by Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist

As compounding pharmacists, we’re tasked with maintaining the highest levels of quality and safety in the medications we provide. It’s often challenging to meet the requirements of current rules and regulations while maintaining a profitable practice. The sourcing of our raw materials and active pharmaceutical ingredients (APIs) is an area where pharmacists must constantly evaluate cost and quality. Unfortunately, not all chemicals or chemical suppliers are created equal and therefore it’s necessary to create a component selection process for your pharmacy to ensure your chemicals meet current guidelines for use by the FDA.

The use of oxytocin as an API has risen in recent years due to emerging research about its usage for a variety of clinical applications. We wanted to shed some light on this chemical and use it as an example for creating API selection criteria in your pharmacy.

Oxytocin 101

Oxytocin is a natural human hormone that is secreted by the hypothalamus and stored in the pituitary gland. It has several FDA approved indications, with labor induction being the most common use. It is available commercially as oxytocin 10 Unit/mL solution for injection.¹

Oxytocin has also been studied for many off label uses as well, including intractable pain, autism, fibromyalgia, migraine, social anxiety, sexual dysfunction, weight loss and vaginal atrophy.^2-9 The most common dosage forms used in compounding are intranasal, sublingual and vaginal preparations.

It is important to note that oxytocin is sensitive to heat and should not be formulated in dosage forms such as rapid dissolve tablets or troches that require heat to make the final product.

Oxytocin Chemical Selection Criteria

At first glance, you may not think twice about choosing various oxytocin salts as an API. We are accustomed to seeing different salt forms of APIs. Lidocaine base vs. lidocaine HCl and dexamethasone vs. dexamethasone sodium phosphate are two common examples. In order to qualify an API for use in your pharmacy, there are several criteria you need to consider. Let’s take a look at oxytocin and one of its salts, oxytocin acetate, to see how these criteria apply.

In order to qualify for use as an API, the Federal Food, Drug and Cosmetic Act (FD&C Act) requires a chemical must meet ONE of the following qualifications:¹⁰

1. The API must be an active ingredient of an FDA approved product.

   1. Oxytocin USP is the active ingredient in commercially available Pitocin®.¹¹

   2. Oxytocin acetate is not an ingredient in an FDA approved product.

2. The API must have a USP monograph.

   1. Oxytocin has a USP monograph.¹²

   2. Oxytocin acetate does not have a USP monograph.

3. The API must be listed on the positive list of bulk drug substances for 503A or 503B pharmacies.^{13, 14}

   1. Oxytocin doesn’t need to be listed here because it meets the previous criteria.

   2. Oxytocin acetate is not found on either of these lists.

In the example above, you can see that oxytocin acetate doesn’t meet any of the eligibility requirements for compounding. Compounding with an unapproved API renders the medication to be adulterated under the FD&C Act and would reclassify the 503A pharmacy as a manufacturer that must follow Current Good Manufacturing (cGMP) guidelines.

Once you’ve determined if a chemical meets the criteria for eligibility for compounding, you must still evaluate the quality of that chemical using the Certificate of Analysis (COA) provided by your supplier. However, there is a misconception among some pharmacy professionals that a COA is the only item you need to scrutinize before approving a chemical.

By using the three criteria above and evaluating a COA, you will be on the right track to choosing the best APIs to use in your compounded preparations.

References

1. American College of Obstetrics and Gynecology (ACOG). (2009) ACOG Practice Bulletin Number 107: Clinical Management Guidelines for Obstetrician-Gynecologists. Induction of Laor. Washington, DC: American College of Obstetricians and Gynecologists.

2. Anderson, P. (2017) Unique Drug Combo Promising for Severe, Intractable Pain. Accessed September 2023 at https://www.medscape.com/viewarticle/887835#vp_2

3. Watanabe T, Kuroda M, Kuwabara H, et al. (2015) Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain.;138:3400-3412. doi:10.1093/brain/awv249

4. Mameli S., Pisanu G.M., Sardo S., et al. (2014) Oxytocin nasal spray in fibromyalgic patients. Rheumatol Int. 34:1047–1052. doi:10.1007/s00296-014-2953-y

5. Anderson, P. (2013) Intranasal Oxytocin Looks Promising for Migraine. Accessed September 2023 at https://www.medscape.com/viewarticle/807277

6. Guastella A.J., Howard A.L., Dadds M.R., et al. (2009) A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder. Psychoneuroendocrinology. 34:917-23.

7. MacDonald K., Feifel D. (2012) Dramatic Improvement in Sexual Function Induced by Intranasal Oxytocin. J SexMed 9:1407–1410.

8. Zhang H., Wu C., Chen Q., et al. (2013)Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models. PLoS One. 8(5):e61477.

9. Jonasson, A. F., Edwall, L., & Uvnas-Moberg, K. (2011). Topical oxytocin reverses vaginal atrophy in postmenopausal women: a double-blind randomized pilot study. Menopause International. 17(4), 120-125.

10. Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act. Accessed September 2023 at https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act

11. Pitocin Package Insert. Accessed September 2023 at https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018261s031lbl.pdf

12. Oxytocin USP Monograph. Accessed August 2023 at https://online.uspnf.com/uspnf/document/1_GUID-19C2CA26-32EE-45C2-BF4E-A12A875B714B_1_en-US?source=Search%20Results&highlight=oxytocin

13. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug and Cosmetic Act. Accessed September 2023 at https://www.fda.gov/media/94155/download

14. Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act. Accessed September 2023 at https://www.fda.gov/media/94164/download