Teprotumumab
FDA Drug Information • Also known as: Tepezza
- Brand Names
- Tepezza
- Drug Class
- Insulin-like Growth Factor-1 Receptor Inhibitor [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Teprotumumab-trbw, an insulin-like growth factor-1 receptor inhibitor (IGF-1R), is a fully human IgG1 monoclonal antibody produced in Chinese hamster ovary (CHO-DG44) cells. It has a molecular weight of approximately 148 kilodaltons. TEPEZZA (teprotumumab-trbw) for injection is supplied as a sterile, preservative-free, white to off-white, lyophilized powder for intravenous infusion. Each single-dose vial delivers 500 mg of teprotumumab-trbw, histidine (7.82 mg), L-histidine hydrochloride monohydrate (33.43 mg), polysorbate 20 (1.05 mg), and trehalose (898.43 mg). After reconstitution with 10 mL of Sterile Water for Injection, USP, the final concentration is 47.6 mg/mL with a pH of 5.5.
What Is Teprotumumab Used For?
1 INDICATIONS AND USAGE TEPEZZA is indicated for the treatment of Thyroid Eye Disease regardless of Thyroid Eye Disease activity or duration. TEPEZZA is an insulin-like growth factor-1 receptor inhibitor indicated for the treatment of Thyroid Eye Disease ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Initiate dosing with 10 mg/kg for first infusion, followed by 20 mg/kg every 3 weeks for 7 additional infusions ( 2.1 ) Administer TEPEZZA by intravenous infusion over 60 to 90 minutes ( 2.3 ) 2.1 Recommended Dosing The recommended dose of TEPEZZA is an intravenous infusion of 10 mg/kg for the initial dose followed by an intravenous infusion of 20 mg/kg every three weeks for 7 additional infusions. 2.2 Reconstitution and Preparation Step 1: Calculate the dose (mg) and determine the number of vials needed for the 10 or 20 mg/kg dosage based on patient weight. Each TEPEZZA vial contains 500 mg of the teprotumumab antibody. Step 2: Using appropriate aseptic technique, reconstitute each TEPEZZA vial with 10 mL of Sterile Water for Injection, USP. Ensure that the stream of diluent is not directed onto the lyophilized powder, which has a cake-like appearance. Do not shake, but gently swirl the solution by rotating the vial until the lyophilized powder is dissolved. The reconstituted solution has a total volume of 10.5 mL. Withdraw 10.5 mL of reconstituted solution to obtain 500 mg. After reconstitution, the final concentration is 47.6 mg/mL. Step 3: The reconstituted TEPEZZA solution must be further diluted in 0.9% Sodium Chloride Injection, USP prior to infusion. To prepare the diluted solution, use 100 mL infusion bags for a dose less than 1800 mg, and 250 mL infusion bags for a dose equal to or greater than 1800 mg. To maintain a constant volume in the infusion bag, a sterile syringe and needle should be used to remove the volume equivalent to the amount of the reconstituted TEPEZZA solution to be placed into the infusion bag. Discard the volume of 0.9% Sodium Chloride Injection, USP withdrawn. Step 4: Withdraw the required volume from the reconstituted TEPEZZA vial(s) based on the patient's weight (in kg) and transfer into the intravenous bag containing 0.9% Sodium Chloride Injection, USP. Mix diluted solution by gentle inversion. Do not shake. If refrigerated prior to administration, allow the diluted solution to reach room temperature prior to infusion. The product does not contain any preservative. The combined storage time of reconstituted TEPEZZA solution in the vial and the diluted solution in the infusion bag containing 0.9% Sodium Chloride Injection, USP is a total of 4 hours at room temperature 20°C to 25°C (68°F to 77°F) or up to 48 hours under refrigerated conditions 2°C to 8°C (36°F to 46°F) protected from light. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Upon reconstitution, TEPEZZA is a nearly colorless or slightly brown, clear to opalescent solution which is free of foreign particulate matter. Discard the solution if any particulate matter or discoloration are observed. Do not freeze the reconstituted or diluted solution. Discard vial(s) and all unused contents. No incompatibilities between...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Infusion Reactions [see Warnings and Precautions (5.1) ] Inflammatory Bowel Disease [see Warnings and Precautions (5.2) ] Hyperglycemia [see Warnings and Precautions (5.3) ] Hearing Impairment Including Hearing Loss [see Warnings and Precautions (5.4) ] Most common adverse reactions (incidence greater than 5%) are muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dry skin, dysgeusia, headache, weight decreased, and nail disorder ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials 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 TEPEZZA was evaluated in two premarketing randomized, double-masked, placebo-controlled clinical trials (Study 1 [NCT01868997] and Study 2 [NCT03298867]) consisting of 170 patients with Thyroid Eye Disease (84 received TEPEZZA and 86 received