Adverse reactions : תופעות לוואי

ADVERSE REACTIONS

Adverse Drug Reaction Overview

Adverse reactions other than those indicative of thyrotoxicosis as a result of therapeutic overdosage, either initially or during the maintenance periods, are rare. See OVERDOSAGE. Seizures have been reported rarely with the institution of levothyroxine sodium therapy.
Pseudotumor cerebri and slipped capital femoral epiphysis have also been reported in children receiving levothyroxine therapy. Over treatment in children may result in craniosynostosis and premature closure of the epiphyses with resultant compromised adult height.


Inadequate doses of SYNTHROID® (levothyroxine sodium tablets) may produce or fail to resolve symptoms of hypothyroidism. Hair loss may occur during the initial months of therapy, but is generally transient. The incidence of continued hair loss is unknown.
Post-Market Adverse Drug Reactions

Adverse reactions associated with SYNTHROID® are primarily those of hyperthyroidism due to therapeutic overdosage. See WARNINGS AND PRECAUTIONS and OVERDOSAGE. They include the following:
Cardiovascular System:             palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction and cardiac arrest;
Central Nervous System:            headache, hyperactivity, nervousness, anxiety, irritability, emotional lability and insomnia;
Dermatologic:                      hair loss, flushing;
Endocrine System:                  decreased bone mineral density;
Gastrointestinal System:           diarrhea, vomiting, abdominal cramps and elevations in liver function tests; 

General:                           fatigue, increased appetite, weight loss, heat intolerance, fever and excessive sweating;
Musculoskeletal System:            tremors, muscle weakness;
Reproductive System:               menstrual irregularities, impaired fertility; Respiratory System:                dyspnea;


Seizures have been reported rarely with the institution of levothyroxine sodium therapy.
Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various GI symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@mo h. gov.il

DRUG INTERACTIONS
Overview
The magnitude and relative clinical importance of the effects noted below are likely to be patient- specific and may vary by such factors as age, gender, race, intercurrent illnesses, dose of either agent, additional concomitant medications, and timing of drug administration. Any agent that alters thyroid hormone synthesis, secretion, distribution, effect on target tissues, metabolism, or ® elimination may alter the optimal therapeutic dose of SYNTHROID (levothyroxine sodium tablets).

Drug-Drug Interactions

Many drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to SYNTHROID®. In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs. A listing of drug-thyroidal axis interactions is contained in Table 1.

The list of drug-thyroidal axis interactions in Table 1 may not be comprehensive due to the introduction of new drugs that interact with the thyroidal axis or the discovery or previously unknown interactions. The prescriber should be aware of this fact and should consult appropriate reference sources (e.g., package inserts of newly approved drugs, medical literature) for additional information if a drug-drug interaction with levothyroxine is suspected.
Table 1.                   Drug-Thyroidal Axis Interactions

Drug or Drug Class                                                   Effect Drugs that may reduce TSH secretion - the reduction is not sustained; therefore, hypothyroidism does not occur Dopamine/Dopamine Agonists              Use of these agents may result in a transient reduction in TSH secretion when Glucocorticoids                         administered at the following doses: dopamine (greater than or equal to 1 mcg/kg/min); glucocorticoids (hydrocortisone greater than or equal to 100 Octreotide                              mg/day or equivalent); octreotide (greater than 100 mcg/day).
Drugs that alter thyroid hormone secretion
Drugs that may decrease thyroid hormone secretion, which may result in hypothyroidism Aminoglutethimide                       Long-term lithium therapy can result in goiter in up to 50% of patients, and Amiodarone                              either subclinical or overt hypothyroidism, each in up to 20% of patients. The fetus, neonate, elderly and euthyroid patients with underlying thyroid disease Iodide (including iodine-containing     (e.g., Hashimotos’s thyroiditis or with Grave’s disease previously treated with radiographic contrast agents)           radioiodine or surgery) are among those individuals who are particularly Lithium                                 susceptible to iodine-induced hypothyroidism. Oral cholecystographic agents Thioamides                              and amiodarone are slowly excreted, producing more prolonged hypothyroidism than parenterally administered iodinated contrast agents. Long- - Methimazole                           term aminoglutethimide therapy may minimally decrease T 4 and T3 levels and - Propylthiouracil (PTU)                increase TSH, although all values remain within normal limits in most patients.
- Carbimazole
Sulfonamides
Tolbutamide
Drugs that may increase thyroid hormone secretion, which may result in hyperthyroidism Amiodarone                              Iodide and drugs that contain pharmacologic amounts of iodide may cause Iodide (including iodine-containing     hyperthyroidism in euthyroid patients with Grave’s disease previously treated with antithyroid drugs or in euthyroid patients with thyroid autonomy (e.g., radiographic contrast agents)           multinodular goiter or hyperfunctioning thyroid adenoma). Hyperthyroidism may develop over several weeks and may persist for several months after therapy discontinuation. Amiodarone may induce hyperthyroidism by causing thyroiditis.
Drug or Drug Class                                                Effect 

