SUMMARY CMI

Thyrogen^®

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.

1. Why am I using Thyrogen?

Thyrogen contains the active ingredient thyrotropin alfa. Thyrogen is used to help in the detection of thyroid cancer cells. Thyrogen is also used in the treatment of thyroid cancer in combination with radioactive iodine. For more information, see Section 1. Why am I using Thyrogen? in the full CMI.

2. What should I know before Thyrogen is given?

Do not use if you have ever had an allergic reaction to thyrotropin alfa 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 Thyrogen? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Thyrogen 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 Thyrogen?

• Your treating physician will decide on the dose that is most suitable.
• Your treating physician will give you two injections of Thyrogen into the muscle of your buttock. The second injection will be given to you a day after the first one.

More instructions can be found in Section 4. How is Thyrogen given? in the full CMI.

5. What should I know while using Thyrogen?

For more information, see Section 5. What should I know while, or after, being given Thyrogen? in the full CMI.

6. Are there any side effects?

Less serious side effects include headache, fatigue, nausea, weakness, vomiting, dizziness, chills, numbness/tingling, fever and diarrhoea. More serious side effects include hoarse voice, difficulty breathing, noisy breathing and itchy rash or hives.

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.

FULL CMI

Thyrogen^®

Active ingredient: Thyrotropin alfa

Consumer Medicine Information (CMI)

This leaflet provides important information about using Thyrogen. 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 Thyrogen.

Where to find information in this leaflet:

1. Why am I using Thyrogen?
2. What should I know before Thyrogen is given?
3. What if I am taking other medicines?
4. How is Thyrogen given?
5. What should I know while, or after, being given Thyrogen?
6. Are there any side effects?
7. Product details

1. Why am I using Thyrogen?

Thyrogen contains the active ingredient Thyrotropin alfa. Thyrogen is a human thyroid stimulating hormone (TSH) manufactured using biotechnology processes.

Thyrogen is used together with a blood test and/or a whole body scan to help in the detection of thyroid cancer cells in patients who have had all or part of their thyroid gland removed as a result of thyroid cancer.

Thyrogen is also used in the treatment of thyroid cancer in combination with radioactive iodine to kill any remaining thyroid cancer cells or normal thyroid tissue after removal of your thyroid. This also allows the doctors to detect more easily any thyroid cancers that may remain after your treatment.

Thyrogen helps your remaining thyroid cells and the cancer cells take up the radioactive iodine so that they will all be killed by the radiation treatment.

How it works

After you have had your cancer operation, your treating physician will need to test you to make sure that there are no remaining cancer cells in your body or that the cancer has not come back or spread to other parts of your body.

Your treating physician will give you thyroid hormone replacement treatment to replace the hormone that your thyroid gland used to make because you have had all or part of your thyroid gland removed.

Having this replacement treatment will also mean that your pituitary gland will produce less of a hormone called thyroid stimulating hormone (TSH).

TSH sticks to the thyroid cancer cells.

For the cancer cell detection tests to be accurate there needs to be a certain amount of TSH in your body. The thyroid hormone replacement treatment that you are getting means that your body will not be making enough TSH for the tests.

Thyrogen imitates TSH made by your body and makes sure that there is enough TSH in your body for the tests. For detection of thyroid cancer cells, Thyrogen will be given to you about 3 days before your blood test and/or whole body scan so that your doctor can find any thyroid cancer cells that might be in your body. For treatment of thyroid cancer, Thyrogen is given to you one day before your dose of radioiodine and up to several days before your scan.

2. What should I know before Thyrogen is given?

Warnings

Do not use Thyrogen if:

• you are allergic to Thyrogen, or any of the ingredients listed at the end of this leaflet.

Always check the ingredients to make sure you can use this medicine.

Check with your doctor or pharmacist if you:

• have reacted to previous treatments with any of the following: severe allergic reaction; difficulty breathing
• take any medicines for any other condition
• have allergies to: any other medicines; any other substances, such as foods, preservatives or dyes

Tell your treating physician if you have heart disease.

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 treating physician if you are pregnant or intend to become pregnant.

Thyrogen may cause harm to your unborn baby. Your treating physician will discuss the possible risks and benefits of having Thyrogen during pregnancy.

Talk to your treating physician if you are breastfeeding or intend to breastfeed.

It is not known whether Thyrogen passes into breast milk. Your doctor will discuss the possible risks and benefits of having Thyrogen during breastfeeding.

Children

The safety of Thyrogen in children has not been studied.

If your child has been prescribed Thyrogen, you may wish to discuss this with your child's treating physician.

