1 INDICATIONS AND USAGE

EGRIFTA® (tesamorelin for injection) is indicated for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy [see Clinical Studies (14)].

2 DOSAGE AND ADMINISTRATION

3 DOSAGE FORMS AND STRENGTHS

EGRIFTA® (tesamorelin for injection) is supplied in a vial containing 2 mg of tesamorelin as a lyophilized powder. The diluent (Sterile Water for Injection, USP 10 mL) is provided in a separate bottle.

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

6 ADVERSE REACTIONS

The most commonly reported adverse reactions are hypersensitivity (e.g., rash, urticaria) reactions due to the effect of GH (e.g., arthralgia, extremity pain, peripheral edema, hyperglycemia, carpal tunnel syndrome), injection site reactions (injection site erythema, pruritis, pain, urticaria, irritation, swelling, hemorrhage).

During the first 26 weeks of treatment (main phase), discontinuations as a result of adverse reactions occurred in 9.6% of patients receiving EGRIFTA® and 6.8% of patients receiving placebo. Apart from patients with hypersensitivity reactions identified during the studies and who were discontinued per protocol (2.2%), the most common reasons for discontinuation of EGRIFTA® treatment were adverse reactions due to the effect of GH (4.2%) and local injection site reactions (4.6%).

During the following 26 weeks of treatment (extension phase), discontinuations as a result of adverse events occurred in 2.4% of patients in the T-T group (patients treated with tesamorelin for Week 0-26 and with tesamorelin for Week 26-52) and 5.2% of patients in the T-P group (patients treated with tesamorelin for Week 0-26 and with placebo for Week 26-52).

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

10 OVERDOSAGE

No data are available on overdosage.

11 DESCRIPTION

EGRIFTA® contains tesamorelin (as the acetate salt), an analog of human growth hormone-releasing factor (GRF). The peptide precursor of tesamorelin acetate is produced synthetically and is comprised of the 44 amino acid sequence of human GRF. Tesamorelin acetate is made by attaching a hexenoyl moiety, a C6 chain with a double bond at position 3, to the tyrosine residue at the N-terminal part of the molecule. The molecular formula of tesamorelin acetate is C221H366N72O67S • x C2H4O2 (x ≈ 7) and its molecular weight (free base) is 5135.9 Daltons. The structural formula of tesamorelin acetate is:

EGRIFTA® is a sterile, white to off-white, preservative-free lyophilized powder for subcutaneous injection. After reconstitution with the supplied diluent (Sterile Water for Injection, USP), a solution of EGRIFTA® is clear and colorless. Each single-use vial of EGRIFTA® contains 2 mg of tesamorelin as the free base (2.2 mg tesamorelin acetate, anhydrous) and the following inactive ingredient: 100 mg mannitol, USP.

12 CLINICAL PHARMACOLOGY

13 NONCLINICAL TOXICOLOGY

14 CLINICAL STUDIES

Two multicenter, randomized, double-blind, placebo-controlled studies were conducted in HIV-infected patients with lipodystrophy and excess abdominal fat (abdominal lipohypertrophy). Both studies (Study 1 and 2) consisted of a 26-week Main Phase and a 26-week Extension Phase. Main inclusion criteria were age 18-65 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/m2, type 1 diabetes, type 2 diabetes, if previously treated 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 2 mg EGRIFTA® 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 (Main Phase) 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 2 mg EGRIFTA® 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.

Main Phase (Baseline to Week 26):

Study 1

This study randomized 412 HIV-infected patients with lipodystrophy and excess abdominal fat to receive either EGRIFTA® (N=273) or placebo (N=137). At baseline for the two groups combined, mean age was 48 years; 86% were male; 75% were white, 14% were Black/African American, and 8% were Hispanic; mean weight was 90 kg; mean BMI was 29 kg/m2; mean waist circumference was 104 cm; mean hip circumference was 100 cm; mean VAT was 176 cm2; mean CD4 cell count was 606 cells/mm3; 69% had undetectable viral load (<50 copies/mL); and 33.7% randomized to EGRIFTA® and 36.6% randomized to placebo had impaired glucose tolerance, while 5.6% randomized to EGRIFTA® and 6.7% randomized to placebo had diet-controlled diabetes mellitus. The twenty-six week completion rate in Study 1 was 80%.

