Levothyroxine 25 micrograms Tablets

Each tablet contains 27.8 micrograms of levothyroxine sodium equivalent to 25 micrograms of levothyroxine sodium anhydrous.

For excipients, see 6.1

Tablet for oral use.

White, circular, convex tablets marked TX25 on one face and CP on the reverse.

Levothyroxine sodium is used for the treatment of thyroid deficiency states.

For oral use

The dose of levothyroxine should be individualised on the basis of clinical response and biochemical tests, and should be monitored regularly to avoid both undertreatment and overtreatment (see section 4.4 Special warnings and precautions for use).

Thyrotoxicosis, hypersensitivity to any component.

Levothyroxine should be used with particular caution in the elderly (see 4.2 Posology and Method of Administration), in patients with long-standing hypothyroidism, and in diabetes where monitoring of insulin or oral hypoglycaemic drug requirement is advisable (see 4.5 Interactions).

To minimise the risk of adverse effects of undetected overtreatment, such as atrial fibrillation and fractures associated with low serum levels of thyroid stimulating hormone (TSH) in older patients, it is important to monitor serum TSH and adjust the dose accordingly during long term use.

Levothyroxine should be used with extreme caution in patients with cardiovascular disorders, including hypertension, angina, heart failure and myocardial infarction. Cardiac disease may be exacerbated by the administration of thyroid hormones, resulting in angina pectoris, myocardial infarction or sudden cardiac death. An electrocardiogram (ECG) performed before starting treatment with levothyroxine may help to distinguish underlying myocardial ischaemia from changes induced by hypothyroidism. In the presence of cardiac disease, dosage should be started cautiously and increased slowly (see 4.2 Posology and method of administration).

In patients with panhypopituitarism or other disorders pre-disposing to adrenal insufficiency, the adrenal insufficiency should be corrected with corticosteroid therapy before commencing treatment with levothyroxine, to prevent precipitation of acute adrenal crisis.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.

Lipid-regulating drugs: Colestyramine or colestipol reduce the absorption of levothyroxine when administered concomitantly; administration of levothyroxine with either colestyramine or colestipol should be separated by four to five hours.

Antacids: Calcium carbonate or antacids containing a combination of aluminium and magnesium may reduce the absorption of levothyroxine.

Antibacterials: Rifampicin enhances thyroid hormone metabolism.

Anticancer drugs: Imatinib. Plasma concentration of levothyroxine possibly reduced by imatinib.

Oral Anticoagulants: Levothyroxine may enhance the effects of anticoagulants such as coumarins (e.g. warfarin) or phenindione; concomitant administration may require a reduction in oral anticoagulant dose.

Antidepressants: Effects of levothyroxine may be decreased by concomitant sertraline. Antidepressant response to tricyclics can be accelerated, but concomitant administration may precipitate cardiac arrhythmias.

Antidiabetics: Requirements for insulin or oral antidiabetic agents may be increased.

Antiepileptics: Carbamazepine, barbiturates including phenobarbital, phenytoin and primidone can accelerate Levothyroxine metabolism

Beta-blockers: may decrease peripheral conversion of Levothyroxine to triiodothyronine. Levothyroxine has the potential to reduce plasma concentrations of propanolol due to increased propranolol metabolism.

General anaesthetics: Ketamine may produce marked hypertension and tachycardia in patients taking levothyroxine.

Cardiac glycosides: Hypothyroid patients may be initially sensitive to digitalis, but may need a gradually increasing dose of cardiac glycosides as treatment with levothyroxine progresses.

Iron salts: Ferrous sulphate reduces absorption of levothyroxine. Administration of levothyroxine and ferrous sulphate should be separated by at least two hours.

Polystyrene Sulphonate resins reduce the absorption of levothyroxine. Administration of levothyroxine and polystyrene sulphate resins should be separated by as much as possible.

Sex hormones: Oestrogens increase and androgens decrease serum thyroxine-binding globulin; thyroid hormone requirements may be increased during oestrogen therapy and reduced during androgen therapy and thyroid function tests affected.

Sympathomimetics: Effects may be enhanced by levothyroxine.

Ulcer-healing drugs: sucralfate or cimetidine may reduce the absorption of levothyroxine.

