Tesamorelin side effects and safety

Warnings and precautions

The label lists seven warnings and precautions. Each is summarised here; the label gives the full wording^[1].

• 5.1 Increased Risk of Neoplasms. preexisting malignancy should be inactive and its treatment complete before starting; discontinue if there is any evidence of recurrent malignancy; consider the increased background risk of malignancies in HIV-positive patients.
• 5.2 Elevated IGF-1 Levels. stimulates GH production and increases serum IGF-1; the effects of prolonged elevation are unknown; monitor IGF-1 and consider discontinuing with persistent elevations (e.g., >3 SDS). After 26 weeks, 47% had IGF-1 >2 SDS and 36% >3 SDS.
• 5.3 Fluid Retention. may occur (edema, arthralgia, carpal tunnel syndrome); either transient or resolves with discontinuation.
• 5.4 Glucose Intolerance or Diabetes Mellitus. may develop; elevated HbA1c (≥6.5%) from baseline to Week 26 in 5% (EGRIFTA) vs 1% (placebo); evaluate glucose before and during therapy; monitor patients with diabetes for development or worsening of retinopathy.
• 5.5 Hypersensitivity Reactions. occurred in 4% of EGRIFTA-treated patients in clinical trials (pruritus, erythema, flushing, urticaria, rash); discontinue if suspected.
• 5.6 Injection Site Reactions. incidence 25% (EGRIFTA) vs 14% (placebo) during the first 26 weeks of clinical trials.
• 5.7 Increased Mortality in Patients with Acute Critical Illness. reported with pharmacologic amounts of growth hormone; consider discontinuing in critically ill patients.

For diabetes risk, label Section 5.4 reports an intent-to-treat hazard odds ratio of 3.3 (CI 1.4, 9.6); Section 6.1 describes the same figure as a hazard ratio.^[1]

Contraindications

According to the label, tesamorelin is contraindicated in^[1]:

• 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.
• Patients with known hypersensitivity to tesamorelin or the excipients in EGRIFTA WR.
• Pregnant women because modifying visceral adipose tissue offers no benefit in a pregnant woman and could result in fetal harm.

Antibodies

Anti-tesamorelin IgG antibodies were detected in 50% of patients at 26 weeks and 47% at 52 weeks. Neutralizing antibodies at Week 52: 10% (to tesamorelin) and 5% (to hGHRH). (Section 12.6)^[1]

Safety findings from other studies

Trial publications report safety observations alongside their outcomes. In the first phase 3 trial, more patients in the tesamorelin group than in the placebo group withdrew because of an adverse event^[3]. In the liver-fat trial in HIV, injection-site complaints were more frequent with tesamorelin, and none were judged serious^[4]. In a 20-week trial in older adults, mild adverse events were reported by 68% of participants on tesamorelin and 36% on placebo^[5]. Those participants are outside the approved population.

What this evidence cannot tell you

• Placebo-controlled exposure in the pivotal trials lasted 26 weeks. The label states that long-term cardiovascular safety has not been established^[1].
• The label states that the effects of prolonged IGF-1 elevation are unknown^[1].
• The safety data come from adults with HIV and lipodystrophy. They may not apply to other people.
• These data describe the FDA-approved product, made under approved manufacturing controls. They do not describe peptide materials sold for research, whose purity, identity and sterility are not assured to that standard.