Get your patient on Egrifta Wr - Tesamorelin (Tesamorelin)

EGRIFTA WR is indicated for the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy.

Limitations of Use:

• Long-term cardiovascular safety of EGRIFTA WR has not been established. Consider risk/benefit of continuation of treatment in patients who have not had a reduction in visceral adipose tissue.
• EGRIFTA WR is not indicated for weight loss management as it has a weight neutral effect.
• There are no data to support improved compliance with anti-retroviral therapies in HIV-positive patients taking EGRIFTA WR.

• The recommendations in this prescribing information only apply to EGRIFTA WR (tesamorelin) for injection 11.6 mg per vial formulation. For recommendations for tesamorelin for injection 2 mg per vial formulation, see the EGRIFTA SV prescribing information. These two formulations and strengths have differences in the dosage, the number of vials required to prepare a dose, reconstitution instructions, and storage requirements. EGRIFTA WR and EGRIFTA SV are not substitutable. (2.1 ).
• The dose of EGRIFTA WR is 1.28 mg (0.16 mL of the reconstituted solution) injected subcutaneously once daily. (2.1 )
• Inject EGRIFTA WR into the abdomen, rotating injection sites. (2.1 , 5.6 )
• Use only the diluent provided, Bacteriostatic Water for Injection, USP, to reconstitute EGRIFTA WR. (2.2 )
• Reconstitute one vial of lyophilized powder with 1.3 mL of diluent. Move the vial in a circle (swirl) to mix all the powder and liquid. Do not shake. (2.2 )
• Inspect the reconstituted vial visually for particulate matter and discoloration. Use only if the solution is clear, colorless and without particulate matter. (2.2 )
• One reconstituted vial provides daily doses for 7 days. Discard unused solution of EGRIFTA WR vial 7 days after mixing. (2.2 )

For injection: 11.6 mg of tesamorelin as a white to off-white lyophilized powder in a single-patient-use vial for reconstitution and a diluent of 30 mL of multiple-dose Bacteriostatic Water for Injection, USP.

• Lactation: HIV-1 infected mothers should not breastfeed to avoid potential postnatal transmission of HIV-1. (8.2 )

EGRIFTA WR is contraindicated in:

• Patients with disruption of the hypothalamic-pituitary axis (4 )
• Patients with active malignancy (4 )
• Patients with known hypersensitivity to tesamorelin or excipients in EGRIFTA WR (4 )
• Pregnancy (4 )

• Increased risk of neoplasms: Preexisting malignancy should be inactive and its treatment complete prior to starting EGRIFTA WR . Discontinue EGRIFTA WR if there is any evidence of recurrent malignancy. (5.1 )
• Elevated IGF-1: EGRIFTA WR stimulates GH production and increases serum IGF-1, a growth factor. The effects of prolonged elevations in IGF-1 levels are unknown. Monitor IGF-1 levels during EGRIFTA WR therapy. Consider discontinuing in patients with persistent elevations. (5.2 )
• Fluid retention: May occur with EGRIFTA WR and may include edema, arthralgia, and carpal tunnel syndrome. (5.3 )
• Glucose intolerance or diabetes mellitus: May develop with EGRIFTA WR use. Evaluate glucose prior to and during therapy. (5.4 )
• Hypersensitivity reactions: Have occurred in clinical trials. Advise patients to seek immediate medical attention and discontinue treatment if suspected. (5.5 )
• Increased mortality in patients with acute critical illness: Consider discontinuation in critically ill patients . (5.7 )

The following important adverse reactions are also described elsewhere in the labeling:

• Increased risk of neoplasms [see Warnings and Precautions (5.1 )]
• Elevated IGF-1 levels [see Warnings and Precautions (5.2 )]
• Fluid retention [see Warnings and Precautions (5.3 )]
• Glucose intolerance or diabetes mellitus [see Warnings and Precautions (5.4 )]
• Hypersensitivity reactions [see Warnings and Precautions (5.5 )]
• Injection site reactions [see Warnings and Precautions (5.6 )]

• Cytochrome P450-metabolized drugs : Monitor patients for potential interactions when administering with EGRIFTA WR . (7.1 )
• Glucocorticoids : Patients receiving glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in maintenance or stress doses following initiation of EGRIFTA WR.  (7.2 )

