Tesamorelin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Subcutaneous:

Egrifta SV: 2 mg (1 ea)

Solution Reconstituted, Subcutaneous [preservative free]:

Egrifta: 1 mg (1 ea)

Pharmacology

Mechanism of Action

Tesamorelin binds to pituitary growth hormone-releasing factor (GRF) receptors and stimulates the secretion of endogenous growth hormone which has anabolic and lipolytic properties. Growth hormone exerts its effects by interacting with receptors on target cells such as osteoblasts, myocytes, hepatocytes, and adipocytes to promote the reduction of total fat mass. These effects are primarily mediated by IGF-1 produced in the liver and in peripheral tissues.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 1 mg vial: Healthy adults: 9.4 ± 3.1 L/kg, HIV-infected patients: 10.5 ± 6.1 L/kg; 2 mg vial: Healthy adults: 4.8 ± 1.9 L/kg.

Time to Peak

9 minutes

Half-Life Elimination

1 mg vial: Healthy adults: 26 minutes, HIV-infected patients: 38 minutes; 2 mg vial: Healthy adults: 8 minutes.

Use: Labeled Indications

HIV-associated lipodystrophy: Reduction of excess abdominal fat in HIV-infected patients with lipodystrophy

Contraindications

Hypersensitivity to tesamorelin or any component of the formulation; disruption of hypothalamic-pituitary-axis due to hypophysectomy, hypopituitarism, pituitary tumor/surgery, head irradiation, or head trauma; active malignancy; pregnancy.

Dosage and Administration

Dosing: Adult

HIV-associated lipodystrophy: SubQ:

1 mg vial: 2 mg once daily.

2 mg vial: 1.4 mg once daily.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Consider discontinuing with persistent elevations of IGF-1 (eg, >3 standard deviation scores). Discontinue if symptoms of hypersensitivity occur.

Reconstitution

1 mg vial: Use provided diluent only. Reconstitute the first 1 mg vial with 2.2 mL diluent; gently roll vial (do not shake) for 30 seconds to mix; reconstitute the second 1 mg vial with the entire solution from first vial; gently roll vial (do not shake) for 30 seconds to mix. Use reconstituted solution immediately after prepared.

2 mg vial: Use provided diluent only. Reconstitute with 0.5 mL diluent; gently roll vial for 30 seconds to mix; do not shake. Use reconstituted solution immediately after prepared.

Administration

SubQ: The abdomen is the preferred site of administration; rotate site within the abdomen. Avoid injection into scar tissue, bruises, or the navel.

Storage

Protect from light and store in original container until time of use. Use reconstituted solution immediately after prepared; do not refrigerate or freeze. Discard if not used immediately.

1 mg vial: Store intact vials refrigerated at 2°C to 8°C (36°F to 46°F). Protect from light and store in original container until time of use. Store supplied diluent (SWFI), syringes, and needles at 20°C to 25°C (68°F to 77°F). Use reconstituted solution immediately after prepared; do not refrigerate or freeze. Discard if not used immediately.

2 mg vial: Store intact vials at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light and store in original container until time of use. Store supplied diluent (SWFI), syringes, and needles at 20°C to 25°C (68°F to 77°F). Use reconstituted solution immediately after prepared; do not refrigerate or freeze. Discard if not used immediately.

Drug Interactions

Cortisone: Tesamorelin may decrease serum concentrations of the active metabolite(s) of Cortisone. Consider therapy modification

Macimorelin: Growth Hormone Products may diminish the diagnostic effect of Macimorelin. Avoid combination

PredniSONE: Tesamorelin may decrease serum concentrations of the active metabolite(s) of PredniSONE. Consider therapy modification

Adverse Reactions

The incidence of adverse reactions generally decreases with treatment continued beyond 26 weeks.