Study 2

This study randomized 404 HIV-infected patients with lipodystrophy and excess abdominal fat to receive either EGRIFTA® (N=270) or placebo (N=126). At baseline for the two groups combined, mean age was 48 years; 84% were male; 77% were white, 12% were Black/African American, and 9% were Hispanic; mean weight was 88 kg; mean BMI was 29 kg/m2; mean waist circumference was 105 cm; mean hip circumference was 100 cm; mean VAT was 189 cm2; mean CD4 cell count was 592 cells/mm3; 83% had undetectable viral load (<50 copies/mL); and 44.1% randomized to EGRIFTA® and 39.7% randomized to placebo had impaired glucose tolerance, while 9.3% randomized to EGRIFTA® and 9.5% randomized to placebo had diet-controlled diabetes mellitus. The twenty-six week completion rate in Study 2 was 74%.

Results for the Main Phases of Studies 1 and 2 are presented in Tables 3 and 4.

Table 3: Changes from Baseline to Week 26 in Visceral Adipose Tissue (cm2) by Treatment Group (Intent-To-Treat Population with Last Observation Carried Forward)

MAIN PHASE (Baseline-Week 26)
	Study 1		Study 2
	EGRIFTA® (N=273)	Placebo (N=137)	EGRIFTA® (N=270)	Placebo (N=126)
Baseline data are expressed as mean (SD); Change refers to least-squares mean (LSM); CI: confidence interval.
* Results derived from the statistical model: Ln(VAT Week 26/VAT Baseline) = Ln(VAT Baseline) + treatment group
Baseline (cm2)	178 (77)	171 (77)	186 (87)	195 (95)
Change (cm2)	-27	4	-21	-0
Mean treatment difference (95% CI)	-31 (-39,-24)		-21 (-29,-12)
Mean change (%)*	-18	2	-14	-2
Mean treatment difference (95% CI)*	-20 (-24, -15)		-12 (-16, -7)

Table 4: Changes from Baseline to Week 26 in IGF-1, IGFBP-3, Weight, and Waist Circumference by Treatment Group (Intent-To-Treat Population with Last Observation Carried Forward)

MAIN PHASE (Baseline-Week 26)
		Study 1		Study 2
		EGRIFTA® (N=273)	Placebo (N=137)	EGRIFTA® (N=270)	Placebo (N=126)
Baseline data are expressed as mean (SD); Change refers to least-squares mean (LSM); CI: confidence interval.
IGF-1 (ng/mL)	Baseline	161 (59)	168 (75)	146 (66)	149 (59)
	Change	107	-15	108	3
	Mean treatment difference (95% CI)	122 (101, 141)		105 (85, 126)
IGFBP-3 (mg/L)	Baseline	3 (1)	3 (1)	3 (1)	3 (1)
	Change	0.4	-0.2	0.8	-0.0
	Mean treatment difference (95% CI)	0.6 (0.5, 0.8)		0.8 (0.5, 1.0)
Weight (kg)	Baseline	90 (14)	90 (14)	89 (14)	87 (16)
	Change	-0.4	0.0	0.5	0.3
	Mean treatment difference (95% CI)	-0.4 (-1.3, 0.5)		0.2 (-0.7, 1.3)
Waist circumference (cm)	Baseline	104 (10)	105 (9)	105 (9)	105 (9)
	Change	-3 (5)	-1 (4)	-2 (5)	-1 (5)
	Mean treatment difference (95% CI)	-2 (-2.8, -0.9)		-1 (-2.5, -0.3)

A subgroup analysis by gender showed that there were no statistical differences in the percent change from baseline in visceral adipose tissue (VAT) and IGF-1 responses, respectively, between males and females.

