Levothyroxine Sodium

Registered South African indications:

• Hypothyroidism 

Contraindications

South African recommendations

• Hypersensitivity to levothyroxine sodium or to any of the excipients
• Untreated hyperthyroidism (levothyroxine new formulation)
• Thyrotoxicosis
• Untreated adrenal insufficiency
• Untreated pituitary insufficiency
• Acute myocardial infarction
• Acute myocarditis
• Acute pancarditis

Recommendations in other jurisdictions

• Hypersensitivity to the active substance or any of the excipients
• Thyrotoxicosis
• Adrenal gland disorder
• Untreated adrenal insufficiency
• Combination therapy of hyperthyroidism with levothyroxine and anti-thyroid agents is not indicated in pregnancy (100μg)

Cautions

• Pregnancy
• Breastfeeding (Recommendations in other jurisdictions)
• Renal impairment (levothyroxine tablets (excluding new formulation)) (South African recommendations)
• Hepatic impairment (levothyroxine tablets (excluding new formulation)) (South African recommendations)
• Renal impairment (Recommendations in other jurisdictions)
• Hepatic impairment (Recommendations in other jurisdictions)
• Elderly
  - Patients >50 years
• Very low birth weight preterm neonates
• Long standing hypothyroidism
• Panhypopituitarism
• Cardiovascular disorders
• Angina
• Coronary artery disease
• Hypertension
• Myocardial insufficiency
• Myocardial infarction
• Diabetes mellitus
• Diabete insipidus
• Abrupt withdrawal of treatment
• History of epilepsy
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosage

Levothyroxine new formulation

The dose for the treatment of any thyroid disorder should be individualized on the basis of clinical response and biochemical tests and should
be monitored regularly

Untreated hypothyroidism

• Oral (tab): Initial: 50-100μg, dly; Titrate by 50μg at intervals of 4-6 weeks until normal metabolism is steadily maintained; Final daily dose may be up to 100-200μg, dly

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Levothyroxine new formulation should preferably be taken on an empty stomach ≥30-60 minutes before breakfast or the first meal of the day. The tablets are swallowed whole, without chewing, with some liquid. For 25μg tablets the break line facilitates breaking to ensure uniform 12.5µg dosing

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If the dose of levothyroxine new formulation is increased too rapidly, symptoms such as diarrhoea, nervousness, rapid pulse, insomnia, tremors and sometimes anginal pain where there is latent myocardial ischaemia may occur and the dosage must be reduced or withheld for a day or two, then restarted at a lower level

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If a scheduled daily dose is missed, the dose should be taken as soon as the patient remembers, unless it is almost time for the next dose. Two doses should not be taken together

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For patients ≥50years, with or without cardiac disease, clinical response is probably a more acceptable criteria of dosage rather that serum levels. See additional prescribing points

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 Levothyroxine tablets (excluding new formulation)

The dose for the treatment of hypothyroidism should be individualised on the basis of clinical response and biochemical tests and should be monitored regularly

Hypothyroidism

• Oral (tab): Initial: 50-100μg, dly; Titrate by 50μg at intervals of 3-4 weeks; May require doses of 200-300μg, dly

- In patients with cardiac failure or coronary artery insufficiency

• Oral (tab): Initial: 25μg, dly; Titrate by 25μg at intervals of 4 weeks if needed

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If too rapid an increase in metabolism is produced (causing diarrhoea, nervousness, rapid pulse, insomnia, tremors and sometimes anginal pain where there is latent myocardial ischaemia), the dosage must be reduced or withheld for a day or two, then begun again at a lower level

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Dose should preferably be taken before breakfast

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Indications and dosages registered in other jurisdictions

Hypothyroidism

• Oral (tab): Initial: 50-100μg, dly; Titrate by 50μg at intervals of 3-4 weeks until normal metabolism is steadily maintained; Final daily dose may be up to 100-200μg, dly

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Doses should preferably be taken before breakfast or your first meal of the day

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For patients aged over 50 years, with or without cardiac disease, clinical response is probably a more acceptable criteria of dosage rather that serum levels. See additional prescribing points

