Tesamorelin (Monograph)

Brand name: Egrifta SV
Drug class: Somatotropin Agonists

Medically reviewed by Drugs.com on Mar 10, 2024. Written by ASHP.

Introduction

Synthetic analog of human growth hormone-releasing factor (GHRF).

Uses for Tesamorelin

HIV-associated Lipodystrophy

Reduction of excess abdominal fat in patients with HIV-associated lipodystrophy. Efficacy of tesamorelin in the treatment of HIV-associated lipodystrophy shown in 2 randomized, multicenter, placebo-controlled trials; however, long-term cardiovascular safety not established, and the manufacturer suggests consideration of the risks and benefits of continuing tesamorelin in patients who fail to demonstrate a reduction in visceral adipose tissue.

Management of HIV-associated lipodystrophy generally includes dietary modifications, exercise, and control of diabetes and dyslipidemias; GHRF analogs, such as tesamorelin, are a potential additional therapeutic option in these patients.

Not indicated for weight loss management (has a weight neutral effect).

Insufficient evidence to support improved compliance with antiretroviral therapies in HIV-infected patients administered tesamorelin.

Currently available as a 2-mg per vial formulation (Egrifta SV) that is given as a 1.4-mg dose. This formulation has demonstrated comparable bioavailability to the 1-mg/vial formulation (Egrifta). Since 2019, only the 2-mg per vial formulation of tesamorelin has been available in the US.

Tesamorelin Dosage and Administration

General

Pretreatment Screening

• Evaluate patients for glucose status prior to initiating therapy.

• Any preexisting malignancies should be inactive and have treatment completed prior to initiating tesamorelin therapy.

Patient Monitoring

• Monitor patients periodically during treatment for development of impaired glucose tolerance or diabetes.

• Monitor patients with diabetes at regular intervals for development or worsening of retinopathy.

• Monitor for signs and symptoms of hypersensitivity reactions (pruritus, erythema, flushing, urticaria, rash).

• Monitor insulin-like growth factor (IGF)-1 levels during therapy.

Administration

The administration, preparation, and dosage recommendations only apply to the 2-mg per vial formulation of tesamorelin acetate (Egrifta SV) that is currently available in the US; the previously available 1-mg per vial formulation of the drug (Egrifta) had different administration and dosage recommendations.

Administer sub-Q into the abdomen once daily.

Rotate injection sites to different areas of the abdomen to reduce the risk of injection site reactions.

Do notinject into scarred or bruised sites; avoid the navel.

Reconstitution

Reconstitute vial containing 2-mg of tesamorelin with 0.5 mL of sterile water for injection (supplied by manufacturer) to provide a solution containing 2 mg/0.5 mL.

Direct the diluent toward sides of vials rather than directly onto powder to avoid foaming; roll vial gently between the hands (do not shake) for 30 seconds until the powder is completely dissolved.

Reconstituted solutions should be clear, colorless, and free from visible particles.

Discard vials of reconstituted solution if not used immediately; do not refrigerate or freeze.

Consult manufacturer’s patient instructions for use for complete information on preparation, reconstitution, and administration of tesamorelin.

Dosage

Available as tesamorelin acetate; dosage expressed in terms of tesamorelin.

Adults

HIV-associated Lipodystrophy

Sub-Q

Inject 1.4 mg (0.35 mL of reconstituted solution) once daily into the abdomen.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Tesamorelin

Contraindications

• Patients with disruption of the hypothalamic-pituitary axis due to hypophysectomy, hypopituitarism, pituitary tumor/surgery, head irradiation, or head trauma.

• Active malignancy. Any preexisting malignancy should be inactive and its treatment complete before initiating tesamorelin therapy.

• Known hypersensitivity to tesamorelin acetate or any ingredient in the formulation.

• Pregnant women because modifying visceral adipose tissue offers no benefit in a pregnant woman and may result in fetal harm.

Warnings/Precautions

Increased Risk of Neoplasm

Carefully consider the risk of new malignancies prior to initiating tesamorelin therapy, based on the increased background risk of malignancies in HIV-positive patients.

Because tesamorelin stimulates the release of endogenous growth hormone (GH), a known growth factor, do not use in patients with active malignancy.

In patients with a history of nonmalignant neoplasms, carefully evaluate the potential benefits of tesamorelin prior to intiating therapy.

