Consumer medicine information

APO-Levothyroxine

Levothyroxine sodium

BRAND INFORMATION

Brand name

APO-Levothyroxine

Active ingredient

Levothyroxine sodium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Levothyroxine.

SUMMARY CMI

APO-Levothyroxine

Consumer Medicine Information (CMI) summary

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

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I using APO-Levothyroxine?

APO-Levothyroxine contains the active ingredient levothyroxine sodium. APO-Levothyroxine is used as replacement therapy in the treatment of thyroid hormone deficiency (hypothyroidism) or for treatment of TSH-responsive tumours.

For more information, see Section 1. Why am I using APO-Levothyroxine? in the full CMI.

2. What should I know before I use APO-Levothyroxine?

Do not use if you have ever had an allergic reaction to levothyroxine sodium 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 use APO-Levothyroxine? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with levothyroxine sodium 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 APO-Levothyroxine?

  • Swallow your tablets whole with a glass of water first thing in the morning on an empty stomach.

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

5. What should I know while using APO-Levothyroxine?

Things you should do
  • Remind any doctors, dentists and pharmacists treating you that you are taking APO-Levothyroxine.
  • Use it exactly as your doctor has prescribed. Discuss with your doctor any problems during or after taking the medicine.
  • Visit your doctor regularly and attend all of your blood tests, so your doctor can check your progress and see whether your dose of APO-Levothyroxine requires adjustment.
  • If you plan to have surgery, tell your doctor or dentist that you are taking APO-Levothyroxine.
  • If you are about to start taking any new medicines, remind your doctor and pharmacist that you are taking APO-Levothyroxine.
  • Ensure you do not run out of medicine over the weekend or on holidays.
Things you should not do
  • Do not stop using this medicine suddenly or change the dose unless your doctor tells you to.
  • Do not switch with other brands unless advised by your doctor.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how APO-Levothyroxine affects you. APO-Levothyroxine may cause lack of concentration or tiredness in some people.
Looking after your medicine
  • Store APO-Levothyroxine below 25°C in the original blister strips.

For more information, see Section 5. What should I know while using APO-Levothyroxine? in the full CMI.

6. Are there any side effects?

Some of the common side effects include nervousness, anxiousness, excitation, restlessness, muscle weakness & cramps.

Serious side effects include fever, shortness of breath, rapid breathing, irregular heart-beats, chest pain, increased blood pressure, allergic reactions such as skin rash.

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.

WARNING: APO-LEVOTHYROXINE is not interchangeable on a same-dose basis with ELTROXIN. If your doctor decides to switch treatment from APO-LEVOTHYROXINE to ELTROXIN, then they should have a plan for monitoring your blood tests and adjusting your dose, if required.

You should not interchange APO-LEVOTHYROXINE and ELTROXIN unless your doctor decides to switch products, and there is a plan for monitoring your blood tests and reviewing your dose.



FULL CMI

APO-Levothyroxine

Active ingredient: levothyroxine sodium

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I using APO-Levothyroxine?

APO-Levothyroxine contains the active ingredient levothyroxine sodium. APO-Levothyroxine is a thyroid hormone which is used as replacement therapy in the treatment of thyroid hormone deficiency. APO-Levothyroxine replaces the shortage of thyroid hormones.

APO-Levothyroxine 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 thyroxine, 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.

APO-Levothyroxine is also used to treat 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.

2. What should I know before I use APO-Levothyroxine?

Warnings

Do not use APO-Levothyroxine if:

  • you are allergic to levothyroxine sodium, any other thyroid hormone, or any of the ingredients listed at the end of this leaflet.
    Some of the symptoms of an allergic reaction to APO-Levothyroxine may include red, itchy skin rashes; difficulty in breathing; swelling of the face or throat or faintness.
    Do not use APO-Levothyroxine after the expiry date (EXP.) printed on the pack.
    If you take APO-Levothyroxine after the expiry date has passed, it may not work as well.
    Always check the ingredients to make sure you can use this medicine.
  • you have untreated hyperthyroidism (overactive thyroid)
  • you have untreated adrenal insufficiency
  • you have thyrotoxicosis (symptomatic excess thyroid hormone)
  • you have acute myocardial infarction (heart attack), acute myocarditis or acute pancarditis (inflamed heart muscle or surrounding tissues)

Check with your doctor if you:

  • you are allergic to any other medicines or any foods, dyes or preservatives.
  • you have or have had any other medical conditions or 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
    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?