Drugs that may decrease T4 absorption, which may result in hypothyroidism Antacids                                Concurrent use may reduce the efficacy of levothyroxine by binding and - Aluminum & Magnesium                  delaying or preventing absorption, potentially resulting in hypothyroidism.
Hydroxides                              Calcium carbonate may form an insoluble chelate with levothyroxine, and ferrous sulfate likely forms a ferric-thyroxine complex. Administer
-Simethicone                            levothyroxine at least four (4) hours apart from these agents. Patients treated Bile Acid Sequestrants                  concomitantly with orlistat and levothyroxine should be monitored for changes - Cholestyramine                        in thyroid function.

- Colestipol Calcium
Carbonate Cation
Exchange Resins
- Sodium Polystyrene Sulfonate
Ferrous Sulfate
Orlistat
Sucralfate
Drugs that may alter T4 and T3 serum transport - but FT4 concentration remains normal; and therefore, the patient remains euthyroid
Drugs that may increase serum                     Drugs that may decrease serum TBG Concentration TBG Concentration
Clofibrate                              Androgens/Anabolic Steroids
Estrogen-containing Oral                Asparaginase
Contraceptives                          Glucocorticoids
Estrogens (oral)                        Slow-Release Nicotinic Acid
Heroin/Methadone
5-Fluorouracil
Mitotane
Tamoxifen
Drugs that may cause protein-binding site replacement
Furosemide (greater than 80 mg IV)      Administration of these agents with levothyroxine results in an initial transient Heparin                                 increase in FT 4. Continued administration results in a decrease in Serum T 4 and normal FT4 and TSH concentrations and, therefore, patients are clinically Hydantoins                              euthyroid. Salicylates inhibit binding of T 4 and T3 to TBG and transthyretin. An Non Steroidal Anti-Inflammatory         initial increase in serum FT4 is followed by return of FT 4 to normal levels with Drugs                                   sustained therapeutic serum saliyclate concentrations, although total T4 levels - Fenamates                             may decrease by as much as 30%.
- Phenylbutazone
Salicylates (greater than 2 g/day)
Drug or Drug Class                                                       Effect 

