WHAT IS THE USUAL 
STARTING DOSE OF 
LEVOTHYROXINE IN 
HYPOTHYROID PATIENTS?

The average replacement dosage of synthetic thyroxine (T4) in adult patients is 1.6 mcg/kg/day. This equates to levothyroxine 112 mcg daily in a 70-kg person. Healthy adult patients may be started on the full replacement dosage of 1.6 mcg/kg/day; however, certain patient populations should be initiated on a lower dose.

Geriatric patients and those with coronary artery disease (CAD) should be started on thyroid supplementation conservatively. Thyroid hormones increase myocardial oxygen demand, which can result in angina, myocardial infarction, or arrhythmias. Additionally, overtreatment with T4 can reduce bone mineral density and increase fracture risk, particularly in elderly patients. The recommended starting dosage of synthetic thyroxine in geriatric patients is 25 to 50 mcg daily and should not exceed 25 mcg daily in patients with CAD. An average replacement dosage in geriatric patients is lower than for healthy adults, and many seniors only require 0.5 mcg/kg 
daily to reach a euthyroid state.


Other special populations to consider when dosing levothyroxine include obese patients and those with subclinical hypothyroidism. In obese patients, T4 requirements are better associated with lean body mass than actual body weight.1 Therefore, lean body weight should be used to calculate dosage to reduce the risk of overdosing. For patients with subclinical hypothyroidism, lower starting dosages are appropriate. If the decision is made to initiate therapy, 1 mcg/kg/day is preferred over higher dosages; alternatively, patients may be started on a fixed dosage of 25 to 50 mcg daily, with titration every 6 weeks based on response.


Most hypothyroid patients can be maintained on levothyroxine dosages of 50 to 200 mcg daily. Doses higher than 300 mcg are rare and should prompt an investigation into compliance, malabsorption, or drug interactions. Thyroid hormones are best absorbed on an empty stomach, and bioavailability is reduced if they are administered with food or enteral feedings. Clinicians should be aware that the levothyroxine dose should be reduced by 50% when changing from the oral to IV formulation. 


The primary benefit of initiating T4 therapy at a full replacement dosage of 1.6 mcg/kg/day is to achieve a euthyroid state more rapidly. If adverse effects relating to oversupplementation are a concern or if a patient has CAD, starting at lower doses and titrating up based on response is prudent. Be aware that combination products containing triiodothyronine (T3) are dosed differently than levothyroxine.


CAN COBALAMIN BE GIVEN ORALLY IN PATIENTS WITH PERNICIOUS ANEMIA?


Pernicious anemia is a common cause of cobalamin (vitamin B12) deficiency and is due to a lack of intrinsic factor (IF). Intrinsic factor is synthesized and secreted by gastric parietal cells and binds to B12. This B12-IF complex is absorbed in the terminal ileum. Autoimmune destruction of the parietal cells (chronic atrophic gastritis) or the presence of anti-intrinsic factor antibodies can lead to pernicious anemia. Treatment has historically been intramuscular injection of cyanocobalamin; however, other routes of administration are effective.


In the presence of intrinsic factor and an intact bowel, small amounts of B12 are readily absorbed. An average Western diet contains approximately 6 mcg of B12 daily, and the recommended dietary allowance (RDA) of B12 is only 2.4 mcg in adults. Although IF was previously thought to be required for absorption of B12, it is now known that approximately 1% of B12 is passively absorbed without the presence of IF or an intact ileum.2 This means that high doses of B12 given orally will be absorbed in quantities sufficient to meet the RDA. Oral replacement dosages for patients with pernicious anemia are usually 1,000 to 2,000 mcg daily. 


Not all patients with pernicious anemia are candidates for oral supplementation. Patients must be compliant with daily dosing. Additionally, because of the possibility of erratic absorption, oral supplementation should begin after cobalamin levels have stabilized with parenteral treatment. Patients with neurologic symptoms due to B12 deficiency should not receive oral supplementation, nor should patients with diarrhea, vomiting, or bowel resection.


A variety of OTC B12 preparations are available, including oral and sublingual tablets, liquids, lozenges, and edible film strips. Recommend a United States Pharmacopeia (USP) Verified product, and advise patients to avoid timed-release preparations. Most clinical trials have used oral tablets. A prescription intranasal formulation is also available, but it is expensive and not well-studied. JAAPA 


Larissa DeDea, PharmD, BCPS, PA-C, is a clinical pharmacist with Northern Arizona Healthcare, Flagstaff, Arizona. In addition to being board certified in pharmacotherapy, she is a graduate of the Yale University PA program.

REFERENCES


1. Santini F, Pinchera A, Marsilli A, et al. Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases. J Clin Endocrinol Metab. 2005;90(1):124-127.


2. PL detail-document, treatment of vitamin B12 deficiency. Pharmacist's Letter/Prescriber's Letter. August 2011.