Tepezza

— THERAPEUTIC CATEGORIES —
  • Miscellaneous ocular agents
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Tepezza Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Teprotumumab-trbw 500mg; per vial; lyophilized pwd for IV infusion after reconstitution and dilution; preservative-free.

    Pharmacological Class

    Human insulin-like growth factor-1 receptor inhibitor (IGF-1R).

    How Supplied

    Single-dose vial—1

    Storage

    Refrigerate at 2° C to 8° C (36° F to 46° F) in original carton until time of use to protect from light. Do not freeze.

    The combined storage time of reconstituted Tepezza solution in the vial and the diluted solution in the infusion bag containing 0.9% Sodium Chloride Injection, USP is a total of 4 hours at room temperature 20° C to 25° C (68° F to 77° F) or up to 48 hours under refrigerated conditions 2° C to 8° C (36° F to 46° F) protected from light.

    Manufacturer

    Horizon Therapeutics USA

    Generic Availability

    NO

    Mechanism of Action

    The mechanism of action of teprotumumab-trbw in patients with thyroid eye disease has not been fully characterized. It binds to IGF-1R blocking its activation and signaling.

    Tepezza Indications

    Indications

    Thyroid eye disease regardless of disease activity or duration.

    Tepezza Dosage and Administration

    Prior to Treatment Evaluations

    Patients who experience infusion reaction: Consider premedicating with antihistamine, antipyretic, corticosteroid and/or administering at a slower infusion rate.

    Adult

    Give 1st two infusions by IV infusion over 90mins; if tolerated, may reduce subsequent infusions to 60mins. Initially 10mg/kg followed by 20mg/kg every 3 weeks for 7 additional infusions.

    Children

    Not established.

    Administration

    Using appropriate aseptic technique, reconstitute each vial with 10mL of Sterile Water for Injection, USP. Reconstituted solution has a volume of 10.5mL. After reconstitution, the final concentration is 47.6mg/mL.

    Reconstituted solution must be further diluted in 0.9% Sodium Chloride Injection, USP prior to infusion. If refrigerated prior to administration, allow the diluted solution to reach room temperature prior to infusion.

    Administer diluted solution intravenously over 90 minutes for the first 2 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.

    Nursing Considerations

    Do not administer as an IV push or bolus. Do not infuse concomitantly with other agents.

    Tepezza Contraindications

    Not Applicable

    Tepezza Boxed Warnings

    Not Applicable

    Tepezza Warnings/Precautions

    Warnings/Precautions

    Exacerbation of preexisting inflammatory bowel disease; if suspected, consider discontinuation. Hyperglycemia may occur; assess for elevated blood glucose, symptoms of hyperglycemia prior to infusion, monitor during treatment. Patients with hyperglycemia or pre-existing diabetes: ensure appropriate glycemic control before and while receiving treatment. Assess for hearing impairment. Advise females of reproductive potential to use effective contraception prior to initiation, during and for 6 months after the last dose. Pregnancy: not recommended. Nursing mothers.

    Warnings/Precautions

    Infusion Reactions

    • Infusion reactions have been reported in approximately 4% of patients in clinical trials.
    • Signs/symptoms: Increased blood pressure, feeling hot, tachycardia, dyspnea, headache, muscular pain.
    • May occur during infusion or within 1.5 hours after administration.
    • Corticosteroids, antihistamines were used to manage; most reactions were mild or moderate in severity.
    • Prior infusion reaction: Consider premedicating with antihistamine, antipyretic, corticosteroid and/or administering at a slower infusion rate.

    Exacerbation of Preexisting Inflammatory Bowel Disease

    • Monitor patients with IBD for disease flare.
    • Consider discontinuing treatment if IBD exacerbation is suspected.

    Hyperglycemia

    • Increased blood glucose may occur with Tepezza treatment.
    • 10% of patients experienced hyperglycemia in clinical trials (two-thirds had pre-existing diabetes/impaired glucose tolerance).
    • Use medications for glycemic control if necessary.
    • Assess elevated blood glucose and symptoms of hyperglycemia before infusion and continue to monitor while on treatment.
    • Ensure patients with hyperglycemia/pre-existing diabetes are under glycemic control before and while on treatment.

