Consumer medicine information

Oroxine

Levothyroxine sodium

BRAND INFORMATION

Brand name

Oroxine

Active ingredient

Levothyroxine sodium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Oroxine.

What is in this leaflet

This leaflet answers some common questions about Oroxine tablets.

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

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

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

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

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

The name of your medicine is Oroxine. It is available in tablets of four different strengths: 50 micrograms, 75 micrograms, 100 microgram and 200 microgram.

The active ingredient is called levothyroxine sodium.

What is it used for

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

Oroxine 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 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.
  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. Oroxine replaces the shortage of thyroid hormones.

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

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

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

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

Before you take it

When you must not take it

Do not take Oroxine if you are allergic to:

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

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

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

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

Before you start to take it

Tell your doctor if:

  1. You are allergic to any other medicines or any foods, dyes or preservatives.
  2. You are pregnant or intend to become pregnant.
    Thyroxine levels will need to be watched carefully during pregnancy. Your dosage of Oroxine may need to be increased while you are pregnant.
    Ask your doctor about the risks and benefits of taking Oroxine during pregnancy.
  3. You are breastfeeding or intend to breastfeed.
    Although small amounts of Oroxine are found in breast milk, women who are breastfeeding should continue treatment with Oroxine.
  4. You have or have had any other medical conditions/ health problems, including:
  • Overactive thyroid gland
  • Adrenal gland problem
  • Hyperthyroidism
  • Heart problems such as cardiovascular disorder
  • High blood pressure
  • Diabetes
  • Long-standing hypothyroidism, an underactive thyroid gland.
  • Problems absorbing nutrients from the gastrointestinal tract

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

Taking other medicines

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

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

  • Anticoagulants, medicines used to thin your blood (eg. Warfarin)
  • Antidepressants, medicines used to treat depression (e.g. Lithium, SSRIs, Tricyclic antidepressants)
  • Antivirals, medicines used to treat HIV/AIDS infection (e.g. ritonavir)
  • Antimalarials, medicines used to treat and prevent malaria (e.g. chloroquine and proguanil)
  • Medicines used to treat diabetes (e.g. insulin)
  • Beta-blockers, medicines used to treat high blood pressure and heart conditions (e.g. propranolol)
  • Ion-exchange resins, medicines used to decrease cholesterol in the blood (e.g. cholestyramine)
  • Corticosteroids, antiinflammatory medicines (e.g. prednisolone and dexamethasone)
  • Oral contraceptives and hormone replacement medicines such as oestrogens 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)

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

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

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

How to take it

Your doctor will decide on the right dose for you.

It may take a few weeks for Oroxine 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.

If you do not understand the instructions on the blister pack, ask your doctor or pharmacist for help.

How much to take

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

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

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

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

Talk to your doctor if you have any further questions.

How to take it

Swallow Oroxine tablets with a glass of water.

When to take it

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

How long to take it

Continue taking it as long as your doctor recommends it.

If you forget to take it

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

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

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

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

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

If you take too much (Overdose)

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

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

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

While you are taking it

Things you must do

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

Immediately stop taking Oroxine 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 Oroxine is not helping your condition.

Visit your doctor regularly. Your doctor needs to check your progress and see whether you need to stop taking the medicine.

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

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

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

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

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

Things you must not do

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

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

Side effects

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

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

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

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

Some people may get other side effects with Oroxine.

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

After taking it

Storage

Store at 2°C to 8°C (Refrigerate. Do not freeze).

Always store tablets in their original blister strips. If you do not keep the tablets in the blister strip they may not keep well.

Laboratory tests have shown that if not stored correctly, there is a reduction in potency of the active ingredient levothyroxine sodium.

In-Use Blisters: A single blister strip can be removed from the carton and stored below 25°C for up to 14 days (2 weeks). After 14 days (2 weeks) of storage below 25°C, discard any remaining tablets.

Where unavoidable (e.g. in warm climates where temperatures regularly exceed 25°C), an in-use blister strip may continue to be stored in a refrigerator at 2°C to 8°C (Refrigerate. Do not freeze) for up to 14 days (2 weeks).

Oroxine tablets can also be stored in Webster packs for 14 days (2 weeks) below 25°C.

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

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

Keep the medicine out of reach of children.

Disposal

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

Product description

What it looks like

Oroxine 50 microgram tablets are white, biconvex, round tablets, scored and marked “50” on one side, plain on the other side.

Oroxine 75 microgram tablets are white, biconvex, round tablets, scored and marked “75” on one side, scored on the other side.

Oroxine 100 microgram tablets are white, biconvex, round tablets, scored and marked “100” on one side, plain on the other side.

Oroxine 200 microgram tablets are white, biconvex, round tablets, scored and marked “200” on one side, plain on the other side.

Blister packs:
Oroxine is available in blister packs.

Ingredients

Each Oroxine tablet contains levothyroxine sodium as the active ingredient.

Each Oroxine tablet contains the following excipients:

  • maize starch
  • lactose monohydrate
  • dextrin and
  • magnesium stearate.

They are free from gluten, sucrose and azo dyes.