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100mg tablet: The tablets should not be subdivided to obtain the desired dose

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In younger patients and in the absence of heart disease, a serum levothyroxine (T4) level of 70-160 nanomoles per litre, or a serum thyrotropin level of less than 5 milli-units per litre should be targeted. A pre-therapy ECG is valuable because ECG changes due to hypothyroidism may be confused with ECG evidence of cardiac ischaemia. If too rapid an increase in metabolism is produced (causing diarrhoea, nervousness, rapid pulse, insomnia, tremors, and sometimes anginal pain where there is latent cardiac ischaemia,) dosage must be reduced, or withheld, for a day or two, and then re-started at a lower dose level

Paed. forms avail. in SA and covered in this monograph: tab

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosage

Levothyroxine new formulation

Congenital hypothyroidism

Neonates and infants

• Oral (tab): Initial: 10-15μg/kg body weight, dly; Treatment duration: 3 months; Adjust dose thereafter on an individual basis according to the clinical findings and thyroid hormone and TSH values; Maintenance: 100-150μg/m² body surface area, dly

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The calculated daily dose equivalent should be rounded to the nearest 25μg to determine the actual prescribed dose. Infants should be given the total daily dose at least half an hour before the first meal of the day

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The dose for children depends on their age, weight and the condition being treated. Regular monitoring is required to make sure he/she gets the right dose

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The largest dose consistent with freedom from toxic effects should be given. The dosage is guided by clinical response, growth assessment and appropriate thyroid function tests - clinically normal pulse rate and absence of diarrhoea or constipation are the most useful indicators. Thyrotrophin levels may remain elevated during the first year of life in children with neonatal hypothyroidism due to resetting of the hypothalamic-pituitary axis

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Acquired hypothyroidism

• Oral (tab): Initial: 12.5-50μg, dly; Titrate at intervals of 2-4 weeks according to clinical findings and thyroid hormone and TSH values until the full replacement dose is reached

Juvenile myxoedema

• Oral (tab): Initial: 25μg, dly; Titrate by 25μg at intervals of 2-4 weeks until mild symptoms of hyperthyroidism is seen; Then reduce dose slightly

Older than 1 year

• Oral (tab): 2.5-5μg/kg/day; The calculated dly dose equivalent should be rounded to the nearest 25μg to determine the actual prescribed dose

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When applicable, tablets are to be disintegrated in some water (10-15ml) and the resultant suspension, which must be prepared freshly as required, is to be administered with some more liquid (5-10ml)

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In congenital hypothyroidism and juvenile myxoedema, the largest dose consistent with freedom from toxic effects should be given. The dosage is guided by clinical response, growth assessment and appropriate thyroid function tests - clinically normal pulse rate and absence of diarrhoea or constipation are the most useful indicators. Thyrotrophin levels may remain elevated during the first year of life in children with neonatal hypothyroidism due to resetting of the hypothalamic-pituitary axis

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Levothyroxine tablets (excluding new formulation)

Cretinism

• Oral (tab): Initial: 25μg, dly; Titrate by 25μg at intervals of 2-4 weeks until mild toxic symptoms appear; Then reduce dose slightly

Juvenile myxoedema

• Oral (tab): Initial: 25μg, dly; Titrate by 25μg at intervals of 2-4 weeks until mild toxic symptoms appear; Then reduce dose slightly

Older than 1 year

• Oral (tab): 2.5-5μg/kg/day; Titrate by 25μg at intervals of 2-4 weeks until mild toxic symptoms appear; Then reduce dose slightly

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Cretinism and juvenille myxoedema: The largest dose consistent with freedom from toxic effects should be given. Clinically, normal pulse rate and absence of diarrhoea or constipation are the most useful indications

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Indications and dosages registered in other jurisdictions

Congenital hypothyroidism

Neonates and infants

• Oral (tab): Initial: 10-15μg/kg body weight, dly; Treatment duration: 3 months; Adjust dose thereafter on an individual basis according to clinical findings and thyroid hormone and TSH values; Maintenance: 100-150μg/m² body surface area, dly