Tesamorelin is a human growth hormone-releasing factor (GRF) analog produced synthetically. It is comprised of the 44 amino acid sequence of human GRF and a hexenoyl moiety, a C6 chain with a double bond at position 3, attached to the tyrosine residue at the N-terminal part of the molecule. Tesamorelin is prepared as an acetate salt. The molecular formula of tesamorelin acetate is C ₂₂₁ H ₃₆₆ N ₇₂ O ₆₇ S • x C ₂ H ₄ O ₂ (x ≈ 7) and its molecular weight (as free base equivalent) is 5135.9 Da. The structural formula of tesamorelin acetate is:

EGRIFTA WR (tesamorelin) for injection is a sterile, white to off-white, preservative-free lyophilized powder for subcutaneous injection. Each single-patient-use vial of EGRIFTA WR contains tesamorelin 11.6 mg (equivalent to approximately 11.9 mg of tesamorelin acetate) and the following inactive ingredients: 145 mg hydroxypropyl betadex, 43.5 mg mannitol. Hydrochloric acid and/or sodium hydroxide may be used to adjust the pH. The pH of EGRIFTA WR is between 4.5 and 7.4. After reconstitution with 1.3 mL of Bacteriostatic Water for Injection, USP, resultant concentration is 8 mg/mL and the solution is clear and colorless. Bacteriostatic Water for Injection, USP contains benzyl alcohol as preservative.

The safety and effectiveness of EGRIFTA WR (11.6 mg/vial formulation) has been established based on adequate and well controlled studies with EGRIFTA (1 mg/vial formulation), as well as a demonstration of comparable bioavailability between the 1.28 mg EGRIFTA WR dose (11.6 mg/vial formulation) and the 2 mg EGRIFTA dose (1 mg/vial formulation) [see Clinical Pharmacology (12.3 )] .

Two multicenter, randomized, double-blind, placebo-controlled studies were conducted in HIV-infected patients with lipodystrophy and excess abdominal fat (abdominal lipohypertrophy). Study 1 and Study 2 consisted of a 26-week Main Phase and a 26-week Extension Phase, respectively. Main inclusion criteria were age 18 to 65 years, a waist circumference ≥95 cm (37.4 inches) and a waist-to-hip ratio ≥0.94 for men and ≥94 cm (37.0 inches) and ≥0.88 for women, respectively, and fasting blood glucose (FBG) <150 mg/dL (8.33 mmol/L). Main exclusion criteria included BMI ≤ 20 kg/m ² , type 1 diabetes mellitus, type 2 diabetes mellitus, previous treatment with insulin or with oral hypoglycemic or insulin-sensitizing agents, history of malignancy, and hypopituitarism. Patients were on a stable anti-retroviral regimen for at least 8 weeks prior to randomization. Patients meeting the inclusion/exclusion criteria were randomized in a 2:1 ratio to receive a 2 mg dose of EGRIFTA (1 mg/vial formulation) or placebo subcutaneously daily for 26 weeks. The primary efficacy assessment for each of these studies was the percent change from baseline to Week 26 in visceral adipose tissue (VAT), as assessed by computed tomography (CT) scan at L4-L5 vertebral level. Secondary endpoints included changes from baseline in patient-reported outcomes related to body image, triglycerides, ratio of total cholesterol to HDL cholesterol, IGF-1 levels, and safety parameters. Other endpoints included changes from baseline in waist circumference, abdominal subcutaneous tissue (SAT), trunk fat, and lean body mass. In both studies, EGRIFTA-treated patients completing the 26-week treatment period were re-randomized to blinded therapy with either daily placebo or a 2 mg dose of EGRIFTA (1 mg/vial formulation) for an additional 26-week treatment period (Extension Phase) in order to assess maintenance of VAT reduction and to gather long-term safety data. For inclusion in the Extension Phase studies, subjects must have completed the Main Phase with FBG ≤ 150 mg/dL.

How Supplied

EGRIFTA WR (tesamorelin) for injection is supplied as a white to off-white lyophilized powder in a 11.6 mg single-patient-use vial with a 30 mL multiple-dose bottle of Bacteriostatic Water for Injection, USP, as diluent.

EGRIFTA WR (NDC 62064-381-04) is available in a package comprised of two boxes, containing 4 (four) 11.6 mg single-patient-use vials of EGRIFTA WR in the Medication Box and 1 (one) multiple-dose 30 mL bottles of Bacteriostatic Water for Injection, USP, diluent with a 28-day supply of disposable syringes, needles and alcohol swabs in the Injection Box.

