Liotrix - Indications, Dosage, Precautions, and More

Overview:

Liotrix is a stable synthetic thyroid hormone preparation. It comes under the class of combination drug preparation or fixed-dose combination (FDC), which contains two active ingredients composed of single-dose preparation. Liotrix is a mixture of synthetic thyroid hormone preparations, levothyroxine sodium (thyroxine, T4), and liothyronine sodium (triiodothyronine, T3) in a ratio by weight of 4:1, respectively. On 21st November 1969, Liotrix was approved by the U.S. Food and Drug Administration (FDA). It is a phenylalanine derivative.

Indications of Liotrix

• Liotrix is used as a thyroid hormone replacement preparation in conditions where there is reduced production or decreased levels of thyroid hormones in the body.

• It treats hypothyroidism (primary, secondary, and tertiary).

• Congenital hypothyroidism.

• Hashimoto’s thyroiditis (autoimmune disorder causing gradual destruction of the thyroid gland).

• Used in goiter (simple, nontoxic, and multinodular) as a suppressing agent of thyroid-stimulating hormone (TSH).

• Thyroid cancer management.

• Used as an adjuvant (to prevent hypothyroidism and goiterogenesis) with antithyroid medications to treat thyrotoxicosis.

• Long-standing myxedema.

Contraindication of Liotrix

• Liotrix is a hormone replacement therapeutic agent and should not be used for weight loss therapy or in treating obesity.

• It is not used in individuals who exhibit hypersensitivity reactions to thyroid hormones.

• Untreated thyrotoxicosis.

• Individuals taking sympathomimetic (adrenergic) drugs due to increased risk of cardiovascular complications.

• Untreated adrenal insufficiency.

• Acute myocardial infarction.

Dosage and Administration

Liotrix is available in six different dosage strengths in tablet form and is orally administered. Each tablet contains T3 and T4 in a ratio of 1:4 because T3 is four times more potent than T4. Since these are hormone substitutes, the dosage is prescribed depending on the levels of thyroid hormone in the blood and clinical investigations.

For Hypothyroidism

• Initial administration begins with a lower dose (half tablet daily) followed by a gradual increase in dosage, especially in elderly patients and those with long-standing and more severe hypothyroidism.

• The dose is increased monthly until a full replacement dose is achieved.

• This stepwise increase in dose is followed to gain drug tolerance and prevent sudden stress on cardiovascular and other organ functions, thereby preventing adverse complications.

• Full replacement dosage is often recommended for children and younger adults with minimal hypothyroidism.

• It is recommended to take it on an empty stomach (preferably early morning), one hour before breakfast, to achieve consistent hormone levels in the blood and also to prevent interference in its absorption by certain food items like coffee, dietary fiber, and soy (reduce the absorption of levothyroxine).

• The maintenance dose of Liotrix is based on the clinical response of hypothyroid patients.

For Patients

What Is Hypothyroidism?

Hypothyroidism is an endocrine disorder due to the thyroid gland's low secretion of thyroid hormones. It is also termed an underactive thyroid or hypothyroid state. The thyroid hormone contains iodine, a key component that plays a vital role in growth and development (intellectual), particularly in children. The thyroid hormone is responsible for maintaining an individual's basal metabolic (BMR) rate. It enhances energy production from nutrients like carbohydrates, proteins, and lipids by increasing their metabolism inside the cells. In decreased production of thyroid hormones, these metabolic activities get lowered, and the affected person becomes sluggish and slow, showing generalized tiredness. Hypothyroidism is seen more in females when compared to males. Middle-aged women, children, young adults, and pregnant women are more prone to develop hypothyroidism. The thyroid gland produces these hormones for essential growth and development, particularly in children, and for regulating energy demands at all age groups. When the thyroid gland does not produce sufficient thyroid hormones (T3 and T4), it results in hypothyroidism.

Symptoms of Hypothyroidism

• Tiredness.

• Intolerance to cold.

• Weight gain.

• Slow heart rate.

• Constipation.

• Depression.

• Loss of hair with dry and coarse skin.

• Swelling of hands and legs.

• In some cases of hypothyroidism, iodine deficiency leads to goiter (swelling in the neck due to enlargement of thyroid glands).

• Cardiac insufficiency and congestive cardiac failure in severe hypothyroidism.

