Chemistry - Prepared synthetically for commercial use, levothyroxine sodium is the levo isomer of thyroxine which is the primary secretion of the thyroid gland. It occurs as an odorless, light yellow to buff-colored, tasteless, hygroscopic powder that is very slightly soluble in water and slightly soluble 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 approximately equivalent to 65 mg (1 grain) of dessicated thyroid.
Storage/Stability/Compatibility - Levothyroxine sodium preparations should be stored at room temperature in tight, light-resistant containers. The injectable product should be reconstituted immediately before use; unused injection should be discarded after reconstituting. Do not mix levothyroxine sodium injection with other drugs or IV fluids.
Pharmacology - Thyroid hormones affect the rate of many physiologic processes including: fat, protein and carbohydrate metabolism, increasing protein synthesis, increasing gluconeogenesis and promoting mobilization and utilization of glycogen stores. Thyroid hormones also increase oxygen consumption, body temperature, heart rate and cardiac output, blood volume, enzyme system activity, and growth and maturity. Thyroid hormone is particularly important for adequate development of the central nervous system. While the exact mechanisms how thyroid hormones exert their effects are not well understood, it is known that thyroid hormones (primarily triiodothyronine) act at the cellular level.
In humans, triiodothyronine (T3) is the primary hormone responsible for activity. Approximately 80% of T3 found in the peripheral tissues is derived from thyroxine (T4) which is the principle hormone released by the thyroid.
Uses/Indications - Levothyroxine sodium is indicated for the treatment of hypothyroidism in all species.
Pharmacokinetics - In dogs, peak plasma concentrations after oral dosing reportedly occur 4-12 hours after administration and the serum half-life is approximately 12-16 hours. There is wide variability from animal to animal, however.
Contraindications/Precautions - Levothyroxine (and other replacement thyroid hormones) are contraindicated in patients with acute myocardial infarction, thyrotoxicosis or untreated adrenal insufficiency. 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. For adverse 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 be reduced and/or temporarily withheld until symptoms subside. Some (10%?) cats may exhibit symptoms 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 (emetics or gastric lavage, cathartics, charcoal) unless contraindicated by the patient’s condition. Treatment is supportive 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 and other catecholamines and sympathomimetics. Thyroid hormones increase the catabolism of vitamin K-dependent clotting factors which may increase the anticoagulation effects in patients on warfarin. In diabetic patients, the addition of thyroid hormones may alter insulin requirements; monitor carefully during initiation of therapy. Estrogens may increase thyroid requirements by increasing TBg. Therapeutic effects of digoxin or digitoxin may be decreased by thyroid hormones. Ketamine may cause tachycardia and hypertension when used in patients receiving thyroid hormones.
Drug/Laboratory Interactions - The following drugs (in humans) that may be used in veterinary species 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↑, lithium carbonate↓, 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↓
a) 10 mg in 70 ml of corn syrup once daily. Monitor T4 levels one week after initiation of therapy. Obtain one blood sample just before administration and on sample 2-3 hours after dosing. (Chen and Li 1987)
Monitoring Parameters -
1) Serum thyroid hormone concentrations (T4/T3). Monitoring before therapy is begun can help confirm diagnosis. After therapy is started wait at least 5-10 days before measuring T4, one month may be better, especially if dosage is ineffective or symptoms of thyrotoxicosis develop. Serum levels should be drawn before the dose and 6-8 hours after. Dosage should be reduced if serum thyroxine levels exceed 100 ng/ml or symptoms of thyrotoxicosis develop.
Client Information - Clients should be instructed in the importance of compliance with therapy as prescribed. Also, review the symptoms that can be seen with too much thyroid supplementation (see Overdosage section above).
Dosage Forms/Preparations/FDA Approval Status - All levothyroxine products require a prescription. There have been bioavailability differences between products reported. It is recommended to use a reputable product and not to change brands indiscriminately.
Veterinary-Approved Products -
Levothyroxine Sodium Tablets 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg; Soloxine® (Daniels), Thyro-Tabs ® (Vet-A-Mix); Thyrozine Tablets® (Anthony) (Rx) Approved for use in dogs.
Levothyroxine Sodium Tablets Chewable (Veterinary) 0.2 mg, 0.5 mg, 0.8 mg; Thyro-Form® (Vet-A-Mix) (Rx) — Approved for use in dogs.
Levothyroxine Sodium Tablets Chewable (Veterinary) 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg; HESKA Chewable Thyroid Supplement for Dogs (Heska); Approved for use in dogs (Rx)
Levothyroxine Sodium Powder (Veterinary) 0.22% (1 gram of T4 in 454 grams of powder): One level teaspoonful contains 12 mg of T4. Available in 1 lb. and 10 lb. containers.; Thyro-L® (Vet-A-Mix) (Rx) — Approved for use in horses.
Human-Approved Products -
Levothyroxine Sodium Tablets 0.025 mg, 0.05 mg, 0.075 mg, 0.088 mg, 0.1 mg, 0.112 mg, 0.125 mg, 0.137 mg, 0.15 mg, 0.175 mg, 0.2 mg, 0.3 mg; Synthroid® (Knoll), Levothroid® (Forest); Levo-T® (Lederle); Levoxyl® (Daniels); Eltroxin® (Roberts); generic, (Rx)
Levothyroxine Powder for Injection 200 micrograms per vial, 500 micrograms/vial in 6 ml and 10 ml vials; Synthroid® (Knoll), Levothroid® (Forest); Levoxine® (Daniels), generic (Rx)
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