Weight loss drugs: Orlistat may decrease levothyrocine absorption which may result in hypothyroidism (monitor for changes in thyroid function).

The safety of levothyroxine during pregnancy has not been established. However, pregnancy occurring in a woman on a maintenance dose of levothyroxine for thyroid deficiency would be expected to proceed normally; however, maternal levothyroxine doses should be monitored as requirements may change during pregnancy.Thyroid hormones appear not to readily cross the placenta. The risk of foetal abnormalities should be weighed against that of untreated hypothyroidism.

The concentration of thyroid hormones excreted into breast milk appears not to be clinically significant but screening for congenital hypothyroidism might be affected.

None

Adverse effects of thyroid hormones are generally associated with excessive dosage and may not be apparent for several days after levothyroxine administration. Such effects normally resolve upon reduction of dosage or temporary withdrawal of the drug.

Cardiovascular tachycardia, palpitation, cardiac arrhythmias and anginal pain (see 4.4 Special warnings and precautions for use)

Gastrointestinal: Diarrhoea, vomiting.

General: Headache, flushing, sweating, fever, heat intolerance.

Immunological: Hypersensitivity reactions (rare) with rash, urticaria, angioedema, fever, eosinophilia or liver dysfunction.

Metabolic: Weight loss

Musculoskeletal: Muscular weakness and cramp. Craniosynostosis in infants and premature closure of the epiphyses in children.

Neurological: Nervousness, excitability, restlessness, insomnia, tremor. Rarely, pseudotumour cerebri (benign intracranial hypertension) in children.

Psychiatric disorders: levothyroxine may induce mania

Skin and subcutaneous tissue disorders: Levothyroxine can cause transient hair loss to occur in children.

Reproductive disorders: Menstrual irregularities.

Symptoms of overdose: In most cases there will be no features. Rarely, features of hyperthyroidism may develop 3-6 days after ingestion with tachycardia, palpitations, atrial fibrillation, hypertension, angina, headache, nervousness/restlessness, confusion, anxiety, insomnia, tremor, heat intolerance, sweating, hyperpyrexia, weight loss, diarrhoea, vomiting and menstrual irregularities. Convulsions, coma and death have occurred. There may be increased toxicity in those with pre-existing heart disease.

Treatment:

Give oral activated charcoal if more than 10mg has been ingested by an adult or more than 5mg by a child, within 1 hour. If more than 10mg has been ingested by an adult or more than 5mg by a child, take blood 6-12 hours after ingestion for measurement of the free thyroxine concentration. The analysis does not need to be done urgently but can wait until the first working day after the incident. Patients with normal free thyroxine concentrations do not require follow up. Those with high concentrations should have outpatient review 3-6 days after ingestion to detect delayed onset hyperthyroidism. Features of clinical hyperthyroidism should be controlled with beta-blockers, e.g. propranolol.

Levothyroxine sodium, a hormone, is employed in the treatment of thyroid deficiency states.

Levothyroxine sodium is incompletely and variably absorbed from the gastrointestinal tract. It is almost completely bound to plasma proteins and has a half-life in the circulation of about a week in healthy persons. A large part of the levothyroxine leaving the circulation is taken up by the liver. Part of a dose of levothyroxine is metabolised to tri-iodothyronine. Levothyroxine is excreted in the urine as free drug, deiodinated metabolites and conjugates. Some levothyroxine is excreted in the faeces.

There are no preclinical data of relevance to the prescriber, which are additional to those already included in other sections.

Lactose

Sucrose fine powder

Maize starch

Magnesium stearate

None

18 months

Do not store above 25°C

Polypropylene or polyethylene containers of 28, 30, 56, 60, 84, 90, 100, 250, 500 or 1000 tablets.

Strip packs of white or clear PVC film and 20 micron aluminium foil of 10, 14, or 28 tablets. The tablets will be packed in multiple strips of 10 tablets i.e. 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100. The tablets will be packed in multiple strips of 14 tablets i.e. 14, 28, 56, 84 and 112 tablets.

None

Wockhardt UK Ltd

Ash Road North

Wrexham

United Kingdom

LL13 9UF.

UK

PL 29831/0130

11/01/2008

01/05/2012