levothyroxine (Synthroid, Levoxyl, L Thyroxine, Levo T, Levothroid, Levothyroxine T4, Levoxine, Tirosint, Unithroid)

Dosing and uses of Synthroid, Levoxyl (levothyroxine)

• Adult
• Pediatric

 

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