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 Thyrogen and affect how it works.

No studies have been carried out on drug interactions.

Your treating physician will decide whether or not to give you Thyrogen.

Check with treating physician if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Thyrogen.

4. How is Thyrogen given?

Your treating physician will give you two injections of Thyrogen into the muscle of your buttock. The second injection will be given to you a day after the first one.

Your treating physician will decide on the dose that is most suitable.

If you use too much Thyrogen (overdose)

There have been no reported overdoses of Thyrogen.

5. What should I know while, or after, being given Thyrogen?

Things you should do

• Keep appointments with your treating physician.

It is important to have your Thyrogen injections at the times your treating physician has told you. This will make sure that there is the right amount of Thyrogen in your body for the cancer cell detection tests to be accurate. It is also important so that the right amount of Thyrogen is present when you have your radioactive iodine treatment after your thyroid surgery.

Remind any doctor, dentist or pharmacist you visit that you have been given Thyrogen.

• Have tests when your treating physician says to.

You are being given Thyrogen to make sure that the tests you will be having can detect any thyroid cancer cells in your body so it is important to have the tests when your doctor tells you to.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Thyrogen affects you.

The effect of Thyrogen on your ability to drive a car or operate machinery has not been studied. Make sure that you know how you react to Thyrogen before you drive a car or operate machinery or do anything else that may be dangerous if you are dizzy, light-headed, tired or drowsy.

Thyrogen may cause dizziness in some people.

Looking after your medicine

• Thyrogen will be stored in the hospital.

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 treating physician, doctor or pharmacist if you have any further questions.

Less serious side effects

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.

7. Product details

This medicine is only available with a doctor's prescription.

What Thyrogen contains

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

What Thyrogen looks like

Thyrogen is a white to off-white powder before it is prepared for injection and a clear, colourless solution after it has been prepared for injection. (Aust R 79777).

Who distributes Thyrogen

Thyrogen^® is registered by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113 Australia
Toll Free Number (medical information): 1800 818 806
Email: [email protected]

This leaflet was prepared in April 2021.

thyr-ccdsv2-cmiv3-12apr21

Published by MIMS June 2021

1 Name of Medicine

Thyrotropin alfa.

2 Qualitative and Quantitative Composition

Thyrotropin alfa 1.1 mg.

3 Pharmaceutical Form

Thyrogen is supplied as a sterile, nonpyrogenic, white to off white, lyophilised product, intended for intramuscular (IM) administration after reconstitution with sterile water for injection. Each vial of Thyrogen contains 1.1 mg thyrotropin alfa.
After reconstitution with 1.2 mL of sterile water for injection, the thyrotropin alfa concentration is 0.9 mg/mL. The pH of the reconstituted solution is approximately 7.0.
For the full list of excipients, see Section 6.1 List of Excipients.

4 Clinical Particulars

4.1 Therapeutic Indications

Thyrogen is indicated for:
1. Use with serum thyroglobulin (Tg) testing, with or without radioactive iodine imaging, undertaken for the detection of thyroid remnants and well differentiated thyroid cancer in post-thyroidectomy patients maintained on hormone suppression therapy.
2. Therapeutic use in post-thyroidectomy patients maintained on hormone suppression therapy in the ablation of thyroid remnant tissue in combination with radioactive iodine.

4.2 Dose and Method of Administration

A two injection regimen is recommended for Thyrogen administration.
The two injection regimen is Thyrogen 0.9 mg intramuscularly (IM), followed by a second 0.9 mg IM injection 24 hours later.
After reconstitution with 1.2 mL sterile water for injection, 1.0 mL solution (0.9 mg thyrotropin alfa) is administered by intramuscular injection to the buttock.
Each vial, after reconstitution with 1.2 mL of sterile water for injection, should be inspected visually for particulate matter or discolouration, before use. Any vials exhibiting particulate matter or discolouration should not be used.
For radioiodine imaging or treatment, radioiodine administration should be given 24 hours following the final Thyrogen injection. Diagnostic scanning should be performed 48 hours after radioiodine administration (72 hours after the final administration of Thyrogen), whereas post-therapy scanning may be delayed additional days to allow background activity to decline.
For serum Tg testing, the serum sample should be obtained 72 hours after the final intramuscular injection of Thyrogen.
The following parameters utilised in the second phase III study are recommended for diagnostic radioiodine scanning with Thyrogen:
A diagnostic activity of 148 MBq ¹³¹I should be used.
Whole body images should be acquired for a minimum of 30 minutes and/or should contain a minimum of 140,000 counts.
Scanning times for single (spot) images of body regions should be 10-15 minutes or less if the minimum number of counts is reached sooner (i.e. 60,000 for a large field of view camera or 35,000 counts for a small field of view camera).
To reduce microbiological hazard, use as soon as practicable after reconstitution/ preparation. If storage after reconstitution is necessary, hold at 2°-8°C for not more than 24 hours and avoid microbial contamination.
Product is for single use in one patient only. Discard any residue.
Injection material should not be mixed with other substances.

