Consumer medicine information

Levothox

Levothyroxine sodium

BRAND INFORMATION

Brand name

Levothox

Active ingredient

Levothyroxine sodium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Levothox.

SUMMARY CMI

LEVOTHOX

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about taking this medicine, speak to your doctor or pharmacist.

1. Why am I taking LEVOTHOX?

LEVOTHOX contains the active ingredient Levothyroxine sodium. LEVOTHOX is used to treat thyroid hormone deficiency also known as Hypothyroidism and TSH-responsive tumours of the thyroid.

For more information, see Section 1. Why am I taking LEVOTHOX? in the full CMI.

2. What should I know before I take LEVOTHOX?

Do not take if you have ever had an allergic reaction to LEVOTHOX or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I take LEVOTHOX? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with LEVOTHOX and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take LEVOTHOX?

  • Your doctor will calculate the right dose for you

More instructions can be found in Section 4. How do I take LEVOTHOX? in the full CMI.

5. What should I know while taking LEVOTHOX?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are taking LEVOTHOX.
  • Do not switch or interchange with other brands unless advised by your doctor.
  • Use it exactly as directed or as your doctor has prescribed
Things you should not do
  • Do not stop using this medicine suddenly
Driving or using machines
  • Be careful before you drive or use any machines or tools where alertness is required, until you know how LEVOTHOX affects you.
Drinking alcohol
  • Tell your doctor if you drink alcohol
Looking after your medicine
  • Store the medicine in a cool dry place where the temperature stays below 25°C. Protect from light.

For more information, see Section 5. What should I know while taking LEVOTHOX? in the full CMI.

6. Are there any side effects?

There is a number of common side effects associated with the use of LEVOTHOX, if they worry you talk to your doctor or pharmacist. There are no serious side effects associated with LEVOTHOX.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

LEVOTHOX

Active ingredient(s): Levothyroxine sodium

Consumer Medicine Information (CMI)

This leaflet provides important information about taking LEVOTHOX. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about taking LEVOTHOX.

Where to find information in this leaflet:

1. Why am I taking LEVOTHOX?
2. What should I know before I take LEVOTHOX?
3. What if I am taking other medicines?
4. How do I take LEVOTHOX?
5. What should I know while taking LEVOTHOX?
6. Are there any side effects?
7. Product details

1. Why am I taking LEVOTHOX?

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

LEVOTHOX is used to treat:

  1. 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.

  1. 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. LEVOTHOX replaces the shortage of thyroid hormones.

Your doctor may have prescribed LEVOTHOX for another reason. Ask your doctor if you have any questions about why this medicine has been prescribed for you.

2. What should I know before I take LEVOTHOX?

Warnings

Do not take LEVOTHOX if:

  • you are allergic to Levothyroxine sodium thyroid hormone (eg. Tertroxin)
  • you are allergic to any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can take this medicine. Some of the symptoms of an allergic reaction may include:
    - difficulty in breathing
    - faintness
    - swelling of the face, lips, tongue or other parts of the body
    - red, itchy skin rashes
  • Do not take LEVOTHOX tablets if the tablet's colour has changed.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

Check with your doctor if you:

  • if you have allergies to any other medicines, foods, preservatives or dyes.
  • take any medicines for any other condition
  • if you have or have had any other medical conditions/health problems, including:
    - Over active thyroid gland
    - Adrenal gland problem
    - Hyperthyroidism
    - Heart problems such as cardiovascular disorder
    - High blood pressure
    - Diabetes
    - Long-standing hypothyroidism, an under active thyroid gland
    - Problems absorbing nutrients from the gastrointestinal tract

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant. Levothyroxine levels will need to be watched carefully during pregnancy. Your dosage of LEVOTHOX may need to be increased while you are pregnant.

Ask your doctor about the risks and benefits of taking LEVOTHOX during pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Although small amounts of LEVOTHOX are found in breast milk, women who are breastfeeding should continue treatment with LEVOTHOX.

3. What if I am taking other medicines?

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

Some medicines may interfere with LEVOTHOX and affect how it works.

