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: IV: 10 mg/kg as a single dose, followed by 20 mg/kg every 3 weeks for 7 additional doses (Douglas 2020; Smith 2017).
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.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
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)
No
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.
Thyroid eye disease: Treatment of thyroid eye disease.
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-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.
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%)
Neuromuscular & skeletal: Muscle spasm (25%)
1% to 10%:
Dermatologic: Xeroderma (8%)
Endocrine & metabolic: Hyperglycemia (10%) (table 1)
|
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%) (Douglas 2020)
Nervous system: Headache (8%)
Otic: Auditory impairment (10% including transient deafness) (Douglas 2020)
There are no contraindications listed in the manufacturer's labeling.
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.
None known.
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
Females of reproductive potential should use effective contraception prior to treatment, during therapy and for 6 months after the last dose of teprotumumab.
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.
It is not known if teprotumumab is present in breast milk.
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.
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.
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.
Solution (reconstituted) (Tepezza Intravenous)
500 mg (per each): $18,565.92
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