Drugs List

Therapeutic Indications

Uses

Assessment of thyroid cancer in conjunction with radioiodine imaging
Increase radio-iodine uptake for ablation of thyroid remnant tissue

For use with serum thyroglobulin (Tg) testing, with or without radioiodine imaging, for the detection of thyroid remnants and well-differentiated thyroid cancer in post-thyroidectomy patients maintained on hormone suppression therapy (THST).

For pre-therapeutic stimulation (in combination with radioiodine) for ablation of thyroid tissue remnants in patients who have undergone a thyroidectomy for well-differentiated thyroid cancer, who have been confirmed negative for distant metastatic thyroid cancer.

Low risk patients with well-differentiated thyroid cancer who have undetectable serum Tg levels on THST and no recombinant human (rh) TSH-stimulated increase of Tg levels may be followed-up by assaying rhTSH-stimulated Tg levels.

Administration

For intramuscular injection into the buttock.

Contraindications

Children under 18 years
Breastfeeding
Pregnancy

Precautions and Warnings

Central nervous system metastasis
End stage renal disease
Spinal metastasis

Advise ability to drive/operate machinery may be affected by side effects
Consider pre-test corticosteroids in patients with spinal/CNS metastases
May produce false negative test
Treatment to be initiated and supervised by a specialist

When used as an alternative to thyroid hormone withdrawal, the combination of whole body scanning and thyroglobulin testing after thyrotropin alfa administration assures the highest sensitivity for detection of thyroid remnants or cancer. If a high suspicion for metastatic disease persists, a confirmatory withdrawal whole body scanning and Tg testing should be considered.

False-negative serum thyroglobulin measurements may be caused by the presence of Tg autoantibodies (expected in 18 to 40% of patients with differentiated thyroid cancer). Therefore, the use of both Tg antibody and Tg assays is advisable.

Before administering thyrotropin alfa, careful evaluation of the benefit risk ratio should be assessed in high risk elderly patients who have heart disease (e.g. valvular heart disease, cardiomyopathy, coronary artery disease and prior or current tachyarrhythmia including atrial fibrillation) and have not undergone a thyroidectomy.

Thyrotropin alfa is known to cause a transient, but significant rise in serum thyroid hormone concentration when given to patients who still have substantial thyroid tissue in situ. Therefore, careful evaluation of individual benefit risk ratio is required for patients with significant residual thyroid tissue.

In patients with thyroid cancer, several cases of stimulated tumour growth have been reported during withdrawal of thyroid hormones for diagnostic procedures due to the subsequent prolonged elevation of thyroid stimulating hormone (TSH) levels. It is therefore theoretically possible that thyrotropin alfa may lead to stimulated tumour growth. However, in clinical trials with thyrotropin alfa, which produces a short-term increase in serum TSH levels, no case of tumour growth has been reported.

Due to elevation of TSH levels after thyrotropin alfa administration, patients with metastatic thyroid cancer in confined spaces such as the brain, spinal cord and orbit or disease infiltrating the neck, may experience local oedema or focal haemorrhage at the site of these metastases which may result in increased tumour size. This could lead to acute symptoms (depending on the anatomical location of the tissue) e.g. hemiplegia, hemiparesis, loss of vision. It is recommended that pre-treatment corticosteroids are considered for patients in whom local tumour expansion may compromise vital anatomic structures.

Pregnancy and Lactation

Pregnancy

The use of thyrotropin alfa is contraindicated during pregnancy.

Animal studies on thyrotropin alfa have not been carried out and it is not known whether it causes foetal harm when administered during pregnancy or whether it can affect reproductive capacity. Thyrotropin does not cross the placenta and there is no correlation between maternal and foetal concentrations of thyrotropin at any time during gestation (Briggs, 2015).

However thyrotropin alfa, when used in combination with diagnostic radioactive Iodine-131 whole body scintigraphy, is contraindicated during pregnancy due to the consequent exposure of the foetus to a high dose of radioactive material.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Thyrotropin alfa is contraindicated during breastfeeding.

Thyrotropin is known to be excreted into breast milk, but in low levels. Hale (2014) suggests that due to thyrotropin being significantly elevated in hypothyroid mothers, if present in milk at high levels, it could theoretically cause hyperthyroid conditions in the breastfed infant.

Thyrotropin alfa is most commonly used with radioactive Iodine-131, which is contraindicated in breastfeeding women. If thyrotropin alfa is being used with radioactive I131, be sure to stop breastfeeding completely (Hale, 2014).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Arthralgia
Asthenia
Atrial fibrillation
Back pain
Chills
Decreased TSH
Diarrhoea
Dizziness
Dyspnoea
Fatigue
Feeling hot
Flushing
Headache
Hemiplegia
Hyperhidrosis
Hypersensitivity reactions
Hyperthyroidism
Influenza
Influenza-like symptoms
Injection site reactions
Local pain (intramuscular injection site)
Loss of vision
Metastatic pain
Myalgia
Nausea
Neck pain
Neoplasm swelling
Pain
Palpitations
Paraesthesia
Pruritus
Pyrexia
Rash
Rash at injection site
Respiratory disorders
Stroke
Taste disturbances
Tremor
Urticaria
Vomiting

Presentation

Powder for solution for injection containing thyrotropin alfa

Drugs List

Therapeutic Indications

Uses

Assessment of thyroid cancer in conjunction with radioiodine imaging
Increase radio-iodine uptake for ablation of thyroid remnant tissue

For use with serum thyroglobulin (Tg) testing, with or without radioiodine imaging, for the detection of thyroid remnants and well-differentiated thyroid cancer in post-thyroidectomy patients maintained on hormone suppression therapy (THST).

