Egrifta (Tesamorelin) and Anesthesia: Perioperative Interaction Guide

What does the Egrifta label say that matters around surgery?

Tesamorelin is a GHRH analog. It binds and stimulates pituitary GRF receptors with potency similar to the body's own GRF, so the pituitary releases more of its own growth hormone, which then raises IGF-1 and IGFBP-3 [1]. Egrifta was first approved on November 10, 2010 for reduction of excess abdominal fat in HIV-infected adults with lipodystrophy, and that is still its only approved use [3][1].

The section of the label that speaks most directly to a surgical admission is the acute critical illness warning, and it appears in both current labels, Egrifta SV (2 mg vial) and Egrifta WR (11.6 mg vial) [1][2]. The label states that increased mortality has been reported in patients with acute critical illness due to complications following open-heart surgery, abdominal surgery or multiple accidental trauma, or in those with acute respiratory failure, after treatment with pharmacologic amounts of growth hormone. It notes that Egrifta is a GHRH and, because it stimulates growth hormone production, says to consider discontinuing Egrifta in critically ill patients [1].

Neither label carries a boxed warning [1][2].

Does tesamorelin change blood sugar around a procedure?

The labels say tesamorelin can cause glucose intolerance or diabetes mellitus. They direct prescribers to evaluate glucose status before starting and to monitor all treated patients periodically [1]. The label adds that if glucose intolerance or diabetes develops, prescribers should consider discontinuing in patients who do not show a clear efficacy response, and that patients with diabetes should be monitored at regular intervals for development or worsening of retinopathy [1].

The label's own rate for that risk: HbA1c of 6.5% or higher from baseline to week 26 developed in 5% of patients on Egrifta versus 1% on placebo, an intent-to-treat hazard ratio of 3.3 (95% CI 1.4 to 9.6) [1].

Group averages in the trials moved little. Study 1, a 412-patient trial of 2 mg daily versus placebo for 26 weeks, reported no significant differences in glycemic measures [4]. Study 2, with 404 patients, reported no change in glucose parameters [5]. A pooled analysis of 806 patients found no clinically meaningful glucose differences [6]. In a 50-patient trial, fasting glucose rose more at 2 weeks on tesamorelin (+9 vs +2 mg/dL) but was no different at 6 months [7].

The label does not specify a perioperative testing schedule for glucose or IGF-1 [1].

IGF-1 before an operation

The label calls for IGF-1 monitoring during therapy and says to consider discontinuing in patients with persistent elevations, for example above 3 SDS, particularly when the fat-loss response is not robust. It also states that the effects of prolonged IGF-1 elevation are unknown [1].

The frequencies are substantial: among patients who received Egrifta for 26 weeks, 47% had IGF-1 above 2 SDS and 36% above 3 SDS, seen as early as 13 weeks; among those who stayed on treatment for 52 weeks, 34% were above 2 SDS and 23% above 3 SDS at the end of treatment [1].

Do anesthetic drugs interact with tesamorelin?

The labels' drug interactions section covers two groups of medicines [1].

The first is drugs metabolized by CYP450 liver enzymes. Published data suggest growth hormone may modulate CYP450-mediated antipyrine clearance, which the label says suggests GH may alter clearance of compounds metabolized by CYP450 liver enzymes. The examples it names are corticosteroids, sex steroids, anticonvulsants and cyclosporine, and it advises monitoring for potential interactions [1]. Anesthetic agents are not among the examples the label names [1].

In healthy subjects, co-administration with simvastatin, a CYP3A substrate, had no significant impact on simvastatin pharmacokinetics. Co-administration with ritonavir produced a 9% decrease in ritonavir AUC and an 11% decrease in Cmax, which the label treats as no significant impact [1].

The second group is glucocorticoids, covered below [1].

Steroids given around surgery

Growth hormone inhibits 11-beta-hydroxysteroid dehydrogenase type 1, the microsomal enzyme required to convert cortisone to its active metabolite cortisol in liver and adipose tissue [1]. Because tesamorelin stimulates growth hormone production, the label says patients receiving glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in maintenance or stress doses after starting Egrifta. Patients treated with cortisone acetate and prednisone may be affected more than others, because conversion of these drugs to their active metabolites depends on 11-beta-HSD1 activity [1].

That instruction is written for people already on glucocorticoid replacement for diagnosed hypoadrenalism [1].

How long does a dose last?

The mean elimination half-life of tesamorelin was 8 minutes in healthy subjects after a single 1.4 mg subcutaneous dose of Egrifta SV [1], and 11 minutes after a single 1.28 mg dose of Egrifta WR [2]. Median Tmax was 0.15 hour in both [1][2]. Absolute bioavailability after a 2 mg dose of the original 1 mg/vial product was under 4% in healthy adults, and total exposure (AUC) was 34% higher in HIV-infected patients than in healthy subjects [1].

How is Egrifta given?

Both products are once-daily subcutaneous injections into the abdomen [1][2]. Egrifta SV is 1.4 mg (0.35 mL of the reconstituted solution). The label says to rotate sites, avoid scar tissue, bruises and the navel, reconstitute only with the supplied Sterile Water for Injection, give the dose immediately and discard what is left [1]. Egrifta WR is 1.28 mg (0.16 mL). Its 11.6 mg vial is reconstituted with 1.3 mL Bacteriostatic Water for Injection, supplies 7 daily doses, and the label says to discard it 7 days after mixing [2]. The label says the two products are not substitutable [2].

Does alcohol interact with Egrifta?

Neither the Egrifta SV nor the Egrifta WR label lists alcohol among drug interactions, and alcohol is not one of the contraindications. Those are disruption of the hypothalamic-pituitary axis, active malignancy, known hypersensitivity to tesamorelin or excipients, and pregnancy [1][2]. The label states that no formal metabolism studies have been performed in humans [1].