TESAMORELIN Drug Interactions: What You Need to Know

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

7.1 Cytochrome P450-Metabolized Drugs Co-administration of tesamorelin with simvastatin, a CYP3A substrate had no significant impact on the pharmacokinetics profiles of simvastatin in healthy subjects <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . EGRIFTA SV stimulates GH production. Published data indicate that GH may modulate cytochrome P450 (CYP450) mediated antipyrine clearance. These data suggest that GH may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, and cyclosporine). Monitor patients for potential interactions when administering EGRIFTA SV in combination with other drugs known to be metabolized by CYP450 liver enzymes.

7.2 Glucocorticoids GH inhibits 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1), a microsomal enzyme required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. EGRIFTA SV stimulates GH production; therefore, patients receiving glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in maintenance or stress doses following initiation of EGRIFTA SV. Patients treated with cortisone acetate and prednisone may be affected more than others because conversion of these drugs to their biologically active metabolites is dependent on the activity of 11βHSD-1.

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 )].

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., &gt;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 &gt;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 &gt;2 and 23% had IGF-1 SDS &gt;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 <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.1 )]</span>.

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.