The P-I-E-N-O Parkinsn's List Drug Database
levothyroxine / SynthroidTM ,LevothroidTM , LevoxylTM
THYROID HORMONE REPLACEMENT
Description: Levothyroxine is a synthetically prepared levo isomer of thyroxine, a hormone secreted by the thyroid gland. Levothyroxine is used in the treatment of primary hypothyroidism of all causes including congenital hypothyroidism (cretinism). The drug is also used in hypothyroidism of pituitary (secondary hypothyroidism) or hypothalamic (tertiary hypothyroidism) origin. Levothyroxine will suppress thyrotropin secretion in the management of goiter and chronic lymphocytic thyroiditis, and it can be used in combination with antithyroid agents to prevent the development of hypothyroidism or goitrogenesis during the treatment of thyrotoxicosis. Intravenous levothyroxine is used to treat myxedema coma or stupor. Levothyroxine therapy is preferred over thyroid and thyroglobulin because the hormonal content of levothyroxine is standardized, and the effects of the drug are more predictable. Levothyroxine has been used clinically since the 1950s.
Mechanism of Action: Levothyroxine exhibits all the actions of endogenous thyroid hormone (see Thyroid Agents Overview). While the actions of thyroid hormone are widespread, in general, they influence the growth and maturation of tissues, increase energy expenditure, and affect the turnover of essentially all substrates. In response to reestablishing physiologic levels of thyroid hormone, thyroid-stimulating hormone (TSH) concentrations correct if the primary disorder is at the level of the thyroid. Levothyroxine provides only TA, of which roughly 30% is deiodinated to TA. Since TA is three times as potent as TA, virtually all of the activity of TA can be ascribed to TA.
Pharmacokinetics: Levothyroxine is administered orally or intravenously. Oral absorption of levothyroxine is variable. The average bioavailability of an oral dose is 50-75%. Absorption can be reduced in patients with malabsorption syndromes, congestive heart failure, or diarrhea. Levothyroxine has a slower onset of action and a longer duration than liothyronine. Full therapeutic effects of levothyroxine may not be evident for 1-3 weeks following oral administration and persist for the same amount of time following cessation of therapy. Patients with myxedema coma who are treated with IV levothyroxine can respond within 8 hours after the initial administration, with maximum effects evident after 24 hours.
Over 99% of levothyroxine is bound to proteins. It is believed that levothyroxine distributes predominantly into the liver and kidney tissues. Thyroid hormone does not appear to cross the placenta, and only minimal amounts are distributed into breast milk. Exogenously administered thyroid hormone is deiodinated in peripheral tissues, with small amounts metabolized in the liver and excreted in the bile. Iodine liberated during metabolism is used for hormone synthesis in the thyroid gland or is excreted in the feces or urine. The half-life of levothyroxine is 6-7 days in euthyroid patients, 9-10 days in hypothyroid patients, and 3-4 days in hyperthyroid patients.
CONTRAINDICATIONS/PRECAUTIONS: Thyroid agents are cardiostimulatory and should be used with great caution in patients with angina pectoris or other preexisting cardiac disease, including hypertension. If adverse cardiac reactions occur, dosages should be reduced. Administration of thyroid agents can increase the risk of developing arrhythmias, and patients with coronary artery disease who are receiving levothyroxine therapy may be at a higher risk for developing arrythmias, particularly during surgery. Thyroid agents are contraindicated in patients with acute myocardial infarction that is not associated with hypothyroidism. Small amounts of levothyroxine may be used in cases of acute myocardial infarction that is complicated or caused by hypothyroidism.
Symptoms of many other endocrine disorders, such as diabetes mellitus, can be unmasked or exacerbated by the administration of thyroid agents. Levothyroxine therapy can alter the dosage requirements of antidiabetic agents, so blood glucose should be monitored closely during concomitant therapy. Withdrawal of thyroid agents can cause hypoglycemia in susceptible patients.
Adrenal insufficiency should be corrected during concomitant administration of thyroid agents because they increase the body's demand for adrenal hormones; administration of thyroid agents to patients with uncontrolled adrenal insufficiency can cause adrenal crisis. Symptoms of adrenal insufficiency can be unmasked or exacerbated by the administration of thyroid agents.
Other possibilities responsible for causing hypothyroidism (e.g., morphologic hypogonadism and nephroses) should be ruled out prior to beginning treatment with levothyroxine. Patients with hypothyroidism secondary to hypopituitarism are likely to have suppressed adrenal function as well, which should be corrected prior to initiating therapy with levothyroxine. Symptoms of hypopituitarism can be unmasked or exacerbated by the administration of thyroid agents.
Thyroid agents are contraindicated in patients with thyrotoxicosis.
The use of thyroid agents for obesity treatment is contraindicated. Normal doses of levothyroxine are not effective in reducing weight in euthyroid patients, and high doses of the drug can cause life-threatening toxic reactions.
DRUG INTERACTIONS: Concomitant use of sympathomimetics and levothyroxine can enhance the effects of either drug on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further.
Drugs that possess hepatic enzyme-inducing properties can increase the catabolism of levothyroxine. These include barbiturates, carbamazepine, phenytoin, and rifampin. Clinicians should be alert for a decreased response to thyroid hormones if any of these agents are used during thyroid hormone therapy.