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The dose for children depends on their age, weight and the condition being treated. Regular monitoring using serum TSH levels, as in adults, is required to make sure he/she gets the right dose. Infants should be given the total daily dose at least half an hour before the first meal of the day

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Acquired hypothyroidism

Children

• Oral (tab): Initial: 12.5-50μg, dly; Titrate gradually at intervals of 2-4 weeks according to clinical findings and thyroid hormone and TSH values until the full replacement dose is reached

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Infants should be given the total daily dose at least half an hour before the first meal of the day

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Juvenile myxoedema

Children

• Oral (tab): Initial: 25μg, dly; Titrate by 25μg at intervals of 2-4 weeks until mild symptoms of hyperthyroidism is seen; Then reduce dose slightly

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In children under 5 years of age, the administration of whole tablets is not recommended. It is also not recommended that tablets are crushed and dispersed in water or other liquids, owing to limited solubility which could lead to dosing inaccuracy. In this age group it is preferable to administer an approved oral solution of levothyroxine

Pregnancy

South African recommendations

Levothyroxine new formulation

• Safe
• Levothyroxine new formulation has been taken by pregnant women and women of childbearing age without any form of definite disturbances in the reproductive process having been observed
• Thyroid hypo- or hyperactivity in the mother may, however, unfavourably influence the foetal and postnatal development, therefore the dosage may need to be adjusted during pregnancy

Levothyroxine tablets (excluding new formulation)

• Safe
• Treatment with thyroid hormones should be given consistently during pregnancy. Dosage requirements may increase during pregnancy
• Experience has shown that there is no evidence of levothyroxine induced teratogenicity and/or foeto-toxicity in humans at the recommended therapeutic dose levels
• Excessively high dose levels of levothyroxine during pregnancy may have a negative effect on foetal and postnatal development

Recommendations in other jurisdictions

• Caution
• The safety of levothyroxine treatment during pregnancy is not known, but any possible risk of foetal abnormalities should be weighed against the risk to the foetus of untreated hypothyroidism
• 100mg: Combination therapy of hyperthyroidism with levothyroxine and anti-thyroid agents is not indicated in pregnancy

Breastfeeding

South African recommendations

Levothyroxine new formulation

• Caution
• Levothyroxine new formulation is excreted in breast milk and this may be sufficient to interfere with neonatal screening for hypothyroidism. It is very important to monitor thyroid function in the mother as well as in the infant regularly

Levothyroxine tablets (excluding new formulation)

• Caution
• Treatment with thyroid hormones should be given consistently during breastfeeding. Levothyroxine is secreted into breast milk during lactation but the concentrations achieved at the recommended therapeutic dose level are not sufficient to cause development of hyperthyroidism or suppression of TSH secretion in the infant. However, thyroid function in mothers and infants should be monitored

Recommendations in other jurisdictions

• Caution
• Levothyroxine is excreted in breast milk in low concentrations, and it is contentious whether this can interfere with neonatal screening

Renal Impairment

South African recommendations

Levothyroxine new formulation

• No dose adjustment recommended

Levothyroxine tablets (excluding new formulation)

• Caution; no information available

Recommendations in other jurisdictions

• Caution; no information available

Hepatic Impairment

South African recommendations

Levothyroxine new formulation

• No dose adjustment recommended

Levothyroxine tablets (excluding new formulation)

• Caution; no information available

Recommendations in other jurisdictions

• Caution; no information available

Elderly

South African recommendations

Levothyroxine new formulation

• Caution; dose adjustment recommended
  ≥50 years: Initially, it is not advisable to exceed 50μg daily; Titrate by 50μg at intervals of 3-4 weeks until stable levels are attained; Final daily dose may be up to 50-200μg, dly
• ≥50 years with cardiac disease: Initial: 25μg, dly OR 50μg on alternate days is more suitable; Titrate by 25μg at intervals of 4 weeks until stable levels are attained; Final daily dose may be up to 50-200μg, dly

Levothyroxine tablets (excluding new formulation)

• Caution; dose adjustment recommended
  Oral (tab): Initial: 12.5μg/day; Titrated slowly at lengthy intervals (e.g. a gradual increment of 12.5μg/day fortnightly); Maintenance: A dose lower than that required for complete correction of TSH levels may be considered

