Protirelin Ampoules

Each ampoule contains 200micrograms of Protirelin (Thyrotrophin-releasing hormone, TRH) in 2ml of solution.

Solution for Injection

The administration of Protirelin provides a means of assessing thyroid function and the reserve of TSH in the pituitary gland and is recommended as a test procedure where such assessment is indicated.

It is particularly useful as a diagnostic test for:

1. Mild hyperthyroidism

2. Ophthalmic Graves' disease

3. Mild or preclinical hypothyroidism

4. Hypopituitarism

5. Hypothalamic disease

It may also be used in place of the T₃ suppression test.

Protirelin ampoules are for intravenous injection.

Intravenous injection

Tests employing intravenous Protirelin are based on the serum TSH response to a standard dose. They provide a means of both quantitative and qualitative assessment of thyroid function. It is essential for each laboratory to establish its own normal range of values for serum TSH before attempting quantitative assessment of Protirelin responses by this means.

Intravenous Protirelin test

a) Blood sample taken for control TSH assay.

b) Protirelin 200µg given as a single bolus injection.

c) Blood sample taken 20 minutes after injection for peak TSH assay.

d) If necessary, a further blood sample may be taken 60 minutes after injection to detect a delayed TSH response.

The ampoule solution should not be diluted.

The elderly

The use of Protirelin in the elderly has been well documented. Dosage requirements and the side-effects are similar to those of younger adults. The response may be decreased in elderly subjects, but this does not interfere with the interpretation of the test results.

Children up to the age of 12

The procedures for administering Protirelin to children are identical to those outlined above. An intravenous dose of 1µg/kg bodyweight may be used.

Interpretation of results

Interpretation of the responses to Protirelin is based on the increase in TSH and/or PBI, T₃ or T₄ levels from the basal values. In normal subjects, there is a prompt rise in serum levels of TSH. The changes observed in various conditions are briefly outlined below:

1. Hyperthyroidism - no rise in serum TSH or thyroid hormone levels.

2. Ophthalmic Graves' disease - often no rise in serum TSH or thyroid hormone levels.

3. Primary hypothyroidism - exaggerated and prolonged rise in serum TSH but no change in thyroid hormone levels.

4. Hypopituitarism - absent or impaired TSH or thyroid hormone response implies diminished TSH reserve.

5. Hypothalamic disease - a rise in serum TSH or thyroid hormone levels can occur in the presence of hypothyroidism; delayed responses are common.

The Protirelin test provides, in most instances, information similar to that obtained from a T₃ suppression test in that an absent or impaired response usually correlates with an absent or impaired response to T₃ suppression.

There are no absolute contra-indications to Protirelin.

In view of the postulated effect of bolus injections of Protirelin on smooth muscle, patients with bronchial asthma or other types of obstructive airways disease should be closely monitored. Caution should always be observed in patients with myocardial ischaemia and severe hypopituitarism.

The secretion of thyrotrophin appears to be modulated by dopaminergic and noradrenergic pathways. The TSH response to Protirelin may be reduced by thyroid hormones, levodopa, phenothiazines, salicylates, bromocriptine, carbamazepine, lithium and by pharmacological doses of corticosteroids.

An increased response may be seen in subjects taking metoclopramide, amiodarone or theophyllines and in men taking oestrogens. Over-treatment with antithyroid drugs may also cause an enhanced response.

Animal studies and clinical experience have shown no evidence of hazard in human pregnancy at the recommended dosage. Nevertheless, the established medical principle of not administering drugs during early pregnancy should be observed.

Breast enlargement and leaking of milk have been reported following the administration of protirelin to lactating women.

None known.

Protirelin is well tolerated. Following rapid intravenous injection, side-effects of a mild and transient nature may be experienced. These comprise nausea, a desire to micturate, a feeling of flushing, slight dizziness and a peculiar taste, and have been attributed to a local action of the bolus of Protirelin on the muscle of the gastro-intestinal and genito-urinary tracts. A transient increase in pulse rate and blood pressure may also be noted.

No symptoms of overdosage have been noted in patients receiving up to 1mg i.v.

Pharmacotherapeutic group: V04CJ.

Protirelin stimulates the secretion of thyroid stimulating hormone (TSH). Intravenous injection results in a prompt rise in serum TSH levels in normal subjects, peak levels being observed about twenty minutes after administration. There is a concomitant rise in serum levels of prolactin.

TSH rapidly disappears from the plasma after intravenous injection. Over 90% is removed within 20 minutes with a half life of about 5.3 minutes. About 5.5% of the dose is excreted in the urine, mostly within 30 minutes.

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Mannitol Ph.Eur

Glacial acetic acid Ph.Eur

Water for Injections Ph.Eur

None known.

Three years.

The recommended maximum storage temperature is 30°C.

Clear glass ampoules coded with orange and black colour rings each containing 2ml of solution, in packs of 10 ampoules.

None.

Cambridge Laboratories Limited

Deltic House

Kingfisher Way

Silverlink Business Park

Wallsend

Tyne & Wear

NE28 9NX

PL 12070/0009

October 2002

July 2003