It may be necessary to adjust the dose of antidiabetic agents if levothyroxine is added or deleted. Thyroid hormones can affect the diabetic state. This represents a pharmacodynamic interaction and not necessarily a pharmacokinetic one.
Ketamine should be administered cautiously to patients receiving levothyroxine because concomitant use can cause marked hypertension and tachycardia.
The administration of estrogens can increase circulating concentrations of thyroxine-binding globulin. Increased amounts of thyroxine-binding globulin reduce the clinical response to levothyroxine. Hypothyroid patients may require larger doses of levothyroxine if an estrogen is added.
Cholestyramine can bind levothyroxine in the GI tract. Although no data are available for colestipol, it would be wise to assume a similar interaction with levothyroxine could occur. At least 4-5 hours should be allowed between the administration of cholestyramine or colestipol and levothyroxine. Simultaneous administration of these drugs can reduce the absorption of the hormone.
Simultaneous administration of levothyroxine with ferrous sulfate has been reported to interfere with the clinical response to levothyroxine. Although the mechanism is yet to be determined, it is possible that iron salts may complex with levothyroxine and reduce its oral bioavailability.
Simultaneous administration of levothyroxine with sucralfate has been reported to interfere with the clinical response to levothyroxine. Although the mechanism is yet to be determined, it is possible that sucralfate may reduce levothyroxine bioavailability.
The effects of indandione- or coumarin-derivative anticoagulants can be altered when thyroid agents are administered concomitantly. It has been shown that by accelerating the metabolic degradation of vitamin K-dependent clotting factors, hyperthyroidism augments the response to warfarin. It is possible that exogenously administered thyroid hormone also can augment the response to warfarin. Prothrombin times should be monitored carefully in patients receiving warfarin and thyroid hormones concomitantly. If levothyroxine is added after warfarin therapy is stabilized, it is recommended that warfarin doses be reduced. No special precautions appear to be necessary if warfarin is added after levothyroxine therapy has already begun.
The metabolism of corticosteroids can be decreased in hypothyroid patients and increased in hyperthyroid patients, so dosage alterations may be required when initiating, changing, or discontinuing levothyroxine therapy.
ADVERSE REACTIONS: Adverse reactions to levothyroxine are rare. Aside from allergic reactions (hives or skin rash), adverse reactions usually indicate overdosage of hormone. Many of the signs and symptoms of thyroid imbalance are subtle and insidious. Manifestations of thyroid hormone overdose or hyperthyroidism include amenorrhea or other menstrual irregularity, palpitations, diarrhea, anorexia, tremors, fever, headache, alopecia, irritability, nervousness, heat intolerance, diaphoresis, insomnia, nausea/vomiting, and weight loss. Excess levothyroxine can indirectly increase the workload on the heart. In patients with underlying cardiac problems, this can produce symptoms such as angina, sinus tachycardia, atrial fibrillation, or congestive heart failure which usually resolve with hyperthyroidism therapy. Elderly patients may only exhibit cardiovascular signs and symptoms which may be resistant to therapy. The clinician should be alert to constellations of symptoms that gradually worsen over time.
Some patients may not be receiving enough thyroid hormone. In these patients, signs or symptoms of underdosage or hypothyroidism may be present and include: lethargy, fatigue, constipation, cold intolerance, weight gain, impaired intellectual performance or other mental status changes, dry skin or hair, deepening of voice, large tongue, and, eventually, myxedema coma. Clinicians should also be aware of the above signs and symptoms to ensure adequate thyroid hormone replacement therapy.
PATIENT INFORMATION:
What do levothyroxine tablets do?
Levothyroxine (SynthroidTM , LevothroidTM ) acts as a replacement for people whose thyroid gland does not produce enough thyroid hormone. Levothyroxine can improve symptoms of thyroid deficiency such as slow speech, lack of energy, weight gain, hair loss, dry thick skin and unusual sensitivity to cold. Levothyroxine also helps to treat a condition called goiter, which is an enlarged thyroid gland. Generic levothyroxine tablets are available.
What should my doctor, dentist, or pharmacist know before I take levothyroxine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take levothyroxine tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with levothyroxine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking levothyroxine?
Serious side effects with levothyroxine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with levothyroxine include:
Some of these symptoms may indicate that your dosage level is not right. Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take levothyroxine?
If you are taking levothyroxine for an underactive thyroid, it may be several weeks before you notice an improvement. Check with your doctor if your symptoms do not improve or if you develop any of the above side effects. It may be necessary for you to take this medicine for the rest of your life; do not stop taking except on your doctor's advice.
Stick to the same brand of levothyroxine if you can. Products from different manufacturers may not work the same; ask your doctor or pharmacist for advice if you are uncertain.
If you are going to have surgery, tell your doctor or dentist that you are taking levothyroxine.
Thyroid hormones can affect blood sugar levels. If you are also have diabetes, you may need to adjust the dose of your diabetic medicine once you are stabilized on levothyroxine.
You may lose some of your hair when you start taking levothyroxine. This usually corrects itself after a time.
If you also have certain types of heart disease, you should be careful when exercising or doing physical work. You can experience chest pain or shortness of breath.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.
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