Egrifta (Tesamorelin) Side Effects: Rare but Serious Adverse Events

What serious adverse events does the label warn about?

Egrifta comes in two current forms, Egrifta SV (2 mg vial, 1.4 mg once daily) and Egrifta WR (11.6 mg vial, 1.28 mg once daily) [1][2]. Both labels, dated July 29, 2026, carry the same warnings: increased risk of neoplasms, elevated IGF-1, fluid retention, glucose intolerance or diabetes mellitus, hypersensitivity reactions and injection-site reactions, plus a caution about patients who are critically ill [1][2].

The safety numbers come from trials of the original 1 mg/vial Egrifta: 740 HIV-infected patients with lipodystrophy were treated, 543 of them during the 26-week placebo-controlled phase, against 263 on placebo [1]. The labels state that reactions with the 1.4 mg and 1.28 mg doses are expected to be similar to those seen with the 2 mg dose of the original product [1][2].

IGF-1 elevation

Tesamorelin binds GRF receptors on pituitary somatotroph cells and increases the body's own growth hormone release, which raises IGF-1 [1]. The label describes IGF-1 as a growth factor and states that the effects of prolonged elevations are unknown [1].

Among patients treated for 26 weeks, 47% had IGF-1 above 2 SDS and 36% above 3 SDS, with the effect appearing as early as 13 weeks; among those treated for 52 weeks, 34% were above 2 SDS and 23% above 3 SDS at the end of treatment [1].

The label asks prescribers to monitor IGF-1 during therapy and to consider discontinuing in patients with persistent elevations, for example above 3 SDS, particularly when the efficacy response is not robust [1].

When tesamorelin was stopped in the extension studies, IGF-1 fell. In patients switched to placebo at week 26, IGF-1 dropped by 137 ng/mL in Study 1 and 135 ng/mL in Study 2 by week 52, against 59 and 25 ng/mL in those who stayed on tesamorelin [1].

Glucose intolerance and new diabetes

The label states that tesamorelin can cause glucose intolerance. From baseline to week 26, HbA1c of 6.5% or higher developed in 5% of treated patients and 1% of placebo patients, a hazard ratio of 3.3 (95% CI 1.4 to 9.6); mean baseline HbA1c was 5.3% in both groups [1].

The label asks prescribers to evaluate glucose status before starting and to monitor patients periodically, to consider discontinuing in patients who develop glucose intolerance or diabetes without a clear efficacy response, and to monitor patients with diabetes at regular intervals for development or worsening of retinopathy [1].

Not every trial found a glycemic signal. In the 412-patient 26-week trial, glycemic measures did not differ significantly between groups [3]. In a 50-patient study, fasting glucose was higher at 2 weeks (a rise of 9 mg/dL vs 2 mg/dL) but not different at 6 months [4]. In a 12-month trial of 61 people with HIV and fatty liver, glucose and HbA1c did not differ [5]. Tesamorelin is approved to reduce excess abdominal fat in adults with HIV-associated lipodystrophy, not to treat fatty liver [1].

Hypersensitivity reactions

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

Antibodies are common. With the original 1 mg/vial product, anti-tesamorelin IgG antibodies were found in 50% of patients at 26 weeks and 47% at 52 weeks, and 85% of the patients who had hypersensitivity reactions had antibodies; at week 52, about 10% of patients had neutralizing antibodies against tesamorelin and about 5% had neutralizing antibodies against human GHRH [1]. Fat loss and the IGF-1 response were similar whether or not antibodies developed [1].

Fluid retention, joint pain and carpal tunnel syndrome

The label describes fluid retention as a labeled reaction that it says is thought to be related to the induction of growth hormone secretion, showing up as edema, joint pain and carpal tunnel syndrome, and it states these are either transient or resolve when treatment is discontinued [1].

In the combined 26-week table, peripheral edema occurred in 6% of treated patients versus 2% on placebo, arthralgia in 13% versus 11%, myalgia in 6% versus 2%, and carpal tunnel syndrome in 1% versus 0% [1].

Neoplasm risk and the active-cancer contraindication

The neoplasm warning opens with the fact that Egrifta induces release of endogenous growth hormone, a known growth factor [1]. Active malignancy is a contraindication, and the label states that any preexisting malignancy should be inactive and its treatment complete before therapy starts [1][2]. For patients with a history of treated and stable malignancy, the label says to start only after careful evaluation of the potential benefit against the risk of reactivating the underlying malignancy; for a history of non-malignant neoplasms, it says to start after careful evaluation of the potential benefit [1]. The Egrifta SV and Egrifta WR labels say to discontinue treatment if there is evidence that a malignancy has recurred [1][2]. The label also tells prescribers to weigh the increased background risk of malignancy in HIV-positive patients when deciding to start [1].

Patients who become critically ill

Increased mortality has been reported after treatment with pharmacologic amounts of growth hormone in acute critical illness from complications of open heart surgery, abdominal surgery, multiple accidental trauma, or acute respiratory failure [1][2]. The label notes that Egrifta is a growth hormone-releasing hormone that stimulates growth hormone production, and says to consider discontinuing in critically ill patients [1][2].

Injection-site reactions

Injection-site reactions occurred in 25% of treated patients and 14% of placebo patients during the first 26 weeks [1]. They include redness, itching, pain, irritation and bruising [1]. The label says to rotate injection sites to different areas of the abdomen to reduce them [1]. The Egrifta SV label says to inject into the abdomen and not into scar tissue, bruises or the navel [1].

Who should not use tesamorelin

Both labels list the same contraindications: disruption of the hypothalamic-pituitary axis (hypophysectomy, hypopituitarism, pituitary tumor or surgery, head irradiation or head trauma), active malignancy, known hypersensitivity to tesamorelin or the excipients, and pregnancy [1][2]. In rats, hydrocephalus occurred in offspring after tesamorelin exposure at about twice the clinical exposure during organogenesis and four times the clinical exposure during lactation [1]. The label says to discontinue if pregnancy occurs [1].

Interactions that change the risk picture

Glucocorticoids. Growth hormone inhibits 11-beta-hydroxysteroid dehydrogenase type 1, the enzyme that converts cortisone to cortisol; the label says patients receiving glucocorticoid replacement for previously diagnosed hypoadrenalism may need higher maintenance or stress doses after starting Egrifta, and that cortisone acetate and prednisone may be affected more than other steroids [1].

CYP450-metabolized drugs. The label says growth hormone may alter clearance of drugs metabolized by CYP450 liver enzymes, naming corticosteroids, sex steroids, anticonvulsants and cyclosporine, and asks prescribers to monitor for interactions [1]. In healthy subjects, tesamorelin had no significant impact on simvastatin pharmacokinetics, and ritonavir exposure fell by 9% (AUC) and 11% (Cmax) [1][2].

What is not established

The label states that long-term cardiovascular safety has not been established [1]. Pharmacokinetics in renal or hepatic impairment are not established, there is no information on use in people over 65, and safety and effectiveness in children are not established [1].