At Week 26, treatment with EGRIFTA® resulted in a reduction from baseline in mean trunk fat of 1.0 kg in Study 1 and 0.8 kg in Study 2, respectively (compared with an increase of 0.4 kg in Study 1 and of 0.2 kg in Study 2, respectively, in patients receiving placebo). Treatment with EGRIFTA® resulted in an increase from baseline in mean lean body mass of 1.3 kg in Study 1 and of 1.2 kg in Study 2, respectively (compared with a decrease of 0.2 kg in Study 1 and of 0.03 kg in Study 2, respectively, in patients receiving placebo).

On average, there were no adverse effects of EGRIFTA® on lipids or subcutaneous adipose tissue (SAT). EGRIFTA® did not adversely alter antiretroviral effectiveness, such as mean circulating levels of CD4 counts or HIV-1 RNA (viral load).

Patient Reported Outcomes

Patients rated the degree of distress associated with their belly appearance on a 9-point rating scale that was then transformed to a score from 0 (extremely upsetting and distressing) to 100 (extremely encouraging). A score of 50 indicated neutral (no feeling either way). A positive change from baseline score indicated improvement, i.e., less distress.

The cumulative distribution of response (change from baseline to 26 weeks) is shown in Figure 1 for both treatment groups. A curve shifted to the right on this scale indicates a greater percentage of patients reporting improvement.

Figure 1. Cumulative Distribution of Response for Belly Appearance Distress

Extension Phase (Weeks 26-52):

In the double-blind Extension Phase, patients on EGRIFTA® completing the 26-week Main Phase were re-randomized to receive 2 mg EGRIFTA® or placebo.

Study 1

This study re-randomized 207 HIV-infected patients with lipodystrophy who completed EGRIFTA® treatment in the Main Phase to receive either EGRIFTA® (N=154) or placebo (N=50) for an additional 26-week duration (3:1 randomization ratio). At baseline (Week 26) for the two groups combined, mean age was 48 years; 88% were male; 78% were white, 12% were Black/African American, and 8% were Hispanic; mean weight was 90 kg; mean BMI was 29 kg/m2; mean waist circumference was 102 cm; mean hip circumference was 100 cm; mean VAT was 145 cm2; mean CD4 cell count was 639 cells/mm3; 68% had undetectable viral load (<50 copies/mL); and for those EGRIFTA®-treated patients completing the 26-week treatment period that were re-randomized to EGRIFTA® (T-T group) or re-randomized to placebo, 36.6% and 32.0%, respectively, had impaired glucose tolerance, while 2.0% re-randomized to EGRIFTA® and 6.0% re-randomized to placebo had diet-controlled diabetes mellitus. The completion rate for patients randomized into the extension phase of Study 1 was 83%.

Study 2

This study re-randomized 177 HIV-infected patients with lipodystrophy who completed EGRIFTA® treatment in the Main Phase to receive either EGRIFTA® (N=92) or placebo (N=85) for an additional 26-week duration (1:1 randomization ratio). At baseline (Week 26) for the two groups combined, mean age was 48 years; 90% were male; 84% were white, 9% were Black/African American, and 7% were Hispanic; mean weight was 89 kg; mean BMI was 28 kg/m2; mean waist circumference was 105 cm; mean hip circumference was 100 cm; mean VAT was 172 cm2; mean CD4 cell count was 579 cells/mm3; 82% had undetectable viral load (<50 copies/mL); and for those EGRIFTA®-treated patients completing the 26-week treatment period that were re-randomized to EGRIFTA® (T-T group) or re-randomized to placebo, 48.9% and 50.6%, respectively, had impaired glucose tolerance, while 4.3% re-randomized to EGRIFTA® and 12.9% re-randomized to placebo had diet-controlled diabetes mellitus. The completion rate for patients randomized into the extension phase of Study 2 was 81%.

Results for the Extension Phases of Studies 1 and 2 are presented in Tables 5 and 6.