Drugs that may alter T4 and T3 metabolism
Drugs that may increase hepatic metabolism, which may result in hypothyroidism Carbamazepine                               Stimulation of hepatic microsomal drug-metabolizing enzyme activity may Hydantoins                                  cause increased hepatic degradation of levothyroxine, resulting in increased levothyroxine requirements. Phenytoin and carbamazepine reduce serum
Phenobarbital                               protein binding of levothyroxine, and total and free T4 may be reduced by 20 to Rifampin                                    40%, but most patients have normal serum TSH levels and are clinically euthyroid.
Drugs that may decrease T4 5'-deiodinase activity
Amiodarone                                  Administration of these enzyme inhibitors decreases the peripheral conversion Beta-adrenergic antagonists                 of T4 to T3, leading to decreased T3 levels. However, serum T4 levels are usually normal but may occasionally be slightly increased. In patients treated - (e.g., propanolol greater than            with large doses of propanolol (greater than 160 mg/day), T 3 and T4 levels 160 mg/day) change slightly, TSH levels remain normal, and patients are clinically Glucocorticoids                             euthyroid. It should be noted that actions of particular beta-adrenergic - (e.g., dexamethasone greater than         antagonists may be impaired when the hypothyroid patient is converted to the or equal to 4 mg/day)                       euthyroid state. Short-term administration of large doses of glucocorticoids may decrease serum T3 concentrations by 30% with minimal change in serum T 4 Propylthiouracil (PTU)                      levels. However, long-term glucocorticoid therapy may result in slightly decreased T 3 and T4 levels due to decreased TBG production (see above).
Miscellaneous
Anticoagulants (oral)                       Thyroid hormones appear to increase the catabolism of vitamin K-dependent - Coumarin Derivatives                      clotting factors, thereby increasing the anticoagulant activity of oral anticoagulants. Concomitant use of these agents impairs the compensatory - Indandione Derivatives                    increases in clotting factor synthesis. Prothrombin time should be carefully monitored in patients taking levothyroxine and oral anticoagulants and the dose of anticoagulant therapy adjusted accordingly.
Antidepressants                             Concurrent use of tri/tetracyclic antidepressants and levothyroxine may increase - Tricyclics (e.g., amitriptyline)          the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines. Toxic effects may include increased risk - Tetracyclics (e.g., maprotiline)          of cardiac arrhythmias and CNS stimulation; onset of action of tricyclics may - Selective Serotonin Reuptake              be accelerated. Administration of sertraline in patients stabilized on Inhibitors (SSRIs; e.g., sertraline)        levothyroxine may result in increased levothyroxine requirements.
Antidiabetic Agents                         Addition of levothyroxine to antidiabetic or insulin therapy may result in - Biguanides                                increased antidiabetic agent or insulin requirements. Careful monitoring of diabetic control is recommended, especially when thyroid therapy is started, - Meglitinides                              changed, or discontinued.
- Sulfonylureas
- Thiazolidinediones
- Insulin
Drug or Drug Class                                                 Effect Cardiac glycosides                   Serum digitalis glycoside levels may be reduced in hyperthyroidism or when the hypothyroid patient is converted to the euthyroid state. Therapeutic effect of digitalis glycosides may be reduced.
Cytokines                            Therapy with interferon-alpha has been associated with the development of - Interferon-alpha                   antithyroid microsomal antibodies in 20% of patients and some have transient hypothyroidism, hyperthyroidism, or both. Patients who have antithyroid - Interleukin-2                      antibodies before treatment are at higher risk for thyroid dysfunction during treatment. Interleukin-2 has been associated with transient painless thyroiditis in 20% of patients. Interferon-beta and -gamma have not been reported to cause thyroid dysfunction.
Growth Hormones                      Excessive use of thyroid hormones with growth hormones may accelerate - Somatropin                         epiphyseal closure. However, untreated hypothyroidism may interfere with growth response to growth hormone.
Ketamine                             Concurrent use may produce marked hypertension and tachycardia; cautious administration to patients receiving thyroid hormone therapy is recommended.
Methylxanthine Bronchodilators       Decreased theophylline clearance may occur in hypothyroid patients; clearance - (e.g., theophylline)               returns to normal when the euthyroid state is achieved.
123        131            99m
Radiographic agents                  Thyroid hormones may reduce the uptake of            I,         I, and     Tc.

Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency Sympathomimetics when sympathomimetic agents are administered to patients with coronary artery disease.
Tyrosine Kinase Inhibitors           Plasma concentration of levothyroxine (thyroxine) possibly reduced by Tyrosine Kinase Inhibitors (e.g. imatinib, sunitinib).

