From commercial to compounded: What you need to know for your thyroid patients

Not all thyroid conditions are the same. Not all patients are the same. As a healthcare provider you know this all too well. When it comes to thyroid balance, too much or too little, and everything is thrown off – changes in mood, weight, and energy level are just some of the many symptoms. The complexity and crossover effect of thyroid function, as well as individual set points, lead to differences in clinical expression – and the challenging part – differences in response to therapeutics.

While commercial medications for the treatment of thyroid imbalance exist, fixed dosing increments and forms, unwanted ingredients, and commercial unavailability may impose limitations for healthcare providers that may result in unmet needs for their patients. With these challenges, providers are tasked to think outside the box – something we know compounders do on the daily. In this blog we will explore compounding options for managing thyroid insufficiency when commercially available products are unavailable or unsuitable to meet patient needs. Let’s break it down.

Personalization
When commercially available products are unavailable or unsuitable to meet patient needs, alternative measures, such as compounding may be required. Defined as the practice of preparing customized compounded medications in accordance with a licensed practitioner’s prescription to address a patient’s unique set of conditions, tolerances, and preferences, pharmaceutical compounding allows providers to consider the following for thyroid treatment plans:

1. Personalize Dosing
Dosing is based on an individual’s age, height, weight, cardiovascular status, concomitant medications, and severity of thyroid imbalance. With so many factors at play, pharmaceutical compounding provides the flexibility to prescribe various dosage strengths and dosage forms that are suitable in meeting the patient’s specific needs.


2. Eliminate Unwanted Ingredients
It is known that lactose, an excipient found in many thyroid preparations, may affect absorption of thyroid drugs and may contribute to patient intolerance2. Gluten, aluminum, and colorants may have similar effects and are also of concern. Compounded thyroid preparations can be made free of unsuitable fillers that may impede drug absorption or impact patient tolerance.


3. Tailor Dosage Form
Part of the pharmaceutical compounding process includes considering alternative dosage forms. At present, thyroid medications are generally commercially available in oral tablet and capsule form3. Other options may include oral liquids for patients unable to swallow tablets/capsules and sublingual forms for patients with refractory hypothyroidism that may be caused by gastric absorption4,5.


4. Consider Combination L-T4/L-T3 Therapy
Levothyroxine (L-T4) is the gold standard for hypothyroid treatment and one of the most commonly prescribed drugs in America6. However, approximately 5-10% of the population continue to have symptoms despite normal TSH and T4 levels7. A hypothesis for this symptom prevalence includes individual differences in the ability to convert L-T4 to its active form, liothyronine (T3), leaving these individuals limited in their ability to achieve therapeutically effective levels. Indeed, genetic differences and age are known to impact this conversion8,9. Taken together, for certain individuals, L-T4 alone may not be able to achieve the desired outcome, creating a rationale for L-T3 supplementation8.

Further contributing to the discussion around combination therapy is the growing evidence supporting patient preference for combination L-T4 + L-T3 therapy. In a 2018 survey of more than 12,000 people with hypothyroidism, desiccated thyroid extract – a naturally derived source of L-T4/L-T3 – was preferred over LT-4 alone10. Although not currently considered by the American Thyroid Association as a first-line treatment option, certain patients may benefit from this therapeutic alternative1. Interestingly, in a 2017 survey of American Thyroid Association members, it was discovered that combination therapy is becoming more commonly prescribed by North American physicians11.

When considering combination L-T4 and L-T3 therapy, providers have the following options available to them:

• Commercially available L-T4 alone + commercially available L-T3 alone. At present, L-T4 and L-T3 are only commercially available as separate medications that would need to be taken independently. While this can be a suitable option for some patients, it can be challenging for others to maintain leading to poor compliance.
  
  
• Compounded L-T4 and L-T3 combination. Simplifying the treatment regimen, L-T4 and L-T3 can be combined into a single dosage form at the desired strength and ratio. Excipient ingredient and dosage form selection can also be tailored when preparing the compounded medication.
  
  
• Commercially available desiccated thyroid extract. Desiccated thyroid extract or DTE is a natural source of combination T4 and T3 that is available in a variety of strengths. The challenge with this medication is the frequent recalls due to inconsistent potency12. Furthermore, certain commercial forms of DTE contain excipients that may interfere with absorption and impact patient tolerance.
  
  
• Compounded desiccated thyroid extract. Compounded DTE can be considered when commercial products are unavailable, when dosage strength or form need to be tailored, or when certain ingredients need to be avoided.

