Consumer medicine information

Eltroxin

Levothyroxine sodium

BRAND INFORMATION

Brand name

Eltroxin

Active ingredient

Levothyroxine sodium

Schedule

What is in this leaflet

This leaflet answers some common questions about Eltroxin tablets.

It does not contain all the available information about the medicine.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Eltroxin against the benefits he or she expects it will have.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

The name of your medicine is Eltroxin. It is available in tablets of six different strengths: 25 micrograms (scored), 50 micrograms, 75 micrograms, 100 micrograms, 125 micrograms and 200 micrograms.

The active ingredient is called levothyroxine sodium.

What is it used for

Levothyroxine sodium is a thyroid hormone. It is used as replacement therapy in the treatment of thyroid hormone deficiency.

Eltroxin is used to treat:

Thyroid hormone deficiency also known as Hypothyroidism.
Hypothyroidism is a disease in which the thyroid gland is underactive and does not produce enough levothyroxine, a hormone, which is important for controlling your metabolism. Symptoms of hypothyroidism include tiredness, muscle weakness, and cramps, feeling the cold, a slow heart rate, dry and flaky skin, hair loss, a deep husky voice and weight gain.
TSH-responsive tumours (certain tumours of the thyroid gland) of the thyroid
For these conditions to be treated, patients need a supply of thyroid hormones in their body. Eltroxin replaces the shortage of thyroid hormones.

Use Eltroxin only as directed. Your doctor may have prescribed Eltroxin for another condition.

Ask your doctor if you have any questions about why the medicine has been prescribed for you.

Ask your doctor if you have any concerns about taking it.

Eltroxin tablets are only available with a doctor’s prescription.

Before you take it

When you must not take it

Do not take Eltroxin if you are allergic to:

Levothyroxine sodium or any other thyroid hormone (eg. Tertroxin)
Any of the inactive ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction to Eltroxin may include red, itchy skin rashes, difficulty in breathing, swelling of the face or throat or faintness.

Do not use Eltroxin after the expiry date (EXP.) printed on the pack. If you take the medicine after the expiry date has passed, it may not work as well.

Do not take the medicine if the packaging shows signs of tampering.

Before you start to take it

Tell your doctor if:

You are allergic to any other medicines or any foods, dyes or preservatives.
You are pregnant or intend to become pregnant.
Levothyroxine levels will need to be watched carefully during pregnancy. Your dosage of Eltroxin may need to be increased while you are pregnant.
Ask your doctor about the risks and benefits of taking Eltroxin during pregnancy.
You are breastfeeding or intend to breastfeed.
Although small amounts of Eltroxin are found in breast milk, women who are breastfeeding should continue treatment with Eltroxin.
You have or have had any other medical conditions/ health problems, including:

Overactive thyroid gland
Adrenal gland problem
Hyperthyroidism
Heart problems such as cardiovascular disorder
High blood pressure
Diabetes
Long-standing hypothyroidism, an underactive thyroid gland
Problems absorbing nutrients from the gastrointestinal tract

If you have not told your doctor about any of the above, tell them before you start to take any Eltroxin.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some of these medicines may interfere with Eltroxin. These include:

Anticoagulants, medicines used to thin your blood (eg. Warfarin)
Antidepressants, medicines used to treat depression (e.g. Lithium, SSRIs, Tricyclic antidepressants)
Antivirals, medicines used to treat HIV/AIDS infection (e.g. ritonavir)
Antimalarials, medicines used to treat and prevent malaria (e.g. chloroquine and proguanil)
Medicines used to treat diabetes (e.g. insulin)
Beta-blockers, medicines used to treat high blood pressure and heart conditions (e.g. propranolol)
Ion-exchange resins, medicines used to decrease cholesterol in the blood (e.g. cholestyramine)
Corticosteroids, antiinflammatory medicines (e.g. prednisolone and dexamethasone)
Oral contraceptives and hormone replacement medicines such as oestrogens, androgens or anabolic steroids
Medicines used for epilepsy (e.g. phenytoin and carbamazepine)
Medicines used to treat heart failure (e.g. digoxin)
Iron supplements
Calcium, magnesium and aluminiumsupplements
Rifampicin, an antibiotic used to treat tuberculosis and other serious infections
Ciprofloxacin, an antibiotic used to treat various infections
Soyabean flour (e.g. some infant formula and other products)
Antacids (e.g. aluminium hydroxide, magnesium hydroxide and calcium carbonate) and proton pump inhibitors, used to reduce stomach acid
Amiodarone, a medicine used to treat irregular heart beat
Oral contrast agents, used before X-ray and scans
Propylthiouracil, a medicine used to treat overactive thyroid and Graves disease
Non-steroidal anti-inflammatory drugs (NSAIDs), medicines used to relieve pain and/or inflammatory conditions including arthritis.
Weight loss drugs (e.g. orlistat)