For pre-therapeutic stimulation (in combination with radioiodine) for ablation of thyroid tissue remnants in patients who have undergone a thyroidectomy for well-differentiated thyroid cancer, who have been confirmed negative for distant metastatic thyroid cancer.

Low risk patients with well-differentiated thyroid cancer who have undetectable serum Tg levels on THST and no recombinant human (rh) TSH-stimulated increase of Tg levels may be followed-up by assaying rhTSH-stimulated Tg levels.

Dosage

Adults

Elderly

Patients with Renal Impairment

Administration

For intramuscular injection into the buttock.

Contraindications

Children under 18 years
Breastfeeding
Pregnancy

Precautions and Warnings

Central nervous system metastasis
End stage renal disease
Spinal metastasis

Advise ability to drive/operate machinery may be affected by side effects
Consider pre-test corticosteroids in patients with spinal/CNS metastases
May produce false negative test
Treatment to be initiated and supervised by a specialist

When used as an alternative to thyroid hormone withdrawal, the combination of whole body scanning and thyroglobulin testing after thyrotropin alfa administration assures the highest sensitivity for detection of thyroid remnants or cancer. If a high suspicion for metastatic disease persists, a confirmatory withdrawal whole body scanning and Tg testing should be considered.

False-negative serum thyroglobulin measurements may be caused by the presence of Tg autoantibodies (expected in 18 to 40% of patients with differentiated thyroid cancer). Therefore, the use of both Tg antibody and Tg assays is advisable.

Before administering thyrotropin alfa, careful evaluation of the benefit risk ratio should be assessed in high risk elderly patients who have heart disease (e.g. valvular heart disease, cardiomyopathy, coronary artery disease and prior or current tachyarrhythmia including atrial fibrillation) and have not undergone a thyroidectomy.

Thyrotropin alfa is known to cause a transient, but significant rise in serum thyroid hormone concentration when given to patients who still have substantial thyroid tissue in situ. Therefore, careful evaluation of individual benefit risk ratio is required for patients with significant residual thyroid tissue.

In patients with thyroid cancer, several cases of stimulated tumour growth have been reported during withdrawal of thyroid hormones for diagnostic procedures due to the subsequent prolonged elevation of thyroid stimulating hormone (TSH) levels. It is therefore theoretically possible that thyrotropin alfa may lead to stimulated tumour growth. However, in clinical trials with thyrotropin alfa, which produces a short-term increase in serum TSH levels, no case of tumour growth has been reported.

Due to elevation of TSH levels after thyrotropin alfa administration, patients with metastatic thyroid cancer in confined spaces such as the brain, spinal cord and orbit or disease infiltrating the neck, may experience local oedema or focal haemorrhage at the site of these metastases which may result in increased tumour size. This could lead to acute symptoms (depending on the anatomical location of the tissue) e.g. hemiplegia, hemiparesis, loss of vision. It is recommended that pre-treatment corticosteroids are considered for patients in whom local tumour expansion may compromise vital anatomic structures.

Pregnancy and Lactation

Pregnancy

The use of thyrotropin alfa is contraindicated during pregnancy.

Animal studies on thyrotropin alfa have not been carried out and it is not known whether it causes foetal harm when administered during pregnancy or whether it can affect reproductive capacity. Thyrotropin does not cross the placenta and there is no correlation between maternal and foetal concentrations of thyrotropin at any time during gestation (Briggs, 2015).

However thyrotropin alfa, when used in combination with diagnostic radioactive Iodine-131 whole body scintigraphy, is contraindicated during pregnancy due to the consequent exposure of the foetus to a high dose of radioactive material.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Thyrotropin alfa is contraindicated during breastfeeding.

Thyrotropin is known to be excreted into breast milk, but in low levels. Hale (2014) suggests that due to thyrotropin being significantly elevated in hypothyroid mothers, if present in milk at high levels, it could theoretically cause hyperthyroid conditions in the breastfed infant.

Thyrotropin alfa is most commonly used with radioactive Iodine-131, which is contraindicated in breastfeeding women. If thyrotropin alfa is being used with radioactive I131, be sure to stop breastfeeding completely (Hale, 2014).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Arthralgia
Asthenia
Atrial fibrillation
Back pain
Chills
Decreased TSH
Diarrhoea
Dizziness
Dyspnoea
Fatigue
Feeling hot
Flushing
Headache
Hemiplegia
Hyperhidrosis
Hypersensitivity reactions
Hyperthyroidism
Influenza
Influenza-like symptoms
Injection site reactions
Local pain (intramuscular injection site)
Loss of vision
Metastatic pain
Myalgia
Nausea
Neck pain
Neoplasm swelling
Pain
Palpitations
Paraesthesia
Pruritus
Pyrexia
Rash
Rash at injection site
Respiratory disorders
Stroke
Taste disturbances
Tremor
Urticaria
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: January 2017

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Joint Formulary Committee. British National Formulary. 72nd ed. London: BMJ Group and Pharmaceutical Press; 2016.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Thyrogen 0.9 mg powder for solution for injection. Genzyme Therapeutics. Revised May 2016.