Table 5: Changes from Week 26 Baseline to Week 52 in Visceral Adipose Tissue (cm2) by Treatment Group (Intent-To-Treat Population with Last Observation Carried Forward)

EXTENSION PHASE (Week 26-52)
	Study 1		Study 2
	T-T* (Week 26-52) (N=154)	T-P† (Week 26-52) (N=50)	T-T* (Week 26-52) (N=92)	T-P† (Week 26-52) (N=85)
Week 26 baseline data are expressed as mean (SD). Change refers to least-squares mean (LSM); CI: confidence interval.
* T-T = tesamorelin for Weeks 0-26 and tesamorelin for Weeks 26-52 † T-P = tesamorelin for Weeks 0-26 and placebo for Weeks 26-52 ‡ Results derived from the statistical model: Ln(VAT Week 52/Week 26) = Ln(Week 26 VAT) + treatment group
Week 26 (cm2)	145 (72)	144 (72)	166 (89)	177 (88)
Change (cm2)	3	25	-11	24
Mean treatment difference (95% CI)	-22 (-34, -10)		-35 (-48, -22)
Mean change (%)‡	0	22	-5	16
Mean treatment difference (95% CI)‡	-17 (-24, -10)		-18 (-24, -11)

Figure 2. shows the percent change in VAT from baseline (Week 0) over time until 52 weeks in completer patients.

Figure 2. Percent Change from Baseline in VAT over Time

Data in Figure 2 are expressed as mean values. T-T (tesamorelin to tesamorelin) refers to the group of patients who received tesamorelin for Weeks 0-26 and were re-randomized to tesamorelin for Weeks 26-52. T-P (tesamorelin to placebo) refers to the group of patients who received tesamorelin for Weeks 0-26 and were re-randomized to placebo for Weeks 26-52. P-T (placebo to tesamorelin) refers to the group of patients who received placebo for Weeks 0-26 and were switched to tesamorelin (treated open label) for Weeks 26-52.

Table 6: Changes from Week 26 Baseline to Week 52 in IGF-1, IGFBP-3, Weight, and Waist Circumference by Treatment Group (Intent-To-Treat Population with Last Observation Carried Forward)

EXTENSION PHASE (Weeks 26-52)
		Study 1		Study 2
		T-T* (Week 26-52) (N=154)	T-P† (Week 26-52) (N=50)	T-T* (Week 26-52) (N=92)	T-P† (Week 26-52) (N=85)
Week 26 baseline data are expressed as mean (SD); Change refers to least-squares mean (LSM); CI: confidence interval.
* T-T = tesamorelin for Week 0-26 and tesamorelin for Week 26-52 † T-P = tesamorelin for Week 0-26 and placebo for Week 26-52
IGF-1 (ng/mL)	Week 26	291 (124)	281 (105)	280 (134)	269 (110)
	Change	-59	-137	-25	-135
	Mean treatment difference (95% CI)	78 (50, 106)		110 (87, 134)
IGFBP-3 (mg/L)	Week 26	3 (1)	3 (1)	3 (1)	3 (1)
	Change	-0.2	-0.5	-0.3	-0.9
	Mean treatment difference (95% CI)	0.3 (-0.0, 0.6)		0.6 (0.3, 0.9)
Weight (kg)	Week 26	89 (14)	92 (17)	89 (13)	90 (14)
	Change	0.2	0.6	-0.5	0.1
	Mean treatment difference (95% CI)	-0.4 (-2, 1)		-0.6 (-2, 1)
Waist circumference (cm)	Week 26	101 (10)	102 (12)	101 (9)	103 (11)
	Change	-0.2	2.4	-1.1	0.2
	Mean treatment difference (95% CI)	-2.6 (-4, -1)		-1.3 (-2, 0)

Patients treated with EGRIFTA® for 52 weeks (T-T group) showed no change between Weeks 26 and 52 in mean trunk fat (increase of 0.1 kg in Study 1 and decrease of 0.5 kg in Study 2, respectively, compared with an increase of 1.4 kg in patients in the T-P group in Study 1 and an increase of 1.09 kg in Study 2, respectively) nor was there a change from Week 26 baseline in mean lean body mass (decrease of 0.1 kg in Study 1 and increase of 0.1 kg in Study 2, respectively, compared with a decrease of 1.8 kg in patients in the T-P group in Study 1 and a decrease of 1.7 kg in Study 2, respectively).

