Tesamorelin
FDA Drug Information • Also known as: Egrifta Sv, Egrifta Wr
- Brand Names
- Egrifta Sv, Egrifta Wr
- Route
- SUBCUTANEOUS
- Dosage Form
- KIT
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Tesamorelin is a human growth hormone-releasing factor (GRF) analog produced synthetically. It is comprised of the 44 amino acid sequence of human GRF and a hexenoyl moiety, a C6 chain with a double bond at position 3, attached to the tyrosine residue at the N-terminal part of the molecule. Tesamorelin is prepared as an acetate salt. The molecular formula of tesamorelin acetate is C 221 H 366 N 72 O 67 S
What Is Tesamorelin Used For?
1 INDICATIONS AND USAGE EGRIFTA SV is indicated for the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy. Limitations of Use: Long-term cardiovascular safety of EGRIFTA SV has not been established. Consider risk/benefit of continuation of treatment in patients who have not had a reduction in visceral adipose tissue. EGRIFTA SV is not indicated for weight loss management as it has a weight neutral effect. There are no data to support improved compliance with anti-retroviral therapies in HIV-positive patients taking EGRIFTA SV. EGRIFTA SV is a growth hormone-releasing factor (GHRF) analog indicated for the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy. ( 1 ) Limitations of use: Long-term cardiovascular safety of EGRIFTA SV has not been established. ( 1 ) Not indicated for weight loss management. ( 1 ) There are no data to support improved compliance with anti-retroviral therapies in HIV-positive patients taking EGRIFTA SV. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION The recommendations in this prescribing information only apply to EGRIFTA SV (tesamorelin) for injection 2 mg per vial formulation. For recommendations for tesamorelin for injection 1 mg per vial formulation, see the EGRIFTA prescribing information. These two formulations and strengths have differences in the dosage, the number of vials required to prepare a dose, reconstitution instructions, and storage requirements. ( 2.1 ). The dose of EGRIFTA SV is 1.4 mg (0.35 mL of the reconstituted solution) injected subcutaneously once daily. ( 2.1 ) Inject EGRIFTA SV into the abdomen, rotating injection sites. ( 2.1 , 5.6 ) Use only the diluent provided, Sterile Water for Injection, to reconstitute EGRIFTA SV. ( 2.2 ) Reconstitute one vial of lyophilized powder with 0.5 mL of diluent. Mix by rolling the vial gently in your hands for 30 seconds. Do not shake. ( 2.2 ) Inspect the reconstituted vial visually for particulate matter and discoloration. Use only if the solution is clear, colorless and without particulate matter. ( 2.2 ) Administer 0.35 mL of EGRIFTA SV immediately following reconstitution and throw away any unused solution and diluent. ( 2.2 ) 2.1 Dosage and Administration
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following important adverse reactions are also described elsewhere in the labeling: Increased risk of neoplasms [see Warnings and Precautions ( 5.1 )] Elevated IGF-1 levels [see Warnings and Precautions ( 5.2 )] Fluid retention [see Warnings and Precautions ( 5.3 )] Glucose intolerance or diabetes mellitus [see Warnings and Precautions ( 5.4 )] Hypersensitivity reactions [see Warnings and Precautions ( 5.5 )] Injection site reactions [see Warnings and Precautions ( 5.6 )] Most commonly reported adverse reactions (>5%): Arthralgia, injection site erythema, injection site pruritus, pain in extremity, peripheral edema, and myalgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact THERA patient support ® toll free at 1-833-23THERA (1-833-238-4372) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of EGRIFTA SV (2 mg/vial formulation) has been established based on clinical trials conducted with EGRIFTA (1 mg/vial formulation). Adverse reactions for the 1.4 mg dose (2 mg/vial formulation) of EGRIFTA SV are expected to be similar to those observed with the 2 mg dose (1 mg/vial formulation) of EGRIFTA [see Clinical Pharmacology ( 12.3 )]. Seven hundred and forty (740) HIV-infected patients with lipodystrophy and excess abdominal fat were treated with EGRIFTA in clinical trials; of these, 543 received EGRIFTA during the initial 26-week placebo-controlled phase. The