Proton Pump Inhibitors               Plasma concentration of levothyroxine (thyroxine) possibly reduced by Proton Pump Inhibitors. Monitoring of TSH plasma level is recommended.
Chloral Hydrate                      These agents have been associated with thyroid hormone and/or TSH level Diazepam                             alterations by various mechanisms.

Ethionamide
Lovastatin
Metoclopramide
6-Mercaptopurine
Nitroprusside
Para-aminosalicylate sodium
Perphenazine
Resorcinol (excessive topical use)
Thiazide Diuretics
TBG = thyroxine-binding globulin



SYNTHROID® Product Monograph                                                                                        Page 15 of 36 Date of Revision: September 3, 2015 and Control No. 185008
Anticoagulants

Levothyroxine levels increase the response to oral anticoagulant therapy. Therefore, a decrease in the dose of anticoagulant may be warranted with correction of the hypothyroid state or when the levothyroxine sodium dose is increased. Prothrombin time should be closely monitored to permit appropriate and timely dosage adjustments (see Table 1).

Digitalis Glycosides

The therapeutic effects of digitalis glycosides may be reduced by SYNTHROID®. Serum digitalis glycoside levels may be decreased when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides (see Table 1).

Orlistat

Hypothyroidism and/or reduced control of hypothyroidism may occur. The mechanism, although not proven, may involve a decreased absorption of iodine salts and/or levothyroxine. Patients treated concomitantly with SYNTHROID® and orlistat should be monitored for changes in thyroid function.

Drug-Food Interactions
Consumption of certain foods may affect levothyroxine absorption thereby necessitating adjustments in dosing.
Soybean flour (infant formula), cotton seed meal, walnuts, calcium and calcium-fortified orange juice, and dietary fibre may bind and decrease the absorption of levothyroxine sodium from the gastrointestinal tract.

Drug-Laboratory Interactions

A number of drugs or moieties are known to alter serum levels of TSH, T4 and T3 and may thereby influence the interpretation of laboratory tests of thyroid function. See DRUG INTERACTIONS.


1.      Drugs such as estrogens and estrogen-containing oral contraceptives increase serum thyroxine-binding globulin (TBG) concentrations. TBG concentrations may also be increased during pregnancy, in infectious hepatitis and acute intermittent porphyria. Decreases in TBG concentrations are observed in nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, and after androgen or corticosteroid therapy.
Familial hyper- or hypothyroxine-binding-globulinemias have been described. The incidence of TBG deficiency is approximately 1 in 9000. Certain drugs such as salicylates inhibit the protein binding of T4. In such cases, the unbound (free) hormone should be measured and/or determination of the free T4 index (FT4I) should be done.
 2.      Persistent clinical and laboratory evidence of hypothyroidism despite an adequate replacement dose suggests either poor patient compliance, impaired absorption, drug interactions, or decreased potency of the preparation due to improper storage.


DOSAGE AND ADMINISTRATION


Dosing Considerations
®
The dosage and rate of administration of SYNTHROID (levothyroxine sodium tablets) is determined by the indication, and must in every case be individualized according to patient response and laboratory findings.


Adult Dosage
Hypothyroidism

The goal of therapy for primary hypothyroidism is to achieve and maintain a clinical and biochemical euthyroid state with consequent resolution of hypothyroid signs and symptoms. The starting dose of SYNTHROID®, the frequency of dose titration, and the optimal full replacement dose must be individualized for every patient, and will be influenced by such factors as age, weight, cardiovascular status, presence of other illness, and the severity and duration of hypothyroid symptoms.


In patients with hypothyroidism resulting from pituitary or hypothalamic disease, the possibility of secondary adrenal insufficiency should be considered, and if present, treated with glucocorticoids prior to initiation of SYNTHROID®.
The adequacy of levothyroxine sodium therapy should be assessed in these patients by measuring FT4, which should be maintained in the upper half of the normal range, in addition to clinical assessment. Measurement of TSH is not a reliable indicator of response to therapy for this condition.

