Tablet Splitting of a Narrow Therapeutic Index Drug: A Case with Levothyroxine Sodium

In some cases, physicians may also prescribe thyroid medication to treat other conditions, such as goiter (enlarged thyroid gland) or certain types of infertility. “First, ask your doctor or pharmacist whether your medication can be safely split. Some medications should not be split (more on that below), but in general, many common ones can, includingaspirin, cholesterol-lowering drugs known as statins, and many high blood pressure and depression drugs. And always use a pill splitter to ensure you’ve split the medication into equal halves. Surprisingly, a Dutch study found that hand breaking tablets was more accurate than using a pill splitter (International Journal of Pharmaceutics, May 15, 2014). So it seems that pharmacists and physicians may need to re-think their advice on splitting pills.

• Additionally, the study found that the distribution of levothyroxine within the tablets was heterogeneous, influenced by the type of binder and manufacturing process used, further complicating the reliability of split tablets.
• Moreover, splitting tablets can compromise the integrity of the medication, affecting its stability and absorption.
• At 0 week time point, the samples were also analyzed for weight variation, content uniformity (CU), and dissolution.

This unpredictability can make it difficult to monitor and manage thyroid hormone levels effectively, potentially leading to fluctuations in symptoms and the need for more frequent blood tests to adjust the dosage. Several types of thyroid medications are available, each with its own active ingredient, dosage forms, and potential side effects. The most common is levothyroxine (brand names include Synthroid, Levothroid, and others), a synthetic form of thyroxine (T4), the primary thyroid hormone produced by the thyroid gland. It’s available in tablet form, typically ranging from 25 mcg to 200 mcg, and is adjusted based on individual needs and blood test results. The consistency and accuracy of dosage when splitting pills are highly variable and depend on several factors.

Concerns regarding tablet splitting: a systematic review

As it concerns levothyroxine tablets, it’s an interesting case because, on the surface, it is fine to do so as it is not an extended or modified-release drug, but there are the concerns that I outlined above. Potency determination for tablet samples was performed on each stability time point. Twenty whole tablets or split portions were transferred to a mortar and ground with a pestle to a fine, homogenous powder. Powder obtained from tablet grinding was aliquot into labeled vials for subsequent potency experiments. Patients can administer it by pouring the contents of the monodose ampule directly into the mouth, using a spoon or mixing it in water. A data matrix was recently added to the monodose ampule to facilitate its use in hospitals, where more complex cases of hypothyroidism are often initially treated.

Potential Side Effects of Thyroid Medication

Tablets are either hand-splitted or use of a variety of tablet splitters has been frequently cited for scored or unscored tablets (1–3). It is an easy-to-use device in which tablets are cut into halves and is reported to have higher patients adherence due to ease of splitting as well as cost benefits (1,2). For instance, Fawell and colleagues (2) in a study of 1,617 patients who were divided into groups that split and did not split tablets found that tablet splitting did not hinder compliance as measured by tablet counting.

Understanding the different types, dosages, potential side effects, and appropriate uses of these medications is vital for effective treatment and patient well-being. Differentiated thyroid cancer is the most common malignancy of endocrine system (1-3) and its prevalence is increasing worldwide. As this pathology mostly occurs in the middle age population and it has excellent prognosis, the patients are expected to live for a long time after diagnosis. Replacement or suppressive therapy with Levothyroxine is the standard therapeutic protocol in these patients following total thyroidectomy and radioactive iodine therapy.

Some hypothyroid patients do best when their thyroid hormone replacement treatment includes a second hormone – T3. T3 therapy can be accomplished by adding the synthetic medication liothyronine (Cytomel) to levothyroxine treatment or taking natural desiccated thyroid (NDT), which includes natural forms of both T4 and T3. Another medication, liothyronine (brand name Cytomel), is a synthetic form of triiodothyronine (T3), a more active form of thyroid hormone. It’s also available in tablet form, usually in smaller doses than levothyroxine. While less frequently prescribed alone, it can be used in combination with levothyroxine or in specific clinical situations. Dosages are carefully determined by a physician based on individual patient requirements and monitored through regular blood tests.

Splitting Thyroid Tablets: Hi Everyone Is it ok… – Thyroid UK

One hundred differentiated thyroid cancer patients who were under suppressive therapy with one and a half 100 µg levothyroxine sodium tablets were included in the study. The serum TSH and T3 levels were measured in all patients at baseline, and then they were randomly divided into two groups. The first group continued taking medication as before and the second group received the same daily dose by taking one 100 and one 50 microgram Levothyroxine tablets. Thyroid function tests were repeated at least three weeks later and the results were compared. To ensure consistency of used drug in patients, all tablets used in these patients were produced by the same company (Iran-hormone Company) that is the most common generic form in Iran. Consumption pattern of Levothyroxine tablet and plasma levels of TSH and T3 and the patients’ weight were recorded at the beginning and the end of the study and the mean changes in TSH and T3 levels and weight in both groups were compared.

It can be noted that the dissolution failures were less pronounced as compared to CU since the specifications are more relaxed for dissolution as compared to CU specifications. Therefore, dissolution might not be the best quality-control test for immediate release split tablets. However, this cannot be generalized, and a case-by-case approach is needed to confirm. It should be noted that dissolution test could prove to be very valuable for extended release tablets synthroid dizziness when they are splittable.

Since manufacturing dates were unknown for the marketed samples, the stability study was conducted 5months before their expiry date which was considered week 0 in our study. Tablets were stored in a controlled condition (temperature between 20°C and 22°C) prior to start of the stability studies. Conducting stability studies 5 months prior to expiry can be used to compare the stability profiles head-to-head since the manufacturing dates for all different marketed tablets might be different.

Health Topics

More serious, but less common, side effects can include irregular heartbeat, chest pain, and allergic reactions. In recognition of the problems of dose consistency, two advisory committee meetings were held in US Food and Drug Administration to discuss the potency and stability issues of levothyroxine sodium drug products. The American Thyroid Association, the Endocrine Society, and the American Association of Clinical Endocrinologists indicated a lack of consistency of clinical performance.