• Breathing difficulty.

• In pregnancy, hypothyroidism leads to miscarriage or stillbirth.

• Neonates born to hypothyroid mothers develop cretinism (underdevelopment of the brain).

• Hypothyroid children show loss of memory and poor concentration skills.

What Is Liotrix and When Is It Prescribed?

Liotrix is a synthetic (not from a natural source) thyroid hormone combination preparation. It contains two thyroid hormones, T3 (triiodothyronine) and T4 (thyroxine), in a ratio of 1:4. It is given orally as tablets. Liotrix is used for the treatment of hypothyroidism (decreased thyroid hormone secretion). Liotrix contains T3 and T4, which get added to the thyroid hormone levels in the body when taken orally and maintain normal levels of thyroid hormones (euthyroid) in the blood. Liotrix is prescribed for the following hypothyroid conditions,

• Severe hypothyroidism.

• Congenital hypothyroidism.

• Myxedema (severe hypothyroidism with cardiac complications).

• Hashimoto's thyroiditis (complete destruction of thyroid cells due to autoimmune reaction).

• Surgical removal of the thyroid gland (due to carcinoma).

• During pregnancy (extreme monitoring is needed).

• Goiter.

• Injury or carcinoma in the anterior pituitary gland (lack of stimulating thyroid hormone).

• Previous chemotherapy with radioactive iodine.

What Are the Warnings and Precautions for Using Liotrix?

• Liotrix should not be used for weight loss and correction of obesity.

• It should not be taken as a dietary supplement.

• Liotrix should not be taken as self-medication on suspecting symptoms.

• Professional consultation and proper evaluation of serum thyroid levels are mandatory before starting thyroid treatments.

• Liotrix contains thyroid hormones that would reflect in the blood levels and produce therapeutic effects. Hence adjustment of dosage should be made only by clinical practitioners or endocrinologists.

• Adjustment of dosages, discontinuing the usage, and restarting should not be done under self-medication.

• Children with hypersensitivity to thyroid hormones must be reported.

• Individuals with adrenal insufficiency must report the condition before taking Liotrix.

• Thyroid replacement must be done with caution in patients with renal failure, diabetes, hypertension, and cardiac dysfunction.

• Patients on oral anti-diabetic drugs and steroid therapy must also be precautioned before taking Liotrix.

• Dosage in pregnant mothers must be closely monitored to prevent thyrotoxicosis (increased thyroid levels in the blood).

• Thyroid hormone levels and TSH levels must be monitored every six months to prevent adverse effects.

• Dosages are customized for a particular individual. Sharing of the same prescriptions is strictly prohibited.

What Are the Side Effects of Using Liotrix?

Liotrix is a hormone replacement drug that does not produce severe side effects. It is safe and recommended under proper clinical evaluation and regular monitoring of serum T3 and T4 levels. The side effects are often related to overdosage, hypersensitivity, or under-evaluated conditions.

• Allergic rashes with itching.

• Wheezing and tightness in the chest.

• Headache.

• Irritable feeling.

• Insomnia (unable to sleep properly).

• Nervous feeling and excitability.

• Heat intolerance.

• Tremors.

• Leg pain with cramps and fever.

• Muscular weakness.

• Change in appetite.

• Unusual weight loss.

• Nausea and vomiting.

• Irregular menstrual flow.

Some Additional Precautionary Measures

• In case of missing a dose on a particular day, continue with regular dosage the following day. Do not add on the dosages.

• Litorix is to be stored in a cool, dry place away from sunlight and should not be frozen.

• Should be kept out of reach of children.

• If the clinical condition remains the same or worsens, do not discontinue the drug. A clinician or endocrinologist is to be consulted immediately.

• In case of accidental overdosage, consult the doctor immediately.

For Doctors

Pharmacodynamics

Thyroid hormones (T3 and T4) are synthesized in thyroid follicular cells by trapping iodine and incorporating it into tyrosine (an amino acid). T4 is the major secretory form, whereas T3 is the more active form of thyroid hormone.T4 is converted into T3 in the peripheral tissues by deiodinases. T3 binds to the thyroid hormone receptors in the cells and increases the oxygen consumption required for various metabolic activities, thereby increasing the basal metabolic rate (BMR).