most commonly reported adverse reactions were hypersensitivity reactions (e.g., rash, urticaria), edema-related reactions (e.g., arthralgia, extremity pain, peripheral edema, and carpal tunnel syndrome), hyperglycemia, and injection site reactions (injection site erythema, pruritus, pain, urticaria, irritation, swelling, and hemorrhage). Adverse reactions that occurred more frequently with EGRIFTA relative to placebo and had an incidence ≥1% during the first 26 weeks across all studies are presented in Table 1 . Table 1. Adverse Reactions Reported in ≥ 1% and More Frequent in EGRIFTA –treated than Placebo Patients during the 26-Week Phase (Combined Studies) * Injection site reaction includes: Injection site erythema, Injection site pruritus, Injection site rash, Injection site urticaria, Injection site pain, Injection site swelling, Injection site irritation, Injection site hemorrhage. Preferred Term Placebo (N=263) EGRIFTA (N=543) Injection site reaction* Arthralgia Pain in extremity Myalgia Edema peripheral Paresthesia Hypoesthesia Rash Dyspepsia Musculoskeletal pain Pain Pruritus Vomiting Musculoskeletal stiffness Blood creatine phosphokinase increased Carpal tunnel syndrome Joint swelling Muscle strain Night sweats Palpitations 6 11 5 2 2 2 2 2 1 1 1 1 0 0 0 0 0 0 0 0 17 13 6 6 6 5 4 4 2 2 2 2 3 2 1 1 1 1 1 1 In the EGRIFTA clinical trials, mean baseline HbA 1c was 5.3% among patients in both the EGRIFTA and placebo groups. Patients receiving EGRIFTA had an increased risk of developing diabetes (HbA 1c level ≥ 6.5%) compared with placebo (5% vs. 1%), with a hazard ratio of 3.3 (CI 1.4, 9.6).
Drug Interactions
7 DRUG 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 [see Clinical Pharmacology ( 12.3 )] . 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.
Contraindications
4 CONTRAINDICATIONS 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 )].
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary EGRIFTA SV is contraindicated in pregnant women because modifying visceral adipose tissue offers no benefit in pregnant women and could result in fetal harm [see Clinical Considerations and Contraindications ( 4 )] . Administration of tesamorelin acetate to rats during organogenesis resulted in hydrocephaly in offspring at a dose of approximately two and four times the clinical dose, based on measured drug exposure (AUC). If EGRIFTA SV is used during pregnancy, or if the patient becomes pregnant while taking it, discontinue EGRIFTA SV. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk During pregnancy, visceral adipose tissue increases due to normal metabolic and hormonal changes. Modifying pregnancy-associated physiologic changes in visceral adipose tissue with EGRIFTA SV offers no known benefit and could result in fetal harm. Data Animal Data Tesamorelin acetate administration to rats during organogenesis and lactation resulted in hydrocephaly in offspring at a dose of approximately two and four times the clinical dose, respectively, based on measured drug exposure (AUC). Actual animal dose was 1.2 mg/kg. During organogenesis, lower doses approximately 0.1 to 1-times the clinical dose caused delayed skull ossification in rats. Actual animal doses were 0.1 to 0.6 mg/kg. No adverse developmental effects occurred in rabbits using doses up to approximately 500 times the clinical dose.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING EGRIFTA SV (tesamorelin) for injection is supplied as a white to off-white lyophilized powder in a 2 mg single-dose vial with a diluent of 10 mL vial of Sterile Water for Injection. EGRIFTA SV (NDC 62064-241-30) is available in a package comprised of two boxes, containing 30 (thirty) 2 mg single-dose vials of EGRIFTA SV in the Medication Box and 30 single-dose 10 mL bottles of Sterile Water for Injection diluent with a 30-day supply of disposable syringes and needles in the Injection Box. Store EGRIFTA SV 2 mg vial at room temperature at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Protect EGRIFTA SV from light by keeping in the original box until time of use. Store the Injection box (containing Sterile Water for Injection, syringes and needles) at room temperature at 20°C to 25°C (68°F to 77°F).
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.