Recommendations in other jurisdictions

• Caution; dose adjustment recommended
  ≥50 years: Initially, it is not advisable to exceed 50μg daily; Titrate by 50μg at intervals of 3-4 weeks until stable levels are attained; Final daily dose may be up to 50-200μg, dly
• ≥50 years with cardiac disease: Initial: 25μg, dly OR 50μg on alternate days is more suitable; Titrate by 25μg at intervals of 4 weeks until stable levels are attained; Final daily dose may be up to 50-200μg, dly

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Tremor
• Restlessness
• Excitability
• Insomnia
• Benign intracranial hypertension
• Headache
• Agitation
• Malaise

Cardiovascular Disorders

• Angina pectoris
• Cardiac arrythmias
• Palpitations
• Tachycardia

Respiratory Disorders

• Dyspnoea

Gastrointestinal Disorders

• Diarrhoea
• Vomiting

Genitourinary Disorders

• Irregular menstruation

Endocrine and Metabolic Disorders

• Weight loss
• Menstrual irregularities
• Heat intolerance
• Transient hair loss
• Flushing
• Fever
• Sweating
• Thyrotoxic crisis
  - Fever
  - Tachycardia
  - Arrhythmia
  - Hypotension
  - Cardiac failure
  - Jaundice
  - Confusion
  - Seizure
  - Coma

Musculoskeletal Disorders

• Muscle spasm
• Muscle weakness
• Arthralgia
• Craniostenosis in infants
• Premature closure of epiphysis in children

Skin and Subcutaneous Tissue Disorders

• Hyperhidrosis
• Rash
• Pruritus
• Flushing
• Transient hair loss

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Oedema

• Warfarin
• Antidiabetic agents
• Metformin
• Insulin
• Tricyclic antidepressants
• Amitriptyline
• Imipramine
• Dosulepin
• Sympathomimetic agents
• Adrenalin
• Phenylephrine
• Cardiac glycosides
• Digoxin
• Non-steroidal anti-inflammatory drugs
• Phenylbutazone
• Acetylsalicylic acid
• Beta blockers
• Propranolol
• Atenolol
• Sotalol
• General anesthetics
• Ketamine
• Amiodarone
• Anticonvulsants
• Carbamazapine
• Phenytoin
• Sertraline
• Antacids
• Proton pump inhibitors
• Calcium salts
• Cimetidine
• Oral iron
• Sucralfate
• Colestipol
• Polystyrene sulphonate resin
• Cholestyramine
• Rifampicin
• Barbiturates
• Primidone
• Imatinib
• Lipid regulating agents
• Lovastatin
• Oestrogen
• Oral contraceptive agents
• Androgens
• Corticosteroids
• Anti-obesity agents
• Orlistat
• Ritonavir

• Thyroid function tests
• ECG

Some cases may require

• Bone mineral density
• Haemodynamic parameters

The function of the thyroid gland is dependent upon 2 main hormones; namely levothyroxine (tetraiodothyronine(T4)) and tri-iodothyronine  (T3). These closely related iodine containing amino acids are incorporated into the glycoprotein thyroglobulin. Levothyroxine (T4) is deiodinated in peripheral tissues to form tri-iodothyronine (T3) which is thought to be the active tissue form of thyroid hormone. T3 is more rapid acting and has a shorter duration of action than levothyroxine. The chief action of Levothyroxine is to increase the rate of cell metabolism.

Tablet 25μg

• Eltroxin NF (Pharmacare) originator
• Euthyrox (Merck) originator
• Synthroid (Abbott)

Tablet 50μg

• Eltroxin (Pharmacare) originator
• Eltroxin NF (Pharmacare) originator
• Euthyrox (Merck) originator
• Synthroid (Abbott)

Tablet 75μg

• Eltroxin NF (Pharmacare) originator

Tablet 100μg

• Eltroxin (Pharmacare) originator
• Eltroxin NF (Pharmacare) originator
• Euthyrox (Merck) originator
• Synthroid (Abbott)

Tablet 200μg

• Eltroxin NF (Pharmacare) originator