Storage and Handling

Store EGRIFTA WR 11.6 mg vial at room temperature at 20°C to 25°C (68°F to 77°F) in the original box to protect from light; excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Store the Injection box (containing Bacteriostatic Water for Injection, syringes, needles and alcohol swabs) at room temperature at 20°C to 25°C (68°F to 77°F). Do not freeze.

INSTRUCTIONS FOR USE

EGRIFTA WR ^TM
(tesamorelin) for injection
for subcutaneous use

• Your healthcare provider should show you how to mix and inject 11.6 mg vial before you inject it for the first time. Ask your healthcare provider if you have any questions.

Important Information You Need to Know Before Injecting EGRIFTA WR 11.6 mg vial

• For subcutaneous injection only (inject directly under the skin).
• There are two EGRIFTA formulations (EGRIFTA WR and EGRIFTA SV) with different recommended dosages. EGRIFTA WR and EGRIFTA SV are not substitutable.
• The recommended daily dose of EGRIFTA WR is 1.28 mg (0.16 mL).
• One (1) EGRIFTA WR 11.6 mg vial must be mixed with 1.3 mL of the Bacteriostatic Water for Injection to prepare for 7 doses [for 7 consecutive daily injections (Day 1 to Day 7) of treatment].
• Do not share your syringe or needles with other people. You may give other people a serious infection or get a serious infection from them.
• Do not use a syringe or needle more than 1 time.
• If supplies are missing, damaged, or expired; or if you have any questions at any time during the mixing or the injection of EGRIFTA WR, call your pharmacist or toll-free at 1-833-23THERA (1-833-238-4372).

Storing EGRIFTA WR

• Store the Medication Box at room temperature between 68°F to 77°F (20°C to 25°C) and keep the EGRIFTA WR vials out of the light.
• Store the Injection Box at room temperature between 68°F to 77°F (20°C to 25°C).
• Do not freeze or refrigerate EGRIFTA WR after it has been mixed with the Bacteriostatic Water for Injection.
• Keep EGRIFTA WR and all medicines out of the reach of children.

Box Content

Medication Box

Supplies for 28 days:

• 4 single-patient use EGRIFTA WR 11.6 mg vials ( mix only 1 vial per week as per weekly mixing )

Injection Box

Supplies for 28 days:

• 1 multiple-dose, 30 mL bottle of Bacteriostatic Water for Injection (to be used for weekly mixing)
• 4 sterile BD Plastipak ^TM 3 mL Syringes with needle attached (clear cap), for weekly mixing
• 33 sterile BD SafetyGlide ^TM syringes with needle attached (orange cap), for daily injection
• 1 box of 100 alcohol swabs

Weekly Mixing (Day 1)

Getting Started

For Weekly Mixing of EGRIFTA WR, follow steps 1 through 23.

For Daily Injection (Day 1 to Day 7), follow steps 24 through 49.

Step 1: Use a well-lit, clean, and flat surface as a working area.
Step 2: Take out the following: (See Figure B )

• One (1) vial of EGRIFTA WR 11.6 mg
• One (1) 30 mL bottle of Bacteriostatic Water for Injection
• One (1) BD Plastipak ^TM 3 mL Syringe with needle attached (clear cap) for Weekly Mixing
• One (1) alcohol swab
• Sharps disposal container

Step 3: Wash and dry your hands well. (See Figure C )

Step 4: Inspect the compact powder in the EGRIFTA WR vial. It should be white to off-white. (See Figure D )

• Do not use the vial if the powder is discolored or has particles in it. Get a new vial, and call your healthcare provider, pharmacist, or contact toll free at 1-833-23THERA (1-833-238-4372).

Step 5: Check the expiration dates (EXP) on the: (See Figure E )

1) EGRIFTA WR vial label

2) Bacteriostatic Water for Injection bottle

• Do not use if expired.

Step 6: Remove the plastic caps from the vial and the bottle . (See Figure F )

Step 7: Clean the top of both the vial and the bottle with an alcohol swab (See Figure G ). Throw away (discard) the alcohol swab after use.

