levothyroxine (Rx)

Frequency Not Defined

Angina pectoris

Arthralgia

Congestive heart failure

Flushing

Increased pulse

Myocardial infarction

Palpitations

Arrhythmias

Cramps

Diarrhea

Nervousness

Anxiety

Choking sensation

Emotional lability

Headache

Heat intolerance

Insomnia

Myasthenia

Pseudomotor cerebri

Alopecia

Weight loss

Infertility

Dyspnea

Fever

Tachycardia

Tremor

Decreased bone mineral density

Postmarketing Reports

Musculoskeletal: Muscle weakness, muscle spasm

Dermatologic: Hair loss, rash

Slipped capital femoral epiphysis (children)

Contraindications

Hypersensitivity to thyroid hormone or other ingredients

Acute MI, thyrotoxicosis, uncorrected adrenal insufficiency

Treatment of obesity or infertility

No contraindications reported by manufacturer for myxedema coma when treated with injection

Cautions

Avoid undertreatment or overtreatment, which may result in adverse effects

Proper dose titration and careful monitoring is critical to prevent persistence of hypothyroidism or development of hyperthyroidism

Use caution in cardiovascular disease, HTN, endocrine disorders, osteoporosis, or myxedema

Over-treatment with levothyroxine may cause increase in heart rate, cardiac wall thickness, and cardiac contractility; may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients; monitor patients receiving concomitant levothyroxine and sympathomimetic agents for signs and symptoms of coronary insufficiency; initiate lower dose in elderly, those with angina pectoris, cardiovascular disease, or in those with severe hypothyroidism

Over- or under-treatment with levothyroxine may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and on glucose and lipid metabolism; titrate dose carefully and monitor response to titration to avoid these effects

Monitor for presence of drug or food interactions when using levothyroxine and adjust dose as necessary; symptoms may be exacerbated or aggravated in patients with diabetes mellitus and insipidus; addition of levothyroxine therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements

Use of oral thyroid hormone drug products is not recommended to treat myxedema coma; administer thyroid hormone products formulated for intravenous administration to treat myxedema coma; myxedema coma is a life-threatening emergency characterized by poor circulation and hypometabolism, and may result in unpredictable absorption of levothyroxine sodium from the gastrointestinal tract

Do NOT generally use levothyroxine sodium preparations interchangeably, due to narrow therapeutic index

Check for bioequivalence if switching brands/generics

Synthroid and unithroid tabs contain lactose

Not recommended for TSH suppression in patients with thyroid nodules

Levoxyl tabs swell in mouth: take with full glass of water to avoid choking

Avoid use in postmenopausal women >60 years with osteoporosis, cardiovascular disease, or systemic illness

Avoid use in patients with large thyroid nodules or long-standing goiters, or low-normal TSH levels

Long-term therapy decreases bone mineral density; use lowest dose in postmenopausal women and women using suppressive doses

Use caution in patients with adrenal insufficiency; may exacerbate symptoms or agravate them; treatment with glucocorticoids should precede levothyroxine therapy adrenal insufficiency present; initiation of thyroid hormone therapy prior to initiating glucocorticoid therapy may precipitate acute adrenal crisis in patients with adrenal insufficiency

Monitor for presence of drug or food interactions when using levothyroxine and adjust dose as necessary

Pregnancy

Experience with levothyroxine use in pregnant women, including data from post-marketing studies, have not reported increased rates of major birth defects or miscarriages; there are risks to mother and fetus associated with untreated hypothyroidism in pregnancy; since TSH levels may increase during pregnancy, TSH should be monitored and levothyroxine dosage adjusted during pregnancy; untreated maternal hypothyroidism may have adverse effect on fetal neurocognitive development

Maternal hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, and premature delivery; untreated maternal hypothyroidism may have adverse effect on fetal neurocognitive development

Pregnancy may increase thyroid hormone requirements. serum TSH level should be monitored and the dosage adjusted during pregnancy; since postpartum TSH levels are similar to preconception values, the dosage should return to the pre-pregnancy dose immediately after delivery

Lactation

Limited published studies report that levothyroxine is present in human milk; however, there is insufficient information to determine effects of levothyroxine on breastfed infant and no available information on effects of levothyroxine on milk production; adequate levothyroxine treatment during lactation may normalize milk production in hypothyroid lactating mothers; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for levothyroxine and any potential adverse effects on breastfed infant from levothyroxine or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Synthetic T4; thyroid hormone increases basal metabolic rate, increases utilization and mobilization of glycogen stores, promotes gluconeogenesis; involved in growth development and stimulates protein synthesis

Absorption

40-80% from GI tract (PO)

Bioavailability: 64% (nonfasting); 79-81% (fasting)

Peak plasma time: 2-4 hr (PO)

Duration: Hypothyroidism, several weeks

Onset, hypothyroidism

• Initial response: 3-5 days (PO); 6-8 hr (IV)
• Maximum effect: Several weeks
• Peak effect: 24 hr (IV)

Onset, myxedema coma

• Initial response: 6-12 hr (IV)
• Peak effect: 24 hr

Distribution

Protein bound: 99%

Vd: 9-10 L

Metabolism

Deiodinated in blood and then 50% converted to active metabolite, triiodothyronine (T3), also by liver

Metabolites: T3 (active)

Elimination

Half-life: 9-10 days (hypothyroid); 3-4 days (hyperthyroid); 6-7 days (euthyroid)

Total body clearance: 0.8-1.4 L/day

Excretion: Urine (major), feces (20%)

IV Preparation

Add 5 mL of NS to vial containing 200 or 500 mcg and shake until a clear solution is obtained; resultant solutions contain approximately 40 or 100 mcg/mL, respectively

Use reconstituted solutions immediately; discard any unused portions

Alternatively, add 2 mL NS to vial containing 200 mcg to produce Synthroid solution containing approximately 100 mcg/mL

Do not admix with IV infusion solutions

Oral Administration

Take tabs with full glass of water preferably 30 min to 1 hr before breakfast on empty stomach

Do not use foods that decrease absorption (soybean products) for administering levothyroxine

Administer oral levothyroxine >4 hr apart from drugs known to interfere with absorption

IV/IM: Administer 50% of PO dose

Patients unable to swallow intact tabs

• Crush appropriate dose and place in 5-10 mL of water
• Administer resultant suspension by spoon or dropper immediately, do NOT store