placebo). Patients were treated with TEPEZZA (10 mg/kg for first infusion and 20 mg/kg for the remaining 7 infusions) or placebo given as an intravenous infusion every 3 weeks for a total of 8 infusions. The majority of patients completed 8 infusions (89% of TEPEZZA patients and 93% of placebo patients). The most common adverse reactions (≥ 5%) that occurred at greater incidence in the TEPEZZA group than in the control group during the treatment period of Studies 1 and 2 are summarized in Table 1. In addition, menstrual disorders (amenorrhea, metrorrhagia, dysmenorrhea) were reported in approximately 23% (5 of 22 patients) of menstruating women treated with TEPEZZA compared to 4% (1 of 25 patients) treated with placebo in the premarketing clinical trials. Table 1. Adverse Reactions Occurring in 5% or More of Patients Treated with TEPEZZA and Greater Incidence than Placebo Adverse Reactions TEPEZZA N = 84 N (%) Placebo N = 86 N (%) Muscle spasms 21 (25%) 6 (7%) Nausea 14 (17%) 8 (9%) Alopecia 11 (13%) 7 (8%) Diarrhea 10 (12%) 7 (8%) Fatigue Fatigue includes asthenia 10 (12%) 6 (7%) Hyperglycemia Hyperglycemia includes blood glucose increase 8 (10%) 1 (1%) Hearing impairment Hearing impairment including hearing loss (deafness, including sensorineural deafness, eustachian tube dysfunction, hyperacusis, hypoacusis, autophony and tinnitus) 8 (10%) 0 Dysgeusia 7 (8%) 0 Headache 7 (8%) 6 (7%) Dry skin 7 (8%) 0 Weight decreased 5 (6%) 0 Nail disorder Nail disorder (includes nail discoloration, nail disorder and onychoclasis) 4 (5%) 0 In clinical trials, gastrointestinal complaints including exacerbation of inflammatory bowel disease were reported. In two postapproval trials, the following were the adverse reactions occurring ≥ 5% of participants treated with TEPEZZA during the double-masked treatment period: muscle spasms (29%), hearing impairment (19%), hyperglycemia (18%) diarrhea (16%), fatigue (13%), headache (13%), alopecia (10%), dry skin (10%), dysgeusia (9%), ear discomfort (9%), and nail disorder (6%). 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of TEPEZZA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal Disorders: bowel perforation, exacerbation of inflammatory bowel disease (IBD), including patients without a prior diagnosis of IBD Metabolism and Nutrition Disorders: diabetic ketoacidosis, hyperosmolar hyperglycemic state (HHS) Otologic: severe hearing impairment including hearing loss, which in some cases may be permanent
Contraindications
4 CONTRAINDICATIONS None. None ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on findings in animals and its mechanism of action inhibiting insulin-like growth factor-1 receptor (IGF-1R) signaling, TEPEZZA may cause fetal harm when administered to a pregnant woman. Adequate and well-controlled studies with TEPEZZA have not been conducted in pregnant women. There are insufficient data with TEPEZZA use in pregnant women to inform any drug associated risks for adverse developmental outcomes. Cynomolgus monkeys dosed once weekly with teprotumumab during pregnancy resulted in placental changes, decreased fetal growth during pregnancy, decreased fetal size and weight, and multiple external and skeletal abnormalities in offspring. Teprotumumab exposure may lead to an increase in fetal loss [see Data ] . Therefore, TEPEZZA should not be used in pregnancy, and appropriate forms of contraception should be implemented prior to initiation, during treatment and for 6 months following the last dose of TEPEZZA. Women of childbearing age should have a pregnancy test performed by their doctor before starting treatment with TEPEZZA. If the patient becomes pregnant during treatment, TEPEZZA should be discontinued and the patient advised of the potential risk to the fetus. The background rate of major birth defects and miscarriage is unknown for the indicated population. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. Data Animal Data In an abridged pilot embryo-fetal development study, seven pregnant cynomolgus monkeys were dosed intravenously at one dose level of teprotumumab, 75 mg/kg (2.8-fold the maximum recommended human dose (MRHD) based on AUC) once weekly from gestation day 20 through the end of gestation. The incidence of abortion was higher for the teprotumumab treated group compared to the control group. Teprotumumab caused decreased fetal growth during pregnancy, decreased fetal size and...
Overdosage
10 OVERDOSAGE No information is available for patients who have received an overdosage.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING TEPEZZA (teprotumumab-trbw) for injection is a sterile, preservative-free, white to off-white lyophilized powder available as follows: Carton containing one 500 mg single-dose vial NDC 75987-130-15 Refrigerate at 2°C to 8°C (36°F to 46°F) in original carton until time of use to protect from light. Do not freeze.
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.