Preparing to Mix EGRIFTA WR

Step 8: Take a BD Plastipak ^TM 3 mL Syringe with needle attached (clear cap) out of its packaging. (See Figure H )

Step 9: Pull the protective clear needle cap straight off and throw it away (discard) (See Figure I ). Make sure the needle is tightly screwed to the syringe.

• Do not twist the needle cap.

Step 10: Pull down the plunger to reach the 1½ mark (1.5 mL) on the syringe to fill it with air. (See Figure J )

Step 11: Insert the needle straight into the top of the Bacteriostatic Water for Injection bottle. (See Figure K )

Step 12: Turn the bottle and syringe upside down. (See Figure L )

Step 13: Push the plunger all the way up (See Figure M ). Some resistance may be felt.

Step 14: Pull down the plunger slowly to reach the 1½ mark (1.5 mL) on the syringe. A visible air pocket and tiny air bubbles in the syringe are normal. (See Figure N )

Step 15: Turn the bottle right side up and remove the needle. (See Figure O )

Step 16: Place the syringe upright and tap it with your finger to force any large air bubbles to rise to the top. (See Figure P )

Step 17: Push the plunger up slowly to remove 0.2 mL of excess water and air out of the syringe and align the top rim of the plunger to the 1.3 mL mark. Some water should come out of the needle. (See Figure Q )

• If you have less than 1.3 mL, repeat step 10 to step 17 until 1.3 mL of water is in the syringe.

Step 18: Put the Bacteriostatic Water for Injection bottle back in the Injection box for the next Weekly Mixing . (See Figure R )

• Throw away (discard) the Bacteriostatic Water for Injection bottle after 28 days of use. Record the date of first use of the Bacteriostatic Water for Injection bottle as indicated on the back side of the Injection Box. The mixing and injection tracker provided inside the injection box can also be used to record this information.

Mixing EGRIFTA WR

Step 19: Insert the needle straight into the top of the EGRIFTA WR vial . (See Figure S )

Step 20: Push the plunger down until the syringe is completely empty. While keeping the plunger down, remove the needle from the vial. (See Figure T )

Step 21: Throw away (discard) the syringe and needle in the sharps container. (See Figure U )

Step 22: Move the vial in a circle (swirl) to mix all the powder and liquid. (See Figure V )

• Do not shake the vial.

Step 23: Let the vial rest for a few seconds until the layer of foam separates and the solution becomes clear and colorless, with no particles in it. (See Figure W )

• Do not use the vial if after a few seconds the solution looks cloudy, is discolored, or has particles in it. Get another vial, and call your healthcare provider, pharmacist, or contact toll free at 1-833-23THERA (1-833-238-4372).

Daily Injection (DAY 1 TO DAY 7)

Preparing to Inject EGRIFTA WR

Step 24: For daily injection of EGRIFTA WR (step 24 through step 49), you will need: (See Figure X )

• One (1) mixed and clear solution of EGRIFTA WR ( prepared during the Weekly Mixing )
• One (1) BD SafetyGlide ^TM syringe with needle attached (orange cap) for injection
• Two (2) alcohol swabs
• One (1) sterile gauze pad
• One (1) adhesive bandage
• Sharps disposal container

Step 25: Wash and dry your hands well. (See Figure Y )

Step 26: Clean the top of the EGRIFTA WR vial with an alcohol swab (See Figure Z ). Throw away (discard) the alcohol swab after use.

Step 27: Take a BD SafetyGlide ^TM syringe with needle attached (orange cap) out of its packaging. (See Figure AA )

Step 28: Twist the orange needle cap to clearly see the graduated markings on the syringe, if needed. (See Figure AB )

Step 29: Pull the orange needle cap straight off and keep it aside. (See Figure AC )

Do not touch the needle.

Step 30: Insert the needle carefully and straight into the top of the vial to avoid bending the needle. (See Figure AD )

• If you bend the needle, use a new syringe.

Step 31: Turn the vial and syringe upside down. (See Figure AE )

Step 32: Pull down the plunger slowly to reach the 18 mark (0.18 mL) . (See Figure AF )

• If you do not have enough liquid in the syringe, repeat step 30 and step 31 .

Step 33: Turn the vial right side up and remove the needle. (See Figure AG )

Step 34: Place the syringe upright and tap it with your finger to force any air bubbles to rise to the top. (See Figure AH )

Step 35: Hold the plunger rod half-way to carefully adjust the volume in step 36 . (See Figure AI )

Step 36: Adjust the plunger to reach exactly the 16 mark (0.16 mL) by slowly pushing the plunger up to remove air and excess liquid from the syringe (See Figure AJ ). Some resistance may be felt when pushing the plunger.