4.3 Contraindications

There are no known contraindications to the use of Thyrogen.

4.4 Special Warnings and Precautions for Use

Thyrogen may be used as an adjunctive diagnostic tool to detect recurrent or residual cancer in combination with radioiodine. Thyroid hormone withdrawal Tg testing with radioiodine imaging remains the standard diagnostic modality to assess the presence, location and extent of thyroid cancer.
The use of Thyrogen in conjunction with Tg testing alone (without radioimaging) should be restricted to patients at low risk of disease recurrence, that is those patients with no clinical evidence of disease who have suppressed serum Tg levels during thyroid hormone suppression therapy.
The use of Thyrogen should be directed by physicians knowledgeable in the management of patients with thyroid cancer.
Even when Thyrogen stimulated Tg testing is performed in combination with radioiodine imaging, there remains a meaningful risk of missing a diagnosis of thyroid cancer or of underestimating the extent of disease.
Thyrogen stimulated Tg levels are generally lower than, and do not correlate with, Tg levels after thyroid hormone withdrawal.
A newly detectable Tg level or a Tg level rising over time after Thyrogen, or a high index of suspicion of metastatic disease, even in the setting of a negative or low stage Thyrogen radioiodine scan, should prompt further evaluation such as thyroid hormone withdrawal to definitively establish the location and extent of thyroid cancer. Note that none of the 31 patients studied with undetectable Thyrogen stimulated Tg levels (< 2.5 nanogram/mL) had metastatic disease, therefore, an undetectable Thyrogen stimulated Tg level suggests the absence of clinically significant disease (see Section 5.1, Clinical trials).
The decisions whether to perform a Thyrogen radioiodine scan in conjunction with a Thyrogen serum Tg test and whether and when to withdraw a patient from thyroid hormone are complex. Pertinent factors in these decisions include the sensitivity of the Tg assay used, the Thyrogen stimulated Tg level obtained, and the index of suspicion of recurrent or persistent local or metastatic disease. In the clinical trials, combination Tg and scan testing did enhance the diagnostic accuracy of Thyrogen in some cases (see Section 5.1, Clinical trials).
Thyrogen should be administered intramuscularly only. It should not be administered intravenously.
Clinicians employ a wide range of ¹³¹I administered activities to achieve remnant ablation. Published studies on the use of Thyrogen to achieve remnant ablation have used ¹³¹I activities of 30 mCi to 110 mCi, and the Genzyme study employed 100 mCi in all patients. Multiple factors contribute to the decision about what activity of ¹³¹I should be administered for a given patient, such as the size of the remnant tissue (e.g. a function of aggressiveness of the surgeon) and the perceived risk of the patient for thyroid cancer recurrence (e.g. a function of patient age, primary tumour type and size, extent of disease). Activities of ¹³¹I in the 100 mCi range or above achieve remnant ablation more frequently than do lower activities but may be associated more often with complications of ¹³¹I treatment, such as salivary gland pain and swelling, persistent dry mouth, dry eyes or altered taste. Clinicians must weigh the risks and benefits when selecting an activity of ¹³¹I to achieve remnant ablation for a given patient.
In clinical trials with thyrotropin alfa, which produces a short-term increase in TSH levels, no case of tumour growth has been reported. In thyroid cancer patients, several cases of stimulated tumour growth have been reported during withdrawal of thyroid hormones for diagnostic procedures due to the subsequent prolonged elevation of TSH levels. There is a low risk of tumour stimulation when Thyrogen is used as an adjunct to radioiodine therapy to achieve remnant ablation.
In the clinical trials performed, the combination of whole body scanning and thyroglobulin testing after Thyrogen administration increased the detection rate for remnant thyroid tissue or cancer when compared to either diagnostic test alone. False negative results may occur with Thyrogen as with other diagnostic modalities. If a high index of suspicion for metastatic disease persists, a confirmatory withdrawal diagnostic or post-therapy whole body scan and thyroglobulin test should be considered.
Caution should be exercised when Thyrogen is administered to patients who have been previously treated with bovine TSH and, in particular, to those patients who have experienced hypersensitivity reactions to bovine TSH.
Thyrogen is known to cause a transient but significant rise in serum thyroid hormone concentration. Therefore, caution should be exercised in patients with a known history of heart disease and with significant residual thyroid tissue. One case of fatal myocardial infarction has been reported in a patient with residual thyroid tissue and a history of heart disease. The event was considered related to Thyrogen induced hyperthyroidism.
Thyroid cancer patients with metastatic disease present in confined spaces such as the brain and spinal cord, orbit or disease infiltrating the neck, may be subject to local oedema or focal haemorrhage at the site of these metastases. Due to the elevation of TSH levels after Thyrogen administration, the patients with metastatic disease may experience symptoms after administration including acute hemiplegia, hemiparesis, pain, or swallowing difficulty. Pretreatment with corticosteroids should be considered in these patients prior to the administration of Thyrogen.
There is a theoretical possibility that Thyrogen, like hormone withdrawal may lead to stimulated tumour growth. However any changes in tumour size reportedly seen with Thyrogen are more likely to be due to oedematous or haemorrhagic changes.
Thyroglobulin (Tg) antibodies will confound the Tg assay and render the Tg levels uninterpretable. Therefore, in such cases, even with a negative or low stage Thyrogen radioiodine scan, consideration should be given to evaluating patients further with, for example, a confirmatory thyroid hormone withdrawal scan to determine the location and extent of thyroid cancer.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Formal interaction studies between Thyrogen and other medicinal products have not been performed. In clinical trials, no interactions were observed between Thyrogen and the thyroid hormones triiodothyronine (T₃) and thyroxine (T₄) when administered concurrently.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

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)

Adverse drug reaction data were derived from postmarketing surveillance and clinical trials. The percentages in the table below represent adverse reactions experienced by 481 thyroid cancer patients who participated in the clinical trials for Thyrogen. Most patients received 2 intramuscular injections, 0.9 mg of thyrotropin alfa per injection, 24 hours apart.
The safety profile of patients who received Thyrogen as adjunctive treatment for radioiodine ablation of thyroid tissue remnants who have undergone a thyroidectomy for well differentiated thyroid cancer did not differ from that of patients who received Thyrogen for diagnostic purposes.
The most common adverse drug reactions (> 5%) reported in clinical trials were nausea (11.9%) and headache (7.3%). Drug reactions reported in ≥ 1% of patients in the combined trials are summarised in Table 1. In some studies, an individual patient may have participated in both the euthyroid phase (Thyrogen) and hypothyroid phase (withdrawal).
In addition, uncommon adverse reactions (≥ 0.1% and < 1%) reported in at least 2 patients in clinical trials included influenza, paraesthesia, feeling hot, ageusia, diarrhoea, dysgeusia, and neck pain. Thyrogen administration may cause transient (< 48 hours) influenza-like symptoms also called flu-like symptoms (FLS), which may include fever (> 38°C), chills/ shivering, myalgia/ arthralgia, fatigue/ asthenia/ malaise and headache (nonfocal) and chills.
Very rare manifestations of hypersensitivity to Thyrogen have been reported in both clinical, postmarketing settings and in special treatment groups with advanced disease: these are urticaria, rash, pruritus, flushing and respiratory signs and symptoms.
Enlargement of residual thyroid tissue or metastases can occur following treatment with Thyrogen. This may lead to acute symptoms which depend on the anatomical location of the tissue. For example, hemiplegia, hemiparesis and/or loss of vision have occurred in patients with CNS metastases. Laryngeal oedema, pain at the site of the metastasis and respiratory distress requiring tracheotomy have also been reported after Thyrogen administration. It is recommended that pretreatment with corticosteroids be considered for patients in whom local tumour expansion may compromise vital anatomic structures.
Mild hypersensitivity reactions consisting of urticaria, rash, pruritus, flushing and respiratory signs and symptoms have been reported in rare cases. However, in clinical trials, no patients have developed antibodies to thyrotropin alfa, either after single or repeated (27 patients) Thyrogen use.
Local oedema, focal haemorrhage or swallowing difficulty have been reported in thyroid cancer patients with metastatic disease in confined spaces such as the brain and spinal cord or disease infiltration of the neck. One case of acute visual loss was reported 24 hours after Thyrogen administration in a patient with metastases to the optic nerve. In addition, one case of laryngeal oedema requiring tracheotomy was reported 24 hours after Thyrogen administration in a patient with metastases to the paratracheal area. Pretreatment with corticosteroids may be considered under such circumstances.
One case of fatal myocardial infarction has been reported in a patient with residual thyroid tissue and a history of heart disease, who received Thyrogen (see Section 4.4 Special Warnings and Precautions for Use).

