Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

LEVOTHYROXINE SODIUM

Chemistry - Prepared synthetically for commercial use, levothyroxine sodium is the levo isomer ofthyroxine which is the primary secretion of the thyroid gland. It occurs as an odorless, light yellowto buff-colored, tasteless, hygroscopic powder that is very slightly soluble in water and slightlysoluble in alcohol. The commercially available powders for injection also contain mannitol.
Levothyroxine sodium may also be known as sodium levothyroxine, thyroxine sodium, L-thyroxine sodium, T4, or T4 thyroxine sodium. 100 micrograms of levothyroxine is approximatelyequivalent to 65 mg (1 grain) of dessicated thyroid.

Storage, Stability, Compatibility

Levothyroxine sodium preparations should be stored at roomtemperature in tight, light-resistant containers. The injectable product should be reconstitutedimmediately before use; unused injection should be discarded after reconstituting. Do not mixlevothyroxine sodium injection with other drugs or IV fluids.

Pharmacology - LEVOTHYROXINE SODIUM

Thyroid hormones affect the rate of many physiologic processes including: fat, protein and carbohydrate metabolism, increasing protein synthesis, increasing gluconeogenesis andpromoting mobilization and utilization of glycogen stores. Thyroid hormones also increase oxygenconsumption, body temperature, heart rate and cardiac output, blood volume, enzyme systemactivity, and growth and maturity. Thyroid hormone is particularly important for adequatedevelopment of the central nervous system. While the exact mechanisms how thyroid hormonesexert their effects are not well understood, it is known that thyroid hormones (primarilytriiodothyronine) act at the cellular level.
In humans, triiodothyronine (T3) is the primary hormone responsible for activity. Approximately80% of T3 found in the peripheral tissues is derived from thyroxine (T4) which is the principlehormone released by the thyroid.
Uses, Indications - Levothyroxine sodium is indicated for the treatment of hypothyroidism in alspecies.

Pharmacokinetics - LEVOTHYROXINE SODIUM

In dogs, peak plasma concentrations after oral dosing reportedly occur 4-12hours after administration and the serum half-life is approximately 12-16 hours. There is widevariability from animal to animal, however.
Contraindications/Precautions - Levothyroxine (and other replacement thyroid hormones) arecontraindicated in patients with acute myocardial infarction, thyrotoxicosis or untreated adrenalinsufficiency. It should be used with caution, and at a lower initial dosage, in patients with concurrent hypoadrenocorticism (treated), cardiac disease, diabetes, or in those who are aged.

Adverse Effects, Warnings

When administered at an appropriate dose to patients requiring thyroid hormone replacement, there should not be any adverse effects associated with therapy. Foradverse effects associated with overdosage, see below.
Overdosage - Chronic overdosage will produce symptoms of hyperthyroidism, including tachycardia, polyphagia, PU/PD, excitability, nervousness and excessive panting. Dosage should bereduced and/or temporarily withheld until symptoms subside. Some (10%?) cats may exhibitsymptoms of "apathetic" (listlessness, anorexia, etc.) hyperthyroidism.
Acute massive overdosage can produce symptoms resembling thyroid storm. After oral ingestion, treatment to reduce absorption of drug should be accomplished using standard protocols (emeticsor gastric lavage, cathartics, charcoal) unless contraindicated by the patient's condition. Treatment issupportive and symptomatic. Oxygen, artificial ventilation, cardiac glycosides, beta blockers (e.g., propranolol), fluids, dextrose and antipyrexic agents have all been suggested for use if necessary.

Drug Interactions

Levothyroxine increases the actions of epinephrine, norepinephrine andother catecholamines and sympathomimetics.
Thyroid hormones increase the catabolism of vitamin K-dependent clotting factors which mayincrease the anticoagulation effects in patients on warfarin.
In diabetic patients, the addition of thyroid hormones may alter insulin requirements; monitorcarefully during initiation of therapy.
Estrogens may increase thyroid requirements by increasing TBg. Therapeutic effects of digoxinor digitoxin may be decreased by thyroid hormones.
Ketamine may cause tachycardia and hypertension when used in patients receiving thyroidhormones.
Drug/Laboratory Interactions - The following drugs (in humans) that may be used in veterinaryspecies may have effects on thyroid function tests; evaluate results accordingly:
Effects on serum T4: aminoglutethimide↓, anabolic steroids/androgens↓, antithyroid drugs (PTU, methimazole)↓, asparaginase↓, barbiturates↓, corticosteroids↓, danazol↓, diazepam↓, estrogens(Note: estrogens may have no effect on canine T3 or T4 concentrations), fluorouracil, heparin↓, insulin, lithium carbonate↓, mitotane (o, p-DDD)↓, nitroprusside↓, phenylbutazone↓, phenytoin↓, propranolol, salicylates (large doses)↓, & sulfonylureas↓.
Effects on serum T3: antithyroid drugs (PTU, methimazole)↓, barbiturates↓, corticosteroids↓, estrogens, fluorouracil, heparin↓, lithium carbonate↓, phenytoin↓, propranolol↓, salicylates(large doses)↓, & thiazides.Effects on T3 uptake resin: anabolic steroids/androgens, antithyroid drugs (PTU, methimazole)↓, asparaginase, corticosteroids, danazol, estrogens↓, fluorouracil↓, heparin, lithiumcarbonate↓, phenylbutazone, & salicylates (large doses).Effects on serum TSH: aminoglutethimide, antithyroid drugs (PTU, methimazole), corticosteroids↓, danazol↓, & lithium carbonate.Effects on Free Thyroxine Index (FTI): antithyroid drugs (PTU, methimazole)↓, barbiturates↓, corticosteroids↓, heparin, lithium carbonate↓, & phenylbutazone↓.

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