Initiate therapy in patients with a history of treated and stable malignancies only after careful consideration of the potential benefits versus risks of reactivation of the underlying malignancy. Discontinue tesamorelin if there is any evidence of recurrent malignancy.

Increased Insulin-like Growth Factor-1 (IGF-1) Concentrations

Tesamorelin stimulates GH production and increases serum concentrations of insulin-like growth factor-1 (IGF-1); the effects of prolonged elevations in IGF-1 levels are unknown.

Monitor IGF-1 concentrations during therapy. Consider discontinuance of therapy in patients who experience persistent IGF-1 elevations (e.g., >3 standard deviation scores [SDS]), particularly if response to therapy is not robust.

Fluid Retention

Fluid retention (thought to be related to induction of GH secretion) reported. Typically manifests as increased tissue turgor and musculoskeletal discomfort resulting in adverse effects such as edema, arthralgia, and carpal tunnel syndrome. Symptoms usually are transient or resolve with drug discontinuance.

Glucose Intolerance or Diabetes Mellitus

Risk of glucose intolerance and diabetes mellitus.

Evaluate glucose status prior to initiating therapy and monitor periodically thereafter in all patients. If patients develop glucose intolerance or diabetes mellitus, consider discontinuance of therapy in patients who do not demonstrate a clear efficacy response.

Monitor patients with diabetes mellitus at regular intervals for potential development or worsening of retinopathy.

Hypersensitivity Reactions

Risk of hypersensitivity reactions (e.g., pruritus, erythema, flushing, urticaria, rash) reported.

If a hypersensitivity reaction is suspected, advise patient to immediately discontinue tesamorelin and promptly seek medical attention.

Injection Site Reactions

Injection site reactions (e.g., erythema, pruritus, pain, irritation, bruising) reported frequently.

Rotate injection sites to different areas of the abdomen to decrease incidence of injection site reactions.

Increased Mortality in Acute Critical Illness

Increased mortality reported in patients with acute critical illness resulting from complications following open heart surgery, abdominal surgery, multiple accidental trauma, or acute respiratory failure after receiving pharmacologic dosages of GH.

Since tesamorelin increases GH production, consider discontinuing the drug in critically ill patients.

Immunogenicity

As with all therapeutic proteins and peptides, there is a potential for immunogenicity with tesamorelin therapy. Possible development of antibodies to tesamorelin acetate. Presence of anti-tesamorelin IgG antibodies does not appear to affect clinical response.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm and is contraindicated for use during pregnancy; fetal anomalies (e.g., hydrocephaly, delayed skull ossification) demonstrated in rats.

If used during pregnancy or patient becomes pregnant, discontinue drug and apprise of potential fetal hazard.

Specific Populations

Pregnancy

Tesamorelin is contraindicated during pregnancy.

Visceral adipose tissue increases during pregnancy as a result of normal metabolic and hormonal changes; modification of this process offers no known clinical benefit and may result in fetal harm.

Lactation

Not known whether tesamorelin is distributed into human milk; its effects on milk production and the breastfed infant also are not known.

Because of the risk of adverse effects in the infant and risk of HIV transmission (in HIV-negative infants) and development of viral resistance (in HIV-positive patients), instruct HIV-infected women receiving tesamorelin not to breast-feed.

Pediatric Use

Safety and efficacy not established in pediatric patients. Use of the drug in pediatric patients with open epiphyses may result in linear growth acceleration and excessive growth. The manufacturer states that tesamorelin is not indicated for use in pediatric patients with open or closed epiphyses.

Geriatric Use

Information not available in patients >65 years of age with HIV-associated lipodystrophy.

Hepatic Impairment

Safety and efficacy not established in patients with hepatic impairment.

Renal Impairment

Safety and efficacy not established in patients with renal impairment.

Common Adverse Effects

Most common adverse effects (>5%): arthralgia, injection site erythema, injection site pruritus, extremity pain, peripheral edema, myalgia.

Drug Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Not likely to substantially affect CYP3A activity. Effect on other CYP isoenzymes not evaluated.

Growth hormone (GH) may alter clearance of drugs known to be metabolized by CYP isoenzymes; carefully monitor for potential interactions if used concomitantly with these drugs.

