Liotrix (Euthyral) - Uses, Dose, Side effects, MOA, Brands

Liotrix (Euthyral) is a combination of levothyroxine (T4 or Thyroxine) and liothyronine (T3, Active form) in a ratio of 4:1. It is used in the management of patients with hypothyroidism.

Liotrix Uses:

  • Hypothyroidism:

    • It is used to replace the deficient thyroid hormones in patients with hypothyroidism.

Note:

  • It is significant to note that the current recommendations for the treatment of hypothyroidism do not recommend the use of combinedIt is significant to note that the current recommendations for the treatment of hypothyroidism do not recommend the use of combined

See: Medicines that interact with T3 and T4.


Liotrix (Euthyral) Dose in Adults:

Liotrix (Euthyral) Dose in the treatment of Hypothyroidism: Oral:

  • Initial:
    • Levothyroxine 25 mcg/liothyronine 6.25 mcg once a day.
    • Patients with long-standing myxedema and those with underlying cardiovascular diseases should be initiated on lower doses initially (levothyroxine 12.5 mcg/liothyronine 3.1 mcg).
    • levothyroxine/liothyronine combinations above levothyroxine monotherapy.
    • Every two or three weeks, the dosage can be raised by levothyroxine 12.5 mcg/liothyronine 3.1 mcg increments.
  • Usual maintenance dose:

    • Liothyronine 12.5 to 25 mcg/levothyroxine 50 to 100 mcg once daily.
    • Patients may be asked for compliance or tested for poor absorption/ excessive drug elimination if the patient has an inadequate response to the treatment.
    • The brand may need to be changed if inactivity of the preparation is suspected.

Liotrix (Euthyral) Dose in Childrens:

Note:

  • In the management of hypothyroidism, the current recommendations do not favour levothyroxine/liothyronine combos over levothyroxine monotherapy.
  • Based on the patient's clinical and biochemical reaction to the medication, the dose should be changed.

Liotrix (Euthyral) Dose in the treatment of Congenital hypothyroidism:

Note: It is important to initiate the infants on full dosage. Oral: Usual daily dosage range:

  • Infants ≤6 months:

    • Liothyronine (T3) 3.1 to 6.25 mcg/levothyroxine (T4):

      • 12.5 to 25 mcg once a day.
  • Infants >6 to 12 months:

    • Liothyronine (T3) 6.25 to 9.35 mcg/levothyroxine (T 4):

      • 25 to 37.5 mcg once a day.
  • Children 1 to 5 years:

    • Liothyronine (T3): 9.35 to 12.5 mcg/levothyroxine (T4):

      • 37.5 to 50 mcg once a day.
  • Children 6 to 12 years:

    • Liothyronine (T3): 12.5 to 18.75 mcg/levothyroxine (T4):

      • 50 to 75 mcg once a day
  • Adolescents:

    • Typical doses > Liothyronine (T3): 18.75 mcg; levothyroxine (T4):

      • 75 mcg once a day.

Liotrix (Euthyral) Pregnancy Risk Category: A

  • The placental barrier is not crossed by endogenous thyroid hormones. The fetal thyroid gland is functional at the end of the first trimester.
  • It is safe to be given during pregnancy. If maternal hypothyroidism goes untreated, it can cause adverse maternal and fetal outcomes.
  • To avoid adverse pregnancy outcomes, it is crucial to maintain normal thyroid hormone function before conception and throughout pregnancy.
  • Hypothyroidism in pregnancy is treated with levothyroxine.

Liotrix use during breastfeeding:

  • Breastmilk is minimally contaminated with endogenous thyroid hormones, which are not harmful to infants.

Dose in Kidney Disease:

There are no dosage adjustments provided in the manufacturer's labeling.

Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer's labeling.


Side effects of Liotrix (Euthyral):

  • Cardiovascular:

    • Cardiac Arrhythmia
    • Chest Pain
    • Increased Blood Pressure
    • Palpitations
    • Tachycardia
  • Central Nervous System:

    • Anxiety
    • Ataxia
    • Headache
    • Insomnia
    • Nervousness
  • Dermatologic:

    • Alopecia
    • Diaphoresis
    • Pruritus
    • Urticaria
  • Endocrine & Metabolic:

    • Menstrual Disease
    • Weight Loss
  • Gastrointestinal:

    • Abdominal Cramps
    • Constipation
    • Diarrhea
    • Increased Appetite
    • Nausea
    • Vomiting
  • Neuromuscular & Skeletal:

    • Myalgia
    • Tremor
    • Tremor Of Hands
  • Respiratory:

    • Dyspnea
  • Miscellaneous:

    • Fever

Contraindications to Liotrix (Euthyral):

  • Allergy to liotrix and any component of the formulation
  • Patients suffering from untreated adrenal insufficiency
  • Patients suffering from untreated thyrotoxicosis.

Warnings and precautions

  • Insufficiency of the adrenal glands:

    • Patients with untreated adrenal insufficiency are not advised to take thyroid hormones.
    • It is important to replace adrenal hormones before you start thyroid hormone replacement.
    • Thyroid hormones can exaggerate symptoms of clinical or subclinical adrenal insufficiency.
  • Cardiovascular disease

    • Patients suffering from ischemic heart disease must be started on low doses of thyroid hormone replacement.
    • This could lead to angina, worsening symptoms, or even worsening the condition.
    • Patients with untreated chronic hypothyroidism are also at risk for developing ischemic heart disease.
  • Diabetes:

    • Thyroid hormones can cause a decrease in glycemic control. Patients with diabetes mellitus or diabetes insipidus should not use it.
  • Myxedema

    • To avoid exacerbating the symptoms, patients suffering from long-term myxedema should receive it in lower doses. These patients should be advised to take caution.

