Teprotumumab (Monograph)

Brand name: Tepezza
Drug class: EENT Drugs, Miscellaneous

Medically reviewed by Drugs.com on Dec 17, 2023. Written by ASHP.

Introduction

Insulin-like growth factor-1 receptor (IGF-1R) inhibitor; an immunoglobulin G1 (IgG1) monoclonal antibody.

Uses for Teprotumumab

Thyroid Eye Disease

Treatment of thyroid eye disease (regardless of thyroid eye disease activity or duration); designated an orphan drug by FDA for this use.

Guidelines recommend use of teprotumumab in active moderate-to-severe thyroid eye disease with significant proptosis and/or diplopia.

Teprotumumab Dosage and Administration

General

Pretreatment Screening

• Obtain blood glucose levels and assess for hyperglycemic symptoms prior to initiating teprotumumab.

• Assess hearing before starting teprotumumab.

Patient Monitoring

• Monitor for infusion reactions during or within 1.5 hours after teprotumumab infusion.

• Monitor blood glucose and assess patients for hyperglycemic symptoms during teprotumumab treatment.

• Assess hearing periodically during and after teprotumumab treatment.

• Monitor patients with inflammatory bowel disease for exacerbations during treatment.

Premedication and Prophylaxis

• In patients who experience an infusion reaction, consider premedication with an antihistamine, antipyretic, and/or corticosteroid, and consider administering subsequent infusions at a slower rate.

Administration

IV Administration

Administer via IV infusion. Do not administer as an IV push or bolus injection.

Commercially available as a lyophilized powder that must be reconstituted and diluted prior to administration.

Do not infuse concomitantly with other medications.

Reconstitution

Calculate dose and determine number of vials needed based on patient weight.

Reconstitute each vial with 10 mL of sterile water for injection.

Do not add diluent directly onto the lyophilized powder.

Gently swirl vial until lyophilized powder is dissolved; do not shake. Reconstituted solution should be a colorless or slightly brown, clear to opalescent solution. Discard if particulate matter or discoloration observed.

Volume of reconstituted solution is 10.5 mL, with a final teprotumumab concentration of 47.6 mg/mL.

Dilution

Dilute reconstituted teprotumumab-trbw solution in 0.9% sodium chloride injection prior to infusion.

To prepare infusion bag, remove and discard a volume of 0.9% sodium chloride injection equivalent to the volume of reconstituted solution that is to be placed into the infusion bag.

Withdraw required volume of teprotumumab-trbw from the vial(s) and transfer it into the bag containing 0.9% sodium chloride injection to make a dilute solution with a total volume of 100 mL (for doses <1800 mg) or 250 mL (for doses ≥1800 mg).

Gently invert bag to mix the dilute solution; do not shake.

Discard any unused vial contents; product does not contain preservative.

No known incompatibilities exist between teprotumumab-trbw and polyethylene, polyvinyl chloride, polyurethane, or polyolefin bags.

Rate of Administration

Administer over 90 minutes for the first 2 infusions.

If well-tolerated, administer subsequent infusions over ≥60 minutes.

If not well-tolerated, administer subsequent infusions over ≥90 minutes.

Dosage

Adults

Thyroid Eye Disease

IV

10 mg/kg via IV infusion for the first dose, then 20 mg/kg via IV infusion every 3 weeks for 7 more infusions.

Special Populations

Hepatic Impairment

No dosage recommendations.

Renal Impairment

No dosage recommendations.

Geriatric Use

No dosage recommendations.

Related/similar drugs

Tepezza

Cautions for Teprotumumab

Contraindications

• None.

Warnings/Precautions

Infusion Reactions

Infusion reactions reported; may occur during any infusion or up to 1.5 hours after an infusion. Signs and symptoms of infusion-related reactions include transient increases in blood pressure, feeling hot, tachycardia, dyspnea, headache, and muscular pain. Most are mild to moderate and can be managed with corticosteroids and antihistamines.

In patients who experience an infusion reaction, consider premedication with an antihistamine, antipyretic, and/or corticosteroid, and/or using a slower infusion rate for all subsequent infusions.

Exacerbation of Preexisting Inflammatory Bowel Disease

May exacerbate preexisting inflammatory bowel disease (IBD).

Monitor for IBD flares, and consider teprotumumab discontinuation in patients with suspected IBD exacerbation.

Hyperglycemia

May cause hyperglycemia or increased blood glucose, particularly in patients with preexisting diabetes or impaired glucose tolerance.

Obtain baseline blood glucose and assess for symptoms of hyperglycemia prior to treatment initiation. Ensure that patients with hyperglycemia or preexisting diabetes are under appropriate glycemic control before and while receiving teprotumumab. Monitor for elevated blood glucose and hyperglycemic symptoms during teprotumumab treatment, and administer medications to control hyperglycemia if necessary.

Hearing Impairment Including Hearing Loss

May cause severe hearing impairment or hearing loss, which may be permanent.

Conduct hearing assessments before, during, and after treatment with teprotumumab, and discuss risks and benefits of teprotumumab treatment with the patient.

Immunogenicity

Potential for immunogenicity exists. In a placebo-controlled study, no patients on teprotumumab developed antidrug antibodies.

Specific Populations

Pregnancy

Inhibits insulin-like growth factor 1 receptor (IGF-1R); based on mechanism of action and findings from animal studies, may cause fetal harm when used during pregnancy.

Advise females of reproductive potential to use effective contraceptive methods prior to teprotumumab initiation, during treatment, and for 6 months after the last dose.

If the patient becomes pregnant, discontinue teprotumumab and advise patient of the potential fetal hazard.

Lactation

Not known whether teprotumumab or its metabolites are distributed into human milk. Effects of the drug on breast-fed infants or milk production unknown.

Females and Males of Reproductive Potential

Advise females of reproductive potential to use effective contraceptive methods prior to teprotumumab initiation, during teprotumumab treatment, and for 6 months after the last dose of teprotumumab.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

No differences in efficacy or safety observed between patients ≥65 years of age and younger patients.

Hepatic Impairment

Effect of hepatic impairment on pharmacokinetics unknown. No clinically significant differences in pharmacokinetics observed based on bilirubin levels (2.7–24.3 mcmol/L), AST levels (11–221 U/L), or ALT levels (7–174 U/L).

Renal Impairment

No clinically significant differences in pharmacokinetics observed in patients with mild to moderate renal impairment (Cl_cr 30–89 mL/minute).

Common Adverse Effects

Most common adverse reactions (>5%): muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dry skin, dysgeusia, headache, decreased weight, nail disorder.

Drug Interactions

No drug interaction studies conducted.

Teprotumumab Pharmacokinetics

Absorption

Special Populations

Pharmacokinetics not significantly impacted by age (18–80 years), gender, race/ethnicity, or weight (46–169 kg).

Distribution

Extent

Not known whether teprotumumab or its metabolites are distributed into human milk.

Elimination

Metabolism

Not fully characterized; expected to occur via proteolysis.

Half-life

20 days.

Stability

Storage

Parenteral

Powder for Injection

Unopened vials: 2–8 °C; store in original packaging to protect from light.

Reconstituted/diluted solution: combined storage time should not exceed 4 hours at 20–25 °C or 48 hours at 2–8 °C. Protect from light. If refrigerated, allow to come to room temperature prior to infusion.

Actions

• Fully human immunoglobulin G₁ (IgG₁) monoclonal antibody specific for insulin-like growth factor-1 receptor (IGF-1R).

• Produced in Chinese hamster ovary (CHO-DG44) cells.

• Binds to IGF-1R and inhibits its activation and signaling; specific mechanism of action in thyroid eye disease unknown.

Advice to Patients

• Advise patients that teprotumumab-trbw may cause infusion-related reactions. Instruct patients regarding the signs and symptoms of infusion-related reactions and to contact their healthcare provider immediately if these signs and symptoms occur.

• Advise specific patients regarding the potential risk for an exacerbation of preexisting inflammatory bowel disease (IBD) and to seek medical advice immediately if they experience diarrhea, with or without blood or rectal bleeding, associated with abdominal pain or cramping/colic, urgency, tenesmus, or incontinence.

• Advise patients on the risk of hyperglycemia and, if diabetic, discuss with a healthcare provider to adjust glycemic control measures (including medications) as appropriate. Encourage compliance with glycemic control.

• Advise patients that teprotumumab-trbw may cause severe hearing impairment including hearing loss, which in some cases may be permanent. Instruct patients to contact their healthcare provider if they experience any signs or symptoms of hearing impairment or any changes in hearing.

• Advise females to inform clinicians if they are or plan to become pregnant or plan to breast-feed. Advise females of reproductive potential that teprotumumab-trbw can cause harm to a fetus. Educate and counsel females of reproductive potential about the need to use effective contraception prior to initiation, during treatment with teprotumumab-trbw, and for 6 months after the last dose of teprotumumab-trbw.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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