There was no adverse effect of EGRIFTA® on lipids or subcutaneous adipose tissue (SAT). EGRIFTA® did not adversely alter antiretroviral effectiveness, such as mean circulating levels of CD4 counts or HIV-1 RNA (viral load).

16 HOW SUPPLIED/STORAGE AND HANDLING

EGRIFTA® (tesamorelin for injection) is supplied as a sterile, white to off-white lyophilized powder. Each single-use vial of EGRIFTA® contains 2 mg of tesamorelin as the free base (2.2 mg tesamorelin acetate, anhydrous) and the following inactive ingredient: 100 mg mannitol, USP.

EGRIFTA® is available in a package comprised of two boxes. One box contains 30 vials of EGRIFTA® and a second box contains 30 single-use 10 mL bottles of reconstitution diluent (Sterile Water for Injection, USP), disposable syringes, and needles sufficient for a 30 day supply.

After reconstitution with Sterile Water for Injection, USP the reconstituted solution concentration is 1 mg/mL and should be injected immediately.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Patient Information and Patient Instructions for Use).

• Fluid retention (5.3) – Advise patients that treatment with EGRIFTA® may cause symptoms consistent with fluid retention, including edema, arthralgia, and carpal tunnel syndrome. These reactions are either transient or resolve with discontinuation of treatment.
• Hypersensitivity Reactions (5.5) – Advise patients that hypersensitivity reactions (e.g., rash, urticaria) may occur during treatment with EGRIFTA®. Advise patients to seek prompt medical attention and to immediately discontinue treatment with EGRIFTA®.
• Injection Site Reactions (5.6) – Advise patients of possible injection site reactions, including injection site erythema, pruritus, pain, irritation, and bruising. To reduce the incidence of injection site reactions, advise patients to rotate the site of injection.
• Counsel patients that they should never share an EGRIFTA® syringe with another person, even if the needle is changed. Sharing of syringes or needles between patients may pose a risk of transmission of infection.

EGRIFTA® is a registered trademark of Theratechnologies Inc.

Distributed by: EMD Serono, Inc., Rockland, MA 02370, USA

Date: 01/2013

Patient Information

EGRIFTA® (eh-GRIF-tuh)

(tesamorelin for injection) for subcutaneous use

Read the Patient Information that comes with EGRIFTA® before you start to take it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is EGRIFTA®?

• EGRIFTA® is an injectable prescription medicine to reduce the excess in abdominal fat in HIV-infected patients with lipodystrophy. EGRIFTA® contains a growth hormone-releasing factor (GRF).
• The impact and safety of EGRIFTA® on cardiovascular health has not been studied.
• EGRIFTA® is not indicated for weight loss management.
• It is not known whether taking EGRIFTA® helps improve compliance with anti-retroviral medications.
• It is not known if EGRIFTA® is safe and effective in children. EGRIFTA® is not recommended to be used in children.

Who should not use EGRIFTA®?

Do not use EGRIFTA® if you:

• have pituitary gland tumor, pituitary gland surgery or other problems related to your pituitary gland
• have active cancer (either newly diagnosed or recurrent) or are receiving treatment for cancer.
• are allergic to tesamorelin or any of the ingredients in EGRIFTA®. See the end of this leaflet for a complete list of ingredients in EGRIFTA®
• are pregnant or become pregnant. If you become pregnant, stop using EGRIFTA® and talk with your healthcare provider. See "What should I tell my healthcare provider before using EGRIFTA®?"

What should I tell my healthcare provider before using EGRIFTA®?

Before using EGRIFTA®, tell your healthcare provider if you:

• have or have had cancer
• have diabetes
• are breastfeeding or plan to breastfeed. It is not known if EGRIFTA® passes into your breast milk. The Centers for Disease Control and Prevention (CDC) recommends that HIV-infected mothers not breastfeed to avoid the risk of passing HIV infection to your baby. Talk with your healthcare provider about the best way to feed your baby if you are taking EGRIFTA®
• have kidney or liver problems
• have any other medical condition.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. EGRIFTA® may affect the way other medicines work, and other medicines may affect how EGRIFTA® works.