    Hearing Impairment Including Hearing Loss

    • Severe hearing impairment (including hearing loss) may occur; in some cases may be permanent.
    • Assess patients’ hearing before, during, and after treatment; consider the benefit/risk of treatment.

    Pregnancy Considerations

    May cause fetal harm based on animal studies and the mechanism of action of inhibiting insulin-like growth factor 1 receptor. Studies with Tepezza have not been conducted in pregnant women. Tepezza should be discontinued in patients who become pregnant.

    Nursing Mother Considerations

    There is no information regarding the presence of Tepezza in human milk, the effects on the breastfed infant or the effects on milk production.

    Pediatric Considerations

    Safety and effectiveness have not been established in pediatric patients. 

    Geriatric Considerations

    No overall differences were observed in clinical trials between patients 65 years or older and younger patients. 

    Renal Impairment Considerations

    No clinically significant differences in the pharmacokinetics of teprotumumab-trbw were observed in patients with mild to moderate renal impairment.

    Hepatic Impairment Considerations

    The effect of hepatic impairment on the pharmacokinetics of teprotumumab-trbw is unknown.

    Other Considerations for Specific Populations

    Females of reproductive potential: Use effective contraception prior to initiation, during treatment, and for 6 months after the last dose.

    Tepezza Pharmacokinetics

    Absorption

    Mean (±standard deviation) estimates for steady-state area under the concentration curve (AUC): 138 (±34) mg•hr/mL.

    Mean (±standard deviation) estimates for peak (Cmax): 632 (±139) mcg/mL.

    Mean (±standard deviation) estimates for trough (Ctrough) concentrations: 176 (±56) mcg/mL.

    Distribution

    Population PK estimated mean (±standard deviation) for central and peripheral volume of distribution: 3.26 (±0.87) L and 4.32 (±0.67) L, respectively.

    Mean (±standard deviation) estimated inter-compartment clearance: 0.74 (±0.16) L/day.

    Metabolism

    Proteolysis.

    Elimination

    Half-life: 20 (±5) days.

    Clearance: 0.27 (±0.08) L/day.

    Tepezza Interactions

    Not Applicable

    Tepezza Adverse Reactions

    Adverse Reactions

    Muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dry skin, dysgeusia, headache; infusion-related reactions.

    Tepezza Clinical Trials

    Clinical Trials

    The approval of Tepezza was supported by data from 2 studies evaluating the safety and efficacy of teprotumumab in a total of 171 patients with active thyroid eye disease. Across both trials, 84 patients were randomly assigned to Tepezza and 87 were randomly assigned to placebo. 

    The primary endpoint was proptosis responder rate at week 24, defined as the percentage of patients with ≥2mm reduction in proptosis in the study eye from baseline, without deterioration in the nonstudy eye (≥2mm increase) in proptosis. 

    Results showed a proptosis responder rate of 71% and 83% in Tepezza-treated patients compared with 20% and 10% with placebo in Study 1 and Study 2, respectively; Tepezza was also associated with improvement in the less severely impacted nonstudy eye. 

    In addition, a subgroup of patients were evaluated for diplopia, a secondary endpoint, using 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. Among these patients, 53% of Tepezza-treated patients (n=35/66) and 25% of placebo-treated patients (n=15/59) were diplopia responders.

    Tepezza Note

    Not Applicable

    Tepezza Patient Counseling

    Patient Counseling

    May cause embryo-fetal toxicity: Advise females of reproductive potential to use effective contraception before initiating, during treatment, and for 6 months after the last dose.

    Infusion-related reactions may occur; instruct patients to recognize the signs/symptoms.

    Inflammatory bowel disease exacerbation is possible; patients experiencing diarrhea, rectal bleeding, abdominal pain, cramping/colic, urgency, tenesmus or incontinence should seek medical advice immediately. 

    Patients with diabetes: Hyperglycemia is possible with treatment; adjust glycemic control measures and encourage compliance.

    Cost Savings Program

    Tepezza Cost and Co-pay Assistance

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