TEPEZZA: Uses, Dosage & Side Effects

What Is TEPEZZA and What Is It Used For?

TEPEZZA contains teprotumumab, a fully human immunoglobulin G1 (IgG1) monoclonal antibody produced using recombinant DNA technology. As a monoclonal antibody, teprotumumab is a highly specialized protein engineered to recognize and bind to one specific molecular target in the body. In the case of TEPEZZA, that target is the insulin-like growth factor-1 receptor (IGF-1R), a transmembrane receptor tyrosine kinase that plays a central role in the pathogenesis of thyroid eye disease.

Thyroid eye disease (TED), also known as Graves' ophthalmopathy or Graves' orbitopathy, is an autoimmune inflammatory condition that affects the tissues surrounding the eyes, including the extraocular muscles and orbital fat. TED is most commonly associated with Graves' disease, an autoimmune disorder in which the thyroid gland produces excessive amounts of thyroid hormone (hyperthyroidism). However, TED can also occur in patients with hypothyroidism or even in those with normal thyroid function (euthyroid Graves' orbitopathy). The condition affects approximately 25–50% of patients with Graves' disease, with moderate-to-severe cases occurring in about 5–6% of patients.

The pathophysiology of TED involves a complex interplay between the immune system and the orbital tissues. In patients with Graves' disease, autoantibodies directed against the thyroid-stimulating hormone receptor (TSHR) cross-react with IGF-1R, which is overexpressed on the surface of orbital fibroblasts. When these autoantibodies bind to and activate IGF-1R on orbital fibroblasts, they trigger a cascade of intracellular signaling events that lead to the production of hyaluronan (a glycosaminoglycan that attracts water and causes tissue swelling), the differentiation of fibroblasts into adipocytes (fat cells), the secretion of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and the expansion and remodeling of orbital tissues. This process results in the hallmark clinical features of TED: proptosis (eye bulging), periorbital edema, diplopia (double vision), and in severe cases, compressive optic neuropathy that can lead to permanent vision loss.

Teprotumumab works by selectively binding to IGF-1R with high affinity, preventing the autoantibody-mediated activation of this receptor on orbital fibroblasts. By blocking IGF-1R signaling, teprotumumab inhibits the downstream inflammatory and fibrotic processes that drive tissue expansion in the orbit. This results in reduced orbital inflammation, decreased hyaluronan production, regression of orbital tissue volume, and ultimately, improvement in proptosis, diplopia, and other clinical manifestations of TED. Notably, teprotumumab also induces the internalization and degradation of IGF-1R from the cell surface, leading to a sustained reduction in receptor availability.

TEPEZZA was evaluated in two pivotal phase III clinical trials that established its efficacy and safety:

• OPTIC Trial: This randomized, double-blind, placebo-controlled, multicenter trial enrolled 83 patients with active, moderate-to-severe TED of recent onset (within 9 months of the first TED symptom). At week 24, 83% of patients in the teprotumumab group achieved a proptosis response (reduction of ≥2 mm in the study eye) compared with 10% in the placebo group (p<0.001). Additionally, 68% of patients with baseline diplopia achieved a meaningful diplopia response versus 29% in the placebo group. The mean reduction in proptosis was 3.32 mm in the teprotumumab group compared with 0.53 mm in the placebo group.
• OPTIC-X Extension Trial: Patients who did not respond adequately to placebo in the OPTIC trial were offered the opportunity to receive teprotumumab in the extension study. Among these crossover patients, 89% achieved a proptosis response after 24 weeks of teprotumumab treatment, confirming the drug's efficacy even in patients whose disease had been present for longer. Furthermore, OPTIC-X provided data on re-treatment, demonstrating that patients who experienced disease flares after initial treatment could benefit from a second course of TEPEZZA.

TEPEZZA was first approved by the U.S. Food and Drug Administration (FDA) in January 2020, making it the first medication specifically approved for the treatment of TED. It subsequently received approval from the European Medicines Agency (EMA) in June 2023. Prior to the approval of teprotumumab, the management of TED was primarily limited to corticosteroids (which have significant side effects with long-term use), orbital radiotherapy (with variable efficacy), and surgical interventions such as orbital decompression, strabismus surgery, and eyelid surgery. TEPEZZA represents a paradigm shift in the treatment of TED by directly targeting the underlying disease mechanism rather than merely managing symptoms.

