perinatology.com
   OBPharm


Home > Reference > OBPharmacopoeia TOC-Public Thyroid Medications and Antithyroid Drugs

THE INFORMATION IN THE OBPHARMTM IS INTENDED SOLELY FOR USE BY THE MEDICAL PROFESSION. IT IS NOT INTENDED FOR LAY PERSONS.

When maternal  thyroid stimulating hormone (TSH) is elevated, measurement of serum free thyroxine (FT4) concentration is necessary to classify the patient's status as either subclinical (SCH) or overt hypothyroidism (OH). SCH is defined as a serum TSH between 2.5 and 10 mIU/L with a normal FT4 concentration[6]

Isloated hypothyroxinemia

  • The American Thyroid Association recommends isolated hypothyroxinemia should not be treated in pregnancy [6,9]

Subclinical Hypothyroidism (SCH)

  •  Women with SCH who are thyroid peroxidase antibody positive (TPO-Ab+)  should be treated  with levothyroxine [6,7]
  •  Women with SCH who are thyroid peroxidase antibody negative (TPO-Ab-)
    • The American Thyroid Association  recommends : There is insufficient evidence to recommend for or against universal LT4 treatment  [6]
    • The Endocrine Society recommends treatment with levothyroxine . Starting dose 50 mcg or more if serum TSH is between 2.5 and 10 mIU/L [7].

Overt Hypothyroidism (OH)

Women with a TSH concentration above the trimester-specific reference interval with a decreased FT4, and all women with a TSH concentration above 10.0 mIU/L irrespective of the level of FT4  are  considered to have OH. [6]

  • Women who are euthyroid on levothyroxine should increase their LT4 dose by 25 to 30% immediately after a missed period or positive pregnancy test [6]
  • The goal of LT4 treatment is to normalize maternal serum TSH values within the trimester-specific pregnancy reference range [6]
  • Monitor the TSH every 4 weeks during  first half of pregnancy
  • Following delivery, LT4 should be reduced to the patient's preconception dose.


Thyroid Medications

Levothyroxine sodium (Levoxyl ® Synthroid®)
Synthetic levothyroxine T4 ,LT4

  • Replacement or supplemental therapy in the treatment of hypothyroidism except the treatment of transient hypothyroidism in the recovery phase of subacute thyroiditis.

      For Nonpregnant Healthy Women
      1.7 mcg/kg/day PO once daily.
      Clinical and laboratory evaluations should be performed at 6 to 8 week intervals (2 to 3    weeks in severely hypothyroid patients), and the dosage adjusted by 12.5 to 25 mcg increments until the serum TSH concentration is normalized and signs and symptoms resolve.

      For Pregnant Healthy Women Some Authorities Recommend an Initial Dose [2-4]
      150 mcg PO once per day OR  day or 2 mcg/kg per day.
      Clinical and laboratory evaluations should be performed at 4 week intervals until the TSH is stable. The dosage adjustment according to the following algorithm has been suggested: 

      For TSH (mU/ml) Increase levothryoxine dosage by
      4 to 10 41 +/- 24 mcg / day
      greater than 10  but less than or equal to 20 65 +/- 19 mcg / day
      greater than 20 105 +/- 32 mcg /day

      For Nonpregnant or Pregnant Women with a history of cardiovascular disease
       12.5 to 50 mcg once daily
      Adjustments of 12.5 to 25 mcg every 3 to 6 weeks until TSH is normalized.
       

  • Myxedema coma:

      300- 500 micrograms IV once. The initial dose is followed by daily intravenous doses of 75 to 100 mcg until the patient is stable and oral administration is feasible. Normal T4 levels are usually achieved in 24 hours.
       

  • Pituitary TSH suppression in the treatment or prevention of various types of euthyroid goiters including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto's thyroiditis), multinodular goiter and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

       As an adjunct to surgery and radioiodine therapy in the treatment of well differentiated (papillary and follicular) thyroid cancer.
      Levothyroxine sodium dose of greater than 2 mcg/kg/day. Generally, TSH is suppressed to <0.1 mU/L. However, in patients with high-risk tumors, the target level for TSH suppression may be <0.01 mU/L.

      In the treatment of benign nodules and nontoxic multinodular goiter.
      "
      TSH is generally suppressed to a higher target (e.g., 0.1—0.5 mU/L for nodules and 0.5—1.0 mU/L for multinodular goiter) than that used for the treatment of thyroid cancer. Levothyroxine sodium is contraindicated if the serum TSH is already suppressed due to the risk of precipitating overt thyrotoxicosis "

Contraindicated in uncorrected adrenal insufficiency, untreated subclinical or overt thyrotoxicosis, and acute MI.

Levoxyl ® is supplied as:
(0.025, 0.05, 0.075, 0.088, 0.1, 0.112, 0.125, 0.137, 0.15, 0.175, 0.2, and 0.3 mg tablets ).

Synthroid® is supplied as:
(0.025, 0.05, 0.075, 0.088, 0.1, 0.112, 0.125, 0.137, 0.15, 0.175, 0.2, and 0.3 mg tablets Powder for intravenous injection: 6 and 10 ml vials containing 0.2 mg or 0.5mg of levothyroxine per vial.