Know the medicines you take. Keep a list with you to show your healthcare provider and pharmacist when you get a new medicine.

How should I use EGRIFTA®?

• Read the detailed "Instructions for Use" that comes with EGRIFTA® before you start using EGRIFTA®. Your healthcare provider will show you how to inject EGRIFTA®.
• Use EGRIFTA® exactly as prescribed by your healthcare provider.
• Inject EGRIFTA® under the skin (subcutaneously) of your stomach area (abdomen).
• Change (rotate) the injection site on your stomach area (abdomen) with each dose. Do not inject EGRIFTA® into scar tissue, bruises or your navel.
• Do not share needles or syringes with other people. Sharing of needles can result in the transmission of infectious diseases, such as HIV.

What are the possible side effects of EGRIFTA®?

EGRIFTA® may cause serious side effects including:

• Serious allergic reaction. Some people taking EGRIFTA® may have an allergic reaction.

  Stop using EGRIFTA® and get emergency help right away if you have any of the following symptoms:

  a rash over your body hives swelling of your face or throat

  shortness of breath or trouble breathing fast heartbeat feeling of faintness or fainting

• Swelling (fluid retention). EGRIFTA® can cause swelling in some parts of your body. Call your healthcare provider if you have an increase in joint pain, or pain or numbness in your hands or wrist (carpal tunnel syndrome).
• Increase in glucose (blood sugar) intolerance and diabetes. Your healthcare provider will measure your blood sugar periodically.
• Injection site reactions. Change (rotate) your injection site to help lower your risk for injection site reactions. Call your healthcare provider for medical advice if you have the following symptoms around the area of the injection site:

  redness itching pain irritation

  bleeding rash swelling

The most common side effects of EGRIFTA® include:

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of EGRIFTA®. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. To report side effects, contact EMD Serono toll-free at 1-800-283-8088 ext. 5563. You may report side effects to FDA at 1-800-FDA-1088.

How do I store EGRIFTA®?

• EGRIFTA® has two boxes dispensed by the pharmacy
  • Store the Medication Box of EGRIFTA® vials in the refrigerator between 2°C and 8°C (36°F and 46°F) until the expiration date, or at or below 25°C (77°F) for 3 months or until the expiration date, whichever occurs first.
  • Store the box of Sterile Water for Injection, syringes and needles at room temperature between 20ºC to 25ºC (68°F to 77°F).
• Keep EGRIFTA® vials in Medication Box away from light.
• Do not freeze.
• Do not use EGRIFTA® after the expiration date printed on the carton and vial labels.
• After mixing, use EGRIFTA® right away and throw away any unused EGRIFTA®. Do not store mixed EGRIFTA®. Also, throw away the used bottle of Sterile Water for Injection.

Keep EGRIFTA® and all medicines out of the reach of children.

General information about the safe and effective use of EGRIFTA®

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use EGRIFTA® for a condition for which it was not prescribed. Do not give EGRIFTA® to other people, even if they have the same symptoms you have. It may harm them.

Do not share your EGRIFTA® syringe with another person, even if the needle is changed. Do not share your EGRIFTA® needles with another person.

This Patient Information leaflet summarizes the most important information about EGRIFTA®. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about EGRIFTA® that is written for healthcare professionals.

For more information about EGRIFTA®, go to www.EGRIFTA.com or contact the AXIS Center toll-free at 1-877-714-2947.

What are the ingredients in EGRIFTA®?

Active ingredient: tesamorelin

Inactive ingredients: mannitol and Sterile Water for Injection

EGRIFTA® is a registered trademark of Theratechnologies Inc.

Distributed by: EMD Serono, Inc., Rockland, MA 02370, USA

Date: 01/2013

Patient Instructions for Use

EGRIFTA® (eh-GRIF-tuh)

(tesamorelin for injection) for subcutaneous use

Be sure that you read, understand, and follow these Patient Instructions for Use before using EGRIFTA®. Your healthcare provider should show you how to mix and inject EGRIFTA® before you inject it for the first time. Ask your healthcare provider if you have any questions.

