[1] Other side effects may include allergic reactions and cancer.[1] Use in pregnancy may harm the baby.[1] It is a manufactured form of growth-hormone-releasing hormone (GHRH).[1]

    Tesamorelin was approved for medical use in the United States in 2010.[1] It is not approved in Europe.[3] In the United States it costs about 6,400 USD per month as of 2021.[4]

    Medical uses

    Dosage

    It is given at a dose of 2 mg once per day.[1]

    Contraindication

    Tesamorelin therapy may cause glucose intolerance and increase the risk of type 2-diabetes, so it is contraindicated in pregnancy.[5] It is also contraindicated in pregnancy (category X) because it may cause harm to fetus. It is also contraindicated in patients affected by hypothalamic-pituitary axis disruption due to pituitary gland tumor, head irradiation and hypopituitarism.[6]

    Side effects

    Injection site redness, peripheral edema, injection site itchiness and diarrhea.[7]

    Mechanism of action

    Tesamorelin is the N-terminally modified compound based on 44 amino acids sequence of human GHRH.[8] This modified synthetic form is more potent and stable than the natural peptide. It is also more resistant to cleavage by the dipeptidyl aminopeptidase than human GHRH.[9] It stimulates the synthesis and release of endogenous GH, with an increase in level of insulin-like growth factor (IGF-1). The released GH then binds with the receptors present on various body organs and regulates the body composition. This regulation is mainly because of the combination of anabolic and lipolytic mechanisms. However, it has been found that the main mechanisms by which Tesamorelin reduces body fat mass are lipolysis followed by reduction in triglycerides level.[10]

    History

    It is produced and developed by Theratechnologies, Inc. of Canada. The drug is a synthetic peptide consisting of all 44 amino acids of human GHRH with the addition of a trans-3-hexenoic acid group.[11]

    See also

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 12 "Tesamorelin". drugs.com. American Society of Health-System Pharmacists. Archived from the original on 19 January 2021. Retrieved 1 October 2021.
    2. ↑ "Egrifta (tesamorelin for injection) for Subcutaneous Use. U.S. Full Prescribing Information" (PDF). EMD Serono, Inc. Archived (PDF) from the original on 18 December 2011. Retrieved 9 April 2016.
    3. 1 2 "Egrifta: Withdrawal of the marketing authorisation application". Archived from the original on 1 October 2021. Retrieved 1 October 2021.
    4. ↑ "Egrifta Prices, Coupons and Patient Assistance Programs". drugs.com. Archived from the original on 19 January 2021. Retrieved 1 October 2021.
    5. ↑ Patel A, Gandhi H, Upaganlawar A (April 2011). "Tesamorelin: A hope for ART-induced lipodystrophy". Journal of Pharmacy & Bioallied Sciences. 3 (2): 319–20. doi:10.4103/0975-7406.80763. PMC 3103937. PMID 21687371.
    6. ↑ DeRuiter J, Holston PL. "Review of Selected NMEs 2011". www.uspharmacist.com. Auburn: Health Information Designs, Inc. Archived from the original on 2019-06-22. Retrieved 2019-06-22.
    7. ↑ Falutz J, Potvin D, Mamputu JC, Assaad H, Zoltowska M, Michaud SE, et al. (March 2010). "Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension". Journal of Acquired Immune Deficiency Syndromes. 53 (3): 311–22. doi:10.1097/qai.0b013e3181cbdaff. PMID 20101189. S2CID 13613924.
    8. ↑ Dhillon S (May 2011). "Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy". Drugs. 71 (8): 1071–91. doi:10.2165/11202240-000000000-00000. PMID 21668043.
    9. ↑ Ferdinandi ES, Brazeau P, High K, Procter B, Fennell S, Dubreuil P (January 2007). "Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue". Basic & Clinical Pharmacology & Toxicology. 100 (1): 49–58. doi:10.1111/j.1742-7843.2007.00008.x. PMID 17214611.
    10. ↑ Benedini S, Terruzzi I, Lazzarin A, Luzi L (2008). "Recombinant human growth hormone: rationale for use in the treatment of HIV-associated lipodystrophy". BioDrugs. 22 (2): 101–12. doi:10.2165/00063030-200822020-00003. PMID 18345707. S2CID 34340539.
    11. ↑ "FDA Application Chemistry Review" (PDF). Archived (PDF) from the original on 2021-06-24. Retrieved 2021-03-25.
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