TSH Suppression in Thyroid Cancer and Thyroid Nodules

The rationale for TSH suppression therapy is that a reduction in TSH secretion may decrease the growth and function of abnormal thyroid tissue. Exogenous thyroid hormone may inhibit recurrence of tumour growth and may produce regression of metastases from well-differentiated (follicular and papillary) carcinoma of the thyroid. It is used as ancillary therapy of these conditions following surgery or radioactive iodine therapy. Medullary and anaplastic carcinoma of the thyroid is unresponsive to TSH suppression therapy. TSH suppression is also used in treating nontoxic solitary nodules and multinodular goiters.
No controlled studies have compared the various degrees of TSH suppression in the treatment of either benign or malignant thyroid nodular disease. Further, the effectiveness of TSH suppression for benign nodular disease is controversial. The dose of SYNTHROID® used for TSH suppression should therefore be individualized by the nature of the disease, the patient being treated, and the desired clinical response, weighing the potential benefits of therapy against the risks of iatrogenic thyrotoxicosis. In general, SYNTHROID® should be given in the smallest dose that will achieve the desired clinical response.


Pediatric Dosage

Congenital or acquired hypothyroidism

The SYNTHROID® pediatric dosage varies with age and body weight. SYNTHROID® should be given at a dose that maintains T4 or free T4 in the upper half of the normal range and serum TSH in the normal range. See WARNINGS AND PRECAUTIONS-Special Populations- Pediatrics. Normalization of TSH may lag significantly behind T4 in some infants. In general, despite the smaller body size of children, the dosage (on a weight basis) required to sustain full development and general thriving is higher than in adults (see Table 2).

Recommended Dose and Dosage Adjustment

Adult Dosage


Hypothyroidism

The usual full replacement dose of SYNTHROID® for younger, healthy adults is approximately                 1.7 mcg/kg/day administered once daily. In the elderly, the full replacement dose may be altered by decreases in T4 metabolism and levothyroxine sodium absorption. Older patients may require less than 1 mcg/kg/day. Children generally require higher doses. See Pediatric Dosage. Women who are maintained on SYNTHROID® during pregnancy may require increased doses. See WARNINGS AND PRECAUTIONS-Special Populations-Pregnant Women.


Therapy is usually initiated in younger, healthy adults at the anticipated full replacement dose. 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 most patients older than 50 years and for patients under 50 years of age with a history of/ underlying cardiac disease, an initial starting dose of 25 to 50 mcg/day of SYNTHROID® is recommended, with gradual increments in dose at six to eight week intervals, as needed. The recommended starting dose of SYNTHROID® in elderly patients with cardiac disease is 12.5 to 25 mcg/day, with gradual dose increments at four to six week intervals. If cardiac symptoms develop or worsen, the cardiac disease should be evaluated and the dose of levothyroxine sodium reduced. Rarely, worsening angina or other signs of cardiac ischemia may prevent achieving a TSH in the normal range. Treatment of subclinical hypothyroidism may require lower than usual replacement doses e.g. 1.0 mcg/kg/day. Patients for whom treatment is not initiated should be monitored yearly for changes in clinical status, TSH, and thyroid antibodies.
Few patients require doses greater than 200 mcg/day. An inadequate response to daily doses of 300 to 400 mcg/day is rare, and may suggest malabsorption, poor patient compliance, and/or drug interactions.

Once optimal replacement is achieved, clinical and laboratory evaluations should be conducted at least annually or whenever warranted by a change in patient status.

Levothyroxine sodium products from different manufacturers should not be used interchangeably unless retesting of the patient and re-titration of the dosage, as necessary, accompanies the product switch.


Myxedema Coma
Myxedema coma represents the extreme expression of severe hypothyroidism and is considered a medical emergency. It is characterized by hypothermia, hypotension, hypoventilation, hyponatremia, and bradycardia. In addition to restoration of normal thyroid hormone levels, therapy should be directed at the correction of electrolyte disturbances and possible infection.

Because the mortality rate of patients with untreated myxedema coma is high, treatment must be started immediately, and should include appropriate supportive therapy and corticosteroids to prevent adrenal insufficiency.
Possible precipitating factors should also be identified and treated.