Liotrix (United States: Not available): Drug Interaction

Risk Factor C (Monitor therapy)

Amezinium

Thyroid Products may enhance the stimulatory effect of Amezinium.

Amiodarone

May diminish the therapeutic effect of Thyroid Products.

Apalutamide

May diminish the therapeutic effect of Thyroid Products.

CarBAMazepine

May decrease the serum concentration of Thyroid Products.

Ciprofloxacin (Systemic)

May decrease the serum concentration of Thyroid Products.

Estrogen Derivatives

May diminish the therapeutic effect of Thyroid Products.

Fosphenytoin

May decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites.

Phenytoin

May decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites.

Piracetam

May enhance the adverse/toxic effect of Thyroid Products. Specifically, symptoms including confusion, irritability, and sleep disorder have been described during concomitant use.

RifAMPin

May decrease the serum concentration of Thyroid Products.

Ritonavir

May diminish the therapeutic effect of Thyroid Products.

Selective Serotonin Reuptake Inhibitors

May diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased.

Somatropin

May diminish the therapeutic effect of Thyroid Products.

Theophylline Derivatives

Thyroid Products may increase the metabolism of Theophylline Derivatives. Exceptions: Dyphylline.

Tricyclic Antidepressants

Thyroid Products may enhance the arrhythmogenic effect of Tricyclic Antidepressants. Thyroid Products may enhance the stimulatory effect of Tricyclic Antidepressants.

Vitamin K Antagonists (eg, warfarin)

Thyroid Products may enhance the anticoagulant effect of Vitamin K Antagonists.

Risk Factor D (Consider therapy modification)

Bile Acid Sequestrants

May decrease the serum concentration of Thyroid Products. Management: Administer oral thyroid products at least 4 h prior to colesevelam, and at least 1 h before or 4-6 h after cholestyramine. Specific recommendations for colestipol are not available. Monitor for decreased concentrations/effects of the thyroid product.

Calcium Polystyrene Sulfonate

May decrease the serum concentration of Thyroid Products. Management: To minimize risk of interaction, separate dosing of oral calcium polystyrene sulfonate and thyroid products (eg, levothyroxine) or administer calcium polystyrene sulfonate rectally. Monitor for signs/symptoms of hypothyroidism with concomitant use (oral).

Calcium Salts

May diminish the therapeutic effect of Thyroid Products. Management: Separate the doses of the thyroid product and the oral calcium supplement by at least 4 hours.

Lanthanum

May decrease the serum concentration of Thyroid Products. Management: Administer oral thyroid products at least two hours before or after lanthanum.

Sodium Polystyrene Sulfonate

May decrease the serum concentration of Thyroid Products. Management: To minimize risk of interaction, separate dosing of oral sodium polystyrene sulfonate and thyroid products (e.g., levothyroxine) or administer sodium polystyrene sulfonate rectally. Monitor for signs/symptoms of hypothyroidism with concomitant use (oral).

Risk Factor X (Avoid combination)

Sodium Iodide I131

Thyroid Products may diminish the therapeutic effect of Sodium Iodide I131.

 

Monitoring parameters:

  • Monitor TSH 6 weeks after treatment initiation or any dose adjustment. Once the thyroid hormone levels stabilize and no dosage adjustment is required, TSH may be measured 4 - 6 monthly and then yearly depending on the patients' condition and clinical situation.
  • Heart rate, blood pressure, and the clinical symptoms of hypo- and hyperthyroidism. Thyroxine (T4) levels.
  • The most accurate test to determine whether thyroid hormone replacement is working well is the TSH test. Despite the patients being clinically thyroidally normal over the first few months, TSH levels may continue to be elevated.
  • "Free" T4 may be monitored in patients with central hypothyroidism and those with low T4 and normal TSH levels.

How to administer Liotrix (Euthyral)?

It is delivered with a glass of water on an empty stomach.


Mechanism of action of Liotrix (Euthyral):

  • It is composed of Thyroxine, T-4, and Triiodothyronine, in a ratio 4:1.
  • The body converts Thyroxine to its active form, T3.
  • It controls metabolism and affects how different tissues develop and grow.
  • Although the precise mechanism of action of thyroid hormones is unknown, it is certain that they exert their effects through protein and DNA synthesis.
  • It stimulates protein synthesis and promotes gluconeogenesis.

The onset of action:

  • Liothyronine (T3 ): About 3 hours

Absorption:

  • Thyroxine (T4 ): 40% to 80%;
  • T3: 95%

Protein binding:

  • T4: Thyroxine is highly attached to plasma proteins such as albumin, thyroxine-binding pre-albumin, and thyroxine-binding globulin.

Metabolism:

  • The liver metabolises it to the active form (triiodothyronine).
  • In the kidney and peripheral, around 80% of T4 is deiodinated; glucuronidation and conjugation also take place. It circulates through the enterohepatic system.

Half-life elimination:

  • T-4 :
    • Euthyroid: 6-7 days;
    • Hyperthyroid: 3-4 days;
    • Hypothyroid: 9-10 days
  • T-3: 2.5 days

Time to peak serum concentration:

  • T-4: 2-4 hours;
  • T-3: 2-3 days

Excretion:

  • Urine (major route of elimination);
  • It is partially excreted in feces

International Brand Names of Liotrix:

  • Thyrolar
  • Euthyral
  • Thyreotom
  • Thyreotom Forte

Liotrix Brand Names in Pakistan:

No Brands Available in Pakistan.