EGRIFTA®

Important Risk Information and Indication for EGRIFTA®

• Disruption of the hypothalamic-pituitary axis due to hypophysectomy, hypopituitarism or pituitary tumor/surgery, head irradiation or head trauma
• Active malignancy (either newly diagnosed or recurrent). Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with EGRIFTA®
• Known hypersensitivity to tesamorelin and/or mannitol
• Women who are pregnant; if pregnancy occurs, discontinue EGRIFTA® therapy

Warnings and Precautions

• Neoplasms: For patients with a history of non-malignant neoplasms, EGRIFTA® therapy should be initiated after careful evaluation of the potential benefit of treatment. For patients with a history of treated and stable malignancies, EGRIFTA® therapy should be initiated only after careful evaluation of the potential benefit of treatment relative to the risk of re-activation of the underlying malignancy. In addition, the decision to start treatment with EGRIFTA® should be considered carefully based on the increased background risk of malignancies in HIV-positive patients
• Elevated IGF-1: EGRIFTA® stimulates GH production and increases serum IGF-1. Given that IGF-1 is a growth factor and the effect of prolonged elevations in IGF-1 levels on the development or progression of malignancies is unknown, IGF-1 levels should be monitored closely during EGRIFTA® therapy. Careful consideration should be given to discontinuing EGRIFTA® in patients with persistent elevations of IGF-1 levels (eg, >3 SDS), particularly if the efficacy response is not robust (eg, based on visceral adipose tissue changes measured by waist circumference or CT scan). During the clinical trials, patients were monitored every three months. Among patients who received EGRIFTA® for 26 weeks, 47.4% had IGF-1 levels greater than 2 standard deviation scores (SDS), and 35.6% 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 33.7% had IGF-1 SDS >2 and 22.6% had IGF-1 SDS >3
• Fluid Retention: Fluid retention may occur during EGRIFTA® therapy and is thought to be related to the induction of GH secretion. It manifests as increased tissue turgor and musculoskeletal discomfort resulting in a variety of adverse reactions (eg, edema, arthralgia, carpal tunnel syndrome) which are either transient or resolve with discontinuation of treatment
• Glucose Intolerance: EGRIFTA® treatment may result in glucose intolerance. Patients treated with EGRIFTA® are at an increased risk of developing diabetes (HbA1c ≥ 6.5%). In clinical trials at week 26, a greater percentage of patients had elevated HbA1c (≥6.5%) in the EGRIFTA® group than in the placebo group (4.5% vs 1.3%). Glucose status should be carefully evaluated prior to initiating EGRIFTA® treatment and monitored periodically for changes in glucose metabolism to diagnose those who develop impaired glucose tolerance or diabetes. Caution should be exercised in treating patients with EGRIFTA® if they develop these conditions and discontinuation of treatment should be considered in patients who do not show a clear efficacy response as judged by the degree of reduction in visceral adipose tissue by waist circumference or CT scan measurements. Since EGRIFTA® increases IGF-1, patients with diabetes who are receiving ongoing treatment with EGRIFTA® should be monitored at regular intervals for potential development or worsening of retinopathy
• Hypersensitivity Reactions: Hypersensitivity reactions may occur in patients treated with EGRIFTA®. Hypersensitivity reactions occurred in 3.6% of patients with HIV-associated lipodystrophy treated with EGRIFTA® in the Phase 3 clinical trials. These reactions included pruritis, erythema, flushing, urticaria, and other rash. In cases of suspected hypersensitivity reactions, patients should be advised to seek prompt medical attention and treatment with EGRIFTA® should be discontinued immediately
• Injection Site Reactions: EGRIFTA® treatment may cause injection site reactions, including injection site erythema, pruritus, pain, irritation, and bruising. The incidence of injection site reactions was 24.5% in EGRIFTA®-treated patients and 14.4% in placebo-treated patients during the first 26 weeks of treatment in the Phase III clinical trials. For patients who continued EGRIFTA® for an additional 26 weeks, the incidence of injection site reactions was 6.1%. In order to reduce the incidence of injection site reactions, it is recommended to rotate the site of injection to different areas of the abdomen
• 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® has not been studied in patients with acute critical illness. Since EGRIFTA® stimulates growth hormone production, careful consideration should be given to discontinuing EGRIFTA® in critically ill patients

Drug Interactions

• Cytochrome P450-Metabolized Drugs: Co-administration of EGRIFTA® with simvastatin, a sensitive CYP3A substrate, showed that EGRIFTA® had no significant impact on the pharmacokinetic profiles of simvastatin in healthy subjects. Because tesamorelin stimulates GH production, careful monitoring is advisable when EGRIFTA® is administered in combination with other drugs known to be metabolized by CYP450 liver enzymes

Immunogenicity

• Antibody formation may occur with the use of therapeutic peptide products. Anti-tesamorelin IgG antibodies were detected in approximately half of patients treated with EGRIFTA® and generally disappeared over time after discontinuation of treatment. Antibodies did not appear to impact the efficacy of EGRIFTA®

Use in Specific Populations

• Nursing Mothers: Because of both the potential for HIV-1 infection transmission and serious adverse reactions in nursing infants, mothers receiving EGRIFTA® should be instructed not to human milk-feed
• Pediatric Use: Safety and effectiveness in pediatric patients have not been established. EGRIFTA® should not be used in children with open epiphyses, among whom excess GH and IGF-1 may result in linear growth acceleration and excessive growth
• Geriatric Use: There is no information on the use of EGRIFTA® in patients greater than 65 years of age with HIV and lipodystrophy
• Renal and Hepatic Impairment: Safety, efficacy, and pharmacokinetics of EGRIFTA® in patients with renal or hepatic impairment have not been established

Adverse Reactions

• During the initial 26 weeks of the study period, discontinuation as a result of adverse reactions occurred in 9.6% of patients receiving EGRIFTA® and 6.8% of patients receiving placebo. During the 26- to 52-week extension phase, discontinuation due to adverse reactions in the group receiving EGRIFTA® for the full 52 weeks was 2.4%

Indication and Usage
EGRIFTA® is indicated for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy

Limitations of use:

• Since the long-term cardiovascular safety and potential long-term cardiovascular benefit of EGRIFTA® treatment have not been studied and are not known, careful consideration should be given whether to continue EGRIFTA® treatment in patients who do not show a clear efficacy response as judged by the degree of reduction in visceral adipose tissue measured by waist circumference or CT scan
• EGRIFTA® is not indicated for weight loss management (weight neutral effect)
• There are no data to support improved compliance with antiretroviral therapies in HIV-positive patients taking EGRIFTA®

For complete disclosure of EGRIFTA® product information, please read the Full Prescribing Information, Patient Information, and Patient Instructions for Use.

For more information about EGRIFTA®, contact the AXIS Center toll-free at 1-877-714-AXIS(2947).

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