Keep this leaflet in case you need to look at it again later.

Important information for use of EGRIFTA®

• After mixing EGRIFTA® with Sterile Water for Injection, it should look clear and colorless, with no particles in it. Do not use EGRIFTA® if it looks cloudy, discolored, or if you see particles in it. Talk to your healthcare provider if you have any questions.
• Do not use EGRIFTA® after the date on the Medication Box and EGRIFTA® vial.
• Do not use a syringe or needle more than 1 time.
• Do not share your EGRIFTA® needles with another person. Sharing of needles can result in the transmission of infectious diseases, such as HIV. Do not share your EGRIFTA® syringe with another person, even if the needle is changed.
• If you are missing any supplies from your Medication Box or Injection Box, or if anything looks damaged call your pharmacist or contact the AXIS Center toll-free at 1-877-714-2947 right away.

Preparing for your EGRIFTA® injection

Step 1: Find a well-lit, clean, and flat surface, such as a table.

Step 2: Gather your supplies:

• Medication Box that contains 30 EGRIFTA® powder vials
• Injection Box that contains the following:

  a)

  30 10-mL bottles of Sterile Water for Injection, used for mixing

  b)

  30 sterile 3-mL syringes with sterile needle already attached (BD 3 mL Syringe)

  c)

  30 individual ½" 27-gauge injection needles (BD Eclipse™ Injection Needle)

• Other Supplies Needed
  • Alcohol pads
  • Sterile gauze
  • A "sharps container" or a puncture resistant container for throwing away needles after you are done with them. The container should be made from hard plastic or metal. Make sure it has a lid. You can also put used syringes or empty vials of medicine in the container.

Material included in Injection Box (a, b, c) and Medication Box (d):

Step 3: Take out the following from your Injection Box:

• A Sterile Water for Injection bottle (Figure A, a)
• A syringe with needle already attached (Figure A, b)
• A ½" 27-gauge injection needle with pink needle shield (Figure A, c)

Step 4: Take one EGRIFTA® vial (Figure A, d) from the Medication Box. Put the box with the remaining vials back in the refrigerator right away.

Step 5: Prepare to use your supplies:

• Wash your hands with soap and water. Dry your hands with a clean towel.
• Take off the plastic caps from the vials of EGRIFTA® and Sterile Water bottle.
• Clean the rubber stopper on top of the vial of EGRIFTA® and Sterile Water bottle with an alcohol swab.

How to mix EGRIFTA®

Step 1: Pick up the syringe with needle attached (Figure A, b), remove the protective cap and insert the needle through the rubber stopper of the bottle of Sterile Water (Figure A, a; see Figure B for illustration). Turn both upside down, and pull back the plunger until the liquid reaches the 2.1 mL mark on the syringe. (See Figure C)

Figure B	Figure C

Step 2: Take the syringe with needle attached out of the Sterile Water bottle and insert the needle into the EGRIFTA® vial. Push the plunger in slowly on a slight angle so water goes down the inside wall of the EGRIFTA® vial instead of directly onto the powder to avoid foaming. (See Figure D)

Figure D

Step 3: While keeping the syringe with needle attached in the vial and the vial upright, roll the vial gently in your hands for 30 seconds, until the Sterile Water and EGRIFTA® powder are mixed well. Do not shake the vial. (See Figure E)

Figure E

Step 4: Still keeping the syringe with needle attached in the vial, turn both until the syringe is straight up. Pull down on the syringe until you see just the tip of the needle going through the rubber stopper, then pull back on the plunger until all the liquid inside the vial goes into the syringe. The level of medicine in the syringe should be around the 2.1 mL syringe mark. (See Figure F)

Figure F

Step 5: Take the needle out of the vial. (See Figure G)

Figure G

Step 6: Place the needle cap on its side against a clean flat surface. Without touching the needle, hold the syringe and slide the needle carefully into the protective cap (See Figure H). Push the cap all the way or until it snaps shut (See Figure I). Do not touch the cap until it covers the needle completely.

