Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intramuscular:
Thyrogen: 1.1 mg (1 ea)
Pharmacology
Mechanism of Action
Thyrotropin alfa, derived from a recombinant DNA source, has the identical amino acid sequence as endogenous human thyroid stimulating hormone (TSH). As a diagnostic tool in conjunction with serum thyroglobulin (Tg) testing, thyrotropin alfa stimulates the secretion of Tg from any remaining thyroid tissues (remnants). Under conditions of successful thyroidectomy and complete ablation, very little serum Tg should be detected under TSH stimulatory conditions; conversely, elevated Tg levels suggest the presence of remnant thyroid tissues. Since the source of TSH is exogenous, stimulation of Tg synthesis can be achieved in euthyroid patients, avoiding the need for thyroid hormone withdrawal.
As an adjunctive agent for radioiodine ablation treatment of thyroid cancer tissue remnants, thyrotropin alfa binds to TSH receptors on these tissues, stimulating the uptake and organification of iodine, including radiolabeled iodine (I131). Cancerous tissue is destroyed via gamma emission from the radioiodine concentrated in these tissues.
Pharmacokinetics/Pharmacodynamics
Time to Peak
Median: 10 hours (range: 3 to 24 hours)
Half-Life Elimination
25 ± 10 hours
Use: Labeled Indications
Diagnostic imaging: Adjunctive diagnostic tool for serum thyroglobulin (Tg) testing (with or without radioiodine imaging) in follow-up of patients with well-differentiated thyroid cancer (DTC) who have previously undergone thyroidectomy.
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-stimulated Tg testing is performed in combination with radioiodine imaging, there is a risk of missing a thyroid cancer diagnosis or of underestimating disease extent. Anti-Tg antibodies may confound Tg assay and render Tg levels uninterpretable; in such cases, even with a negative or low-stage thyrotropin alfa radioiodine scan, consider further patient evaluation.
Thyroid tissue remnant ablation: Adjunctive treatment for radioiodine ablation of thyroid tissue remnants after total or near-total thyroidectomy in patients with well-differentiated thyroid cancer without evidence of metastatic disease.
Limitations of use: The effect of thyrotropin alfa on long-term thyroid cancer outcomes has not been determined. Due to relatively small clinical experience, it is not possible to conclude if long-term thyroid cancer outcomes would be equivalent after thyrotropin alfa use or withholding thyroid hormone for TSH elevation prior to remnant ablation.
Guideline recommendations: The American Thyroid Association guidelines recommend thyrotropin alfa as a reasonable alternative to thyroid hormone withdrawal prior to remnant ablation or adjuvant therapy in patients with low- or intermediate-risk DTC without extensive lymph node involvement. Thyrotropin alfa may also be considered in intermediate-risk DTC with extensive lymph node disease (but without distance metastases), though the evidence is of lower quality (ATA [Haugen 2015]).
Contraindications
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to thyrotropin alfa or any component of the formulation.
Dosage and Administration
Dosing: Adult
Note: Consider pretreatment with glucocorticoids for patients in whom local tumor expansion may compromise vital anatomic structures.
Diagnostic imaging: IM: 0.9 mg, followed 24 hours later by a second 0.9 mg dose; obtain serum Tg sample 72 hours after the second thyrotropin alfa injection.
Thyroid tissue remnant ablation: IM: 0.9 mg, followed 24 hours later by a second 0.9 mg dose.
Oral radioiodine should be administered 24 hours following the second thyrotropin alfa injection (for diagnostic scanning and remnant ablation). Perform diagnostic scanning 48 hours after radioiodine administration (72 hours after the second thyrotropin alfa injection).
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
Reconstitute each vial with 1.2 mL of sterile water for injection to a concentration of 0.9 mg/mL. Gently swirl vial until dissolved; do not shake. Reconstituted solution should be clear and colorless; do not use if cloudy or discolored.
Administration
IM: Administer only by IM injection into the buttock. Do not administer IV.
Storage
Store intact vials at 2°C to 8°C (36°F to 46°F). Protect from light. May store reconstituted solution for up to 24 hours between 2°C and 8°C (36°F and 46°F); avoid microbial contamination. If reconstituted solution is not refrigerated, use within 3 hours.
Drug Interactions
There are no known significant interactions.
Test Interactions
Thyroglobulin assay may be confounded by thyroglobulin antibodies, possibly leading to misinterpreted or difficult to interpret thyroglobulin levels. Routine measurement of TSH levels after thyrotropin alfa use is not recommended.
Adverse Reactions
>10%: Gastrointestinal: Nausea (11%)
1% to 10%:
Central nervous system: Headache (6%), dizziness (2%), fatigue (2%)
Gastrointestinal: Vomiting (2%)
Neuromuscular & skeletal: Weakness (1%)
Frequency not defined: Endocrine & metabolic: Altered thyroid hormone levels (increased)
<1%, postmarketing, and/or case reports: Cerebrovascular accident (with and without physiologic symptoms like unilateral weakness), flu-like symptoms (transient; including arthralgia, chills, fever, malaise, myalgia, shivering), hypersensitivity reaction (including dyspnea, flushing, pruritus, skin rash, urticaria), injection site reaction (including bruising, erythema, pain, and pruritus)
Warnings/Precautions
Concerns related to adverse effects:
- Hyperthyroidism: Thyrotropin alfa use may cause a transient (over 7 to 14 days) and significant rise in serum thyroid hormone concentration in patients with substantial in situ thyroid tissue or with functional thyroid cancer metastases. Thyrotropin alfa-induced hyperthyroidism may result in serious complications in patients with certain risk factors (heart disease, advanced age, extensive metastatic disease, or with underlying serious illness); consider hospitalization for administration and subsequent observation. Deaths within 24 hours of thyrotropin alfa administration have been reported.
- Stroke: Postmarketing reports of stroke or symptoms suggestive of stroke (eg, unilateral weakness) have occurred within 3 days (range: 20 minutes to 3 days) of thyrotropin alfa administration in patients without known CNS metastases. The majority of these patients had risk factors for stroke (eg, smokers, history of migraine) or were young females taking oral contraceptives. Patients should be well hydrated prior to thyrotropin alfa administration.
- Tumor growth: Sudden, rapid, and painful growth of residual thyroid tissue or distant metastases may occur following thyrotropin alfa administration. Symptoms are associated with tissue location and include acute hemiplegia, hemiparesis, and vision loss 1 to 3 days after administration. Laryngeal edema, pain at site of distant metastases, and respiratory distress requiring tracheotomy have also been reported. Consider glucocorticoid premedication in patients where local tumor enlargement may compromise vital structures.
Disease-related concerns:
- Cardiovascular disease: Patients with known history of heart disease in the presence of significant residual thyroid tissue are at increased risk for thyrotropin alfa-induced hyperthyroidism.
- Renal impairment: Thyrotropin alfa elimination is significantly reduced in dialysis-dependent end-stage renal disease, leading to prolonged elevation of TSH levels.
Special populations:
- Elderly: Elderly patients with residual thyroid tissue are at increased risk for thyrotropin alfa-induced hyperthyroidism.
Monitoring Parameters
Monitor for neurologic adverse events (hemiplegia, hemiparesis, stroke, weakness); dyspnea, dysphonia, stridor or other symptoms of local tumor growth, signs/symptoms of hyperthyroidism
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal reproduction studies have not been conducted. Effects on the fetus or pregnant female are unknown.
Patient Education
What is this drug used for?
- It is used to treat thyroid cancer.
- It is used to check thyroglobulin levels.
Frequently reported side effects of this drug
- Nausea
- Headache
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
