Tepezza®
Teprotumumab-trbw · intravenous infusion
Injections & Implants
Approved uses
Thyroid eye disease, active
10 mg/kg IV once, then 20 mg/kg IV every 3 weeks for 7 additional infusions, 8 in total
Proptosis falls about 2.8 mm by week 24, with 83% reaching a response.
Thyroid eye disease, chronic and low activity
10 mg/kg IV once, then 20 mg/kg IV every 3 weeks for 7 additional infusions, 8 in total
In long-standing inactive disease proptosis improves 1.5 mm over placebo, about half the active-disease effect.
OFF-LABELNot in the FDA label for this product
Retreatment after nonresponse or disease flare
Second course of 8 infusions over 24 weeks, the OPTIC-X protocol
Open-label ext · n=13
Open-label extension of OPTIC, no control arm and very small numbers: of 8 initial responders who flared, 5 (62.5%) responded again on retreatment with a mean proptosis reduction of 1.9 mm (SD 1.2) from the extension baseline, and of 5 initial nonresponders retreated, 2 responded, 1 fell short at 1.5 mm, and 2 discontinued early. The 37 previously placebo-treated patients, whose median disease duration was 12.9 months versus 6.3 months in OPTIC, responded at 89.2%, which is what supports treating longer-duration disease. Mild hearing impairment recurred in 2 patients on retreatment.
Contraindications
None.
Available Forms500 mg lyophilized powder in a single-dose vial, one vial per carton, 47.6 mg/mL after reconstitution with 10 mL Sterile Water for Injection
Mechanism of ActionFully human IgG1 monoclonal antibody that binds insulin-like growth factor-1 receptor (IGF-1R) and blocks its activation and signaling. The label states the mechanism in thyroid eye disease has not been fully characterized; in the phase 3 trial the blockade reduced proptosis, and extraocular muscle volume, orbital fat volume, or both fell in the 6 treated patients who underwent orbital imaging.
Warnings & Precautions
- Hearing impairment: May cause severe hearing impairment including hearing loss that is in some cases permanent; assess hearing before, during, and after the infusion course and weigh benefit against risk with the patient.
- Infusion reactions: Reported in approximately 4% of treated patients, during any infusion or within 1.5 hours after, usually mild to moderate and manageable with corticosteroids and antihistamines; interrupt or slow the infusion, then premedicate and run subsequent infusions slower.
- Inflammatory bowel disease exacerbation: Reported including in patients with no prior IBD diagnosis; discontinue if an exacerbation is suspected.
- Hyperglycemia: Occurred in 10% of premarketing trial patients, two-thirds of whom had preexisting diabetes or impaired glucose tolerance; confirm glycemic control before infusion and monitor throughout treatment.
Common Side Effects
- Systemic, premarketing trials: Muscle spasms 25%, nausea 17%, alopecia 13%, diarrhea 12%, fatigue 12%, hyperglycemia 10%, dysgeusia 8%, headache 8%, dry skin 8%, weight decreased 6%, nail disorder 5%.
- Otologic: Hearing impairment 10% versus 0% on placebo in the premarketing trials and 19% in two postapproval trials, spanning deafness including sensorineural deafness, eustachian tube dysfunction, hyperacusis, hypoacusis, autophony, and tinnitus.
- Otologic follow-up series: 22 of 27 patients (81.5%) developed new otologic symptoms after a mean of 3.8 infusions in a prospective single-center series, and 6 of 11 with subjective hearing loss had not recovered at a mean 39 weeks after the last infusion.
- Menstrual disorders: Amenorrhea, metrorrhagia, or dysmenorrhea in 23% (5 of 22) of menstruating women versus 4% (1 of 25) on placebo.
- Serious postmarketing events: Bowel perforation, inflammatory bowel disease exacerbation including in patients with no prior IBD diagnosis, diabetic ketoacidosis, hyperosmolar hyperglycemic state, and severe hearing impairment including permanent hearing loss.
Pregnancy & LactationPregnancy: Should not be used in pregnancy, based on IGF-1R inhibition and on animal findings. Cynomolgus monkeys dosed at 2.8 times the maximum recommended human dose by AUC had a higher incidence of abortion, decreased fetal growth and placental size, and multiple external and skeletal abnormalities in every exposed fetus. Pregnancy test before starting and effective contraception before, during, and for 6 months after the last dose.
Lactation: No information on presence in human milk, effects on the breastfed infant, or effects on milk production.
Pediatric UseSafety and effectiveness not established in pediatric patients.