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

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Thyroxine levels need to be watched carefully during pregnancy. Your dosage of APO-Levothyroxine may need to be increased while you are pregnant.

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

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Although small amounts of levothyroxine are found in breast milk, women who are breastfeeding should continue treatment with APO-Levothyroxine.

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

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 APO-Levothyroxine. These include:

  • 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. cholestyramine)
  • corticosteroids, anti inflammatory medicines (e.g. prednisolone and dexamethasone)
  • oral contraceptives and hormone replacement medicines such as oestrogens and androgens
  • medicines used for epilepsy (e.g. phenytoin and carbamazepine)
  • medicines used to treat heart failure (e.g. digoxin)
  • iron supplements
  • calcium 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)
  • 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)
  • ketamine, an anaesthetic
  • pentobarbitone, a sedative
  • dihydrotachysterol, a form of vitamin D

These medicines may affect how well APO-Levothyroxine works or react with it resulting in unwanted or sometimes serious side effects.

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

4. How do I take APO-Levothyroxine?

How much to take

  • It may take a few weeks for APO-Levothyroxine 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.
  • 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.
  • If you do not understand the instructions on the blister pack, ask your doctor or pharmacist for help.
  • Your doctor will monitor your blood tests to make sure APO-Levothyroxine is working for you.
  • Do not change your dose of APO-Levothyroxine unless your doctor tells you to do so.
  • Swallow APO-Levothyroxine tablets with a glass of water.

When to take APO-Levothyroxine

APO-Levothyroxine 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 APO-Levothyroxine

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 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 APO-Levothyroxine

If you think that you have used too much APO-Levothyroxine, you may need urgent medical attention.

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.

Symptoms of overdose include restlessness; vomiting; flushing; breathing difficulties; chest pain; convulsions or paralysis.

5. What should I know while using APO-Levothyroxine?

Things you should do

  • Tell any other doctors, dentists and pharmacists who are treating you that you are taking APO-Levothyroxine.
  • Use it exactly as your doctor has prescribed.
  • Tell your doctor if you feel the medicine is not helping your condition.
  • Always discuss with your doctor any problems or difficulties during or after taking the medicine.
  • Visit your doctor regularly and attend your blood tests. Your doctor needs to check your progress and see whether you need to stop taking APO-Levothyroxine or adjust your dose.
  • If you plan to have surgery, tell your doctor or dentist that you are taking APO-Levothyroxine.
  • If you are about to start taking any new medicines, remind your doctor and pharmacist that you are taking APO-Levothyroxine.
  • Ensure you do not run out of medicine over the weekend or on holidays.

Call your doctor straight away and immediately stop taking APO-Levothyroxine if a skin rash or other allergic reaction occurs.

Things you should not do

  • Do not stop using this medicine suddenly or change the dose unless your doctor tells you to.
  • Do not switch with other brands unless advised by your doctor.
  • 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 until you know how APO-Levothyroxine affects you.

APO-Levothyroxine may cause lack of concentration or tiredness in some people.

Looking after your medicine

  • Store below 25°C. Protect from light.
  • Always store tablets in their original blister strips. If you do not keep the tablets in the blister strip they may not keep as well.

Follow the instructions in the carton 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.

Getting rid of any unwanted medicine

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

Do not use 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
Mental function-related:
  • nervousness, anxiousness, excitation, restlessness
  • lack of concentration
  • irritability
Muscle-related:
  • muscle weakness & cramps
  • unusual movements including tremor
Sleep-related:
  • inability to sleep, sleep disturbances
Digestive track-related:
  • diarrhoea, stomach cramp, nausea, vomiting
  • increased appetite
Body temperature-related:
  • heat intolerance, excessive sweating, flushing
Pain-related:
  • headache
Weight changes-related
  • weight loss
Menstrual cycle-related:
  • menstrual irregularities
Sex drive-related:
  • decreased libido
Hair-related:
  • hair loss
Exhaustion-related:
  • tiredness
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Body temperature-related:
  • fever
Breathing-related:
  • shortness of breath
  • rapid breathing
Heart-related:
  • irregular heart beats
Pain-related
  • chest pain
Blood pressure-related:
  • increased blood pressure
Allergic reactions-related:
  • skin rash
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

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 APO-Levothyroxine contains

Active ingredient
(main ingredient)		levothyroxine sodium
Other ingredients
(inactive ingredients)		lactose monohydrate, maize starch, gelatin, croscarmellose sodium, magnesium stearate
Potential allergenssugars as lactose

This medicine includes sugars as lactose monohydrate.

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

What APO-Levothyroxine looks like

APO-Levothyroxine comes in tablets of 7 strengths:

25 µg tablets: Round and white tablets with debossed on one side with “25” and scored in the shape of “+” sign on the other side. (AUST R 374890)

50 µg tablets: Round and white tablets with debossed on one side with “50” and scored in the shape of “+” sign on the other side. (AUST R 374892)

75 µg tablets: Round and white tablets with debossed on one side with “75” and scored in the shape of “+” sign on the other side. (AUST R 374910)

100 µg tablets: Round and white tablets with debossed on one side with “100” and scored in the shape of “+” sign on the other side. (AUST R 374922)

125 µg tablets: Round and white tablets with debossed on one side with “125” and scored in the shape of “+” sign on the other side. (AUST R 374923)

150 µg tablets: Round and white tablets with debossed on one side with “150” and scored in the shape of “+” sign on the other side. (AUST R 374924)

200 µg tablets: Round and white tablets with debossed on one side with “200” and scored in the shape of “+” sign on the other side. (AUST R 374925)

Who distributes APO-Levothyroxine

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel Street
Cremorne VIC 3121
www.arrotex.com.au

This leaflet was prepared in November 2023.

Published by MIMS January 2024

BRAND INFORMATION

Brand name

APO-Levothyroxine

Active ingredient

Levothyroxine sodium

Schedule

S4

 

Notes

Distributed by Arrotex Pharmaceuticals Pty Ltd

1 Name of Medicine

Levothyroxine sodium.

2 Qualitative and Quantitative Composition

APO-Levothyroxine tablets are available in seven strengths and contain levothyroxine sodium 25, 50, 75, 100, 125, 150 or 200 micrograms as the active ingredient.
They also contain sugars as lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

APO-Levothyroxine 25 microgram tablets are round white tablets with debossed on one side with "25" and scored in the shape of "+" sign on the other side.
APO-Levothyroxine 50 microgram tablets are round white tablets with debossed on one side with "50" and scored in the shape of "+" sign on the other side.
APO-Levothyroxine 75 microgram tablets are round white tablets with debossed on one side with "75" and scored in the shape of "+" sign on the other side.
APO-Levothyroxine 100 microgram tablets are round white tablets with debossed on one side with "100" and scored in the shape of "+" sign on the other side.
APO-Levothyroxine 125 microgram tablets are round white tablets with debossed on one side with "125" and scored in the shape of "+" sign on the other side.
APO-Levothyroxine 150 microgram tablets are round white tablets with debossed on one side with "150" and scored in the shape of "+" sign on the other side.
APO-Levothyroxine 200 microgram tablets are round white tablets with debossed on one side with "200" and scored in the shape of "+" sign on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

APO-Levothyroxine is indicated for the management of demonstrated thyroid hormone deficiency.
APO-Levothyroxine 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 sodium 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. Thyroxine 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 thyroxine is recommended when starting therapy or changing the dose.

Adults.

Initial dose.

Commence with thyroxine 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, thyroxine 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.

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

Do not interchange APO-Levothyroxine and Eltroxin. If a decision is made to switch from APO-Levothyroxine 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, APO-Levothyroxine 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 levothyroxine sodium 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 levothyroxine 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 sodium 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 levothyroxine sodium 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 sodium 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 levothyroxine sodium.

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

Use in hepatic impairment.

In spite of the major involvement of the liver in levothyroxine sodium 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 sodium 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. Levothyroxine sodium 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 levothyroxine sodium will increase the therapeutic effects of oral anticoagulants. Therefore, an increase in the dosage of levothyroxine sodium 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 sodium in hypothyroid patients may be decreased by concomitant use of sertraline, therefore resulting in an increase in levothyroxine sodium requirements.

Insulin and antidiabetic agents e.g. sulfonylurea.

Levothyroxine sodium 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 triiodothyronine.

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

Due to concurrent use of ion-exchange resins with levothyroxine sodium, the effects of levothyroxine sodium 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 sodium. Therefore, corticosteroid dosage may need to be adjusted.

Oestrogen.

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

Antiepileptics e.g. phenytoin, carbamazepine and barbiturates.

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

Ritonavir.

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

Antimalarials.

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

Antibacterials e.g. rifampicin and ciprofloxacin.

Rifampicin may increase the hepatic degradation of levothyroxine sodium, 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 sodium 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 sodium, 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 sodium, there may be an increase in the effects of both drugs, which may lead to a risk of coronary insufficiency.

Digoxin.

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

In addition.

Thyroxine can enhance the clinical effects of pentobarbitone and dihydrotachysterol. Therefore, the adjustment of dosage may be necessary.
The clinical effect of thyroxine 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 sodium.
Soy-containing compounds and high fibre diets can decrease the intestinal absorption of levothyroxine sodium. Therefore, a dosage adjustment of levothyroxine sodium 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 thyroxine, 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 thyroxine 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, thyroxine 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, thyroxine therapy should be optimised before conception, and monitored during pregnancy by measurement of serum TSH and thyroxine levels. The thyroxine 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 thyroxine 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 foetus is at risk. Clinical experience does not indicate any adverse effects on the foetus when thyroxine 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 foetus having been observed.
 Women who are breastfeeding should continue to take levothyroxine sodium. 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 sodium 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 cramps, nausea, diarrhoea, vomiting, malabsorption.

Immune system.

Hypersensitivity reactions such as skin 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, sweating, flushing, fatigue and increased appetite.

Endocrine system.

Hyperthyroidism.

Investigations.

Decreased bone mineral density.

4.9 Overdose

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.
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 tri-iodothyronine.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Levothyroxine sodium 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.

No data available.

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, thyroxine is extensively protein bound, principally to thyroxine-binding globulin (TBG) and also to a lesser extent to thyroxine-binding prealbumin (TBPA) or to albumin.
Thyroxine is distributed into most body tissues and fluids with the highest concentration occurring in the liver and kidneys. A minimal amount of thyroxine 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. Thyroxine 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.

Thyroxine 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

APO-Levothyroxine tablets contain the active ingredient, levothyroxine sodium. They also contain the excipients lactose monohydrate, maize starch, gelatin, croscarmellose sodium 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. Protect from light.

6.5 Nature and Contents of Container

PVC/PE/PVDC/AL blisters of 200 tablets.

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

Levothyroxine sodium is a monosodium salt of the levo isomer of thyroxine, the principal secretion of the thyroid gland. It has the molecular formula C15H10I4NNaO4 and a molecular weight of 798.86.
Levothyroxine sodium is almost white to pale brownish-yellow, odourless, tasteless, hygroscopic, amorphous or crystalline powder. On exposure to light, it may acquire a slight pink colour. It is very slightly soluble in water and alcohol, however is insoluble in acetone, chloroform and ether. It dissolves in aqueous solutions of alkali hydroxides and in hot solutions of alkali carbonates.

Chemical structure.


CAS number.

55-03-8.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes