Levothyroxine is a synthetic levoisomer of thyroxine (T4), similar to the endogenous hormone produced by the thyroid gland. Thyroxine is de-iodinated to form triiodothyronine (T3) in the peripheral tissues. T3 enters the cell and binds to nuclear thyroid hormone receptors, and the hormone-receptor complex, in turn, triggers gene expression and produces proteins required in the regulation of cellular respiration, thermogenesis, cellular growth and differentiation, and metabolism of proteins, carbohydrates, and lipids. T4 and T3 also possess cardiac stimulatory effect.
Levothyroxine is a manufactured form of the thyroid hormone, thyroxine (T4). It is used to treat thyroid hormone deficiency including the severe form known as myxedema coma. It may also be used to treat and prevent certain types of thyroid tumors. It is not indicated for weight loss. Levothyroxine is taken by mouth or given by injection into a vein. Maximum effect from a specific dose can take up to six weeks to occur. The major hormone derived from the thyroid gland.
Mechanism of Action of Levothyroxine
Levothyroxine acts like the endogenous thyroid hormone thyroxine (T4, a tetra-iodinated tyrosine derivative). In the liver and kidney, T4 is converted to T3, the active metabolite. In order to increase solubility, the thyroid hormones attach to thyroid hormone binding proteins, thyroxin-binding globulin, and thyroxine-binding prealbumin (transthyretin). Transport and binding to thyroid hormone receptors in the cytoplasm and nucleus then take place. Thus by acting as a replacement for natural thyroxine, symptoms of thyroxine deficiency are relieved. Levothyroxine (T4) is a synthetically prepared levo isomer of thyroxine, the major hormone secreted from the thyroid gland. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine (T3) which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid hormone increases the metabolic rate of cells of all tissues in the body.
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Levothyroxine acts like the endogenous thyroid hormone thyroxine (T4, a tetra-iodinated tyrosine derivative). In the liver and kidney, T4 is converted to T3, the active metabolite. In order to increase solubility, the thyroid hormones attach to thyroid hormone binding proteins, thyroxin-binding globulin, and thyroxine-binding prealbumin (transthyretin). Transport and binding to thyroid hormone receptors in the cytoplasm and nucleus then take place. Thus by acting as a replacement for natural thyroxine, symptoms of thyroxin deficiency are relieved.
Indications of Levothyroxine
- Hypothyroidism
- Hashimoto’s disease
- Underactive thyroid
- Hypothyroidism, after thyroid removal
- TSH suppression
- Thyroid suppression test
- Myxedema Coma
- Euthyroid goiter
- Thyrotropin dependent thyroid cancer
- For use alone or in combination with antithyroid agents to treat hypothyroidism, goiter, chronic lymphocytic thyroiditis, myxedema coma, and stupor.
Contra-Indications of Levothyroxine
- Overactive thyroid gland
- Thyrotoxicosis crisis
- Diabetes
- Pituitary hormone deficiency
- Addison’s disease
- Osteoporosis
- Decreased calcification or density of bone
- Allergies to thyroid
Dosage of Levothyroxine
Strengths: 25 mcg; 50 mcg;75 mcg ;100 mcg;125 mcg ;150 mcg ;200 mcg ; 300 mcg
Hypothyroidism
Elderly patients with cardiac disease
- Initial dose: 12.5 to 25 mcg orally per day, with gradual dose increments at 4 to 6-week intervals
- The dose is generally adjusted in 12.5 to 25 mcg increments until the patient with primary hypothyroidism is clinically euthyroid and the serum TSH has normalized.
TSH Suppression
TSH suppression in well-differentiated thyroid cancer &thyroid nodules
- The target level for TSH suppression in these conditions has not been established. The efficacy of TSH suppression for the benign nodular disease is controversial. Therefore, the dose of this drug used for TSH suppression should be individualized based on the specific disease and the patient being treated.
- In the treatment of well differentiated (papillary and follicular) thyroid cancer, this drug is used as an adjunct to surgery and radioiodine therapy. Generally, TSH is suppressed to less than 0.1 international units per liter (mg/L), and this usually requires a dose of greater than 2 mcg/kg/day. However, in patients with high-risk tumors, the target level for TSH suppression may be less than 0.01 mU/L.
- In the treatment of benign nodules and nontoxic multinodular goiter, TSH is generally suppressed to a higher target (e.g., 0.1 to 0.5 mU/L for nodules and 0.5 to 1.0 mU/L for multinodular goiter) than that used for the treatment of thyroid cancer. This drug is contraindicated if the serum TSH is already suppressed due to the risk of precipitating overt thyrotoxicosis.
Hypothyroidism
Hypothyroidism in adult and in children in whom growth& puberty and complete
- Average full replacement dose: 1.7 mcg/kg/day (e.g., 100 to 125 mcg/day for a 70 kg adult) orally
- Older patients may require less than 1 mcg/kg/day
- Doses greater than 200 mcg/day orally are seldom required
- An inadequate response to oral daily doses of 300 mcg/day or greater is rare and may indicate poor compliance, malabsorption, and/or drug interactions
For most patients older than 50 years or for patients under 50years of age with the underlying cardiac disease
- Initial dose: 25 to 50 mcg/day, with gradual increments in dose at 6 to 8-week intervals, as needed
Patients with hyperthyroidism
- Initial dose: 12.5 to 50 mcg orally once a day; dosage can be increased in 12.5 to 25 mcg/day increments every 2 to 4 weeks (accompanied by clinical and laboratory assessment, until the TSH level is normalized)
Patients with secondary (pituitary) or tertiary(hypothalamic) hyperthyroidism
- The oral dose should be titrated until the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal range
Side Effects of Levothyroxine
The most common
- chest pain, irregular heartbeat, or shortness of breath
- rapid or irregular heartbeat or pulse
- heart palpitations
- increased appetite
- weight loss
- dizziness
- drowsiness
- dry mouth
- a headache
- joint pain
- nausea and vomiting
- Severe stomach ache
- diarrhea,
- anorexia,
- flatulence,
- a headache,
- fainting, fast or pounding heartbeats.
More common
- weight loss
- Syndrome of inappropriate secretion of antidiuretic hormone
- Fast or irregular heartbeat
- fever
- Back pain
- dizziness
- a headache
- increased cough
- Acid or sour stomach
- decreased appetite
- Agitation
- chest congestion
- chest pain
- cold sweats
- confusion
- decreased sexual ability or desire
- diarrhea or loose stools
- heartburn
- sleepiness or unusual dro
- Aggressive or violent behavior
- Thoughts about suicide or dying
- witness
- stomach or abdominal cramps, gas, or pain
- trouble sleeping
Less common
- change in sense of taste
- congestion
- discouragement, feeling sad, or empty
- Acting on dangerous impulses
- New or worse depression
- New or worse anxiety or panic attacks
- Agitation, restlessness, anger, or irritability
- Trouble sleeping
- An increase in activity or talking more than normal
Drug Interactions of Levothyroxine
Levothyroxine may interact with following drugs, supplements& may decrease the efficacy of the drugs
- antacids (e.g., aluminum hydroxide, calcium carbonate, magnesium hydroxide)
- anticonvulsants (e.g., carbamazepine, phenytoin, phenobarbital)
- antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- birth control pills containing estrogen
- calcium carbonate
- calcium polystyrene sulfonate
- iron supplements (e.g., ferrous fumarate, ferrous gluconate,ferrous sulfate)
- magnesium supplements (e.g., magnesium hydroxide, magnesium oxide)
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- calcitriol
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- carvedilol
- ciprofloxacin
- oral corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
- cyclosporine
- folic acid
- gabapentin
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- lansoprazole
- loperamide
- losartan
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- multivitamins/minerals with iron,
- montelukast
- ondansetron
- phenytoin
- proton pump inhibitors (e.g., lansoprazole, omeprazole)
- ranitidine
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
- sildenafil
- “statin” anti-cholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
- theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
- thiazide diuretics (e.g., chlorothiazide, hydrochlorothiazide)
- tramadol
- tricyclic antidepressants (e.g., amitriptyline, desipramine, )
- warfarin
Pregnancy & Lactation
FDA Pregnancy Category A
Pregnancy
Levothyroxine should be taken throughout pregnancy to regulate the levels of thyroid hormone for the pregnant mother and the developing baby. If you become pregnant while taking this medication, contact your doctor as soon as possible. Your doctor may want to monitor your thyroid function more closely while you are pregnant.
Breast-feeding
Only a small amount of thyroid hormone is passed into breast milk. The use of appropriate amounts of this medication by breast-feeding women has not been shown to cause harm for breast-fed babies.
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