Corticosteroids

GH inhibits 11β-hydroxysteroid dehydrogenase type 1, the enzyme required for conversion of cortisone to cortisol. Therefore, patients receiving corticosteroid replacement therapy (particularly with cortisone acetate or prednisone) for hypoadrenalism may require an increase in maintenance corticosteroid dosage or supplemental stress-related corticosteroid doses following initiation of tesamorelin.

Specific Drugs

Tesamorelin Pharmacokinetics

Absorption

Bioavailability

Systemic exposure (AUC and C_max) of tesamorelin was similar between 1.4-mg doses (2 mg/vial formulation) and 2-mg doses (1 mg/vial formulation).

Absolute bioavailability <4% in healthy adults following sub-Q administration of a 2-mg dose.

Peak plasma concentrations achieved in approximately 0.15 hours.

Extent of absorption (AUC) was 34% higher in HIV-infected patients compared with healthy individuals; C_max was similar between these groups.

Distribution

Extent

Not known whether tesamorelin is distributed into human milk.

Elimination

Metabolism

No formal drug metabolism studies performed to date in humans.

Half-life

Mean elimination half-life of 8 minutes in healthy individuals given a single 1.4-mg dose sub-Q.

Mean elimination half-life of 18.6 minutes in HIV-infected patients given a single 2-mg dose sub-Q. After multiple dosing (once daily for 14 days), the mean elimination half-life was 37.8 minutes.

Stability

Storage

Parenteral

Powder for Injection

Store at 25°C (excursions permitted between 15–30°C) in the original carton and protected from light; diluent and other supplies should be stored at controlled room temperature (20–25°C).

Actions

• Synthetic analog of human GHRF; stimulates synthesis and release of growth hormone (GH) from pituitary somatotroph cells. Also increases production of IGF-1 by the liver and peripheral tissues.

• GH (deficient in patients with HIV-associated lipodystrophy) produces anabolic and lipolytic effects by interacting with specific receptors on target cells (e.g., chondrocytes, osteoblasts, myocytes, hepatocytes, adipocytes). Some of these effects are mediated by IGF-1.

• Shown in vitro to bind to and stimulate GHRF receptors with similar potency to that of the native protein.

• Does not substantially affect other pituitary hormones (i.e., thyroid-stimulating hormone [TSH], luteinizing hormone [LH], adrenocorticotropic hormone [ACTH], prolactin).

Advice to Patients

• Advise patient to read manufacturer's patient information and instructions for use.

• Risk of malignancy; importance of informing patients about the increased background risk of malignancies in HIV-positive patients and for patients with a history of neoplasms, informing them about the risk of malignancy recurrence.

• Risk of elevated insulin-like growth factor (IGF)-1 concentrations; importance of informing patients that periodic monitoring of IGF-1 levels is necessary during therapy.

• Risk of fluid retention; importance of advising patients of possible manifestations of fluid retention, including edema, arthralgia, and carpal tunnel syndrome.

• Risk of glucose intolerance and diabetes mellitus. Importance of advising patients that they will be monitored for development of impaired glucose tolerance or diabetes mellitus; patients with preexisting diabetes mellitus may need adjustments to their antidiabetic regimen.

• Risk of hypersensitivity reactions; importance of informing patients to immediately discontinue treatment and promptly seek medical attention if a hypersensitivity reaction (e.g., rash, hives, itching, swelling of the face or throat, breathing difficulties, fast heartbeat, feelings of faintness or fainting, reddening or flushing of skin) occurs.

• Importance of advising patients of the possibility of injection site reactions (e.g., redness, itching, pain, irritation, bruising, bleeding, rash, swelling) and to rotate injection sites to reduce the risk of injection site reactions.

• Importance of not sharing syringes and needles used to administer the drug with other individuals since this may result in transmission of infectious diseases.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Tesamorelin offers no known benefit and there is a risk of fetal harm if administered to pregnant women; if pregnancy occurs during therapy, discontinue drug immediately and apprise patient of potential harm to the fetus. Importance of advising women to discontinue nursing because of the potential for HIV transmission and serious adverse effects in nursing infants.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and/or herbal products, as well as any concomitant illness (e.g., cancer, diabetes).

• Importance of informing patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Tesamorelin acetate is available in the US through a special restricted distribution program.

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