These hormones increase the sensitivity of the tissues to catecholamines, such as adrenaline, and influence protein synthesis. Thyroid hormones facilitate the proper development and differentiation of tissues and cells in the body. The most pronounced action of thyroid hormones is to enhance the use of energy-giving nutritional components. The derivatives of thyroid hormones initiate the downregulation of these metabolic cycles. Hence, they are essential for metabolizing carbohydrates, lipids, and proteins. They also enhance the growth and developmental maturation of various organ systems, especially the central nervous system.

The secretion of these hormones is controlled by the thyroid-stimulating hormone (TSH) from the anterior pituitary gland. The regulation of thyroid secretion is by a negative feedback mechanism. When T3 and T4 levels decrease in the blood, TSH secretion is increased to stimulate more production of thyroid hormones. Adequate levels of T3 and T4 in the blood inhibit the release of TSH. Liotrix, a synthetic preparation of T3 and T4, acts as a replacement substitute in hormone deficiency (hypothyroid state) and exerts a similar feedback regulation on TSH.

Chemical Taxonomy of Liotrix

Pharmacokinetics

The route of entry is oral administration, and their bioavailability is 50 % to 95 %. T3 is a more potent and active form that is absorbed more rapidly than T4 after oral ingestion; the half-life of T3 is 2.5 days, whereas T4 varies by clinical thyroid conditions. In the euthyroid state (normal level), the half-life of T4 is six to seven days, three to four days in the hyperthyroid state, and in the hypothyroid condition, it is nine to ten days. The onset of action starts within 48 hours when the peak plasma levels reach 12 to 48 hours. The absorption rate is 95 % for T3 and 40 % to 80 % for T4. Maximum effects of action last up to eight to ten days. T3 usually exists in free form, whereas 99 % of T4 are protein bound. Triiodothyronine (metabolic form) is metabolized predominantly in the liver and, to an extent, in the kidneys and intestinal walls. Thyroid hormone metabolites are primarily eliminated in the urine by the kidneys.

Drug Interactions

• Liotrix increases vasoconstricting activities of vasopressin.

• Excretion of Liotrix is decreased in combination with cyclosporine.

• The risk for adverse effects is enhanced when combined with Amphetamine and Liotrix.

• Metabolism of Nicotine is decreased with Liotrix.

• The risk or severity of cardiac adverse effects can be increased when norepinephrine is combined with Liotrix.

• Liotrix reduces the efficacy of Metformin.

• The severity of bleeding increases when Liotrix is combined with Warfarin and Dicoumarol.

Toxicity

Liotrix was initially developed when studies suggested that T4 and T3 serum levels were regulated by direct thyroid gland secretion. Subsequent studies proved that the thyroid gland secretes T4 more than ten times compared to T3, and also 85 % of T4 eventually is deionized to T3 in the peripheral tissues. Recent evidence suggests that the administration of T4 is sufficient in milder hypothyroidism, and combination therapy should be considered only during severe conditions (myxedema, Hashimoto's thyroiditis, etc.). The toxicity of Liotrix is attributed to this pharmacodynamic aspect since misinterpreting T3-T4 combination administration would lead to supratherapeutic levels of T3, resulting in Liotrix toxicity. The following are symptoms of toxicity,

• Thyrotoxicosis (due to supraphysiologic plasma T3 levels).

• Cardiotoxicity.

• Hypermetabolic complications.

• Increased weight loss.

• Increased appetite.

• Palpitations.

• Nervousness.

• Diarrhea.

• Abdominal cramps.

• Sweating.

• Tachycardia.

• Increased pulse rate and blood pressure.

• Cardiac arrhythmias.

• Tremors.

• Insomnia.

• Heat intolerance.

• Fever.

• Menstrual irregularities.

Points to Ponder for Doctors

Liotrix prescription must always follow TSH, serum T3, and T4 evaluation. Regular monitoring of the clinical response is essential. T3 gets metabolized easily, whereas it takes weeks for T4 levels to show in the blood. Misinterpreting the levels would lead to adverse effects. Dosage for children would require additional monitoring as it is calculated according to the children's body weight. Liotrix should be used only to achieve a euthyroid state, and vigilant monitoring is needed to prevent complications due to excessive levels of thyroid hormones.