Tesamorelin (20mg – 200mg)

Tesamorelin

		Peptide Sciences	Liberty Peptides
Cost per milligram	$2.70 – $4.30	$15.00	$5.50
Purity	99.1%	98.4%	98.78%
Certified Endotoxin-safe	Yes	No	No
Independently Tested	Yes	No	No

• Peptide Partners Manufacturer ID: WF03
• Batch ID: TS20250722

 

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Overview

(For educational purposes only)

Tesamorelin represents a significant advancement in the treatment of HIV-associated lipodystrophy, functioning as a synthetic analog of human growth hormone-releasing hormone (GHRH). This peptide-based medication specifically targets excess abdominal fat accumulation in HIV patients while preserving the body’s natural hormonal regulation patterns. Though facing recent regulatory challenges with newer formulations, tesamorelin remains an important therapeutic option for addressing a common and distressing complication of HIV treatment.

Molecular Structure and Pharmacological Properties

Tesamorelin is a 44-amino acid synthetic peptide that closely resembles natural human growth hormone-releasing factor (GRF) with strategic modifications to enhance its therapeutic properties.

Chemical Composition

The molecular structure of tesamorelin features several distinctive characteristics:

• Complete 44-amino acid sequence of human GRF with a hexenoyl moiety attachment
• The hexenoyl group (a C6 chain with a double bond at position 3) is anchored to the tyrosine residue at the N-terminal portion of the molecule^[1][2]
• Molecular formula of C221H366N72O67S – xC2H4O2, where x averages 7.4 acetate counter ions per peptide molecule^[1]
• Molecular weight of 5135.9 Daltons for the free base and approximately 5579 Daltons for tesamorelin acetate^[1]
• Appears as a white to off-white amorphous powder^[1]
• Freely soluble in acetic acid, soluble in water, and slightly soluble in methanol^[1][2]

The addition of the hydrophobic hexenoyl side chain is crucial to tesamorelin’s therapeutic profile, as it increases resistance to enzymatic degradation in human serum while maintaining binding affinity to GHRH receptors comparable to the natural hormone^[2].

Mechanism of Action

Tesamorelin operates through specific receptor-mediated pathways to influence growth hormone secretion:

• Binds to GHRH receptors on pituitary somatotroph cells, stimulating synthesis and release of endogenous growth hormone^[2][3]
• Increases plasma levels of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3)^[4]
• Regulates body composition through a combination of anabolic and lipolytic mechanisms^[3]
• Primarily reduces abdominal fat mass through lipolysis followed by reduction in triglyceride levels^[3]

Unlike direct growth hormone administration, tesamorelin preserves the body’s natural pulsatile pattern of GH secretion, potentially offering a more physiologic approach to hormone modulation.

Therapeutic Applications

Tesamorelin has a specific FDA-approved indication and several limitations on its use.

FDA-Approved Indication

Tesamorelin is specifically indicated for:

• Reduction of excess abdominal fat in HIV-infected patients with lipodystrophy^[5][6][7][8]

This targeted application addresses a significant complication of HIV treatment that can cause both medical and psychological distress for patients.

Limitations of Use

Important limitations include:

• Not indicated for weight loss management, as it has a weight-neutral effect^[6][7]
• Careful consideration should be given to continuing treatment in patients who don’t show clear efficacy responses in visceral adipose tissue reduction^[7]
• Long-term cardiovascular safety and potential benefits have not been established^[7]

Pharmacokinetic Profile

Tesamorelin demonstrates distinctive pharmacokinetic properties that influence its clinical application.

• Rapid absorption following subcutaneous administration, with peak concentrations reached in 5-20 minutes^[8]
• Limited bioavailability (<4%) following a 2 mg subcutaneous dose^[4]
• Half-life of approximately 26 minutes in healthy subjects and 38 minutes in HIV-infected patients^[4]
• Volume of distribution of 9.4±3.1 L/kg in healthy subjects and 10.5±6.1 L/kg in HIV-infected patients^[4]

The relatively short half-life necessitates daily administration to maintain therapeutic effects.

Clinical Administration

Proper administration is essential for achieving optimal therapeutic outcomes with tesamorelin.

