levothyroxine (Synthroid, Levoxyl, L Thyroxine, Levo T, Levothroid, Levothyroxine T4, Levoxine, Tirosint, Unithroid)
Classes: Thyroid Products
Dosing and uses of Synthroid, Levoxyl (levothyroxine)
Adult dosage forms and strengths
tablet
- 25mcg, 50mcg, 75mcg, 88mcg, 100mcg, 112mcg
- 125mcg, 137mcg, 150mcg, 175mcg, 200mcg, 300mcg
capsule (Tirosint)
- 13mcg, 25mcg, 50mcg, 75mcg, 88mcg
- 100mcg, 112 mcg, 125mcg, 137 mcg, 150mcg
powder for injection
- 100mcg/vial
- 200mcg/vial
- 500mcg/vial
Mild Hypothyroidism
1.7 mcg/kg or 100-125 mcg PO qDay; not to exceed 300 mcg/day
>50 years (or <50 yr with CV disease)
- Usual initial dose: 25-50 mcg/day
- May adjust dose by 12.5-25 mcg q6-8Week
>50 years with CV disease
- Usual initial dose: 12.5-25 mcg PO qDay
- May adjust dose by 12.5-25 mcg q4-6weeks until patient becomes euthyroid and serum TSH concentration normalized; adjustments q6-8weeks also used
- Dose range: 100-125 mcg PO qDay
Severe Hypothyroidism
Initial: 12.5-25 mcg PO qDay
Adjust dose by 25 mcg/day q2-4Week PRn
Subclinical Hypothyroidism
Initial: 1 mcg/kg PO qDay may be adequate, Or
If replacement therapy not initiated, monitor patient annually for clinical status
Myxedema Coma
300-500 mcg IV once, THEN 50-100 mcg qDay until patient is able to tolerate oral administration; may consider smaller doses in patients with cardiovascular disease
Organ Preservation (Orphan)
Preservation of organ function in brain-dead organ donors
Orphan indication sponsor
- Fera Pharmaceuticals, LLC; 134 Birch Hill Road; Locust Valley, NY 11560
Dosing Considerations
Lower dose of Tirosint capsules may be required compared with standard T4 tablets for hypothyroidism in patients with impaired gastric acid secretion to reach their target TSH levels; Tirosint has shown improved absorption compared with conventional T4 tablets
Check for bioequivalence if switching brands/generics, OR every week after switching from one levothyroxine sodium preparation to another
Monitor serum thyroid levels; patient may be asymptomatic
Monitoring
- Initially evaluate patients q6-8Week
- Once normalization of thyroid function and serum TSH conc achieved, evaluate q6-12mo
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 50% of PO
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
Pediatric dosage forms and strengths
tablet
- 25mcg, 50mcg, 75mcg, 88mcg, 100mcg, 112mcg
- 125mcg, 137mcg, 150mcg, 175mcg, 200mcg, 300mcg
capsule (Tirosint)
- 13mcg, 25mcg, 50mcg, 75mcg, 88mcg
- 100mcg, 112 mcg, 125mcg, 137 mcg, 150mcg
powder for injection
- 200mcg/vial
- 500mcg/vial
Hypothyroidism
Age 1-3 months
- 10-15 mcg/kg/day PO
- 5-7.5 mcg/kg/day IV/IM
- Use lower starting dose (25 mcg/day) if patient at risk of cardiac failure; if initial serum T4 lower than 5 mcg/dL begin treatment at higher dose (50 mcg/day)
Age 3-6 months
- 8-10 mcg/kg/day PO, OR
- 25-50 mcg/day PO
- 4-7.5 mcg/kg/day IV/IM
Age 6-12 months
- 6-8 mcg/kg/day PO, OR
- 50-75 mcg/day PO
- 3-6 mcg/kg/day IV/IM
Age 1-5 years
- 5-6 mcg/kg/day PO, OR
- 75-100 mcg/day PO
- 2.5-4.5 mcg/kg/day IV/IM
Age 6-12 years
- 4-5 mcg/kg/day PO, OR
- 100-125 mcg/day PO
- 2-3.75 mcg/kg/day IV/IM
>12 years
- 2-3 mcg/kg/day PO, OR
- 150 mcg/day PO
- 1-2.25 mcg/kg/day IV/IM
Dosing considerations
- Check for bioequivalence if switching brands/generics
- May minimize hyperactivity in older children by initiating dose at 1/4 of recommended dose; increase by that amount each week until full dose achieved
- Start children with severe or chronic hypothyroidism at 25 mcg/day; adjust dose by 25 mcg qweek
Administration
Take tabs with full glass of water before breakfast on empty stomach
Do not use foods that decrease absorption (soybean infant formula) for administering levothyroxine
Administer oral levothyroxine >4 hr apart from drugs known to interfere with absorption
IV/IM 50-75% of PO
Patients unable to swallow intact tabs/caps
- Tablets: Crush appropriate dose and place in 5-10 mL of water; administer resultant suspension by spoon or dropper immediately, do NOT store
- Capsules: Do not administer capsule to children unable to swallow capsule whole
Synthroid, Levoxyl (levothyroxine) adverse (side) effects
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
Warnings
Black box warnings
Thyroid hormones, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss
In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction; larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.
Contraindications
Hypersensitivity to thyroid hormone or other ingredients
Acute MI, thyrotoxicosis, untreated 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
Use caution in cardiovascular disease, HTN, endocrine disorders, osteoporosis, or myxedema
Initiate lower dose in elderly, those with angina pectoris, cardiovascular disease, or in those with severe hypothyroidism
Symptoms may be exacerbated or aggravated in patients with diabetes mellitus and insipidus
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 whould precede levothyroxine therapy adrenal insufficiency present
Pregnancy and lactation
Pregnancy category: A
Lactation: Enters breast milk; use caution
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.
Pharmacology of Synthroid, Levoxyl (levothyroxine)
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%)
Administration
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