TEPEZZA
Clinical safety rating
cautionComprehensive clinical and safety monograph for TEPEZZA (TEPEZZA).
Comprehensive clinical and safety monograph for TEPEZZA (TEPEZZA).
Treatment of Thyroid Eye Disease
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. |
| Molecular Weight | 145 |
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 | No adequate human data; animal studies not available; use only if potential benefit justifies risk to fetus. |
| 2nd trimester | No adequate human data; use only if potential benefit justifies risk. |
| 3rd trimester | No adequate human data; may cause fetal harm based on mechanism (IGF-1R inhibition); consider risks. |
Clinical note
Comprehensive clinical and safety monograph for TEPEZZA (TEPEZZA).
| Placental transfer | IgG1 monoclonal antibody; expected to cross placenta, especially in second and third trimesters. |
| Breastfeeding | No data on presence in human milk; due to potential for serious adverse reactions in breastfed infants, advise against breastfeeding during treatment and for 3 months after last dose. |
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to teprotumumab or any excipients
| 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. |
| Food/Dietary | No specific food interactions have been reported. However, patients with diabetes should monitor carbohydrate intake due to potential hyperglycemia. Alcohol may exacerbate dehydration from diarrhea or other GI side effects. |
| Clinical Pearls | Teprotumumab (TEPEZZA) is an IGF-1 receptor antagonist used for thyroid eye disease (TED). Monitor for infusion reactions, hyperglycemia (especially in diabetic patients), and exacerbation of inflammatory bowel disease. Contraindicated in patients with history of thromboembolic events. Ensure baseline HbA1c and pregnancy test before initiation. Do not administer live vaccines during therapy. Consider discontinuing in patients who develop severe infusion reactions or new-onset diabetes. |
| Patient Advice | This medication is given as an intravenous infusion every 3 weeks for a total of 8 infusions. · Common side effects include muscle cramps, nausea, diarrhea, hair loss, and fatigue. · You may experience an increase in blood sugar; monitor glucose if you have diabetes. · Report any symptoms of infusion reactions (fever, chills, rash, difficulty breathing) during or after infusion. · Avoid becoming pregnant during treatment and for 6 months after the last dose; use effective contraception. · Do not receive any live vaccines while on this medication. · Notify your doctor if you have a history of inflammatory bowel disease or if you develop new abdominal pain or bloody diarrhea. |
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