Here to Support Your Thyroid Compounding

Having the right tools to compound thyroid is an important part of the overall planning process when establishing personalized medications for patient-specific needs. From quality premade bases to reliable compounding equipment, and formulation support – all are vital pieces to the puzzle.

Bases

For capsules, Medisca CapsuBlend®-S is an ideal option. A premixed excipient blend, this base is recommended for highly soluble active ingredients, such as Thyroid, USP, and features improved drug dissolution13. This base is free of lactose, corn, and gluten.

For rapid dissolve tablets, Medisca Medi-RDT™ Base is a finely granulated powder that is compatible with a wide range of active ingredients. It has a significantly faster wetting time (5 seconds) and disintegrating time (93 seconds) compared to similar products on the market, and is free of preservatives, dyes, sugar, lactose, and gluten.

For liquid compounding, Medisca Oral Mix is an alcohol and dye-free vehicle that brings together the suspending properties of Medisca Oral Suspend and the cherry flavoring properties of Medisca Oral Syrup. A one-step vehicle that helps deliver elegant, flavourful, and physically stable suspensions.

Equipment

After selecting the appropriate base for your patient’s needs, equipment such as the Profiller Capsule Filling System and Medi-RDT Kit, and mixing technology such as the Inversina and Medisca MAZ can change the way you compound by making the process quicker, easier, reproducible, and more efficient.

Services

Don’t do it alone. Day-to-day Compounding Service Support is available – everything from access to an online formula databank, to daily compounding support with our team of Compounding Service experts, and clinical consultation support with our subject matter experts.

Education

The education opportunity is also plentiful – From LP3 Network’s renowned Hormone Seminar to their free webinar on Alternative Approaches to Hypothyroid Therapy.



References

References below are for information only and not for the purpose of representing or suggesting any ingredients or formulations for any indications.

1. Jonklaas, J., et al. (2014). Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid 24(12): 1670-1751.
2. Virili, C., Antonelli, A., Santaguida, M. G., Benvenga, S., & Centanni, M. (2019). Gastrointestinal Malabsorption of Thyroxine. Endocrine Reviews, 40(1), 118–136.
3. Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2022. Available from: http://online.lexi.com. Subscription required to view.
4. Tortora A, La Sala D, Vitale M. (2019) Switch from tablet levothyroxine to oral solution resolved reduced absorption by intestinal parasitosis. Endocrinol Diabetes Metab Case Rep. 2019 Mar 21;2019:19-0026. doi: 10.1530/EDM-19-0026
5. Peirce, C. Ippolito S., et al. (2018) Treatment of refractory and severe hypothyroidism with sublingual levothyroxine in liquid formulation. Endocrine 60, 193–196
6. Fuentes, A.V., et al. (2018). Comprehension of top 200 prescribed drugs in the US as a resource for pharmacy teaching, training and practice. Pharmacy (Basel), 6(2): 43.
7. Tariq, A., et al. (2018). Effects of long-term combination LT4 and LT3 therapy for improving hypothyroidism and overall quality of life. South Med J, 111(6): 363-369.
8. Biondi, B., & Wartofsky, L. (2012). Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism? The Journal of Clinical Endocrinology & Metabolism, 97(7), 2256-2271.
9. Bégin ME, Langlois MF, Lorrain D, Cunnane SC. (2008) Thyroid Function and Cognition during Aging. Current Gerontology in Geriatrics Research. 2008:474868. doi: 10.1155/2008/474868. Epub 2008 Sep 1.
10. Peterson S.J., et al. (2018). An online survey of hypothyroid patients captured predominantly dissatisfied individuals. Thyroid. 28:707–721.
11. Jonklaas, J., Tefera, E., & Shara, N. (2019). Short-term time trends in prescribing therapy for hypothyroidism: Results of a survey of American Thyroid Association members. Frontiers Endocrinology, 30.
12. Mangieri, C.N. & Lund, M.H. (1970). Potency of United Stated pharmacopeia dessicated thyroid tablets as determined by the antigoitrogenic assay in rats. Journal of Clinical Endocrinology & Metabolism, 30, 102-104
13. Pinheiro, V.A., Danopoulos, P., Demirdjian, L., Nogueira, R.J.L., & Dubois, F. (2013). In vitro evaluation of extemporaneously compounded immediate-release capsules with premixed excipients, based on the biopharmaceutics classification system (BCS) of the drugs. IJPC, 17(5): 423-431.