These medicines may affect how well Eltroxin works, or react with it resulting in unwanted or sometimes serious side effects.

This list is not exhaustive. Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking it.

Before you start to take any other medicine, tell your doctor or pharmacist that you are taking Eltroxin.

How to take it

Your doctor will decide on the right dose for you.

It may take a few weeks for Eltroxin to begin working. Until it begins working you may not notice any change in your symptoms.

Follow your doctor's instructions carefully, as they may differ from the information contained in this leaflet.

How much to take

The usual starting dose for adults is 50 to 100 micrograms daily. The dose may be increased over time. The average adult maintenance dose is 100 to 200 micrograms. Lower doses are used in the elderly and children. Your doctor will calculate the dose required for you.

Your doctor will monitor your blood tests to make sure Eltroxin is working for you.

Carefully follow the dosage instructions, as given by your doctor.

Do not change your dose unless your doctor tells you to do so.

Talk to your doctor if you have any further questions.

How to take it

Swallow Eltroxin tablets with a glass of water.

When to take it

Eltroxin tablets should be taken first thing in the morning on an empty stomach, at least 30 minutes and preferably 60 minutes before any food or other medications .

How long to take it

Continue taking it as long as your doctor recommends it.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take your dose as soon as you remember, and then go back to taking it as you would normally.

Do not take a double dose to make up for the dose that you missed.

If you are unsure about whether to take your next dose, speak to your doctor or pharmacist.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have taken too much Eltroxin. Do this even if there are no signs of discomfort or poisoning.

If you take too much you may have the following symptoms: restlessness; vomiting; flushing; breathing difficulties; chest pain; convulsions or paralysis.

Keep your doctor, pharmacist, Accident and Emergency phone numbers handy.

While you are taking it

Things you must do

Do not switch or interchange with other brands unless advised by your doctor.

Immediately stop taking Eltroxin if a skin rash or other allergic reaction occurs.

Use it exactly as directed or as your doctor has prescribed.

Tell your doctor if you feel Eltroxin is not helping your condition.

Visit your doctor regularly. Your doctor needs to check your progress.

Tell any other doctors, dentists and pharmacists who are treating you that you are using Eltroxin.

Always discuss with your doctor any problems or difficulties during or after taking it.

If you plan to have surgery, tell your doctor or dentist that you are taking Eltroxin.

If you are about to start taking any new medicines, remind your doctor and pharmacist that you are taking Eltroxin.

Ensure you do not run out of medicine over the weekend or on holidays.

Things you must not do

Do not drive or operate machinery where alertness is required, until you know how the medicine affects you.

Do not give this medicine to anyone else, even if his or her symptoms seem similar to yours.

Side effects

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking it.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

nervousness
anxiousness
excitation
restlessness
muscle weakness & cramps
inability to sleep
sleep disturbances
unusual movements, including tremor
headache
lack of concentration
diarrhoea
stomach cramp
nausea
vomiting
heat intolerance
excessive sweating
flushing
weight loss
menstrual irregularities
decreased libido
fever
shortness of breath
rapid breathing
irregular heart beats
chest pain
increased blood pressure
allergic reactions such as skin rash
hair loss
irritability
increased appetite
tiredness

Some people may get other side effects with Eltroxin.

Check with your doctor as soon as possible if you have any problems while taking it even if you do not think the problems are connected with this medicine or are not listed in this leaflet.

After using it

Storage

Store below 25°C.

Store in the original package. Keep the bottle tightly closed. Protect from light. If you do not keep the tablets in the bottle they may not keep well.

Do not store Eltroxin, or any other medicines in a bathroom or near a sink. Do not leave it in the car or on windowsills. Heat and dampness can destroy some medicines.