Dosing and Administration

Tesamorelin follows a specific administration protocol:

• Supplied as a lyophilized powder requiring reconstitution before use^[6][8]
• Administered as a subcutaneous injection once daily^[6][8]
• Should be used at approximately the same time each day^[6][8]
• Injected into the abdominal area below the navel, avoiding the navel itself and any scarred, reddened, irritated, infected, or bruised areas^[6][8]
• Administration sites should be rotated to minimize local reactions^[8]

Safety Profile and Adverse Effects

Understanding tesamorelin’s safety profile is important for appropriate patient selection and management.

Common Adverse Effects

The most frequently reported side effects include:

• Injection site reactions (redness, itching, pain, irritation, swelling, bleeding, or bruising)^[9][3]
• Muscle aches or spasms^[9]
• Sleep disturbances (insomnia)^[9]
• Night sweats^[9]
• Gastrointestinal symptoms (nausea, vomiting, upset stomach, diarrhea)^[9][3]
• Peripheral edema^[3]
• Rash or skin itching^[9]

Serious Adverse Effects

More serious but less common adverse effects include:

• Allergic reactions (hives, breathing difficulties, facial swelling)^[9]
• Musculoskeletal pain or stiffness^[9]
• Peripheral neuropathy (numbness or tingling in hands or fingers)^[9]
• Cardiac symptoms (pounding heartbeats or chest fluttering)^[9]
• Hyperglycemia (increased thirst, urination, hunger, dry mouth, fruity breath odor)^[9]

In clinical trials, adverse reactions led to discontinuation in 4.2% of patients due to GH-related effects and 4.6% due to injection site reactions^[7].

Contraindications

Tesamorelin is contraindicated in several populations:

• Pregnant women (pregnancy category X) due to potential fetal harm^[3]
• Patients with hypothalamic-pituitary axis disruption from conditions like pituitary tumors, head irradiation, or hypopituitarism^[3]
• Caution is advised in patients at risk for diabetes, as tesamorelin may cause glucose intolerance and increase type 2 diabetes risk^[3]

Recent Developments

The regulatory landscape for tesamorelin continues to evolve with recent developments affecting its formulations.

In January 2024, the FDA issued a Complete Response Letter regarding the F8 formulation of tesamorelin^[5]. This concentrated version would have been 8 times more concentrated than the original Egrifta and 2 times more concentrated than the current Egrifta SV formulation^[5]. The FDA requested clarifications on chemistry, manufacturing, controls, microbiology, assays, impurities, stability, and potential immunogenicity risks^[5].

Despite this setback for the newer formulation, Egrifta SV continues to be commercially available in the US market^[5].

Conclusion

Tesamorelin represents an important therapeutic option for addressing HIV-associated lipodystrophy, a condition that can significantly impact patient quality of life. By stimulating endogenous growth hormone production through GHRH receptor activation, tesamorelin offers a targeted approach to reducing excess abdominal fat while maintaining more physiologic hormone patterns than direct growth hormone administration.

The medication’s specific chemical modifications enhance its stability and resistance to enzymatic degradation, though its short half-life necessitates daily administration. While generally well-tolerated, healthcare providers must carefully consider the potential risks, particularly regarding glucose metabolism, when selecting appropriate candidates for therapy.

As research and development continue, future formulations may offer improved convenience and patient adherence, though recent regulatory challenges highlight the complexities of bringing such innovations to market. For now, tesamorelin remains a valuable component in the comprehensive management of metabolic complications associated with HIV infection and its treatment.

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1. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022505Orig1s000ChemR.pdf
2. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022505Orig1s000ClinPharmR.pdf
3. https://en.wikipedia.org/wiki/Tesamorelin
4. https://go.drugbank.com/drugs/DB08869
5. https://www.empr.com/home/news/drugs-in-the-pipeline/fda-denies-approval-of-f8-formulation-of-tesamorelin-for-hiv-related-lipodystrophy/
6. https://www.afwomensmed.com/health-library/hw-view.php?DOCHWID=a611035
7. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022505s004lbl.pdf
8. https://medlineplus.gov/druginfo/meds/a611035.html
9. https://www.rxlist.com/tesamorelin/generic-drug.htm