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. Therefore, oral thyroid hormone drug products, such as SYNTHROID®, are not recommended to treat this condition. Thyroid hormone products formulated for intravenous administration should be administered.

TSH Suppression in Thyroid Cancer and Thyroid Nodules
For well-differentiated thyroid cancer, TSH is generally suppressed to less than 0.1 mU/L. Doses of SYNTHROID® greater than 2 mcg/kg/day are usually required. The efficacy of TSH suppression in reducing the size of benign thyroid nodules and in preventing nodule regrowth after surgery is controversial. Nevertheless, when treatment with SYNTHROID® is warranted, TSH is generally suppressed to a higher target range (e.g., 0.1 to 0.3 ® mU/L) than that employed for the treatment of thyroid cancer. SYNTHROID therapy may also be considered for patients with nontoxic multinodular goiter who have a TSH in the normal range, to moderately suppress TSH (e.g., 0.1 to 0.3 mU/L).


SYNTHROID® should be administered with caution to patients in whom there is a suspicion of thyroid gland autonomy, in view of the fact that the effects of exogenous hormone administration will be additive to endogenous thyroid hormone production.
Pediatric Dosage

Congenital or acquired hypothyroidism
Therapy is usually initiated at the full replacement dose (see Table 2). Infants and neonates with very low (< 5 mcg/dL) or undetectable serum T4 levels should be started at higher end of the dosage range (e.g., 50 mcg daily).
A lower dose (e.g., 25 mcg daily) should be considered for neonates at risk of cardiac failure, increasing every few days until a full maintenance dose is reached. In children with severe, longstanding hypothyroidism or pre-existing ® cardiac insufficiency, SYNTHROID should be initiated gradually, with an initial 25 mcg dose for two weeks, then increasing by 25 mcg every 2 to 4 weeks until the desired dose, based on serum T4 and TSH levels, is achieved. See WARNINGS AND PRECAUTIONS-Special Populations- Pediatrics.


Table 2.                  Dosage Guidelines for Pediatric Hypothyroidism 

Daily dose (mcg) per kg
Age of body weight *
0 - 3 months                                               10 – 15
3 - 6 months                                                8 – 10
6 - 12 months                                                6–8
1 - 5 years                                                5–6
6 - 12 years                                                4–5
> 12 years but growth and puberty incomplete                               2–3 Growth and puberty complete                                       1.6– 1.7 *    To be adjusted on the basis of clinical response and laboratory tests. See WARNINGS AND PRECAUTIONS-Special Populations-Pediatrics.


Serum T4 and TSH measurements should be evaluated at the following intervals, with subsequent dosage adjustments to normalize serum total T4 or FT4 and TSH:


2 and 4 weeks after therapy initiation, until complete normalization of TSH, every 1 to 2 months during the first year of life,every 2 to 3 months between 1 and 3 years of age, every 3 to 12 months thereafter until growth is completed


Evaluation at more frequent intervals is indicated when compliance is questioned or abnormal laboratory values are obtained. Patient evaluation is also advisable approximately 2 to 4 weeks after any change in SYNTHROID® dose.


Missed Dose
A missed dose of one tablet can be taken with the next dose. If more than 2 tablets are missed, the patient should consult with their doctor.


Administration

Pediatrics

SYNTHROID® Tablets may be given to infants and children who cannot swallow intact tablets by crushing the tablet and suspending the freshly crushed tablet in a small amount of water (5 to 10 mL), breast milk or non-soybean based formula. The suspension can be given by spoon or dropper. DO NOT STORE THE SUSPENSION FOR ANY PERIOD OF TIME. The crushed tablet may also be sprinkled over a small amount of food, such as apple sauce. Foods or formula containing large amounts of soybean, ® fibre, or iron should not be used for administering SYNTHROID .