  • Anticoagulants, medicines used to thin your blood (e.g. 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. colestyramine)
  • Corticosteroids, anti-inflammatory medicines (e.g. prednisolone and dexamethasone)
  • Oral contraceptives and hormone replacement medicines such as estrogens, 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 aluminium supplements
  • 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 LEVOTHOX 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.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect LEVOTHOX.

4. How do I take LEVOTHOX?

How much to take

  • Your doctor will calculate the right dose for you.
  • 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.
  • Take LEVOTHOX only as directed
  • Follow your doctor's instructions carefully, as they may differ from the information contained in this leaflet.
  • It may take a few weeks for LEVOTHOX to begin working. Until it begins working you may not notice any change in your symptoms.
  • Do not change your dosage unless your doctor tells you to do so.
  • Your doctor will monitor your blood tests to make sure LEVOTHOX is working for you.
  • Use LEVOTHOX, until your doctor tells you to stop.
  • Talk to your doctor if you have any questions
  • Swallow LEVOTHOX tablets with a glass of water

When to take LEVOTHOX

  • LEVOTHOX 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

If you forget to take LEVOTHOX

LEVOTHOX should be used regularly at the same time each day.

If you miss your dose at the usual time, and 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 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 use too much LEVOTHOX

If you think that you have used too much LEVOTHOX, you may need urgent medical attention. If you take too much you may have the following symptoms: restlessness; vomiting; flushing; breathing difficulties; chest pain; convulsions or paralysis.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while taking LEVOTHOX?

Things you should do

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

Immediately stop taking LEVOTHOX 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 LEVOTHOX is not helping your condition.

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

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

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

Call your doctor straight away if you:

  • plan to have surgery
  • are about to start taking any new medicines.

Remind any doctor, dentist or pharmacist you visit that you are using LEVOTHOX.

Things you should not do

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

Driving or using machines

Be careful before you drive or use any machines or tools where alertness is required, until you know how LEVOTHOX affects you.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Store in the original package
  • Store the medicine in a cool dry place where the temperature stays below 25°C. Protect from light.

Do not take LEVOTHOX tablets if the tablet's colour has changed.

Follow the instructions on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

When to discard your medicine

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.

Getting rid of any unwanted medicine

If you no longer need to take this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not take this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
General disorders:
  • Nervousness
  • Anxiousness
  • Excitation
  • Restlessness
  • Increased blood pressure
  • Muscle weakness and cramps
  • Inability to sleep
  • Sleep disturbance
  • Unusual movements, including tremor
  • Headache
  • Lack of concentration
  • Heat intolerance
  • Excessive sweating
  • Flushing
  • Weight loss
  • Fever
  • Hair loss
  • Irritability
  • Tiredness
Gastrointestinal disorders:
  • Diarrhoea
  • Stomach cramp
  • Nausea
  • Vomiting
  • Increased appetite
Respiratory tract disorders:
  • Shortness of breath
  • Rapid breathing
  • Irregular heart beats
  • Chest pain
Skin and subcutaneous tissue disorders:
  • Allergic reaction such as skin rash
Reproductive system disorders:
  • Menstrual irregularities
  • Decreased libido
Speak to your doctor if you have any of these less serious side effects and they worry you.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell even if you do not think the problems are connected with medicine or are not listed in this leaflet.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What LEVOTHOX contains

Active ingredient
(main ingredient)		Levothyroxine sodium
Other ingredients
(inactive ingredients)
  • microcrystalline cellulose
  • light magnesium oxide
  • sodium starch glycollate
  • sodium stearyl fumarate
The coating contains Lake blend as below:
25 microgram tablets: Sunset yellow FCF Aluminium lake.
75 microgram tablets: Lake Blend LB-505008 Purple (ID#110747)
88 microgram tablets: Lake Blend LB-510028 Green (ID#117692)
100 microgram tablets: Lake Blend LB-520044 Yellow (ID#117693)
112 microgram tablets: Lake Blend LB-540042 Pink (ID#117694)
125 microgram tablets: Lake Blend LB-575003 Brown (ID#110743)
137 microgram tablets: Brilliant Blue FCF Aluminium Lake
150 microgram tablets: Indigo Carmine Aluminium Lake
175 microgram tablets: Lake Blend LB-500017 Purple (ID#117689)
200 microgram tablets: Allura Red AC Aluminium Lake
Potential allergensNot applicable

Do not take this medicine if you are allergic to any of these ingredients.