Do not take ELTROXIN tablets if the tablet’s colour has changed.

Keep the medicine out of reach of children.

Disposal

If your doctor tells you to stop taking this medicine or it has passed its expiry date, ask your pharmacist what to do with any left over.

Product description

What it looks like

Eltroxin 25 microgram tablets are round, white, flat tablets marked with ‘25’ on one side and bisected on the other side.

Eltroxin 50 microgram tablets are round, white, flat tablets marked with ‘50’ on one side and ‘L01’ on the other side.

Eltroxin 75 microgram tablets are round, white, flat tablets marked with ‘75’ on one side and ‘L02’ on the other side.

Eltroxin 100 microgram tablets are round, white, flat tablets marked with ‘100’ on one side and ‘L10’ on the other side.

Eltroxin 125 microgram tablets are round, white, flat tablets marked with ‘125’ on one side and ‘L12’ on the other side.

Eltroxin 200 microgram tablets are round, white, flat tablets marked with ‘200’ on one side and ‘L21’ on the other side.

Eltroxin is available in bottles of 200 tablets.

Ingredients

Each Eltroxin tablet contains levothyroxine sodium as the active ingredient.

Each Eltroxin tablet contains the following excipients:

microcrystalline cellulose
maize starch
purified talc
colloidal anhydrous silica
magnesium stearate

They are free from gluten, sucrose, lactose and azo dyes.

Sponsor

Aspen Pharma Pty Ltd
34-36 Chandos St
St Leonards NSW 2065

The Australian Registration Numbers are:

Eltroxin 25 microgram:
AUST R 206944
Eltroxin 50 microgram:
AUST R 206960
Eltroxin 75 microgram:
AUST R 206961
Eltroxin 100 microgram:
AUST R 206963
Eltroxin 125 microgram:
AUST R 206974
Eltroxin 200 microgram:
AUST R 206954

This leaflet was revised in October 2017.

Published by MIMS December 2017

BRAND INFORMATION

Brand name

Eltroxin

Active ingredient

Levothyroxine sodium

Schedule

1 Name of Medicine

Levothyroxine sodium.

2 Qualitative and Quantitative Composition

Each tablet contains levothyroxine sodium as the active ingredient. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

25 microgram.

Round, white coloured, flat, bevelled tablets debossed with '25' on one side and bisected on the other side.

50 microgram.

Round, white coloured, flat, bevelled tablets debossed with '50' on one side and 'L01' on the other side.

75 microgram.

Round, white coloured, flat, bevelled tablets debossed with '75' on one side and 'L02' on the other side.

88 microgram.

Round, white coloured, flat, bevelled tablets debossed with '88' on one side and 'L07' on the other side.

100 microgram.

Round, white coloured, flat, bevelled tablets debossed with '100' on one side and 'L10' on the other side.

112 microgram.

Round, white coloured, flat, bevelled tablets debossed with '112' on one side and 'L11' on the other side.

125 microgram.

Round, white coloured, flat, bevelled tablets debossed with '125' on one side and 'L12' on the other side.

137 microgram.

Round, white coloured, flat, bevelled tablets debossed with '137' on one side and 'L15' on the other side.

150 microgram.

Round, white coloured, flat, bevelled tablets debossed with '150' on one side and 'L17' on the other side.

175 microgram.

Round, white coloured, flat, bevelled tablets debossed with '175' on one side and 'L20' on the other side.

200 microgram.

Round, white coloured, flat, bevelled tablets debossed with '200' on one side and 'L21' on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Eltroxin is indicated for the management of demonstrated thyroid hormone deficiency.
Eltroxin is also used to suppress thyrotropin (TSH) for the management of TSH responsive tumours of the thyroid.

4.2 Dose and Method of Administration

Levothyroxine is best taken as a single daily dose first thing in the morning. It should be taken with water and on an empty stomach, and at least 30 minutes and preferably 60 minutes before the intake of any food or other medications. Levothyroxine is best ingested in the fasting state, as food will impair absorption.
The dose should be individualised on the basis of clinical response and biochemical tests. Regular monitoring of TSH and levothyroxine is recommended when starting therapy or changing the dose.

Adults.

Initial dose.

