TEPEZZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TEPEZZA (TEPEZZA).
TEPEZZA (teprotumumab-trbw) is an insulin-like growth factor-1 receptor (IGF-1R) antagonist. It binds to IGF-1R, blocking activation by IGF-1 and IGF-2, thereby inhibiting downstream signaling pathways involved in the pathogenesis of thyroid eye disease, including orbital fibroblast activation, adipogenesis, and inflammation.
| Metabolism | Metabolized via catabolic pathways into small peptides and amino acids; no specific CYP450 metabolism. |
| Excretion | Primarily eliminated via reticuloendothelial system; renal excretion minimal (<5% unchanged in urine); fecal excretion negligible. |
| Half-life | Terminal elimination half-life approximately 21 days (range 18–24 days); supports monthly IV dosing for sustained suppression of IGF-1 receptor signaling. |
| Protein binding | Not extensively studied; likely low protein binding (<10%) as a monoclonal antibody; no specific binding proteins identified. |
| Volume of Distribution | Vd approximately 3.5–5.0 L (0.05–0.07 L/kg for 70 kg adult); distribution limited to plasma and interstitial space, consistent with IgG distribution. |
| Bioavailability | 100% intravenous; not bioavailable via oral or other routes due to protein structure. |
| Onset of Action | Clinical response observed within 2–4 weeks after first IV infusion; maximal effect on proptosis and diplopia typically by 6–8 weeks. |
| Duration of Action | Duration of action persists for 6–12 months after completing 8-infusion course; effects may wane after 1 year; retreatment may be considered if disease reactivates. |
TEPEZZA (teprotumumab-trbw) is administered as an intravenous infusion over 60 minutes. The recommended dose is 10 mg/kg for the initial dose, followed by 20 mg/kg every 3 weeks for a total of 8 infusions.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment is recommended for patients with mild to moderate renal impairment (eGFR 30-89 mL/min). The drug has not been studied in severe renal impairment (eGFR <30 mL/min) or end-stage renal disease. |
| Liver impairment | No dose adjustment is recommended for patients with mild to moderate hepatic impairment (Child-Pugh class A or B). TEPEZZA has not been studied in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | The safety and effectiveness of TEPEZZA have not been established in pediatric patients (<18 years). No weight-based pediatric dosing guidelines are available. |
| Geriatric use | No specific dose adjustment is required for geriatric patients. Clinical studies included patients up to 82 years of age, and no overall differences in safety or efficacy were observed between older and younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TEPEZZA (TEPEZZA).
| Breastfeeding | There are no data on the presence of teprotumumab in human milk, effects on the breastfed infant, or effects on milk production. Monoclonal antibodies are typically transferred into breast milk in small amounts during the first few days postpartum, with minimal absorption due to gastrointestinal degradation. Due to the potential for adverse reactions in nursing infants, advise patients to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Tepezza (teprotumumab) is an IGF-1 receptor antagonist. In animal studies, no fetal harm was observed at doses up to 2.5 times the human exposure based on AUC. However, human data are insufficient. Because IGF-1 receptor inhibition may theoretically affect fetal growth and development, Tepezza should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. No trimester-specific risks have been established due to lack of data. |
■ FDA Black Box Warning
None
| Serious Effects |
None
| Precautions | Infusion reactions, exacerbation of preexisting inflammatory bowel disease, hyperglycemia (including new-onset diabetes or worsening of preexisting diabetes), and potential for embryo-fetal toxicity. |
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| Fetal Monitoring | No specific clinical monitoring is required for maternal or fetal effects beyond standard prenatal care. However, because Tepezza may cause hyperglycemia (monitor glucose levels as recommended), and pregnancy can exacerbate this, additional glucose monitoring may be warranted. If used during pregnancy, consider periodic ultrasound to monitor fetal growth. |
| Fertility Effects | There are no human data on the effect of Tepezza on fertility. In animal studies, there was no impairment of male or female fertility at exposures up to 2.5 times the human exposure. |