What LEVOTHOX looks like

LEVOTHOX 50 microgram: Round shaped, White coloured, uncoated tablets, break line on both sides and debossed with “P” and “2” on one side and plain on other side (AUST R 364022).

LEVOTHOX 75 microgram: Round shaped, Violet coloured, uncoated tablets, break line on both sides and debossed with “P” and “3” on one side and plain on other side (AUST R 363982).

LEVOTHOX 100 microgram: Round shaped, Yellow coloured, uncoated tablets, break line on both sides and debossed with “P” and “14” on one side and plain on other side (AUST R 364002).

LEVOTHOX 200 microgram: Round shaped, Pink coloured, uncoated tablets, break line on both sides and debossed with “P” and “11” on one side and plain on other side (AUST R 364009).

Who distributes LEVOTHOX

Sponsor

Accord Healthcare Pty Ltd
Level 24, 570 Bourke St
Melbourne VIC 3000
Australia
Phone: 1800 134 988
Email: [email protected]

Distributor

LEVOTHOX is distributed in Australia by:

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in June 2023

Published by MIMS July 2023

BRAND INFORMATION

Brand name

Levothox

Active ingredient

Levothyroxine sodium

Schedule

S4

 

1 Name of Medicine

Levothyroxine sodium.

2 Qualitative and Quantitative Composition

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

3 Pharmaceutical Form

Oral tablets.

Levothox 25 microgram.

Round, orange coloured, uncoated tablets, with a break line on both sides. Debossed with "P" and "1" on one side and plain on the other side.

Levothox 50 microgram.

Round, white coloured, uncoated tablets, with a break line on both sides. Debossed with "P" and "2" on one side and plain on the other side.

Levothox 75 microgram.

Round, violet coloured, uncoated tablets, with a break line on both sides. Debossed with "P" and "3" on one side and plain on the other side.

Levothox 88 microgram.

Round, olive coloured, uncoated tablets, with a break line on both sides. Debossed with "P" and "4" on one side and plain on the other side.

Levothox 100 microgram.

Round shaped, yellow coloured, uncoated tablets, with a break line on both sides. Debossed with "P" and "14" on one side and plain on the other side.

Levothox 112 microgram.

Round, rose coloured, uncoated tablets, with a break line on both sides. Debossed with "P" and "6" on one side and plain on the other side.

Levothox 125 microgram.

Round, brown coloured, uncoated tablets, with a break line on both sides. Debossed with "P" and "7" on one side and plain on the other side.

Levothox 137 microgram.

Round, turquoise coloured, uncoated tablets, with a break line on both sides. Debossed with "P" and "8" on one side and plain on the other side.

Levothox 150 microgram.

Round, blue coloured, uncoated tablets, with a break line on both sides. Debossed with "P" and "9" on one side and plain on the other side.

Levothox 175 microgram.

Round, lilac coloured, uncoated tablets, with a break line on both sides. Debossed with "P" and "10" on one side and plain on the other side.

Levothox 200 microgram.

Round, pink coloured, uncoated tablets, with a break line on both sides. Debossed with "P" and "11" on one side and plain on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Levothox is indicated for the management of demonstrated thyroid hormone deficiency.
Levothox 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 microgram daily. Increase the daily dose by 25 to 50 microgram according to response at not less than 4-weekly intervals, up to 100 to 200 microgram 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 1 ½ 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.

See Table 1.

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

Levothox is bioequivalent to Eltroxin.
Do not interchange Levothox and Eutroxsig/Oroxine. If a decision is made to switch from Eutroxsig/Oroxine to Levothox, 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, Levothox 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 Levothox 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 Levothox 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 post-menopausal 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 levothyroxine 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 Levothox therapy is initiated, changed or discontinued. Adjustments in the dosage of these agents should only be made accordingly if necessary.