10%:

Immunologic: Antibody development (47% to 50%; neutralizing: 5% to 10%)

Local: Injection site reaction (17% to 25%)

Neuromuscular & skeletal: Arthralgia (13%)

1% to 10%:

Cardiovascular: Peripheral edema (6%), palpitations (1%)

Central nervous system: Paresthesia (5%), hypoesthesia (4%), pain (2%), carpal tunnel syndrome (1%)

Dermatologic: Skin rash (4%), pruritus (2%), night sweats (1%)

Gastrointestinal: Vomiting (3%), dyspepsia (2%)

Hematologic & oncologic: Diabetes mellitus (5%), elevated glycosylated hemoglobin (5%)

Hypersensitivity: Hypersensitivity reaction (4%)

Neuromuscular & skeletal: Limb pain (6%), myalgia (6%), muscle rigidity (2%), musculoskeletal pain (2%), increased creatine phosphokinase in blood specimen (1%), joint swelling (1%), muscle strain (1%)

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity reactions (eg, pruritus, erythema, flushing, urticaria, rash) may occur. If hypersensitivity is suspected, discontinue and instruct patient to seek immediate medical attention.
• Fluid retention: Use may result in peripheral edema manifested by increased skin turgor and musculoskeletal discomfort. May be transient or resolve upon treatment discontinuation.
• Injection-site reactions: Injection-site reactions (including erythema, pruritus, pain, irritation, and bruising) may occur. Rotating the site of injection to different areas of the abdomen may reduce incidence of reactions.

Disease-related concerns:

• Diabetes: May increase risk of development of diabetes due to glucose intolerance. Evaluate glucose status prior to treatment initiation; monitor periodically for glucose metabolism changes. Patients with diabetes should be monitored for the development or worsening of retinopathy due to increased IGF-1 levels.
• Malignancy: Release of endogenous growth hormone and increased serum IGF-1 may increase the risk for development or reactivation of malignancies. Use is contraindicated in patients with active malignancies; treatment for prior malignancy should be completed prior to initiation of tesamorelin. IGF-1 levels should be monitored during treatment; consider discontinuing with persistent IGF-1 elevations (eg, >3 standard deviation scores). Discontinue treatment with any evidence of recurrent malignancy.
• Acute critical illness: Growth hormone is associated with an increased risk of mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery, trauma, or acute respiratory failure. Consider discontinuing in critically ill patients.

Special populations:

• Pediatric: Should not be used in children due to risk of excess growth (gigantism); do not use in children with open or closed epiphyses.

Other warnings/precautions:

• Appropriate use: Not indicated for weight loss management. Due to a lack of long-term cardiovascular safety/benefit data, carefully consider whether continuation of treatment is warranted in patients who do not demonstrate efficacy (based on degree of reduction of visceral adipose tissue). There are no data supporting improved compliance of antiretroviral therapy with concomitant tesamorelin.

Monitoring Parameters

Serum IGF-1 levels should be monitored at baseline and during therapy due to the potential increased risk of malignancy from sustained elevation of IGF-1 levels. Serum glucose (prior to treatment initiation); monitor periodically for glucose metabolism changes. Monitor for retinopathy in patients with diabetes. Visceral adipose tissue (by waist circumference or CT scan). Monitor for fluid retention.

Pregnancy

Pregnancy Considerations

Use is contraindicated in pregnant females.

During pregnancy, there is an increased deposition of visceral adipose tissue due to metabolic and hormonal changes. Tesamorelin decreases the deposition of visceral fat and could potentially cause harm to the unborn fetus. If pregnancy occurs during treatment, discontinue tesamorelin.

Patient Education

What is this drug used for?

• It is used to lower belly fat in patients with HIV.

Frequently reported side effects of this drug

• Muscle pain
• Joint pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Fast heartbeat
• Dizziness
• Passing out
• Flushing
• Shortness of breath
• Painful extremities
• Burning or numbness feeling
• Swelling
• Weight gain
• Trouble breathing
• Injection site pain, redness, swelling, itching, bleeding, or irritation
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.