Table 3 summarizes the DOSAGE AND ADMINISTRATION of SYNTHROID®.
Table 3.                 Dosing and Administration

Interval For
Medical                Patient                               Dosing          Monitoring/ Condition(s)                              Starting Dose                          Dosing             Therapeutic Goal Population                           Increment
Increment
Congenital                                    10-15                                                Free T4 level in Neonate                          12.5 mcg/day        4-6 weeks*
Hypothyroidism                                mcg/kg/day                                          upper half of normal 1-2 months (until 1         range
Free T4 level in
Congenital/Acquired                                                            year), 2-3 months Infants/Children      See Table 2      25 mcg/day                        upper half of normal Hypothyroidism                                                               (until 3 years), 3- range, normal TSH
12 months
Congenital                                                                 thereafter*      T4 level in upper half Hypothyroidism with           Neonate          25 mcg/day      12.5 mcg/day         4-6 weeks*      of normal range, risk of heart failure                                                                                 normal TSH Severe Congenital                                                                                     Free T4 level in Hypothyroidism               Neonate          50 mcg/day       25 mcg/day         2-4 weeks*      upper half of normal (T4 < 5 mcg/dL)                                                                                    range, normal TSH Hypothyroidism with                                                                                 Normal TSH (age- 1.6-1.7
Completed Growth             Children                        25-50 mcg/day         6-8 weeks        specific reference mcg/kg/day and Puberty                                                                                           range) Adults <50                                                               Normal TSH (between Hypothyroidism                            1.7 mcg/kg/day   25-50 mcg/day         6-8 weeks years                                                                    0.5 and 2.0 mU/L) Adults >50
25-50 mcg/day 12.5-25 mcg/day          6-8 weeks years
Interval For
Medical                Patient                                Dosing            Monitoring/ Condition(s)                              Starting Dose                             Dosing              Therapeutic Goal Population                            Increment
Increment
Hypothyroidism with        Adults <50                                                                   Normal TSH (between 25-50 mcg/day 12.5-25 mcg/day             6-8 weeks
Cardiac Disease            years                                                                       0.5 and 2.0 mU/L) Adults >50           12.5-25
12.5-25 mcg/day          4-6 weeks years              mcg/day
Severe                 Adults < 50           12.5-25                                                 Normal TSH (between 25 mcg/day            2-4 weeks
Hypothyroidism                years             mcg/day                                                  0.5 and 2.0 mU/L) Normal TSH (age-
Infants/Children       25 mcg/day        25 mcg/day            2-4 weeks specific reference
Hypothyroidism (short                                                                                          range) period) or Recently      Adults > 50            < 1.7                                                  Normal TSH (between 25-50 mcg/day           6-8 weeks
Treated with             years            mcg/kg/day                                                 0.5 and 2.0 mU/L) Hyperthyroidism
Every 4 weeks             Normal TSH
1.7                           during first half of    (trimester- specific) mcg/kg/day                           pregnancy; at        and FT4 in the upper Hypothyroidism with         Pregnant                                                 least once         third of normal range (Increased dose     25-50 mcg/day
Pregnancy                Women                                               between week 26 may                                                     1st trimester: < 2.5 be required)                           and 32;                   mU/L approximately 6
2nd trimester: < 3.0 weeks
Secondary                                                                                             Free T43rd mU/L        trimester: level in upper
Not Specified          **                **              postpartum
**
Hypothyroidism                                                                                          third 2 mcg/kg/day 25-50 mcg/day             6-8 weeks follicular) Thyroid                                                                                    for patients with Cancers                                                                                          high risk tumors Benign Nodules and                               1.7-2                                                 TSH 0.1 – 0.3 mU/L for Nontoxic            Not Specified       mcg/kg/day       25-50 mcg/day           6-8 weeks        nodules and Multinodular Goiter                          (Suppression                                                    for not                                                   multinodular
**Depending on age, duration of hypothyroidism and cardiovascular risk factor <0.1 mU/L)                                                   goiter
*For Congenital Hypothyroidism, the current guidelines recommend a 2 week monitoring interval at the beginning of therapy until normalization of TSH levels