How to titrate up Zepbound (teprotumumab) 7.5 MG/0.5ML Solution Auto-injector for thyroid eye disease?

Zepbound Dosing Does Not Apply to Thyroid Eye Disease

The medication you're asking about appears to be confused: "Zepbound" is tirzepatide (a GLP-1/GIP agonist for diabetes and weight loss), NOT teprotumumab (Tepezza), which is the FDA-approved treatment for thyroid eye disease. If you meant Tepezza (teprotumumab), the correct dosing regimen is detailed below.

Tepezza (Teprotumumab) Standard Dosing Protocol

For thyroid eye disease, teprotumumab is administered as an initial intravenous infusion of 10 mg/kg, followed by 20 mg/kg every 3 weeks for seven additional infusions, totaling eight infusions over 24 weeks. 1, 2

Specific Dosing Schedule:

• First infusion: 10 mg/kg IV 1, 2
• Infusions 2-8: 20 mg/kg IV every 3 weeks 1, 2
• Total treatment duration: 24 weeks (approximately 6 months) 2, 3

This dosing regimen provides sustained insulin-like growth factor-1 receptor (IGF-IR) saturation (>90%) throughout the treatment interval, with steady-state peak concentrations of 643 µg/mL and trough concentrations of 157 µg/mL. 1

Pre-Treatment Requirements and Monitoring

Baseline Assessment (Before Starting Treatment):

• Establish baseline proptosis by exophthalmometry to track response 4
• Document Clinical Activity Score (CAS) - treatment is indicated for active moderate-to-severe disease (CAS ≥4) 2, 3
• Screen for optic neuropathy: visual acuity, color vision, visual fields, pupillary exam, fundus examination 4
• Assess diplopia using standardized Gorman grading 4, 2
• Baseline audiometry - critical given hearing impairment risk 4, 5
• Verify thyroid function is controlled before initiating therapy 4

Critical Safety Monitoring During Treatment:

• Hearing tests after 4th and 8th infusions - hearing loss can be permanent in rare cases 4, 5
• Monitor for hyperglycemia - particularly in patients with diabetes or pre-diabetes 3
• Assess for muscle spasms (18% incidence) and diarrhea 3

Contraindications and Cautions

Do not use teprotumumab in patients with:

• Inflammatory bowel disease 5
• Pregnancy 5
• Pre-existing significant hearing loss (use with extreme caution and counsel extensively about hearing risk) 4, 5

Expected Treatment Response Timeline

Short-term Response (Week 24):

• Proptosis reduction ≥2 mm: 77-83% of patients 2, 3
• Diplopia improvement ≥1 grade: 68% of patients 2
• Disease inactivation (CAS ≤1): 59% of patients 2
• Mean proptosis reduction: 2.82 mm 2

Long-term Maintenance (Week 72,51 weeks post-treatment):

• Proptosis response maintained: 67-91% of patients 6
• Diplopia response maintained: 69-73% of patients 6
• Disease inactivation maintained: 70% of patients 6
• Only 18% required additional TED therapy over 99 weeks following final dose 6

Retreatment Considerations

If considering a second course of teprotumumab:

• Re-establish baseline measurements (proptosis, CAS, diplopia, audiometry) 4
• Document active disease: CAS ≥3 indicates active inflammation; CAS ≥5 with symptoms demonstrates active moderate-to-severe disease warranting retreatment 4
• Repeat audiometry is mandatory before retreatment given cumulative hearing risk 4
• Prior positive response (as documented in 2021) suggests high likelihood of benefit with retreatment 4

Alternative Treatments if Inadequate Response:

• Orbital decompression surgery 4
• High-dose corticosteroids 4
• Orbital radiation 4
• Strabismus surgery for persistent diplopia 4

Common Pitfalls to Avoid

• Do not confuse Zepbound (tirzepatide) with Tepezza (teprotumumab) - these are completely different medications for different conditions
• Do not skip baseline audiometry - hearing loss is a serious adverse effect that requires monitoring 4, 5
• Do not initiate treatment without confirming thyroid function is controlled - uncontrolled thyroid disease can worsen outcomes 4, 7
• Do not overlook smoking status - smoking significantly increases TED severity and may reduce treatment efficacy 4, 7