Hyperthyroidism.

Lower doses of levothyroxine 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 anti-thyroid medication, may have increased sensitivity to levothyroxine.

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 levothyroxine 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 levothyroxine 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. Levothox 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.

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 levothyroxine will increase the therapeutic effects of oral anticoagulants. Therefore, an increase in the dosage of levothyroxine 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 levothyroxine in hypothyroid patients may be decreased by concomitant use of sertraline, therefore resulting in an increase in levothyroxine requirements.

Insulin and antidiabetic agents e.g. sulfonylurea.

Levothyroxine 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. colestyramine, sodium polystyrene sulfonate or colestipol.

Due to concurrent use of ion-exchange resins with levothyroxine, the effects of levothyroxine may be reduced due to the resin binding to levothyroxine in the gastrointestinal tract, causing a delay or impairment in levothyroxine 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 levothyroxine. Therefore, corticosteroid dosage may need to be adjusted.

Estrogen.

In patients with a non-functioning thyroid gland, estrogen may increase the serum thyroxine-binding globulin, therefore generating an increase in levothyroxine requirements.

Antiepileptics e.g. phenytoin, carbamazepine and barbiturates.

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

Ritonavir.

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

Antimalarials.

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

Antibacterials e.g. rifampicin and ciprofloxacin.

Rifampicin may increase the hepatic degradation of levothyroxine, therefore resulting in an increase in levothyroxine requirements.
Oral ciprofloxacin may decrease the absorption of levothyroxine. 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 levothyroxine requirements.

Ketamine.

Cautious administration of ketamine is recommended in patients on levothyroxine 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 levothyroxine, 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 levothyroxine, 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 triiodothyronine. 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 pentobarbital 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 post-partum.
Monitoring of TSH concentrations can give guidance. Thyroxine-binding globulin (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 breast feeding should continue to take Levothox. 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 levothyroxine 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, telangiectasia, hyperhidrosis, 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, hypoglycemia 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 triiodothyronine.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Levothox 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 between reference registered products (Eltroxin versus Eutroxsig/Oroxine).

A single dose, 2-period, 2-treatment, crossover study compared the T4 levels of 31 healthy, fasting adults after a supra-therapeutic 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 (and as a result, Levothox) 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 pre-albumin (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 triiodothyronine. Approximately 40% of levothyroxine sodium is metabolised to the inactive reverse triiodothyronine, 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

Levothox tablets contain the following excipients: microcrystalline cellulose, light magnesium oxide, sodium starch glycollate and sodium stearylfumarate. They also contain Lake Blend colouring agents as below:

25 microgram tablets.

Sunset yellow FCF Aluminium lake.

75 microgram tablets.

Lake Blend LB-505008 Purple (ID#110747).

88 microgram tablets.

Lake Blend LB-510028 Green (ID#117692).

100 microgram tablets.

Lake Blend LB-520044 Yellow (ID#117693).

112 microgram tablets.

Lake Blend LB-540042 Pink (ID#117694).

125 microgram tablets.

Lake Blend LB-575003 Brown (ID#110743).

137 microgram tablets.

Brilliant Blue FCF Aluminium Lake.

150 microgram tablets.

Indigo Carmine Aluminium Lake.

175 microgram tablets.

Lake Blend LB-500017 Purple (ID#117689).

200 microgram tablets.

Allura Red AC Aluminium Lake.

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. Keep container tightly closed.

6.5 Nature and Contents of Container

Levothox is approved for supply in blister packs of 100 tablets. Blisters are made of an amber, thermoformable PVC/EVOH/ACLAR film, and a hard tempered aluminium foil with a heat seal lacquer. Tablets are also approved for supply in HDPE bottle packs with child resistant closures of 90 and 200 tablets.*
* All tablet strengths and pack sizes may not be available in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Levothyroxine sodium, is a monosodium salt of the levo isomer of thyroxine, the principal secretion of the thyroid gland. It has the following chemical structure:
It has the molecular formula C15H10I4NNaO4 and a molecular weight of 798.86.

CAS number.

55-03-8 (anhydrous form).

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes