Class: EENT Drugs, Miscellaneous
Chemical Name: Immunoglobulin G1, anti-(human insulin-like growth factor I receptor) (human monoclonal heavy chain), disulfide with human monoclonal light chain, dimer
Molecular Formula: C6476H10012N1748O2000S40
CAS Number: 1036734-93-6
Teprotumumab-trbw, an anti-insulin-like growth factor-1 receptor (anti-IGF-1R) monoclonal antibody, reduces proptosis and diplopia in patients with thyroid eye disease.
Uses for Teprotumumab-trbw
Teprotumumab-trbw has the following uses:
Teprotumumab-trbw is an insulin-like growth factor-1 receptor inhibitor indicated for the treatment of thyroid eye disease.
Teprotumumab-trbw Dosage and Administration
Teprotumumab-trbw is available in the following dosage form(s) and strength(s):
For Injection: 500 mg lyophilized powder in a single-dose vial for reconstitution.
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosage and Administration
Initiate dosing with 10 mg/kg for first infusion, followed by 20 mg/kg every 3 weeks for 7 additional infusions.
Administer teprotumumab-trbw by intravenous infusion over 60 to 90 minutes.
Cautions for Teprotumumab-trbw
Teprotumumab-trbw may cause infusion reactions. Infusion reactions have been reported in approximately 4% of patients treated with teprotumumab-trbw. Signs and symptoms of infusion-related reactions include transient increases in blood pressure, feeling hot, tachycardia, dyspnea, headache, and muscular pain. Infusion reactions may occur during any of the infusions or within 1.5 hours after an infusion. Reported infusion reactions are usually mild or moderate in severity and can usually be successfully managed with corticosteroids and antihistamines. In patients who experience an infusion reaction, consideration should be given to premedicating with an antihistamine, antipyretic, and/or corticosteroid and/or administering all subsequent infusions at a slower infusion rate.
Exacerbation of Preexisting Inflammatory Bowel Disease
Teprotumumab-trbw may cause an exacerbation of preexisting inflammatory bowel disease (IBD). Monitor patients with IBD for flare of disease. If IBD exacerbation is suspected, consider discontinuation of teprotumumab-trbw.
Hyperglycemia or increased blood glucose may occur in patients treated with teprotumumab-trbw. In clinical trials, 10% of patients (two-thirds of whom had preexisting diabetes or impaired glucose tolerance) experienced hyperglycemia. Hyperglycemic events should be controlled with medications for glycemic control, if necessary.
Monitor patients for elevated blood glucose and symptoms of hyperglycemia while on treatment with teprotumumab-trbw. Patients with preexisting diabetes should be under appropriate glycemic control before receiving teprotumumab-trbw.
Risk Summary: Based on findings in animals and its mechanism of action inhibiting insulin-like growth factor-1 receptor (IGF-1R), teprotumumab-trbw may cause fetal harm when administered to a pregnant woman. Adequate and well-controlled studies with teprotumumab-trbw have not been conducted in pregnant women. There are insufficient data with teprotumumab-trbw use in pregnant women to inform any drug-associated risks for adverse developmental outcomes. In utero teprotumumab exposure in cynomolgus monkeys dosed once weekly with teprotumumab throughout pregnancy resulted in external and skeletal abnormalities. Teprotumumab exposure may lead to an increase in fetal loss. Therefore, teprotumumab-trbw 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 teprotumumab-trbw. If the patient becomes pregnant during treatment, teprotumumab-trbw 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.
Animal Data: In an abridged pilot embryofetal 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 weight at caesarean section, decreased placental weight and size, and decreased amniotic fluid volume. Multiple external and skeletal abnormalities were observed in each exposed fetus, including misshapen cranium, closely set eyes, micrognathia, pointing and narrowing of the nose, and ossification abnormalities of skull bones, sternebrae, carpals, tarsals, and teeth. The test dose, 75 mg/kg of teprotumumab, was the maternal no observed adverse effect level (NOAEL).
Based on mechanism of action inhibiting IGF-1R, postnatal exposure to teprotumumab may cause harm.
Risk Summary: There is no information regarding the presence of teprotumumab-trbw in human milk, the effects on the breast-fed infant, or the effects on milk production.
Females and Males of Reproductive Potential
Based on its mechanism of action inhibiting IGF-1R, teprotumumab-trbw may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception prior to initiation, during treatment, and for 6 months after the last dose of teprotumumab-trbw.
Safety and effectiveness have not been established in pediatric patients.
Of the 171 patients in the two randomized trials, 15% were 65 years of age or older; the number of patients 65 years or older was similar between treatment groups. No overall differences in efficacy or safety were observed between patients 65 years or older and younger patients (less than 65 years of age).
Common Adverse Effects
Most common adverse reactions (incidence greater than 5%) are muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dry skin, dysgeusia, and headache.
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Please see product labeling for drug interaction information.
Mechanism of Action
Teprotumumab-trbw's mechanism of action in patients with thyroid eye disease has not been fully characterized. Teprotumumab-trbw binds to IGF-1R and blocks its activation and signaling.
Advice to Patients
Advise females of reproductive potential that teprotumumab-trbw can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy.
Educate and counsel females of reproductive potential about the need to use effective contraception prior to initiation, during treatment, and for 6 months after the last dose of teprotumumab-trbw.
Advise patients that teprotumumab-trbw may cause infusion reactions that can occur at any time. Instruct patients to recognize the signs and symptoms of infusion reaction and to contact their healthcare provider immediately for signs or symptoms of potential infusion-related reactions.
Exacerbation of Inflammatory Bowel Disease
Advise patients on the risk of inflammatory bowel disease (IBD) and to seek medical advice immediately if they experience diarrhea, with or without blood or rectal bleeding, associated with abdominal pain or cramping/colic, urgency, tenesmus, or incontinence.
Advise patients on the risk of hyperglycemia and, if diabetic, discuss with healthcare provider to adjust glycemic control medications as appropriate. Encourage compliance with glycemic control.
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Injection, Powder, Lyophilized, For Solution
Horizon Therapeutics USA Inc.
AHFS Drug Information. © Copyright 2021, Selected Revisions February 24, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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