tesamorelin 2 MG Injection

INDICATIONS AND USAGE EGRIFTA SV 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 SV has not been established. Consider risk/benefit of continuation of treatment in patients who have not had a reduction in visceral adipose tissue. EGRIFTA SV 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 SV. EGRIFTA SV is a growth hormone-releasing factor (GHRF) analog indicated for the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy. ( 1 ) Limitations of use: Long-term cardiovascular safety of EGRIFTA SV has not been established. ( 1 ) Not indicated for weight loss management. ( 1 ) There are no data to support improved compliance with anti-retroviral therapies in HIV-positive patients taking EGRIFTA SV. ( 1 )

DOSAGE AND ADMINISTRATION 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 ) 2.1 Recommended Dosage and Administration Instructions There are two EGRIFTA formulations (EGRIFTA WR and EGRIFTA SV) with different recommended dosages. 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. The dosage and administration recommendations in this prescribing information only apply to EGRIFTA WR (tesamorelin) for injection 11.6 mg per vial formulation. For dosage and administration recommendations for tesamorelin for injection 2 mg per vial formulation, see the EGRIFTA SV prescribing information. The recommended dosage of EGRIFTA WR is 1.28 mg subcutaneously once daily. Inject EGRIFTA WR into the abdomen. Rotate injection sites to different areas of the abdomen [see Warnings and Precautions ( 5.6 )]. Do not inject into scar tissue, bruises or the navel. 2.2 Reconstitution Procedure Instruct patients to read the Instructions for Use enclosed in the EGRIFTA WR Injection Box. Use only the diluent provided, Bacteriostatic Water for Injection, to reconstitute EGRIFTA WR. Reconstitute 1 vial of EGRIFTA WR lyophilized powder with 1.3 mL of diluent (8 mg per mL). Move the vial in a circle (swirl) to mix all the powder and liquid. Do not shake. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. EGRIFTA WR is a clear, colorless solution. Do not use if solid particles appear or if the solution is cloudy or colored. One reconstituted EGRIFTA WR vial provides daily doses for 7 consecutive days. One dose of EGRIFTA WR is 1.28 mg in 0.16 mL of the reconstituted solution. Store reconstituted EGRIFTA WR at room temperature at 20°C to 25°C (68°F to 77°F). Discard unused solution of EGRIFTA WR 7 days after mixing. Do not freeze.

WARNINGS AND PRECAUTIONS 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 ) 5.1 Increased Risk of Neoplasms New Malignancy Carefully consider the decision to start treatment with EGRIFTA WR based on the increased background risk of malignancies in HIV-positive patients. Active Malignancy EGRIFTA WR induces the release of endogenous growth hormone (GH), a known growth factor. Do not treat patients with active malignancy with EGRIFTA WR [see Contraindications ( 4 )] . History of Malignancy For patients with a history of non-malignant neoplasms, initiate EGRIFTA WR therapy after careful evaluation of the potential benefit of treatment. For patients with a history of treated and stable malignancies, initiate EGRIFTA WR therapy only after careful evaluation of the potential benefit of treatment relative to the risk of re-activation of the underlying malignancy. Discontinue EGRIFTA WR if there is any evidence of recurrent malignancy. 5.2 Elevated IGF-1 Levels 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 EGRIFTA WR in patients with persistent elevations of IGF-1 levels (e.g., >3 SDS), particularly if the efficacy response is not robust. Among patients who received EGRIFTA for 26 weeks, 47% had IGF-1 levels greater than 2 standard deviation scores (SDS), and 36% had SDS >3, with this effect seen as early as 13 weeks of treatment. Among those patients who remained on EGRIFTA for a total of 52 weeks, at the end of treatment, 34% had IGF-1 SDS >2 and 23% had IGF-1 SDS >3. 5.3 Fluid Retention Fluid retention may occur during EGRIFTA WR therapy and is thought to be related to the induction of GH secretion. This manifests as increased tissue turgor and musculoskeletal discomfort resulting in adverse reactions (e.g. edema, arthralgia, and carpal tunnel syndrome) which are either transient or resolve with discontinuation of treatment. 5.4 Glucose Intolerance or Diabetes Mellitus EGRIFTA WR treatment can result in glucose intolerance. During clinical trials, the percentages of patients with elevated HbA 1c (≥ 6.5%) from baseline to Week 26 were 5% and 1% in the EGRIFTA and placebo groups, respectively. An increased risk of developing diabetes with EGRIFTA (HbA 1c level ≥ 6.5%) relative to placebo was observed [intent-to-treat hazard odds ratio of 3.3 (CI 1.4, 9.6)]. Evaluate glucose status prior to initiating EGRIFTA WR. Monitor all patients treated with EGRIFTA WR periodically to diagnose those who develop impaired glucose tolerance or diabetes. If patients treated with EGRIFTA WR develop glucose intolerance or diabetes, consider discontinuing EGRIFTA WR in patients who do not show a clear efficacy response. EGRIFTA WR increases IGF-1, monitor patients with diabetes who are receiving treatment with TESAMORELIN for injection at regular intervals for potential development or worsening of retinopathy. 5.5 Hypersensitivity Reactions Hypersensitivity reactions occurred in 4% of patients treated with EGRIFTA in clinical trials. Reactions included pruritus, erythema, flushing, urticaria, and rash. In cases of suspected hypersensitivity reactions, advise patients to seek prompt medical attention and immediately discontinue treatment with EGRIFTA WR. 5.6 Injection Site Reactions EGRIFTA WR treatment may cause injection site reactions, including injection site erythema, pruritus, pain, irritation, and bruising. The incidence of injection site reactions was 25% in EGRIFTA treated patients and 14% in placebo-treated patients during the first 26 weeks of treatment in clinical trials. Rotate injection sites to different areas of the abdomen to decrease injection site reactions [see Dosage and Administration ( 2.1 )]. 5.7 Increased Mortality in Patients with Acute Critical Illness Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of growth hormone. EGRIFTA WR is a growth hormone-releasing hormone (GHRH) and since it stimulates growth hormone production, consider discontinuing EGRIFTA WR in critically ill patients.

CONTRAINDICATIONS EGRIFTA SV 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 SV ( 4 ) Pregnancy ( 4 ) EGRIFTA SV is contraindicated in: Patients with disruption of the hypothalamic-pituitary axis due to hypophysectomy, hypopituitarism, pituitary tumor/surgery, head irradiation or head trauma. Patients with active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy [see Warnings and Precautions ( 5.1 )] . Patients with known hypersensitivity to tesamorelin or the excipients in EGRIFTA SV [see Warnings and Precautions ( 5.5 )]. Pregnant women because modifying visceral adipose tissue offers no benefit in a pregnant woman and could result in fetal harm [see Use in Specific Populations ( 8.1 )].

Mechanism of Action 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.