 


The recommended treatment of maternal hypothyroidism is with administration of oral levothyroxine It is strongly recommended not to use other thyroid preparations such as T3 or desiccated thyroid. [6, 7]

Approximate Equivalent Strengths of Various Thyroid Preparations
 

Drug → Thyroid Tablets, USP
(Armour® Thyroid)
Liotrix Tablets, USP
(Thyrolar™)
Liothronine Tablets, USP
(Cytomel®)
Levothyroxine Tablets, USP
(Unithroid® , Levoxyl® , Levothroid® , Synthroid® )
Approx. Dose Equivalent 1/4 grain
(15 mg)
1/4   25 mcg (.025 mg)
Approx. Dose Equivalent 1/2 grain
(30 mg)
1/2 12.5 mcg 50 mcg (.05 mg)
Approx. Dose Equivalent 1 grain
(60 mg)
1 25 mcg 100 mcg ( .1 mg)
Approx. Dose Equivalent 1 1/2 grains (90 mg) 1 1/2 37.5 mcg 150 mcg (.15 mg)
Approx. Dose Equivalent 2 grains
 (120 mg)
2 50 mcg 200 mcg (.2 mg)
Approx. Dose Equivalent 3grains
(180 mg)
3 75 mcg 300 mcg (.3 mg)


United States Pharmacopoeia — Drug Information 2000, 20th Edition, Drug Information for the Health Care Professional; Vol. 1, pp. 2980-2986. World Color Book Services, Versailles, KY.


Hyperthyroidism

  • When maternal TSH is less than 0.1mIU/L a FT4 should be obtained. Subclinical hyperthyroidism is defined as low or undetectable serum TSH with normal free thyroxine (FT4) .  Overt hyperthyroidism is defined as low or undetectable serum TSH with elevated free thyroxine (FT4) . TSH receptor antibody (TRAb) and/or total T3 (TT3)  levels may help to clarify the cause of the hyperthyroidism if  the patient has a prior history of thyroid disease  or has findings such as ophthalmopathy, goiter, or thyroid nodules on examination

Subclinical hyperthyroidism

  • Treatment of subclinical hyperthyroidism does not appear to improve pregnancy outcome but may adversely affect the fetus [7]

Gestational (transient) hyperthyroidism

  • Elevated hCG may cause increased FT4 and suppressed or undetectable serum TSH . This occurs commonly with hyperemesis gravidarum. FT4 typically returns to normal by 15 to 18 weeks .Treatment with antithyroid drugs (ATDs) is not indicated. [6]

Overt Hyperthyroidism

  • The most common cause of hyperthyroidism is Graves disease.
  • Untreated maternal thyrotoxicosis is associated with an increased risk of intrauterine growth restriction, preeclampsia, congestive heart failure , thyroid storm , and fetal death [7].
  • For overt hyperthyroidism the goal of treatment is to maintain FT4 values at, or just above the upper limit of normal, while utilizing the smallest possible dose of antithyroid drugs [6,7].
  • Propylthiouracil (PTU) is preferred for pregnant women in the first trimester because methimazole (MMI) may be associated an increased risk for congenital birth defects [10]. 

  • Because PTU may rarely be associated with severe liver toxicity it is recommended that methimazole be used  after the first trimester [6, 7,10].

  • 10 mg of MMI is approximately equivalent to 100–150 mg of PTU [6, 7]

Antithyroid drugs

Thyroid Storm
Order set
(needs to be updated)


Propylthiouracil (PTU)

Antithyroid drug. Suppresses thyroid hormone production by interfering with the organification of iodine. Inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3). The total daily dosage is usually given in 3 divided doses at approximately 8-hour intervals.

  • Treatment of hyperthyroidism [5].
    Starting dose is 50 to 100 mg orally every 8 hours.  In patients with severe hyperthyroidism, very large goiters, or both, the beginning dosage usually should be 400 mg daily; an occasional patient will require 600 to 900 mg/daily initially. The usual maintenance dosage is 100 to 150 mg daily
     
  •   Free T4 is tested every two weeks and the dosage is adjusted to keep the FT4 in upper
        third of normal range. Reduce the dosage by 1/2 after FT4 begins to improve. The TSH will
        remain suppressed for weeks or months. Thyroid tests usually normalize within 3 to 8
        weeks.
        Consider obtaining a baseline leukocyte count and prothrombin time.

Agranulocytosis is potentially the most serious adverse reaction. Symptoms include fever, sore throat, and malaise. Other adverse reactions include but are not limited to , aplastic anemia, metallic taste in mouth, arthralgia, myalgia, nausea, hepatitis, jaundice, lupus-like syndrome, vasculitis, hypothrombinemia, neuropathies,headache, vertigo, interstitial pneumonitis, insulin autoimmune syndrome (hypoglycemia).

Discontinue drug if agranulocytosis, aplastic anemia, hepatitis, fever, or exfoliative dermatitis occur.

(50 mg tablets)

May produce fetal goiter and hypothyroidism.

Breast feeding appears to be safe in mothers taking less than 300 mg of  PTU per day. PTU should be given after feeding in divided doses [6]




Methimazole (MMI) (Tapazole) [6,12]
Antithyroid drug. Suppresses thyroid hormone production by interfering with the organification of iodine. The total daily dosage is usually given in 3 divided doses at approximately 8-hour intervals.

  • Treatment of hyperthyroidism .
    The initial daily dosage is 5 to 15 mg for mild hyperthyroidism, 30 to 40 mg for moderately severe hyperthyroidism, and 60 mg for severe hyperthyroidism, divided into 3 doses at 8-hour intervals. The maintenance dosage is 5 to 15 mg day
     
  • Free T4 is tested every two weeks and the dosage is adjusted to keep the FT4 in upper
        third of normal range. Reduce the dosage by 1/2 after FT4 begins to improve. The TSH will
        remain suppressed for weeks or months. Thyroid tests usually normalize within 3 to 8
        weeks.
        Consider obtaining baseline leukocyte count and prothrombin time.

Agranulocytosis is potentially the most serious adverse reaction. Symptoms include fever, sore throat, and malaise. Other adverse reactions include but are not limited to , aplastic anemia, metallic taste in mouth, arthralgia, myalgia, nausea, hepatitis, jaundice, lupus-like syndrome, vasculitis, hypothrombinemia, neuropathies,headache, vertigo, interstitial pneumonitis, insulin autoimmune syndrome (hypoglycemia).

Discontinue drug if agranulocytosis, aplastic anemia, hepatitis, fever, or exfoliative dermatitis occur.

May produce fetal goiter and hypothyroidism.

Breast feeding appears to be safe in mothers taking less than 30 mg of  MMI per day. MMI should be given after feeding in divided doses [6]

(5, 10 mg tablets).


Propranolol (Inderal®)
Beta blocker

  • For the relief of the adrenergic symptoms of hyperthyroidism such as tremor, palpitations, heat intolerance, and nervousness.

    20 to 40 mg every 6 to 8 hours. Adjust dose to keep heart rate at 70 to 90 beats per minute. Beta blockade can be tapered after the free T4 has returned to normal range (~ 3 weeks) [5].

Avoid abrupt cessation of drug. Contraindicated in asthma, AV block, and overt heart failure.
(10, 20,40,60, 80  mg tablets)



REFERENCES

1.ACOG practice bulletin. Thyroid disease in pregnancy. Number 37, August 2002. American College of Obstetrics and Gynecology. Int J Gynaecol Obstet. 2002;79(2):171-80. PMID: 12481755
2. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87:489-499.PMID: 11836274
3. Montoro MN.Management of hypothyroidism during pregnancy.Clin Obstet Gynecol. 1997;40(1):65-80. pp 77 PMID:9103950
4. Kaplan MM Monitoring thyroxine treatment during pregnancy.Thyroid. 1992 ;2(2):147-52. PMID:1525583
5. Mestman JH. Hyperthyroidism in pregnancy.Clin Obstet Gynecol. 1997 Mar;40(1):45-64. PMID:9103949
6. Stagnaro-Green A, ert al. American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum.Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011 Oct;21(10):1081-125.PMID .21787128 
7.De Groot L, et. al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline.. J Clin Endocrinol Metab. 2012 Aug;97(8):2543-65. doi: 10.1210/jc.2011-2803. Review.
PMID: 22869843
8. Haddow JE, Palomaki GE, Allan WC, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341:549–555. [
9.. Lazarus JH, et. al., Antenatal thyroid screening and childhood cognitive function.
N Engl J Med. 2012 Feb 9;366(6):493-501. doi: 10.1056/NEJMoa1106104. Erratum in: N Engl J Med. 2012 Apr 26;366(17):1650. PMID: 22316443
10. Hackmon R, et al., The safety of methimazole and propylthiouracil in pregnancy: a systematic review.
J Obstet Gynaecol Can. 2012 Nov;34(11):1077-86. PMID: 23231846
11 Propylthiouracil packae insert  NCS HealthCare of KY, Inc dba Vangard Lab http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c46c4f31-121c-43a8-9538-53ae1288812e
12. Tapazole package insert. Pfizer Laboratories Div Pfizer Inchttp://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4280e008-bbaf-4cc7-b588-3b4303016067
13. Goodwin TM et al. Transient hyperthyroidism and hyperemesis gravidarum: clinical aspects. Am J Obstet Gynecol. 1992 Sep;167(3):648-52. PMID: 138238914.
14. Tan JY, et. al., Transient hyperthyroidism of hyperemesis gravidarum. BJOG. 2002 Jun;109(6):683-8. PMID: 1211864
 

Reviewed by Mark Curran, M.D., F.A.C.O.G.
For corrections or comments please contact : hawk112_1@hotmail.com

   

Home | About | Disclaimer | Privacy | Contact
Copyright © 2010 -2014 by Focus Information Technology.
All rights reserved