Commence with levothyroxine 50 to 100 micrograms daily. Increase the daily dose by 25 to 50 micrograms according to response at not less than 4 weekly intervals, up to 100 to 200 micrograms daily.
In patients aged 60 years and over and in those with ischaemic heart disease, levothyroxine therapy should normally be initiated with low doses (25 or 50 microgram/day).
Wherever possible, whole tablets should be taken (e.g. if the dose required is 150 microgram then 1 x 100 microgram tablet and 1 x 50 microgram tablet should be taken, rather than 1½ x 100 microgram tablets).
When there is no contraindication to full thyroxine replacement, a TSH level of about 1 mU/L with a serum thyroxine level in the high-normal range, usually indicates optimal therapy.

Maintenance doses.

Adults.

100 to 200 microgram per day.

Children.

Congenital and acquired hypothyroidism (see Table 1).

Note.

The lowest dose compatible with clinical euthyroidism and satisfactory laboratory values should be used.

4.3 Contraindications

Known hypersensitivity to thyroxine, which has been described rarely; untreated hyperthyroidism; uncorrected primary or secondary adrenal insufficiency; thyrotoxicosis; acute myocardial infarction uncomplicated by hypothyroidism; acute myocarditis; acute pancarditis.

4.4 Special Warnings and Precautions for Use

Do not interchange Eltroxin and Eutroxsig/ Oroxine. If a decision is made to switch from Eutroxsig/ Oroxine to Eltroxin, then prescribers should be aware that dose adjustment may be required; TSH should be monitored.

Initiation of therapy.

In the elderly or patients with ischaemic heart disease, Eltroxin should not be initiated at more than 50 microgram/day and dose then be gradually increased (see Section 4.2 Dose and Method of Administration).

Presence of cardiac disorder.

Extreme caution is required in patients with a cardiovascular disorder. In the event of cardiovascular effects, the dosage of Eltroxin should be lowered. Even smaller initial dosage (e.g. 12.5 to 25 microgram/day) should be used with increments of not more than 25 microgram/day at not less than two week intervals. If this routine is not tolerated because of angina, increments should be further reduced with prolongation of the intervals between changes. The use of a β-blocker may help to control angina.

Cortisone deficiency.

Corticosteroid replacement therapy must precede initiation of Eltroxin therapy to avoid Addisonian crisis in such conditions as hypopituitarism and adrenal insufficiency.

Effects on bone mineral density.

In women, long-term levothyroxine sodium therapy has been associated with increased bone resorption, thereby decreasing bone mineral density, especially in postmenopausal women on greater than replacement doses or in women who are receiving suppressive doses of levothyroxine sodium. The increased bone resorption may be associated with increased serum levels and urinary excretion of calcium and phosphorus, elevations in bone alkaline phosphate and suppressed serum parathyroid hormone levels. Therefore, it is recommended that patients receiving levothyroxine sodium be given the minimum dose necessary to achieve and desired clinical and biochemical response.

Diabetes.

Caution is also required when Eltroxin is given to hypothyroid patients with diabetes mellitus or diabetes insipidus, as it may cause the required dosage of insulin and oral antidiabetic agents to be increased. Careful monitoring of diabetic control is recommended, especially when Eltroxin therapy is initiated, changed or discontinued. Adjustments in the dosage of these agents should only be made accordingly if necessary.

Hyperthyroidism.

Lower doses of Eltroxin may be required in patients with a history of hyperthyroidism, as such patients may have residual autonomous thyroid function.

Thyrotoxicosis.

Patients who have thyrotoxicosis who are being treated with antithyroid medication, may have increased sensitivity to Eltroxin.

Long standing hypothyroidism and myxoedema.

Caution is also required for patients with long standing hypothyroidism or myxoedema, as they are more sensitive to thyroid hormones.

Levothyroxine should not be used for the treatment of obesity or 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 anorectic effects.

Malabsorption syndromes.

Levothyroxine absorption is decreased in patients with malabsorption syndromes. It is advised to treat the malabsorption condition to ensure effective levothyroxine treatment with regular levothyroxine dose.

Use in hepatic impairment.

In spite of the major involvement of the liver in Eltroxin metabolism, there is no evidence that dosage should be modified in the presence of cirrhosis. However, thyroid function tests may be influenced and need careful interpretation.

Use in renal impairment.