Postmarketing surveillance.

Reporting suspected adverse effects.

4.9 Overdose

There has been no reported experience of overdose in humans. However, in clinical trials, three patients experienced symptoms after receiving higher doses than those recommended. Two patients had nausea after a 2.7 mg IM dose, and in one of these patients, the event was accompanied by weakness, dizziness and headache. Another patient experienced nausea, vomiting and hot flushes after a 3.6 mg IM dose. In addition, one patient experienced symptoms after receiving Thyrogen intravenously. This patient received 0.3 mg Thyrogen as a single intravenous bolus and 15 minutes later, experienced severe nausea, vomiting, diaphoresis, hypotension (BP decreased from 115/66 mmHg to 81/44 mmHg) and tachycardia (pulse increased from 75 to 117 bpm).
For general advice on management of overdose, contact the Poisons Information Centre, telephone number 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Pituitary and Hypothalamic Hormones and Analogues, Anterior Pituitary Lobe Hormones and Analogues; ATC code: H01AB01.

Mechanism of action.

Clinical trials.

Thyrogen - stimulated Tg testing alone and in combination with diagnostic radioiodine imaging: comparison with results after thyroid hormone withdrawal.

Thyrogen - stimulated Tg testing alone and in combination with diagnostic radioiodine imaging in patients with confirmed metastatic disease.

Quality of life (diagnostic indication).

Hypothyroid signs and symptoms (diagnostic indication).

Quality of life (remnant ablation).

Hypothyroid signs and symptoms (remnant ablation).

5.2 Pharmacokinetic Properties

The pharmacokinetics of Thyrogen were studied in 16 patients with well differentiated thyroid cancer given a single 0.9 mg IM dose. Mean peak concentrations of 116 ± 38 mU/L were reached between 13 ± 8 hours after injection (median of 10 hours). The mean apparent elimination half-life was 22 ± 9 hours. The organ(s) of TSH clearance in man have not been identified, but studies of pituitary derived TSH suggest the involvement of the liver and kidneys (see Section 4.4 Special Warnings and Precautions for Use).

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

36 mg mannitol, 1.4 mg monobasic sodium phosphate monohydrate, 3.7 mg dibasic sodium phosphate heptahydrate, 2.4 mg sodium chloride.

6.2 Incompatibilities

Injection material should not be mixed with other substances.

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.
To reduce microbiological hazard, use as soon as practicable after reconstitution / preparation. If storage after reconstitution is necessary, hold at 2°-8°C for not more than 24 hours, and avoid microbial contamination.

6.4 Special Precautions for Storage

Thyrogen powder for injection should be stored at 2°-8°C. Refrigerate. Do not freeze.
Do not use Thyrogen after the expiry date on the vial. Protect from light.

6.5 Nature and Contents of Container

Thyrogen is supplied as a kit containing two 5 mL vials of thyrotropin alfa per kit. Each vial, after reconstitution with Sterile Water for Injection, (1.2 mL), contains thyrotropin alfa 0.9 mg/mL.
The closure of each 5 mL glass vial consists of a grey, 20 mm siliconised butyl rubber stopper with an aluminium seal and a plastic flip-off cap.
The vials contain no antimicrobial agent and should be used only once.

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

Thyrogen powder for injection contains a highly purified recombinant form of human thyroid stimulating hormone (TSH), a glycoprotein which is produced by recombinant DNA technology. Thyrotropin alfa is synthesised in a genetically modified Chinese hamster ovary cell line.
Thyrotropin alfa is a heterodimeric glycoprotein comprised of two noncovalently linked subunits; an alpha subunit of 92 amino acid residues containing two N-linked glycosylation sites and a beta subunit of 118 residues containing one N-linked glycosylation site. The amino acid sequence of thyrotropin alfa is identical to that of human pituitary thyroid stimulating hormone.
Both thyrotropin alfa and naturally occurring human pituitary thyroid stimulating hormone are synthesised as a mixture of glycosylation variants. Unlike pituitary TSH, which is secreted as a mixture of sialylated and sulphated forms, thyrotropin alfa is sialylated but not sulphated. The biological activity of thyrotropin alfa is determined by a cell based bioassay. In this assay, cells expressing a functional TSH receptor and a cAMP responsive element coupled to a heterologous reporter gene, luciferase, enable the measurement of rhTSH activity by measuring the luciferase response. The specific activity of thyrotropin alfa using the cell based bioassay is determined relative to an internal Genzyme reference standard that was calibrated against the World Health Organisation (WHO) human TSH reference standard.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes