Tepezza Drug Information
Generic name: TEPROTUMUMAB
Insulin-like Growth Factor-1 Receptor Inhibitor [EPC]
Uses of Tepezza
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
Dosage & Administration of Tepezza
Administration Administer the diluted solution intravenously over at least 90 minutes for the first two infusions. If well tolerated, the minimum time for subsequent infusions can be reduced to 60 minutes. If not well tolerated, the minimum time for subsequent infusions should remain at 90 minutes, and pre-medication is recommended for subsequent infusions.
Do not administer as an intravenous push or bolus. TEPEZZA should not be infused concomitantly with other agents.
Side Effects of Tepezza
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 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.
Table 1. Adverse Reactions Occurring in 5% or More of Patients Treated with TEPEZZA and Greater Incidence than Placebo 0 In clinical trials, gastrointestinal complaints including exacerbation of inflammatory bowel disease were reported. 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
| 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 |
Warnings & Cautions for Tepezza
Infusion Reactions TEPEZZA may cause infusion reactions
Infusion reactions have been reported in approximately 4% of patients treated with TEPEZZA. 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 pre-medicating with an antihistamine, antipyretic, corticosteroid and/or administering all subsequent infusions at a slower infusion rate.
Inflammatory Bowel Disease TEPEZZA may cause an exacerbation of inflammatory bowel disease (IBD). IBD has been reported in some patients without a prior diagnosis of IBD. Monitor patients for signs and symptoms of IBD.
If IBD exacerbation is suspected, discontinue use of TEPEZZA.
Hyperglycemia Hyperglycemia or increased blood glucose may occur in patients treated with TEPEZZA. In the premarketing 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.
Assess patients for elevated blood glucose and symptoms of hyperglycemia prior to infusion and continue to monitor while on treatment with TEPEZZA. Ensure patients with hyperglycemia or preexisting diabetes are under appropriate glycemic control before and while receiving TEPEZZA.
Hearing Impairment Including Hearing Loss TEPEZZA may cause severe hearing impairment including hearing loss, which in some cases may be permanent. Assess patients' hearing before, during, and after treatment with TEPEZZA and consider the benefit-risk of treatment with patients.
Pregnancy Safety for Tepezza
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. 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 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.
Pediatric Use of Tepezza
Pediatric Use Safety and effectiveness have not been established in pediatric patients.
Overdosage Information for Tepezza
No information is available for patients who have received an overdosage.
Clinical Studies of Tepezza
Patients were randomized to receive TEPEZZA or placebo in a 1:1 ratio. Patients had a clinical diagnosis of Thyroid Eye Disease with symptoms and were euthyroid or had thyroxine and free triiodothyronine levels less than 50% above or below normal limits. Prior surgical treatment for Thyroid Eye Disease was not permitted.
A total of 84 patients were randomized to TEPEZZA and 87 patients were randomized to placebo. The majority (73%) were female. At baseline, 27% of patients were smokers.
The proptosis responder rate at week 24 was defined as the percentage of patients with ≥ 2 mm reduction in proptosis in the study eye from baseline, without deterioration in the non-study eye (≥ 2 mm increase) in proptosis. Additional evaluations included signs and symptoms of Thyroid Eye Disease including pain, gaze evoked orbital pain, swelling, eyelid erythema, redness, chemosis, inflammation, clinical activity score and assessments of functional vision and patient appearance. Results for proptosis are found in Table 2.
Table 2. Efficacy Results in Patients with Thyroid Eye Disease in, improvement of proptosis as measured by mean change from Baseline was observed as early as 6 weeks and continued to improve through week 24 as shown in Figure 1. Similar results were seen in Study 1.
Figure 1. Change from Baseline in Proptosis over 24 Weeks in Study 2 P < 0.01 at each timepoint TEPEZZA also led to improvement in the less severely impacted "fellow" eye. Diplopia (double vision) was evaluated in a subgroup of patients that had diplopia at baseline in Study 1 and 2.
Results are shown in Table 3. Table 3. Figure 1 Subgroups Examination of age and gender subgroups did not identify differences in response to TEPEZZA among these subgroups.
Reduction in proptosis was similar between smokers and non-smokers in both studies.
| Study 1 | Study 2 | |||||
|---|---|---|---|---|---|---|
| Teprotumumab (N = 42) | Placebo (N = 45) | Difference (95% CI) | Teprotumumab (N = 41) | Placebo (N = 42) | Difference (95% CI) | |
| Proptosis responder rate at week 24, % (n) Difference and its corresponding 95% Confidence Interval (CI) is based on a weighted average of the difference within each randomization stratum (tobacco user, tobacco non-use) using CMH weights. | 71% (30) | 20% (9) | 51% (33, 69) | 83% (34) | 10% (4) | 73% (59, 88) |
| Proptosis (mm) average change from baseline through week 24, LS Mean (SE) Results were obtained from an MMRM with an unstructured covariance matrix and including treatment, smoking status, baseline value, visit, treatment by visit, and visit by baseline value interaction as fixed effects. A change from baseline of 0 was imputed at the first post-baseline visit for any subject without a post baseline value. | -2.5 (0.2) | -0.2 (0.2) | -2.3 (-2.8, -1.8) | -2.8 (0.2) | -0.5 (0.2) | -2.3 (-2.8, -1.8) |
| Parameter | TEPEZZA (n = 66) | Placebo (n = 59) |
|---|---|---|
| P < 0.01 | ||
| Diplopia | ||
| Responder rate Diplopia was evaluated on a 4-point scale where scores ranged from 0 for no diplopia to 3 for constant diplopia. A diplopia responder was defined as a patient with baseline diplopia > 0 and a score of 0 at week 24. at week 24, % (n) | 53% (35) | 25% (15) |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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