Figure H

Figure I

Step 7: With the cap on the needle, remove the needle by holding the syringe firmly and twisting the cap counterclockwise (to the left). (See Figure J)

Figure J

Step 8: Place the injection needle (Figure A, c), with its white protective cap in place, onto the syringe. Hold the syringe firmly and twist the cap clockwise (to the right) until it closes securely. (See Figure K)

Figure K

Where do I inject EGRIFTA®?

You should inject EGRIFTA® into the skin on your stomach (abdomen). (See Figure L)

• Pick an injection site that is around your belly button to the left or right.
• Stay away from any area with scar tissue, bruises, reddening, infection, or irritation.
• Avoid areas with any hard bumps from previous injections.
• Change your injection site from one day to the next. This may help prevent bruising or irritation. You may want to keep a note of the date and location of each daily injection to help you remember.

Figure L

How to inject EGRIFTA®

• Pick up the syringe and pull the cap straight off the injection needle. Do not twist it. (See Figure M)

Figure M

• Tap the syringe gently with your finger to force any air bubbles to rise to the top. Press the plunger to push bubbles out. (See Figure N)

Figure N

• Clean the injection site you have selected with an alcohol swab and let it dry. Hold the syringe in one hand. Use your other hand to hold a cleaned fold of skin for your injection. Hold the skin between your thumb and fingers. (See Figure O)

Figure O

• Hold the syringe at a right angle to the skin, like a dart. Push the injection needle into the skin with a quick motion. Most of the needle should go beneath the skin surface. (See Figure P)

Figure P

• Remove your hand from the pinched area of skin after the needle goes in. Make sure the needle stays in the skin. (See Figure Q)

Figure Q

• Slowly push the plunger all the way down until all of the medicine in the syringe has been injected under the skin.
• Pull the injection needle out of your skin when the syringe is empty:
  • Be careful to pull it out at the same angle you put it in
  • Flip back the pink needle shield until it snaps, covering the injection needle completely. Keep pressing until you hear a click, that means the injection needle is protected. (See Figure R)

Figure R

• Use a piece of sterile gauze to rub the injection site clean. If there is bleeding, apply pressure to the injection site with gauze for 30 seconds. If bleeding continues, apply a bandage to the site.

How should I dispose of the used syringes, needles, bottles and vials?

• If you accidentally prick another person with a used needle, that person should be informed to contact a healthcare provider right away about the accident.
• Never reuse or recycle needles or syringes.
• Never throw used needles, syringes, or the sharps container into the trash.
• Throw away used syringes, needles, EGRIFTA® vials and Sterile Water for Injection bottle in a puncture-proof container, sharps container, or a hard container like a coffee can.
• Speak to your pharmacist or other healthcare provider about the proper disposal of the sharps container and all other used materials. There may be local or state laws about how to throw away used needles and syringes.
• Keep the sharps container away from children and pets.

How do I store EGRIFTA®?

• EGRIFTA® has two boxes dispensed by the pharmacy
  • Store the Medication Box of EGRIFTA® vials in the refrigerator between 2°C and 8°C (36°F and 46°F) until the expiration date, or at or below 25°C (77°F) for 3 months or until the expiration date, whichever occurs first.
  • Store the Injection Box of Sterile Water for Injection, syringes and needles at room temperature between 20ºC to 25ºC (68°F to 77°F).
• Keep EGRIFTA® vials away from light.
• Do not freeze.
• After mixing, use EGRIFTA® right away and throw away any unused EGRIFTA®. Do not store mixed EGRIFTA®. Also, throw away the used bottle of Sterile Water for Injection.
• Do not use EGRIFTA® after the expiration date printed on the Medication Box and vial labels.

Keep EGRIFTA® and all medicines out of the reach of children.

EGRIFTA® is a registered trademark of Theratechnologies Inc.

Distributed by: EMD Serono, Inc., Rockland, MA 02370, USA

Date: 01/2013

PACKAGE LABEL PRINCIPAL DISPLAY PANEL