There is no evidence that Eltroxin dosage should be modified in the presence of renal failure. However, thyroid function tests may be influenced and need careful interpretation.

Use in the elderly.

These patients may be more sensitive to the effects of thyroid hormones. Eltroxin should be gradually introduced in the elderly and in those with long standing hypothyroidism, so that any sudden increases in metabolic demands may be avoided. Individualisation of dosage is recommended and caution is required, as occult cardiac disease may be present.

Paediatric use.

Studies performed have not yet demonstrated paediatric specific problems that would limit the usefulness of thyroid hormones in children. However, neonates should be carefully observed for evidence of altered thyroid functions. This caution is required as the infant pituitary gland is relatively insensitive to negative feedback effects of thyroid hormones. The parents of children who are receiving the thyroid agent need to be aware that partial loss of hair may occur during the first few months of therapy. However this effect is usually transient and subsequent regrowth usually occurs.
Haemodynamic parameters should be monitored when levothyroxine therapy is initiated in very low birth weight preterm neonates as circulatory collapse may occur due to the immature adrenal function.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Oral anticoagulants, coumarin or indandione derivative e.g. warfarin.

Depending on the thyroid status of the patient, concurrent use of oral anticoagulants with Eltroxin will increase the therapeutic effects of oral anticoagulants. Therefore, an increase in the dosage of Eltroxin may necessitate a decrease in the oral anticoagulant dosage. Adjustment of oral anticoagulant dosage is recommended on the basis of prothrombin time. Patients should be observed closely for adverse effects.

SSRIs e.g. sertraline.

The effects of Eltroxin in hypothyroid patients may be decreased by concomitant use of sertraline, therefore resulting in an increase in Eltroxin requirements.

Insulin and antidiabetic agents e.g. sulfonylurea.

Eltroxin may increase the required dosage of insulin and other oral antidiabetic drugs. Therefore, careful monitoring of diabetic control is recommended.

Beta-adrenergic blocking agents e.g. propranolol.

These agents may decrease the peripheral conversion of thyroxine to tri-iodothyronine.

Ion exchange resins e.g. cholestyramine, sodium polystyrene sulphonate or colestipol.

Due to concurrent use of ion exchange resins with Eltroxin, the effects of Eltroxin may be reduced due to the resin binding to Eltroxin in the gastrointestinal tract, causing a delay or impairment in Eltroxin absorption. An interval of 4 to 5 hours between the administration of the two medications is recommended.

Corticosteroids e.g. prednisolone and dexamethasone.

The clearance of corticosteroids may be increased in hyperthyroid patients and decreased in hypothyroid patients solely due to the administration, changes in dosage and discontinuation of Eltroxin. Therefore, corticosteroid dosage may need to be adjusted.

Oestrogen.

In patients with a nonfunctioning thyroid gland, oestrogen may increase the serum thyroxine binding globulin, therefore generating an increase in Eltroxin requirements.

Antiepileptics e.g. phenytoin, carbamazepine and barbiturates.

These agents may increase the hepatic degradation of Eltroxin, therefore resulting in an increase in Eltroxin requirements.

Ritonavir.

Ritonavir may interact with Eltroxin, therefore resulting in an increase in Eltroxin requirements.

Antimalarials.

The combined use of chloroquine and proguanil may increase the hepatic degradation of Eltroxin, therefore resulting in an increase in Eltroxin requirements.

Antibacterials e.g. rifampicin and ciprofloxacin.

Rifampicin may increase the hepatic degradation of Eltroxin, therefore resulting in an increase in Eltroxin requirements.
Oral ciprofloxacin may decrease the absorption of Eltroxin. An interval of 6 hours between the administration of the two medications is recommended.

Androgens and anabolic steroids.

Androgens may decrease the concentration of the serum thyroxine binding globulin, therefore generating a decrease in Eltroxin requirements.

Ketamine.

Cautious administration of ketamine is recommended in patients on Eltroxin therapy, as marked hypertension and tachycardia may occur.

Lithium.

Due to the direct action of lithium on the thyroid gland, inhibition of thyroid hormones may result, leading to clinical hypothyroidism.

Tricyclic antidepressants.

Due to concurrent use with Eltroxin, an increase in the sensitivity to catecholamines may occur, therefore increasing the therapeutic and toxic effects of both drugs.

