Egrifta (Tesamorelin) Geriatric (65+) Caregiver Administration Guidance

What does the label say about tesamorelin in adults over 65?

Both current labels, Egrifta SV (2 mg vial) and Egrifta WR (11.6 mg vial), make the same statement in their geriatric use section: there is no information on the use of the drug in patients greater than 65 years of age [1][2]. Ages 18 to 65 were a main inclusion criterion for the two pivotal trials [1][2]. The labeled instructions apply as written, and the labels direct patients to read the Instructions for Use enclosed in the medication box [1][2].

Tesamorelin is approved only for reduction of excess abdominal fat in HIV-infected adults with lipodystrophy [1]. The label says it is not indicated for weight loss management because it has a weight-neutral effect, and that long-term cardiovascular safety has not been established [1].

Which product is in the box, SV or WR?

The labels say Egrifta SV and Egrifta WR are not substitutable, because they differ in dose, number of vials, reconstitution instructions and storage [2].

• Egrifta SV is a 2 mg vial reconstituted with 0.5 mL of diluent to 2 mg per 0.5 mL. The dose is 1.4 mg, which is 0.35 mL of that solution, injected subcutaneously once daily [1].
• Egrifta WR is an 11.6 mg vial reconstituted with 1.3 mL of Bacteriostatic Water for Injection to 8 mg per mL. The dose is 1.28 mg, which is 0.16 mL, injected subcutaneously once daily [2].

The pivotal trials used 2 mg daily of the original 1 mg-per-vial Egrifta formulation; the current Egrifta SV and Egrifta WR have different labeled doses [1][2]. FDA accepted the Egrifta SV 1.4 mg dose because its exposure (Cmax and AUC) is similar to that 2 mg dose [1]. One Egrifta WR vial supplies seven daily doses, and the label says to discard the unused solution 7 days after mixing [2].

Mixing Egrifta SV: what the label specifies

For Egrifta SV, the label calls for 0.5 mL of the provided Sterile Water for Injection, gentle rolling for 30 seconds without shaking, inspection for a clear and colorless solution without particles, and injection of 0.35 mL immediately after mixing [1].

The reconstituted vial is 0.5 mL and the dose is 0.35 mL. The label says to throw away any unused solution and diluent, and not to freeze or refrigerate the reconstituted solution [1].

Mixing Egrifta WR: what the label specifies

Egrifta WR uses a different diluent and a different technique: 1.3 mL of the supplied Bacteriostatic Water for Injection, USP, mixed by moving the vial in a circle to swirl the powder and liquid, without shaking [2]. The reconstituted solution is 8 mg per mL, and a dose is 0.16 mL [2]. The label says to store reconstituted Egrifta WR at room temperature, 20°C to 25°C (68°F to 77°F), to discard the vial 7 days after mixing, and not to freeze it [2].

Where the injection goes

Both labels specify the abdomen, with rotation of injection sites to different areas of the abdomen, and no injection into scar tissue, bruises or the navel [1][2]. The label states that rotating sites decreases injection site reactions [1]. Injection site reactions were reported in 25% of tesamorelin-treated patients and 14% of placebo-treated patients during the first 26 weeks of the trials [1].

What the label says to monitor

IGF-1. Tesamorelin stimulates growth hormone production and raises serum IGF-1, a growth factor, and the effects of prolonged elevation are unknown [1]. The label says to monitor IGF-1 during therapy and to consider discontinuing in patients with persistent elevations, for example above 3 SDS, particularly if the efficacy response is not robust [1]. Among patients treated for 26 weeks, 47% had IGF-1 above 2 SDS and 36% above 3 SDS; among those treated for 52 weeks, 34% and 23% [1].

Glucose. Tesamorelin can cause glucose intolerance or diabetes mellitus [1]. In the trials, HbA1c rising to 6.5% or higher from baseline to week 26 occurred in 5% of tesamorelin patients and 1% of placebo patients, a hazard ratio of 3.3 (CI 1.4, 9.6) [1]. The label says to evaluate glucose status before starting and to monitor patients periodically during therapy, and to monitor patients with diabetes at regular intervals for potential development or worsening of retinopathy [1]. The initial trial phase excluded people with type 1 or type 2 diabetes and those previously treated with insulin or oral glucose-lowering drugs; some participants in the extension phase had diet-controlled diabetes [1].

Fluid retention. The label lists edema, arthralgia and carpal tunnel syndrome as fluid-retention reactions, described as transient or resolving with discontinuation [1]. Peripheral edema was reported in 6% of tesamorelin patients and 2% of placebo patients; arthralgia in 13% and 11%; myalgia in 6% and 2% [1].

Hypersensitivity. Hypersensitivity reactions occurred in 4% of tesamorelin-treated patients in clinical trials and included itching, redness, flushing, hives and rash [1]. The label advises patients to seek prompt medical attention and to immediately discontinue treatment if a hypersensitivity reaction is suspected [1].

Acute critical illness. Increased mortality has been reported after treatment with pharmacologic amounts of growth hormone in patients with acute critical illness following open heart surgery, abdominal surgery, multiple accidental trauma, or acute respiratory failure, and the label says to consider discontinuing tesamorelin in critically ill patients [1].

Malignancy. Tesamorelin induces release of endogenous growth hormone, a known growth factor; the label says to discontinue if there is evidence of recurrent malignancy [1].

Interactions the label flags

Glucocorticoids. Growth hormone inhibits 11β-hydroxysteroid dehydrogenase type 1, the enzyme needed to convert cortisone to cortisol in liver and fat tissue [1]. The label says patients receiving glucocorticoid replacement for previously diagnosed hypoadrenalism may need an increase in maintenance or stress doses after starting tesamorelin, and that cortisone acetate and prednisone may be affected more than other steroids [1].

Drugs cleared by CYP450 enzymes. The label states that published data suggest growth hormone may alter clearance of compounds metabolized by CYP450 liver enzymes, naming corticosteroids, sex steroids, anticonvulsants and cyclosporine, and says to monitor patients for potential interactions [1]. In healthy subjects, tesamorelin had no significant impact on simvastatin pharmacokinetics [1].

Contraindications

The labels list four: disruption of the hypothalamic-pituitary axis due to hypophysectomy, hypopituitarism, pituitary tumor or surgery, head irradiation or head trauma; active malignancy; known hypersensitivity to tesamorelin or the excipients in the product; and pregnancy [1][2]. Any pre-existing malignancy should be inactive and its treatment complete before starting therapy [1].