What are shortage alternatives for Clinisol 15%?

Comment by InpharmD Researcher

A comprehensive literature search did not identify any comparative studies on therapeutic alternatives for Clinisol 15% sulfate-free parenteral nutrition solution. According to the American Society of Health-system Pharmacists (ASHP), several products are listed as available options, including Aminosyn II 10%, Plenamine 15%, and Travasol 10%, but there is no evidence to suggest they are interchangeable with Clinisol 15%. One source lists certain amino acid solutions as therapeutically equivalent (Tables 1 and 2) while acknowledging substitution can present challenges due to differences in pH, electrolytes, and excipients, which may impact stability, compatibility, and clinical outcomes.

Background

Per the American Society of Health-System Pharmacists (ASHP) current drug shortage database, Baxter has the Clinisol 15% injection (sulfite-free) on shortage due to manufacturing delays. The panel has listed the following products as available options, but did not make any comments regarding their interchangeability with Clinisol 15%: Aminosyn II (sulfite-free) injection 10%, Aminosyn II (sulfite-free) injection 15%, Plenamine injection 15%, Premasol (sulfite-free) injection 10%, Prosol (sulfite-free) injection 20%, Travasol injection 10%, and TrophAmine injection 10%. It was stated that Baxter has 15% Clinisol 500 mL containers available in limited supply. While the American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines provide general recommendations for managing shortages of parenteral nutrition products, no specific substitutions for any product were suggested. [1], [2]

A 2018 paper presented at the National Home Infusion Association annual conference provides systematic strategies for surviving shortages and managing parenteral nutrition (PN) patients. It was highlighted that product substitution, though often seen as a simple solution for shortages, can cause compounding challenges with PN components, affecting compatibility, stability, and sterility due to differences in pH, electrolytes, active components, and excipients. Substituting therapeutically equivalent products can present unique challenges, particularly with amino acid (AA) solutions. Table 1 outlines the pH differences across various brands of standard AA solutions available in the U.S., while Table 2 lists specialty AA solutions. The author stated that the AA products in Table 1, including Aminosyn 8.5% and 10%, Aminosyn II 10% and 15%, Travasol 10%, Clinisol 15%, Prosol 20%, FreAmine III 10%, and Plenamine 15%, are considered therapeutically equivalent gram for gram and can be substituted with the expectation of achieving similar clinical outcomes. Though no other discussion on Clinisol was provided, it was mentioned that substituting Aminosyn for Travasol in a total nutrient admixture (TNA) compromises stability due to Aminosyn’s lower pH, while FreAmine III is acceptable because its higher pH supports stability. However, FreAmine’s higher pH increases the risk of calcium-phosphate precipitation, especially if phosphorus content or a specific solubility curve isn’t accounted for. Sulfite preservatives in AA solutions mainly affect vitamin stability, such as thiamine. The article did not discuss Clinisol or its acceptable alternatives in further detail. [3]

In a 2020 letter B. Braun Medical Inc. informed their consumers regarding a temporary allocation of Plenamine™ 15% Amino Acids Injection 1000 mL due to a temporary delay in the release of Active Pharmaceutical Ingredient (API) impacting product manufacturing. In the meantime, the manufacturer recommended the use of either a 15% Clinisol amino acid injection or the 15% Aminosyn™ II as substitutes. It’s important to note that the manufacturer did not supply any comparative evidence to support this recommendation. [4]

References:

[1] American Society of Health-System Pharmacists (ASHP). Current Drug Shortages. Amino acid products. Updated September 6, 2024. Accessed October 2, 2024. https://www.ashp.org/drug-shortages/current-shortages/drug-shortage-detail.aspx?id=564&loginreturnUrl=SSOCheckOnly
[2] American Society for Parenteral and Enteral Nutrition (ASPEN). Parenteral Nutrition Amino Acids Product Shortage Considerations. Updated April 20, 2016. Accessed October 2, 2024. https://www.nutritioncare.org/News/General_News/Parenteral_Nutrition_Amino_Acids_Product_Shortage_Considerations/
[3] Rollins CJ. Surviving shortages and managing parenteral nutrition patients. Presented at: NHIA Annual Conference; April 25, 2018; Phoenix, AZ. Accessed October 2, 2024. https://nhia.org/documents/CE_June_july_2018.pdf
[4] B. Braun Medical Inc.Temporary Allocation on Plenamine. Published December 2020. Accessed October 2, 2024. https://www.nutritioncare.org/uploadedFiles/News/20-0455_Plenamine_Allocation_Customer_Ltr_B%20Braun_120120.pdf

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

What are shortage alternatives for Clinisol 15%?

Level of evidence

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Please see Tables 1-2 for your response.


 

Standard Amino Acid Products Available in the U.S.

Brand Name pH pH Range Product Concentrations; Relative Additives
Aminosyn 5.2 4.5 – 6.0 8.5%, 10%
Aminosyn II 5.8 5.0 – 6.5 10%, 15%
Travasol 6.0 5.0 – 7.0 10%
Clinisol 6.0 5.0 – 7.0 15%
Prosol 6.0 5.5 – 6.5 20%
FreAmine III 6.5 6.0 – 7.0 10%; 0.1 mMol P/g AA; Sodium sulfite
Plenamine 5.6 5.2 – 6.0 15%; Sodium metabisulfite

 

References:

Adapted from:
Rollins CJ. Surviving shortages and managing parenteral nutrition patients. Presented at: NHIA Annual Conference; April 25, 2018; Phoenix, AZ. Accessed on October 2, 2024. https://nhia.org/documents/CE_June_july_2018.pdf

 

Specialty Amino Acid Products Available in the U.S.

Brand Name pH pH Range Intended Use/Population; Notes
Aminosyn HBC 5.2 4.5 – 6.0 Stress
FreAmine HBC 6.5 6.0 – 7.0 Stress
HepatAmine 6.5 6.0 – 6.8 Liver Failure; 0.1 mmol P/g AA
Aminosyn RF 5.2 4.5 – 6.0 Renal Failure; essential amino acid + Arginine
NephrAmine 6.5 6.0 – 7.0 Renal Failure; essential amino acid only
Aminosyn PF 5.5 5.0 – 6.5 Pediatric
Premasol 5.5 5.0 – 6.0 Pediatric, equivalent of TrophAmine
TrophAmine 5.5 5.0 – 6.0 Pediatric

 

References:

Adapted from:
Rollins CJ. Surviving shortages and managing parenteral nutrition patients. Presented at: NHIA Annual Conference; April 25, 2018; Phoenix, AZ. Accessed on October 2, 2024. https://nhia.org/documents/CE_June_july_2018.pdf