Consumer medicine information

Levothyroxine Sandoz

Levothyroxine sodium

BRAND INFORMATION

Brand name

Levothyroxine Sandoz

Active ingredient

Levothyroxine sodium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Levothyroxine Sandoz.

SUMMARY CMI

Levothyroxine Sandoz®

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 Levothyroxine Sandoz?

Levothyroxine Sandoz contains the active ingredient levothyroxine sodium. Levothyroxine Sandoz is used as replacement therapy in the treatment of thyroid deficiency. For more information, see Section 1. Why am I using Levothyroxine Sandoz? in the full CMI.

2. What should I know before I use Levothyroxine Sandoz?

Do not use Levothyroxine Sandoz 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 Levothyroxine Sandoz? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Levothyroxine Sandoz 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 use Levothyroxine Sandoz?

  • 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.
  • Swallow the tablets with a glass of water in the morning on an empty stomach, at least 30 minutes and preferably 60 minutes before any food or other medicines. More instructions can be found in Section 4. How do I use Levothyroxine Sandoz? in the full CMI.

5. What should I know while using Levothyroxine Sandoz?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Levothyroxine Sandoz.
  • Do not switch or interchange with other brands unless advised by your doctor.
  • Ensure you do not run out of medicine over the weekend or on holidays.
Things you should not do
  • Do not give this medicine to anyone else, even if his or her symptoms seem similar to yours.
Driving or using machines
  • Do not drive or operate machinery where alertness is required, until you know how it affects you.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
Looking after your medicine
  • Store below 25°C. Protect from light.

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

6. Are there any side effects?

Common side effects: nervousness, anxiousness, excitation, inability to sleep, diarrhoea, stomach cramp, headache, muscle weakness and cramps. Serious side effects: allergic reactions such as skin rash, irregular heart beats, chest pain, shortness of breath. 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: Levothyroxine Sandoz cannot be switched for the same dose of ELTROXIN. If your doctor decides to switch treatment from ELTROXIN to Levothyroxine Sandoz, then they should have a plan for monitoring your blood tests and adjust your dose if needed.

You should not change from Levothyroxine Sandoz to ELTROXIN unless your doctor decides to switch products, and there is a plan for monitoring your blood tests and reviewing your dose.



FULL CMI

Levothyroxine Sandoz®

Active ingredient(s): levothyroxine sodium

Consumer Medicine Information (CMI)

This leaflet provides important information about using Levothyroxine Sandoz. 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 Levothyroxine Sandoz.

Where to find information in this leaflet:

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

1. Why am I using Levothyroxine Sandoz?

Levothyroxine Sandoz contains the active ingredient levothyroxine sodium, which is a thyroid hormone.

Levothyroxine Sandoz is used as replacement therapy in the treatment of thyroid deficiency.

2. What should I know before I use Levothyroxine Sandoz?

Warnings

Do not use Levothyroxine Sandoz if:

  • you are allergic to levothyroxine sodium, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine. Some of the symptoms of an allergic reaction may include:
    - red, itchy skin rashes
    - difficulty in breathing
    - swelling of the face or throat
    - faintness
  • the packaging shows signs of tampering.

Check with your doctor if you:

  • are allergic to any other medicines or foods, dyes or preservatives.
  • have any other medical conditions:
    - 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
  • take any medicines for any other condition

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.

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

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

Although small amounts of the medicine are found in breast milk, women who are breastfeeding should continue treatment with Levothyroxine Sandoz.

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 Levothyroxine Sandoz and affect how it works. 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. colestyramine)
  • corticosteroids, anti inflammatory medicines (e.g. prednisolone and dexamethasone)
  • oral contraceptives and hormone replacement medicines such as estrogens 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)

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

4. How do I use Levothyroxine Sandoz?

How much to take

  • Follow the instructions and dosage provided by your doctor.
  • It may take a few weeks for Levothyroxine Sandoz to begin working. Until it begins working you may not notice any change in your symptoms.
  • 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 Levothyroxine Sandoz is working for you.
  • Do not change your dose of Levothyroxine Sandoz unless your doctor tells you to do so.

When to take Levothyroxine Sandoz

  • Levothyroxine Sandoz 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 to take Levothyroxine Sandoz

  • Swallow Levothyroxine Sandoz tablets with a glass of water.

How to long to take Levothyroxine Sandoz

  • Continue taking Levothyroxine Sandoz as long as your doctor recommends it.

If you forget to use Levothyroxine Sandoz

Levothyroxine Sandoz should be used regularly at the same time each day.

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 Levothyroxine Sandoz

If you think that you have used too much Levothyroxine Sandoz, 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.

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

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

5. What should I know while using Levothyroxine Sandoz

Things you should do

  • Do not switch or interchange with other brands unless advised by your doctor.
  • Immediately stop taking Levothyroxine Sandoz if a skin rash or other allergic reaction occurs.
  • Use it exactly as your doctor has prescribed.
  • Tell your doctor if you feel the medicine is not helping your condition.
  • Visit your doctor regularly.
    Your doctor needs to check your progress and see whether you need to stop taking Levothyroxine Sandoz.
  • Always discuss with your doctor any problems or difficulties during or after taking the medicine.
  • If you plan to have surgery, tell your doctor or dentist that you are taking Levothyroxine Sandoz.
  • If you are about to start taking any new medicines, remind your doctor and pharmacist that you are taking Levothyroxine Sandoz.
  • Ensure you do not run out of medicine over the weekend or on holidays.

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

Things you should not do

  • Do not stop 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 Levothyroxine Sandoz affects you.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Store below 25°C. Protect from light.

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
Mood related
  • nervousness
  • anxiousness
  • excitation
  • restlessness
  • inability to sleep
  • sleep disturbances
  • lack of concentration
  • irritability
Gastrointestinal/ Gut related
  • diarrhoea
  • stomach cramp
  • nausea
  • vomiting
Metabolism related
  • weight loss
  • tiredness
  • excessive sweating
  • flushing
  • increased appetite
Skin related
  • hair loss
Others
  • headache
  • muscle weakness & cramps
  • heat intolerance
  • menstrual irregularities
  • decreased libido
  • fever
  • unusual movements, including tremor
Speak to your doctor if you have any of these less serious side effects and they worry you.
They are generally mild and do not cause patients to stop taking Levothyroxine Sandoz.

Serious side effects

Serious side effectsWhat to do
Allergy related
  • allergic reactions such as skin rash
Lungs related
  • shortness of breath
  • rapid breathing
Heart related
  • chest pain
  • increased blood pressure
  • irregular heart beats
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 Levothyroxine Sandoz contains

Active ingredient
(main ingredient)		levothyroxine sodium
Other ingredients
(inactive ingredients)
  • maize starch
  • lactose monohydrate
  • gelatin
  • croscarmellose sodium
  • magnesium stearate
Potential allergens
  • Sugars as lactose
    (50 mcg, 75 mcg, 100 mcg)
  • Lactose
    (200 mcg)

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

What Levothyroxine Sandoz looks like

Levothyroxine Sandoz 50 microgram – white, round tablet, debossed “50” on one side, and scored in the shape of “+” sign on the other side (Aust R 387274).

Levothyroxine Sandoz 75 microgram – white, round tablet, debossed “75” on one side and scored in the shape of “+” sign on the other side (Aust R 387277).

Levothyroxine Sandoz 100 microgram – white, round tablet, debossed “100” on one side, and scored in the shape of “+” sign on the other side (Aust R 387276).

Levothyroxine Sandoz 200 microgram – white, round tablet, debossed “200” on one side, and scored in the shape of “+” sign on the other side (Aust R 387275).

Pack size of 200.

Who distributes Levothyroxine Sandoz

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park, NSW 2113
Tel: 1800 726 369

This leaflet was prepared in March 2023.

Published by MIMS December 2023

BRAND INFORMATION

Brand name

Levothyroxine Sandoz

Active ingredient

Levothyroxine sodium

Schedule

S4

 

1 Name of Medicine

Levothyroxine sodium.

2 Qualitative and Quantitative Composition

Levothyroxine Sandoz tablets are available in four strengths and contain levothyroxine sodium 50, 75, 100 or 200 micrograms as the active ingredient.

Excipients with known effect.

Sugars as lactose (50, 75 and 100 micrograms), lactose (200 micrograms).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

50 microgram.

White, round tablet, debossed "50" on one side, and scored in the shape of "+" sign on the other side.

75 microgram.

White, round tablet, debossed "75" on one side and scored in the shape of "+" sign on the other side.

100 microgram.

White, round tablet, debossed "100" on one side, and scored in the shape of "+" sign on the other side.

200 microgram.

White, round tablet, debossed "200" on one side, and scored in the shape of "+" sign on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Levothyroxine Sandoz is indicated for the management of demonstrated thyroid hormone deficiency.
Levothyroxine Sandoz 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

Levothyroxine Sandoz is bioequivalent to Oroxine/Eutroxsig. Do not interchange Levothyroxine Sandoz and Eltroxin. If a decision is made to switch from Levothyroxine Sandoz 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, 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 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 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 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 myxodema.

Caution is also required for patients with long-standing hypothyroidism or myxodema, 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. Levothyroxine 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 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 triiodothyronine.

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 hypothydroidism.

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.

Thyroxine can enhance the clinical effects of pentobarbital 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.
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 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 post-partum.
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 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 fetus having been observed.
 Women who are breast feeding should continue to take levothyroxine. 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)

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 cramps, nausea, diarrhoea, vomiting, malabsorption.

Immune system.

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

Endocrine system.

Hyperthyroidism.

Investigations.

Decreased bone mineral density.

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.

4.9 Overdose

Within three to six days after ingestion any or all of the symptoms and signs listed under 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 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Levothyroxine 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 pre-albumin (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-idothyronine. Approximately 40% of levothyroxine sodium is metabolised to the inactive reverse tri-idothyronine, 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

Maize starch, lactose monohydrate, gelatin, croscarmellose sodium and magnesium stearate.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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

Levothyroxine Sandoz tablets are packed in PVC/PE/PVDC/Aluminium blister packs 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)

Schedule 4 (S4) - Prescription Only Medicine.

Summary Table of Changes