Sponsor

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

The Australian Registration Numbers are:

  • Oroxine 50 micrograms: AUST R 125498
  • Oroxine 75 micrograms: AUST R 144108
  • Oroxine 100 micrograms: AUST R 125499
  • Oroxine 200 micrograms: AUST R 125500.

This leaflet was revised in May 2020.

Published by MIMS August 2020

BRAND INFORMATION

Brand name

Oroxine

Active ingredient

Levothyroxine sodium

Schedule

S4

 

1 Name of Medicine

Levothyroxine sodium.

2 Qualitative and Quantitative Composition

Oroxine tablets are available in four strengths and contain levothyroxine sodium 50, 75, 100 or 200 micrograms as the active ingredient. They also contain the following excipients: maize starch, lactose monohydrate, dextrin and magnesium stearate.

3 Pharmaceutical Form

White, biconvex, round tablets.

4 Clinical Particulars

4.1 Therapeutic Indications

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

4.2 Dose and Method of Administration

Thyroxine 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 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, 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 to 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 Oroxine and Eltroxin. If a decision is made to switch from Oroxine to Eltroxin, then prescribers should be aware that dose adjustment may be required; TSH should be monitored.

Initiation of therapy.

In the elderly or patients with ischaemic heart disease, Oroxine 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 Oroxine 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 Oroxine 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 Oroxine 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 Oroxine therapy is initiated, changed or discontinued. Adjustments in the dosage of these agents should only be made accordingly if necessary.

Hyperthyroidism.

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

Thyrotoxicosis.

Patients who have thyrotoxicosis and who are being treated with anti-thyroid medication may have increased sensitivity to Oroxine.

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

Insulin and antidiabetic agents e.g. sulfonylurea.

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

Beta-adrenergic blocking agents e.g. propranolol.

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

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

Due to concurrent use of ion-exchange resins with Oroxine, the effects of Oroxine may be reduced due to the resin binding to Oroxine in the gastrointestinal tract, causing a delay or impairment in Oroxine 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 Oroxine. 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 Oroxine requirements.

Antiepileptics e.g. phenytoin, carbamazepine and barbiturates.

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

Ritonavir.

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

Antimalarials.

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

Antibacterials e.g. rifampicin and ciprofloxacin.

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

Ketamine.

Cautious administration of ketamine is recommended in patients on Oroxine 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 Oroxine, 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 Oroxine, 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 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 pentobarbitone and dihydrotachysterol. Therefore, the adjustment of dosage may be necessary.
The clinical effect of levothyroxine can be reduced by soya flour, sucralfate, calcium-, aluminium-, magnesium-, iron supplements, lanthanum, sevelamer, and proton pump inhibitors - which interfere with absorption from the gastrointestinal tract. If these substances are taken, then their ingestion should be separated by several hours from the ingestion of levothyroxine.
Soy-containing compounds and high fibre diets can decrease the intestinal absorption of levothyroxine. Therefore, a dosage adjustment of levothyroxine may be necessary, in particular at the beginning or after termination of nutrition with soy supplements.
Thyroid function tests can be modified, without changes in clinical effect of 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 breastfeeding should continue to take Oroxine. 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 Oroxine 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, hypoglycaemia or fluid loss should be initiated as necessary. Of various adrenergic β-blockers, propranolol has been used commonly to control cardiac arrhythmia and other manifestations. Reserpine, guanethidine and digoxin have also been used. Exchange transfusion has been recommended for progressive deterioration.
When overdose does occur, there must be an extended follow-up period as symptoms may be delayed for several days due to the gradual peripheral conversion of thyroxine to tri-iodothyronine.
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.

Oroxine 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-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

Maize starch, lactose monohydrate, dextrin 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 at 2°C to 8°C. (Refrigerate. Do not freeze.)
Laboratory tests have shown that if not stored correctly, there is a reduction in potency of the active ingredient levothyroxine sodium.
A single blister strip can be removed from the carton and stored below 25°C for up to 14 days (2 weeks). After 14 days (2 weeks) of storage below 25°C, discard any remaining tablets. Where unavoidable (i.e. in warm climates where temperatures regularly exceed 25°C), a used blister strip (i.e. a blister strip that is being used) of Oroxine tablets may be stored at 2°C to 8°C (Refrigerate. Do not freeze) for up to 14 days (2 weeks).
Oroxine tablets can also be stored in Webster packs for up to 14 days (2 weeks) below 25°C.

6.5 Nature and Contents of Container

50 microgram.

White, biconvex, round tablet, scored and marked "50" on one side, plain on the other side in Al/Al blister packs of 150 and 200.

75 microgram.

White, biconvex, round tablet, scored and marked "75" on one side and scored on the other side in Al/Al blister packs of 200.

100 microgram.

White, biconvex, round tablet, scored and marked "100" on one side, plain on the other side in Al/Al blister packs of 150 and 200.

200 microgram.

White, biconvex, round tablet, scored and marked "200" on one side, plain on the other side in Al/Al blister packs of 150 and 200.
(Note: Not all pack sizes may be marketed).

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