What Should You Know Before Taking TEPEZZA?

Contraindications

The absolute contraindications to TEPEZZA use include hypersensitivity (allergy) to teprotumumab or to any of the excipients in the formulation. The excipients in TEPEZZA include histidine, histidine hydrochloride monohydrate, polysorbate 20, and trehalose dihydrate. If you have a known allergy to any of these substances, you must not use TEPEZZA.

Critically, TEPEZZA must not be used during pregnancy. Teprotumumab targets the IGF-1R pathway, which plays an essential role in fetal growth and development. Based on its mechanism of action, TEPEZZA is expected to cause harm to an unborn baby if administered during pregnancy. This contraindication is absolute, and pregnancy must be excluded before initiating treatment.

Warnings and Precautions

Before starting TEPEZZA, discuss the following important safety considerations with your healthcare provider:

• Hearing problems: TEPEZZA can cause hearing-related adverse effects, including hearing loss, tinnitus (ringing in the ears), ear fullness, autophony (hearing your own voice louder than normal), and muffled hearing. In some cases, hearing loss has been reported as severe and potentially permanent. If you have a pre-existing history of hearing problems or use hearing aids, your symptoms may worsen during or after treatment. Your doctor will conduct hearing assessments (audiometry) before starting treatment, during treatment, and for at least 6 months after completing treatment. You should avoid exposure to loud noises during the treatment period and report any hearing changes to your doctor immediately. If hearing loss occurs that requires medical treatment, affects your ability to perform daily activities, or worsens, your doctor may discontinue TEPEZZA therapy.
• High blood sugar (hyperglycemia): TEPEZZA can cause elevated blood glucose levels, particularly in patients with pre-existing diabetes or prediabetes. In rare cases, serious hyperglycemic events including diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) have been reported. Your blood sugar will be monitored before treatment, during treatment, and for up to 6 months after treatment completion. If your diabetes is not well controlled with current medications, discuss this with your doctor before starting TEPEZZA. It is important to ensure adequate blood glucose management before initiating therapy.
• Infusion-related reactions: As with all intravenous biological therapies, infusion-related reactions can occur during or after TEPEZZA administration. Symptoms may include breathing difficulties, chest pain, skin flushing or rash, chills, nausea, dizziness, rapid heartbeat, or loss of consciousness. You will be monitored during the infusion and for 90 minutes afterward. Report any symptoms to your healthcare team immediately, especially if they occur after the monitoring period.
• Inflammatory bowel disease (IBD): TEPEZZA may worsen pre-existing inflammatory bowel disease, including ulcerative colitis and Crohn's disease. If you have IBD, discuss this with your doctor before starting treatment. If you notice signs of an IBD flare during treatment (increased loose stools with abdominal pain or cramping, or blood in your stool), contact your doctor or seek medical attention promptly.
• Smoking: Smoking is a well-established risk factor for the development and worsening of thyroid eye disease. You should stop smoking before beginning TEPEZZA treatment. Your doctor may also need to monitor your blood pressure before and during treatment.

Children and Adolescents

TEPEZZA is not recommended for use in children or adolescents under 18 years of age. The safety and efficacy of teprotumumab have not been established in pediatric patients. Thyroid eye disease is exceedingly rare in children, and if it occurs, different management approaches may be appropriate. The IGF-1R pathway plays an important role in normal growth and development, and the effects of blocking this pathway in growing individuals have not been studied.

Pregnancy and Breastfeeding

TEPEZZA is contraindicated during pregnancy. If you think you may be pregnant or are planning to become pregnant, consult your doctor before receiving this medication. As a monoclonal antibody (IgG1), teprotumumab is expected to cross the placenta, particularly during the second and third trimesters of pregnancy. Given its mechanism of action targeting IGF-1R, which is essential for fetal growth, development, and organogenesis, TEPEZZA may cause fetal harm.

Women of childbearing potential must use effective contraception during treatment with TEPEZZA and for at least 6 months after the last infusion. If you become pregnant during treatment, discontinue TEPEZZA immediately and contact your healthcare provider. Your doctor can provide guidance on the appropriate type of contraception for you during the treatment period.

It is not known whether teprotumumab is excreted in human breast milk. Human IgG antibodies are known to be present in breast milk. A risk to the breastfed infant cannot be excluded. If you are breastfeeding or planning to breastfeed, discuss the potential risks and benefits with your doctor before starting TEPEZZA treatment.

Driving and Operating Machinery

During TEPEZZA treatment, you may experience fatigue or headache. These symptoms could impair your ability to drive or operate machinery. Do not drive or use machinery if you experience these symptoms. Otherwise, TEPEZZA is not expected to directly affect your driving ability based on its pharmacological properties.

How Does TEPEZZA Interact with Other Drugs?

As a monoclonal antibody, teprotumumab is not metabolized by hepatic cytochrome P450 (CYP) enzymes and is instead cleared through general protein catabolic pathways. This means that traditional pharmacokinetic drug-drug interactions are not expected with TEPEZZA. The antibody is degraded into small peptides and amino acids by the same catabolic processes that break down endogenous immunoglobulin G (IgG).

While formal drug interaction studies have not been conducted, clinicians should be aware of potential pharmacodynamic interactions that could increase the risk of adverse effects, particularly hearing-related toxicity. TEPEZZA can cause hearing problems on its own, and combining it with other ototoxic medications may amplify this risk.

The following table summarizes the key drug interactions to be aware of when using TEPEZZA:

It is important to inform your healthcare provider about all medications you are currently taking, including prescription medications, over-the-counter drugs, and herbal supplements. While no formal contraindications exist for specific drug combinations with TEPEZZA, the potential additive ototoxic effects with certain medications warrant careful clinical consideration and enhanced monitoring. Your doctor will evaluate the benefit-risk ratio of concurrent medications and may adjust your treatment plan accordingly.

What Is the Correct Dosage of TEPEZZA?

TEPEZZA is administered exclusively in a healthcare facility under the supervision of qualified healthcare professionals experienced in the management of infusion therapies. The medication is given as an intravenous (IV) infusion, meaning it is delivered directly into a vein through a drip. You cannot self-administer TEPEZZA at home.

Adults

The standard treatment course for TEPEZZA consists of 8 infusions, administered once every 3 weeks (every 21 days). The dosing schedule is weight-based and follows a step-up approach:

The infusion time is determined by your doctor based on how well you tolerate the treatment. The first two infusions must be administered over at least 90 minutes. If these are well tolerated, subsequent infusions (3 through 8) may be administered over a minimum of 60 minutes. If the 60-minute infusion is not well tolerated, the infusion time will be extended back to 90 minutes, the infusion rate will be reduced, and premedication may be recommended for subsequent infusions.

You will be monitored during each infusion and for 90 minutes afterward for signs of infusion-related reactions. Healthcare professionals will also monitor your blood sugar levels before each infusion and adjust diabetes medications if needed. The total treatment course takes approximately 24 weeks (about 6 months) to complete.

Children

TEPEZZA is not recommended for use in children or adolescents under 18 years of age. No dosing information is available for pediatric patients, as the safety and efficacy of teprotumumab have not been established in this population.

Elderly

No dose adjustment is required for elderly patients based on age alone. In the clinical trial program, patients up to 80 years of age were included, and no clinically meaningful differences in safety or efficacy were observed between older and younger patients. However, elderly patients may have a higher prevalence of comorbidities such as diabetes and pre-existing hearing impairment, which require careful monitoring during TEPEZZA treatment.

Missed Dose

If you miss a scheduled TEPEZZA infusion, contact your healthcare provider immediately to arrange a new appointment. Your doctor will determine the appropriate timing for your next infusion based on when your last dose was administered. It is important to maintain the regular 3-week dosing interval as closely as possible to ensure optimal treatment outcomes. Do not attempt to make up for a missed dose by receiving a double dose.

Overdose

Because TEPEZZA is administered by healthcare professionals in a controlled clinical setting, the risk of overdose is very low. The dose is carefully calculated based on your body weight before each infusion. In the unlikely event of an overdose, your healthcare team will monitor you closely for any signs or symptoms of adverse effects and provide supportive care as needed. There is no specific antidote for teprotumumab overdose.

What Are the Side Effects of TEPEZZA?

Like all medicines, TEPEZZA can cause side effects, although not everybody gets them. The side effects are classified below by frequency based on data from clinical trials and post-marketing experience. It is important to understand that the benefits of TEPEZZA treatment for thyroid eye disease must be weighed against the potential risks of these side effects, and your doctor will help you make an informed decision about treatment.

Some side effects require immediate medical attention. Tell your doctor or healthcare team right away if you experience symptoms of an infusion-related reaction during or after the infusion, signs of very high blood sugar (especially diabetic ketoacidosis or hyperglycemic hyperosmolar state), or any changes in your hearing.

The most frequently reported side effects in clinical trials were muscle cramps, which affected approximately 25% of patients in the teprotumumab group. These cramps were typically mild to moderate in severity and manageable. Hair loss (alopecia) was reported in approximately 13% of patients and was generally reversible after treatment completion. Hearing-related adverse events were reported in approximately 10% of patients, with some cases of hearing loss persisting beyond the treatment period.

Hyperglycemia is a particularly important side effect for patients with pre-existing diabetes or prediabetes. TEPEZZA blocks IGF-1R, which plays a role in glucose metabolism and insulin signaling. This inhibition can lead to elevated blood glucose levels, and in rare but serious cases, diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS). Both of these conditions are medical emergencies requiring immediate treatment. Symptoms of DKA include excessive thirst, frequent urination, nausea, vomiting, confusion, abdominal pain, rapid breathing, and fruity-smelling breath. Symptoms of HHS include extreme thirst, drowsiness, confusion, and very high blood sugar levels over several days.

Infusion-related reactions occurred in up to 10% of patients and were generally mild to moderate. Symptoms included breathing difficulties, chest pain, skin flushing or rash, chills, nausea, dizziness, and rapid heartbeat. In rare cases, more severe reactions including loss of consciousness have been reported. Premedication may be recommended for patients who have experienced infusion-related reactions.

How Should You Store TEPEZZA?

TEPEZZA is a hospital-based medication that is stored and handled by healthcare professionals. You will not need to store TEPEZZA at home. However, understanding the storage requirements helps ensure you receive a properly preserved product during each infusion visit.

The key storage requirements for TEPEZZA are as follows:

• Unopened vials: Store refrigerated at 2–8°C (36–46°F). Do not freeze. Keep the vial in the outer carton to protect from light.
• Reconstituted solution (in vial): Stable for up to 4 hours at room temperature (20–25°C) or up to 48 hours refrigerated (2–8°C).
• Diluted solution (in infusion bag): Stable for up to 24 hours refrigerated (2–8°C) followed by up to 24 hours at room temperature (20–25°C). If the diluted solution has been refrigerated, it should reach room temperature before infusion.
• Do not use after the expiration date printed on the outer carton and vial label (EXP). The expiration date refers to the last day of that month.

From a microbiological standpoint, the reconstituted and diluted product should be used immediately. If not used immediately, storage times and conditions before use are the responsibility of the healthcare facility, and should not normally exceed 24 hours at 2–8°C, unless reconstitution and dilution have been performed under controlled and validated aseptic conditions.

Keep all medicines out of the sight and reach of children. Do not dispose of any medications via wastewater or household waste. Healthcare facilities dispose of unused medication according to local regulations.

What Does TEPEZZA Contain?

Each vial of TEPEZZA contains the following components:

• Active ingredient: Teprotumumab 500 mg per single-dose vial. After reconstitution with 10 mL of water for injections, the resulting solution has a total volume of 10.5 mL, giving a final concentration of 47.6 mg/mL.
• Excipients (inactive ingredients): Histidine, histidine hydrochloride monohydrate, polysorbate 20 (E432), and trehalose dihydrate. The polysorbate 20 content is 1.05 mg per 10.5 mL reconstituted volume. Polysorbates may cause allergic reactions in some individuals.

TEPEZZA is supplied as a powder for concentrate for solution for infusion (lyophilized powder) in a glass vial with a rubber stopper. The powder is white to off-white in appearance and is provided in a single-dose vial. Each carton contains one vial. After reconstitution, the solution is nearly colorless to slightly brown, clear to opalescent, and free from visible particles. The reconstituted solution should be inspected for particulate matter and discoloration before administration, and discarded if particles or discoloration are observed.

TEPEZZA must not be administered simultaneously with other medications through the same infusion line. No incompatibilities have been observed between teprotumumab and infusion bags and intravenous administration sets made of polyethylene (PE), polyvinyl chloride (PVC), polyurethane (PUR), or polyolefin (PO).