LEVOTHYROXINE TABLETS B.P. 25MCG - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Levothyroxine 25 micrograms Tablets BP

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

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

For the full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Tablet for oral use.

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

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Levothyroxine sodium is used in adults and children for the treatment of thyroid deficiency states.

4.2 Posology and method of administration

Posology

In younger patients, and in the absence of heart disease, a serum Levothyroxine (T4) level of 70 to 160 nanomols per litre, or a serum thyrotrophin level of less than 5 milli-units per litre should be targeted. A pretherapy ECG is valuable because ECG changes due to hypothyroidism may be confused with ECG evidence of cardiac ischaemia. If too rapid an increase in metabolism is produced (causing diarrhoea, nervousness, rapid pulse, insomnia, tremors, and sometimes anginal pain where there is latent cardiac ischaemia,) dosage must be reduced, or withheld, for a day or two, and then re-started at a lower dose level.

Adults: Initially, 50 to 100 micrograms daily (two to four tablets daily), preferably taken before breakfast or your first meal of the day. Adjust at three to four week intervals by 50 micrograms until normal metabolism is steadily maintained. The final dose may be up to 100 to 200 micrograms.

Elderly: as for patients aged over 50 years

For patients over 50 years, initially, it is not advisable to exceed 50 micrograms daily. In this condition, the daily dose may be increased by 50 micrograms at intervals of every 3–4 weeks, until stable thyroxine levels are attained. The final daily dose may be up to 50 to 200 micrograms.

Patients over 50 years with cardiac disease:

Where there is cardiac disease, 25 micrograms daily or 50 micrograms on alternate days is more suitable. In this condition, the daily dosage may be increased by 25 microgram increments at intervals of every 4 weeks, until stable thyroxine levels are attained. The final daily dose may be up to 50 to 200 micrograms.

For patients aged over 50 years, with or without cardiac disease, clinical response is probably a more acceptable criteria of dosage rather that serum levels.

Paediatric population

The maintenance dose is generally 100 to 150 micrograms per m2 body surface area. The dose for children depends on their age, weight and the condition being treated. Regular monitoring using serum TSH levels, as in adults, is required to make sure he/she gets the right dose. Infants should be given the total daily dose at least half an hour before the first meal of the day.

Congenital hypothyroidism in infants:

For neonates and infants with congenital hypothyroidism, where rapid replacement is important, the initial recommended dosage is 10 to 15 micrograms per kg body weight per day for the first three months. Thereafter, the dose should be adjusted individually according to the clinical findings and thyroid hormone and TSH values.

Acquired hypothyroidism in children:

For children with acquired hypothyroidism, the initial recommended dosage is 12.5–50 micrograms per day. The dose should be increased gradually every two to four weeks according to the clinical findings and thyroid hormone and TSH values until the full replacement dose is reached.

Infants should be given the total daily dose at least half an hour before the first meal of the day.

Juvenile myxoedema in children:

The initial recommended dosage is 25 micrograms daily. In such conditions, the daily

dose may be increased by 25 micrograms at intervals of every 2 – 4 weeks, until mild symptoms of hyperthyroidism is seen. The dose will then be reduced slightly.

In children under 5 years of age, the administration of whole tablets is not recommended. It is also not recommended that tablets are crushed and dispersed in water or other liquids, owing to limited solubility which could lead to dosing inaccuracy. In this age group it is preferable to administer an approved oral solution of levothyroxine.

Method of administration

For oral use.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

Thyrotoxicosis

Adrenal gland disorder or adrenal insufficiency

4.4 Special warnings and precautions for use

Levothyroxine should be introduced very gradually in patients aged over 50 years (see section 4.2) and those with long standing hypothyroidism to avoid any sudden increase in metabolic demands.

Patients with panhypopituitarism or other causes predisposing to adrenal insufficiency may react to levothyroxine treatment, and it is advisable to start corticosteroid therapy before giving levothyroxine to such patients.

Levothyroxine should be used with caution in patients with cardiovascular disorders, including angina, coronary artery disease, hypertension, and in the elderly who have a greater likelihood of occult cardiac disease.

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.

In individuals suspected to have cardiovascular disease or to be at high risk, it is important to perform an ECG prior to commencement of levothyroxine treatment in order to detect changes consistent with ischaemia in which case, levothyroxine should be initiated at a low dose, followed by cautious dose escalation to avoid worsening of ischaemia or precipitation of an infarct.

Thyroid replacement therapy may cause an increase in dosage requirements of insulin or other anti-diabetic therapy (such as metformin). Care is needed for patients with diabetes mellitus, and diabetes insipidus.

See note above regarding withdrawal of treatment.

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

Subclinical hyperthyroidism may be associated with bone loss. To minimise the risk of osteoporosis, dosage of levothyroxine sodium should be titrated to the lowest possible effective level.

Parents of children receiving thyroid agent should be advised that partial loss of hair may occur during the first few months of therapy, but this effect is usually transient and subsequent regrowth usually occurs.

4.4 Special warnings and precautions for use

Levothyroxine should be introduced very gradually in patients aged over 50 years (see section 4.2) and those with long standing hypothyroidism to avoid any sudden increase in metabolic demands.

Patients with panhypopituitarism or other causes predisposing to adrenal insufficiency may react to levothyroxine treatment, and it is advisable to start corticosteroid therapy before giving levothyroxine to such patients.

Levothyroxine should be used with caution in patients with cardiovascular disorders, including angina, coronary artery disease, hypertension, and in the elderly who have a greater likelihood of occult cardiac disease.

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.

In individuals suspected to have cardiovascular disease or to be at high risk, it is important to perform an ECG prior to commencement of levothyroxine treatment in order to detect changes consistent with ischaemia in which case, levothyroxine should be initiated at a low dose, followed by cautious dose escalation to avoid worsening of ischaemia or precipitation of an infarct.

Thyroid replacement therapy may cause an increase in dosage requirements of insulin or other anti-diabetic therapy (such as metformin). Care is needed for patients with diabetes mellitus, and diabetes insipidus.

See note above regarding withdrawal of treatment.

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

Subclinical hyperthyroidism may be associated with bone loss. To minimise the risk of osteoporosis, dosage of levothyroxine sodium should be titrated to the lowest possible effective level.

Parents of children receiving thyroid agent should be advised that partial loss of hair may occur during the first few months of therapy, but 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.

4.6 Fertility, pregnancy and lactation

Pregnancy

The safety of levothyroxine treatment during pregnancy is not known, but any possible risk of foetal abnormalities should be weighed against the risk to the foetus of untreated hypothyroidism.

Breastfeeding

Levothyroxine is excreted in breast milk in low concentrations, and it is contentious whether this can interfere with neonatal screening.

4.7 Effects on ability to drive and use machines

Levothyroxine has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Side-effects are usually indicative of excessive dosage and usually disappear on reduction of dosage or withdrawal of treatment for a few days. Adverse reactions listed below have been observed during clinical studies and/or during marketed use and are based on clinical trial data and classified according to MedDRA System Organ Class. Frequency categories are defined according to the following convention:

Not known (cannot be estimated from the available data)

1Some patients may experience a severe reaction to high levels of thyroid hormone.

This is called a „thyroid crisis“ with any of the following symptoms: Hyperpyrexia, tachycardia, arrhythmia, hypotension, cardiac failure, jaundice, confusion, seizure and coma

Paediatric population

Heat intolerance, transient hair loss, benign intracranial hypertension, craniostenosis in infants and premature closure of epiphysis in children.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms

In most cases there will be no features. Signs of an overdose may include: chest pain (angina), tachycardia or arrhythmia, muscle cramps, headache, restlessness, flushing, sweating, diarrhoea, tremor, insomnia and hyperpyrexia. These signs can take up to 5 days to appear.

Atrial fibrillation may develop. Convulsions occurred in one child. There may be increased toxicity in those with pre-existing heart disease.

Management:

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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: thyroid hormones, ATC code: H03AA01

Levothyroxine 25 micrograms Tablets contain Levothyroxine sodium used for the treatment of hypothyroidism. Levothyroxine is deiodinated in peripheral tissues to form triiodothyronine which is thought to be the active tissue form of thyroid hormone. Triiodothyronine has a rapid action but a shorter duration of activity than Levothyroxine.

The chief action of Levothyroxine is to increase the rate of cell metabolism.

5.2 Pharmacokinetic properties

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 subjects.

A large portion 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 is limited placental transfer of Levothyroxine.

5.3 Preclinical safety data

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

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose

Sucrose fine powder

Maize starch

Magnesium stearate

6.2 Incompatibilities

None.

6.3 Shelf life

18 months.

6.4 Special precautions for storage

Do not store above 25°C

6.5 Nature and contents of container

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.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Wockhardt UK Ltd

Ash Road North

Wrexham LL13 9UF

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 29831/0130

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

04/05/2010