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Teprotumumab: Drug information

Teprotumumab: Drug information
(For additional information see "Teprotumumab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Tepezza
Pharmacologic Category
  • Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antagonist;
  • Monoclonal Antibody
Dosing: Adult

Note: If an infusion-related reaction occurred with a prior dose, administer subsequent infusions at a slower rate, and/or consider premedication with an antihistamine, antipyretic, and/or corticosteroid.

Thyroid eye disease

Thyroid eye disease: IV: 10 mg/kg as a single dose, followed by 20 mg/kg every 3 weeks for 7 additional doses (Ref).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; however, there are no significant differences in the pharmacokinetics of teprotumumab in patients with CrCl ≥30 mL/minute.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions (Significant): Considerations
Hearing impairment

Hearing impairment (auditory impairment) has been reported with teprotumumab. Autophony, deafness, eustachian tube disease, hearing loss, hyperacusis, hypoacusis, sensorineural hearing loss, and tinnitus have been reported and may be irreversible despite discontinuation of therapy (Ref).

Mechanism: Not clearly established; inhibition of insulin-like growth factor-1 (IGF-1), which regulates the development, maintenance, and protection of hearing within the inner ear, may be a possible mechanism (Ref).

Onset: Varied; tinnitus has been reported by the second dose and hearing loss after the fifth dose (Ref). Hearing loss has also been reported 10 days after the first dose (Ref).

Risk factors:

• History of ontological insult, including age-related hearing loss, loud noise exposure, and other conditions that degrade baseline hearing function (Ref)

• Concurrent ototoxic medications (Ref)

Hyperglycemia

Hyperglycemia or increased blood glucose commonly occurred during clinical trials. Hyperglycemia occurred more frequently in patients with preexisting diabetes or impaired glucose tolerance; these patients were also more likely to develop grade 3 or grade 4 hyperglycemia. Hyperglycemia was able to be controlled after adjustment of medication for diabetes (Ref). Patients without diabetes experienced intermittent grade 1 hyperglycemia at a rate similar to placebo (Ref). No evidence of residual worsening of glycemic control was seen after completion of the teprotumumab regimen (Ref).

Mechanism: Dose-related; teprotumumab binds to insulin-like growth factor-1 receptor inhibitor (IGF-1R) and blocks its activation and signaling. Because teprotumumab shows no detectable affinity for insulin receptors, hyperglycemia is hypothesized to result from IGF-IR inhibition (Ref). Inhibition of IGF-1R may result in a reduction in feedback inhibition of growth hormone secretion; as a result, growth hormone is elevated which can cause insulin resistance and increased gluconeogenesis and subsequent hyperglycemia (Ref).

Onset: Varied; occurred within 21 days after the last dose in one clinical trial (Ref).

Risk factors:

• Preexisting diabetes; Note: In clinical trials, two-thirds of patients who developed hyperglycemia had impaired glucose tolerance or preexisting diabetes at baseline.

Infusion reactions

Infusion-related reactions frequently occurred in clinical trials (Ref); reported symptoms include transient increases in blood pressure, feeling hot, tachycardia, dyspnea, headache, and muscular pain. Reported infusion reactions are usually mild or moderate in severity and resolve with treatment. A grade 2 nonanaphylactic reaction following the first dose that resulted in drug discontinuation has been reported (Ref).

Onset: Rapid; may occur during or within 1.5 hours after any infusion.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Dermatologic: Alopecia (13%)

Endocrine & metabolic: Amenorrhea (≤23%)

Gastrointestinal: Diarrhea (12%), nausea (17%)

Genitourinary: Dysmenorrhea (≤23%), uterine hemorrhage (≤23%)

Nervous system: Fatigue (12%; including asthenia)

Neuromuscular & skeletal: Muscle spasm (25%)

1% to 10%:

Dermatologic: Nail disease (5%; including nail discoloration and onychoclasis), xeroderma (8%)

Endocrine & metabolic: Hyperglycemia (10%) (table 1), weight loss (6%)

Teprotumumab: Adverse Reaction: Hyperglycemia

Drug (Teprotumumab)

Placebo

Number of Patients (Teprotumumab)

Number of Patients (Placebo)

Comments

10%

1%

84

86

2/3 of studied patients had preexisting diabetes or impaired glucose intolerance

Gastrointestinal: Dysgeusia (8%)

Hypersensitivity: Infusion-related reaction (~4%)

Nervous system: Headache (8%)

Otic: Auditory impairment (10%; including autophony, deafness, hearing loss, eustachian tube disease, hyperacusis, hypoacusis, sensorineural hearing loss, and tinnitus)

Postmarketing:

Endocrine & metabolic: Diabetes mellitus with hyperosmolar coma (Shah 2022), diabetic ketoacidosis

Gastrointestinal: Ulcerative colitis (Safo 2021)

Nervous system: Cognitive dysfunction (Hoang 2021), encephalopathy (Yee 2023)

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Disease-related concerns:

• Inflammatory bowel disease: Use may exacerbate preexisting inflammatory bowel disease (IBD). Monitor patients with IBD for flare of disease and discontinue use if IBD exacerbation is suspected.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Tepezza: teprotumumab-trbw 500 mg (1 ea)

Generic Equivalent Available: US

No

Pricing: US

Solution (reconstituted) (Tepezza Intravenous)

500 mg (per each): $19,104.36

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

IV: Infuse over 90 minutes for the first 2 infusions; may reduce infusion time to 60 minutes for subsequent infusions if well tolerated. Do NOT administer as IV push or bolus.

Use: Labeled Indications

Thyroid eye disease: Treatment of thyroid eye disease regardless of thyroid eye disease activity or duration.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Reproductive Considerations

Females of reproductive potential should use effective contraception prior to treatment, during therapy and for 6 months after the last dose of teprotumumab.

Pregnancy Considerations

Teprotumumab is a humanized monoclonal antibody (IgG1). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to teprotumumab may cause fetal harm.

Breastfeeding Considerations

It is not known if teprotumumab is present in breast milk.

Monitoring Parameters

Assess hearing prior to initiation, during, and after treatment; signs and symptoms of infusion reactions (eg, increased BP, feeling hot, tachycardia, dyspnea, headache, muscular pain); blood glucose and symptoms of hyperglycemia prior to infusion and during treatment; ensure proper glucose control in patient with hyperglycemia or pre-existing diabetes mellitus prior to initiation and during treatment.

Monitor patients with IBD for disease exacerbations.

Mechanism of Action

Teprotumumab's mechanism of action in patients with thyroid eye disease has not been fully characterized. Teprotumumab binds to insulin-like growth factor-1 receptor and blocks its activation and signaling.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vd (two-compartment model): Central: 3.26 ± 0.87 L; Peripheral: 4.32 ± 0.67 L.

Metabolism: Expected to undergo metabolism via proteolysis.

Half-life elimination: 20 ± 5 days.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (PR) Puerto Rico: Tepezza
  1. Chow A, Silkiss RZ. Teprotumumab-associated chronic hearing loss screening and proposed treatments. BMJ Case Rep. 2022;15(4):e248335. doi:10.1136/bcr-2021-248335 [PubMed 35418378]
  2. Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382(4):341-352. doi:10.1056/NEJMoa1910434. [PubMed 31971679]
  3. Hoang TD, Nguyen NT, Chou E, Shakir MK. Rapidly progressive cognitive decline associated with teprotumumab in thyroid eye disease. BMJ Case Rep. 2021;14(5):e242153. doi:10.1136/bcr-2021-242153 [PubMed 33972303]
  4. Hwang CJ, Eftekhari K. Teprotumumab for thyroid eye disease. Int Ophthalmol Clin. 2020;60(2):47-55. doi:10.1097/IIO.0000000000000307 [PubMed 32205652]
  5. Lu TJ, Amarikwa L, Winn BJ, Inserra M, Dosiou C, Kossler AL. Oral corticosteroids for teprotumumab-related hearing loss: a case report. Case Rep Ophthalmol. 2023;14(1):134-139. doi:10.1159/000529422 [PubMed 37034380]
  6. Ma H, Zhang T, Shen H, Cao H, Du J. The adverse events profile of anti-IGF-1R monoclonal antibodies in cancer therapy. Br J Clin Pharmacol. 2014;77(6):917-928. doi:10.1111/bcp.12228 [PubMed 24033707]
  7. Najjar W, Yu J. Audiologic demonstration of ototoxicity from teprotumumab treatment in a patient with thyroid eye disease. OTO Open. 2022;6(2):2473974X221097097. doi:10.1177/2473974X221097097 [PubMed 35509619]
  8. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. doi:10.1155/2012/985646. [PubMed 22235228]
  9. Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. doi:10.1002/bdrb.20201. [PubMed 19626656]
  10. Safo MB, Silkiss RZ. A case of ulcerative colitis associated with teprotumumab treatment for thyroid eye disease. Am J Ophthalmol Case Rep. 2021;22:101069. doi:10.1016/j.ajoc.2021.101069 [PubMed 33817409]
  11. Shah K, Charitou M. A novel case of hyperglycemic hyperosmolar state after the use of teprotumumab in a patient with thyroid eye disease. AACE Clin Case Rep. 2022;8(4):148-149. doi:10.1016/j.aace.2022.01.004 [PubMed 35959086]
  12. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748-1761. doi:10.1056/NEJMoa1614949. [PubMed 28467880]
  13. Tepezza (teprotumumab) [prescribing information]. Deerfield, IL: Horizon Therapeutics USA Inc; July 2023.
  14. Yee MD, McCarthy J, Quinn B, Surani A. Teprotumumab-induced encephalopathy: a rare side effect of a novel therapeutic. WMJ. 2023;122(2):134-137. [PubMed 37141481]
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