• No air pockets should be left.

Note: This is your recommended daily dose of EGRIFTA WR: 1.28 mg (0.16 mL).

Step 37: Safely place the orange needle cap on the needle. (See Figure AK )

Step 38: Keep the mixed EGRIFTA WR vial for the next Daily Injections in the Medication Box at room temperature up to 77°F (25°C). (See Figure AL )

Injecting EGRIFTA WR

Step 39: Choose an injection site on the stomach area (abdomen) that is at least 2 inches (5 cm) away from your belly button . (See the green area in Figure AM )

• Do not inject into your belly button, nor on areas with scar tissue, bruises or on any hard bumps from previous injections.
• Rotate the site for each injection. This may help prevent bruising or irritation.

Step 40: Clean the injection site with a new alcohol swab and let it dry. (See Figure AN )

Step 41: Remove the orange needle cap and throw it away (discard). (See Figure AO )

• Do not touch the needle.
• Do not move the plunger.

Step 42: Pinch a fold of skin at your cleaned injection site between your thumb and fingers. (See Figure AP )

Step 43: Insert the needle straight into the skin. (See Figure AQ )

Step 44: Remove your hand from the pinched area of skin, while keeping the needle in the skin. (See Figure AR )

Step 45: Push the plunger all the way down until all the medicine in the syringe has been injected under the skin. (See Figure AS )

Step 46: Pull the needle out. (See Figure AT )

Step 47: Hold the syringe and carefully slide up the white safety needle shield along the needle until you hear a "click". (See Figure AU )

Step 48: Throw away (discard) the syringe with the needle attached into the sharps container. (See Figure AV )

Step 49: If there is bleeding at the injection site, use gauze to apply pressure and apply an adhesive bandage if necessary.

For the next Daily Injection (Day 2 to Day 7) go directly to step 24 of this Instructions for Use.

Throw away (discard) the EGRIFTA WR vial after it has been used for 7 Daily Injections (DAY 1 TO DAY 7).

Disposing of EGRIFTA WR

• Do not recap the needle with the needle cap after you inject EGRIFTA WR.
• Throw away (discard) the EGRIFTA WR vial after it has been used for 7 Daily Injections (DAY 1 TO DAY 7).
• Throw away (discard) the Bacteriostatic Water for Injection bottle after 28 days of use.
• Put your used EGRIFTA WR needles and syringes in an FDA-cleared sharps disposal container right away after use.
• Do not throw away (dispose of) loose needles and syringes in your household trash.
• If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:

- made of a heavy-duty plastic,
- can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
- upright and stable during use,
- leak-resistant, and
- properly labeled to warn of hazardous waste inside the container.

• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDAs website at: https://www.fda.gov/safesharpsdisposal.
• Do not throw away (dispose of) your used sharps disposal container in your household trash unless your community guidelines permit this.
• Do not recycle your used sharps disposal container.
• If another person receives a needle stick with a used needle, that person should be told to contact a healthcare provider right away.
• Keep the sharps container away from children and pets.
• If you have any questions , call your healthcare provider, or you can call toll free at 1-833-23THERA (1-833-238-4372) for more information.

Manufactured by: Theratechnologies Inc., 2015 Peel Street, Suite 1100, Montréal, Québec, Canada H3A 1T8

Revised: March 2025

EGRIFTA WR is a trademark of Theratechnologies Inc.

In vitro, tesamorelin binds and stimulates human GRF receptors with similar potency as the endogenous GRF [see Clinical Pharmacology (12.2 )].

Growth hormone-releasing factor (GHRF), also known as growth hormone-releasing hormone (GHRH), is a hypothalamic peptide that acts on the pituitary somatotroph cells to stimulate the synthesis and pulsatile release of endogenous growth hormone (GH), which is both anabolic and lipolytic. GH exerts its effects by interacting with specific receptors on a variety of target cells, including chondrocytes, osteoblasts, myocytes, hepatocytes, and adipocytes, resulting in a host of pharmacodynamic effects. Some, but not all these effects, are primarily mediated by IGF-1 produced in the liver and in peripheral tissues.