Sympathomimetics.

Due to concurrent use with Eltroxin, there may be an increase in the effects of both drugs, which may lead to a risk of coronary insufficiency.

Digoxin.

Levothyroxine may reduce the clinical effects of digoxin.

Medicines that (partially) inhibit the peripheral transformation of T4 to T3.

Propranolol, amiodarone, lithium, iodide, oral contrast agents, propylthiouracil and glucocorticoids can occasionally decrease the peripheral conversion of thyroxine to tri-iodothyronine. However, any dose adjustment should be based on TSH levels.

Weight loss drugs.

Orlistat may decrease levothyroxine absorption which may result in hypothyroidism. To avoid this orlistat and levothyroxine should be administered at least 4 hours apart. Regular monitoring for changes in thyroid function is required.

In addition.

Levothyroxine can enhance the clinical effects of pentobarbitone and dihydrotachysterol. Therefore, the adjustment of dosage may be necessary.
The clinical effect of levothyroxine can be reduced by soya flour, sucralfate, calcium, aluminium, magnesium, iron supplements, lanthanum sevelamer, and proton pump inhibitors which interfere with absorption from the gastrointestinal tract. If these substances are taken, then their ingestion should be separated by several hours from the ingestion of levothyroxine.
Soy-containing compounds and high fibre diets can decrease the intestinal absorption of levothyroxine. Therefore, a dosage adjustment of levothyroxine may be necessary, in particular at the beginning or after termination of nutrition with soy supplements.
Thyroid function tests can be modified, without changes in clinical effect of levothyroxine, by some NSAIDs, salicylates, diazepam, heparin and fenclofenac.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There is no information available on the possible effects of levothyroxine on human fertility.
(Category A)
If overt hypothyroidism is diagnosed during pregnancy, thyroid function test results should be normalised as rapidly as possible. In newly diagnosed hypothyroidism in pregnancy, levothyroxine dosage should be titrated rapidly, for example 1.5-2.0 microgram/kg/day may be required for initial replacement. If hypothyroidism has been diagnosed before pregnancy, levothyroxine therapy should be optimised before conception, and monitored during pregnancy by measurement of serum TSH and levothyroxine levels. The levothyroxine dose commonly needs incremental adjustments by 4-6 weeks of gestation and may require a 25-40% increase in dosage. It is recommended that those levels should be re-evaluated every 3 to 4 weeks during the first and second trimesters, with levothyroxine dosage changes as appropriate. The requirement is likely to decrease postpartum.
Monitoring of TSH concentrations can give guidance. TBG increases during pregnancy and therefore total T₄ and T₃ may appear to be elevated. Measurement of free T₄ and T₃ may be more appropriate. There is contradictory evidence concerning the passage of T₄ and T₃ across the placenta but it is unlikely that the fetus is at risk. Clinical experience does not indicate any adverse effects on the fetus when levothyroxine is administered during pregnancy.
Australian categorisation definition of Category A: drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.
Women who are breastfeeding should continue to take Eltroxin. In euthyroid women, breast milk contains negligible amounts of thyroid hormone.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.
Individual patients vary in response to both the maintenance dose of Eltroxin and to the size and frequency of dose increments. Too large an increment or too high a replacement dose can lead to manifestations of thyrotoxicosis which include:

Cardiovascular.

Chest pain, increased blood pressure, tachycardia, cardiac arrhythmias, palpitations, angina pectoris, myocardial ischaemia, myocardial infarction, cardiac failure, death.

Nervous system.

Irritability, anxiety, nervousness, agitation, restlessness, tremors, headache, poor concentration, affect lability, sleep disturbance, insomnia, mania, psychosis, psychotic depression, seizures, petit mal status epilepticus, benign intracranial hypertension (especially in children).

Gastrointestinal system.

Abdominal pain, nausea, diarrhoea, vomiting, malabsorption.

Immune system.

Hypersensitivity reactions such as rash, pruritus, anaphylactic reactions.

Skin.

Warmth, erythema, telangectiasia, hyperhydrosis, alopecia, hyperpigmentation.

Respiratory system.

Increased minute ventilation, tachypnoea, and dyspnoea.

Neuromuscular system.

Myopathy, lid lag, muscle weakness, muscle spasm, epiphyses premature fusion (in children).

Reproductive system.

Amenorrhoea, menstruation irregular, decreased libido, gynaecomastia (in male), infertility.

Metabolic.

Pyrexia, glucose intolerance, weight loss, premature craniosynostosis (in children), TRH suppression, temperature intolerance, flushing, fatigue and increased appetite.

Endocrine system.

Hyperthyroidism.

Investigations.

Decreased bone mineral density.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
Within three to six days after ingestion any or all of the symptoms and signs listed (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)) may become evident. They may progress to 'thyroid storm', with hyperpyrexia, convulsions, heart failure, coma and subsequent death.

Treatment of overdose.

Early treatment has included gastric lavage, induced emesis and ingestion of activated charcoal. Oxygen may need to be administered and ventilation may need to be maintained. Treatment is usually symptomatic and supportive. Measures to control fever, hypoglycaemia or fluid loss should be initiated as necessary. Of various adrenergic β-blockers, propranolol has been used commonly to control cardiac arrhythmia and other manifestations. Reserpine, guanethidine and digoxin have also been used. Exchange transfusion has been recommended for progressive deterioration.
When overdose does occur, there must be an extended follow-up period as symptoms may be delayed for several days due to the gradual peripheral conversion of thyroxine to tri-iodothyronine.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Eltroxin is used as thyroid replacement therapy for the treatment of hypothyroidism. The principal pharmacological effect of thyroid hormones is to increase the metabolic rate of body tissues. Thyroid hormones are also involved in the regulation of cell growth and differentiation. Thyroxine is the major component of normal secretions of the thyroid gland; therefore it is the essential determinant of normal thyroid function.

Clinical trials.

Comparison to reference registered products (Eutroxsig/ Oroxine).

A single dose, 2 period, 2 treatment, crossover study compared the T4 levels of 31 healthy, fasting adults after a supratherapeutic dose of Eltroxin (600 microgram) versus the same dose of Oroxine (600 microgram). For uncorrected total T4, the results for the ratio of Eltroxin/ Oroxine were AUC0-t = 89.1% (90% CI: 84.7%, 93.7%); Cmax = 86.2% (82.1%, 90.6%). This suggests that Eltroxin may be less bioavailable than Oroxine.

5.2 Pharmacokinetic Properties

Absorption.

Levothyroxine sodium is variably but adequately absorbed from the gastrointestinal tract following oral administration. Approximately 50 to 75% of levothyroxine sodium is absorbed. Studies in humans indicate that levothyroxine sodium is absorbed from the jejunum and ileum and in the duodenum. Fasting will only increase the extent of absorption, whereas malabsorption will only cause a decrease in absorption. Following the initiation of therapy, levothyroxine sodium has a slow onset of action as the peak therapeutic effect occurs between 3 to 4 weeks. It also has a long duration of action occurring between 1 to 3 weeks, even following the discontinuance of the drug.

Distribution.

Levothyroxine sodium apparently undergoes enterohepatic circulation. Once inside the circulation, levothyroxine is extensively protein bound, principally to thyroxine binding globulin (TBG) and also to a lesser extent to thyroxine binding prealbumin (TBPA) or to albumin. Levothyroxine is distributed into most body tissues and fluids with the highest concentration occurring in the liver and kidneys. A minimal amount of levothyroxine is distributed into breast milk.

Metabolism.

Levothyroxine sodium has a plasma half-life in euthyroidism of about 6 to 7 days. In hypothyroidism, the half-life is prolonged between 9 to 10 days. However, the half-life is reduced between 3 to 4 days in hyperthyroidism. Levothyroxine is primarily metabolised in the liver and in the kidney to tri-iodothyronine. Approximately 40% of levothyroxine sodium is metabolised to the inactive reverse tri-iodothyronine, which both undergo further deiodination to inactive metabolites. About 85% of the levothyroxine sodium metabolised daily is deiodinated.

Excretion.

Levothyroxine is reported to undergo enterohepatic recycling and is excreted in faeces.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

Animal studies to determine the carcinogenic or mutagenic potential of thyroid agents have not been established. However, there is epidemiological evidence against the use of thyroid supplements enhancing the risk of breast cancer.

6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, maize starch, purified talc, colloidal anhydrous silica and magnesium stearate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Store in the original container and protect from light. Keep the container tightly closed.