Navigating the Post-Shortage Era

Clinical Considerations for Compounded Tirzepatide and Semaglutide

The FDA’s recent declaration ending the tirzepatide and semaglutide shortages—effective October 2024 and February 2025, respectively—marks a pivotal moment in managing obesity and type 2 diabetes.  

While commercial supplies of these GLP-1 receptor agonists are now stabilized, compounding pharmacies remain a critical option for patients requiring clinically distinct formulations.  

Here’s what physicians need to know about accessing compounded versions and fostering collaborative care. 

Regulatory Shifts and Compounded Medications

The FDA’s enforcement discretion for compounding pharmacies producing tirzepatide and semaglutide phase out March 19, 2025 (tirzepatide) and May 22, 2025 (semaglutide). ^{1, 10} However, 503A pharmacies may still compound these drugs if they meet clinical difference criteria under Section 503A of the Federal Food Drug & Cosmetics Act.  

Valid clinical differences include: 

• Added therapeutic agents (e.g., B vitamins for metabolic support)^{2, 12}

• Alternative delivery systems (e.g., orally disintegrating tablets for patients with needle phobia).^{8, 14} 

• Custom dosages (e.g., micro-titrations for patients sensitive to standard doses).^{7, 12} 

Physicians must document the clinical rationale for compounded versions, emphasizing how they address unmet patient needs.^{9, 14} 

Strengthening the Physician-Pharmacist Partnership  

Collaboration between prescribers and compounding pharmacists is essential to optimize patient outcomes. Key benefits include: 

1. Tailored Therapies: Pharmacists translate clinical needs into formulations (e.g., combining GLP-1s with B vitamins for potential metabolic support).^{3, 8} 

1. Precaution & Oversight: Pharmacists identify drug interactions, verify ingredient quality, and ensure sterility.^{5, 6} 

1. Adherence Support: Custom delivery methods (e.g., transdermal gels) improve compliance in patients struggling with injections.^{3, 13}

Determining When Compounding Is Necessary  

Compounded medications should be reserved for cases where FDA-approved options are unsuitable. Consider compounding when: 

1. Commercial Products Lack Flexibility: 

• A patient requires a dose outside standard increments (e.g., 0.125 mg semaglutide).^{8, 9}

• Allergies to inactive ingredients necessitate reformulation.^{7, 14} 

1. Unique Delivery Needs Exist: 

• Liquid formulations for patients with swallowing difficulties.^{3, 12}

• Topical gels for localized fat reduction in lipodystrophy.¹³ 

1. Combination Therapies Are Indicated: 

• Tirzepatide compounded with B Vitamins for potential reduction of nausea.^{8, 9} 

Documentation Requirements:

• Specify the clinical difference (e.g., “ODT form required due to needle phobia”). ^{9, 14} 
• Partner with 503A pharmacies accredited by PCAB or USP <795>/<797> compliant facilities.^{3, 13}