Thyrotropin Alfa (Monograph)

Brand name: Thyrogen
Drug class: Thyroid Function
Chemical name: human thyroid stimulating hormone (recombinant) (rhTSH)
Molecular formula: C₁₀₃₉H₁₆₀₂N₂₇₄O₃₀₇S₂₇ • C₄₃₇H₆₈₂N₁₂₂O₁₃₄S₁₃ • C₆₀₂H₉₂₀N₁₅₂O₁₇₃S₁₄
CAS number: 194100-83-9

Introduction

Thyrotropin alfa is a diagnostic agent used for assessment of thyroid function.

Uses for Thyrotropin Alfa

Thyrotropin alfa has the following uses:

Thyrotropin alfa is a thyroid stimulating hormone indicated for use as an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer who have previously undergone thyroidectomy.

Thyrotropin alfa also is indicated for use as an adjunctive treatment for radioiodine ablation of thyroid tissue remnants in patients who have undergone a near-total or total thyroidectomy for well-differentiated thyroid cancer and who do not have evidence of distant metastatic thyroid cancer.

Thyrotropin alfa has the following limitations of use:

Thyrotropin alfa-stimulated Tg levels are generally lower than, and do not correlate with Tg levels after thyroid hormone withdrawal.

Even when thyrotropin alfa-Tg testing is performed in combination with radioiodine imaging, there remains a risk of missing a diagnosis of thyroid cancer or underestimating the extent of the disease.

Anti-Tg Antibodies may confound the Tg assay and render Tg levels uninterpretable.

The effect of thyrotropin alfa on long term thyroid cancer outcomes has not been determined.

Thyrotropin Alfa Dosage and Administration

General

Thyrotropin alfa is available in the following dosage form(s) and strength(s):

Lyophilized powder containing 1.1 mg of thyrotropin alfa for single use after reconstitution with Sterile Water for Injection.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Thyrotropin alfa should be used by physicians knowledgeable in the management of patients with thyroid cancer.

• A two-injection regimen is recommended: thyrotropin alfa 0.9 mg is administered intramuscularly, followed by a second 0.9 mg intramuscular injection 24 hours later.

• Pretreatment with glucocorticoids should be considered for patients in whom tumor expansion may compromise vital anatomic structures.

• Oral radioiodine should be given 24 hours after the second injection of thyrotropin alfa in both remnant ablation and diagnostic scanning. The activity of ¹³¹I is carefully selected at the discretion of the nuclear medicine physician.

• Diagnostic scanning should be performed 48 hours after the radioiodine administration.

• For serum thyroglobulin testing, the serum sample should be obtained 72 hours after the final injection of thyrotropin alfa.

Related/similar drugs

glucagon, doxorubicin, Armour Thyroid, mannitol, NP Thyroid, Lexiscan, cabozantinib

Cautions for Thyrotropin Alfa

Contraindications

None.

Warnings/Precautions

Thyrotropin Alfa-induced Hyperthyroidism

When given to patients who have substantial thyroid tissue still in situ or functional thyroid cancer metastases, thyrotropin alfa is known to cause a transient (over 7 to 14 days) but significant rise in serum thyroid hormone concentration. There have been reports of death in non-thyroidectomized patients and in patients with distant metastatic thyroid cancer in which events leading to death occurred within 24 hours after administration of thyrotropin alfa. Patients with residual thyroid tissue at risk for thyrotropin alfa-induced hyperthyroidism include the elderly and those with a known history of heart disease. Hospitalization for administration of thyrotropin alfa and post-administration observation in patients at risk should be considered.

Stroke

There are postmarketing reports of radiologically-confirmed stroke and neurological findings suggestive of stroke unconfirmed radiologically (e.g., unilateral weakness) occurring within 72 hours (range 20 minutes to three days) of thyrotropin alfa administration in patients without known central nervous system metastases. The majority of such patients were young women taking oral contraceptives at the time of their event or had other risk factors for stroke, such as smoking or a history of migraine headaches. The relationship between thyrotropin alfa administration and stroke is unknown. Patients should be well-hydrated prior to treatment with thyrotropin alfa.

Sudden Rapid Tumor Enlargement

Sudden, rapid and painful enlargement of residual thyroid tissue or distant metastases can occur following treatment with thyrotropin alfa. This may lead to acute symptoms, which depend on the anatomical location of the tissue. Such symptoms include acute hemiplegia, hemiparesis, and loss of vision one to three days after thyrotropin alfa administration. Laryngeal edema, pain at the site of distant metastasis, and respiratory distress requiring tracheotomy have also been reported after thyrotropin alfa administration.

Pretreatment with glucocorticoids should be considered for patients in whom tumor expansion may compromise vital anatomic structures.

Specific Populations

Pregnancy

Pregnancy Category C.

Animal reproduction studies have not been conducted with thyrotropin alfa.

It is also not known whether thyrotropin alfa can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Thyrotropin alfa should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when thyrotropin alfa is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

In pooled clinical studies of thyrotropin alfa, 60 patients (12%) were >65 years, and 421 (88%) were ≤ 65 years of age. Results from controlled trials do not indicate a difference in the safety and efficacy of thyrotropin alfa between adult patients less than 65 years and those over 65 years of age.

Renal Impairment

Elimination of thyrotropin alfa is significantly slower in dialysis-dependent end stage renal disease (ESRD) patients, resulting in prolonged elevation of TSH levels.

Common Adverse Effects

The most common adverse reactions reported in clinical trials were nausea and headache.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Thyrotropin (TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroid hormone. Binding of thyrotropin alfa to TSH receptors on normal thyroid epithelial cells or on well-differentiated thyroid cancer tissue stimulates iodine uptake and organification, and synthesis and secretion of thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4).

The effect of thyroid stimulating hormone activation of thyroid cells is to increase uptake of radioiodine to allow scan detection or radioiodine killing of thyroid cells. TSH activation also leads to the release of thyroglobulin by thyroid cells. Thyroglobulin functions as a tumor marker which is detected in blood specimens.

Advice to Patients

Adverse Reactions

Inform patients that the most common adverse events from clinical experience were nausea and headache.

Advise patients to seek immediate medical attention should they experience severe symptoms.

Important Information

Prior to thyrotropin alfa administration, counsel patients to seek care immediately for any neurologic symptoms occurring after administration of the drug.

Inform patients for whom thyrotropin alfa induced hyperthyroidism could have serious consequences, hospitalization for administration of thyrotropin alfa and post-administrative observation should be considered.

Dosing and Administration

Patients should be instructed that thyrotropin alfa is for intramuscular administration into the buttock only. Thyrotropin alfa should not be administered intravenously.

Inform patients the treatment regimen is two doses of thyrotropin alfa administered at a 24 hour interval.

Encourage patients to remain hydrated prior to treatment with thyrotropin alfa.

Schedule of Procedures

Inform patients that if diagnostic scanning will be performed, radioiodine will be given 24 hours after the second injection of thyrotropin alfa, and patients should return for the scan 48 hours after radioiodine administration.

Inform patients that if serum Tg testing is performed, blood will be drawn 72 hours or later after the second injection of thyrotropin alfa.

Inform patients that if remnant ablation is performed radioiodine will be administered 24 hours after the second injection of thyrotropin alfa.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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