Thyrotropin Alfa

FDA Drug Information • Also known as: Thyrogen

Brand Names: Thyrogen
Dosage Form: INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Product Type: DRUG FOR FURTHER PROCESSING

Description

11 DESCRIPTION Thyrotropin alfa, a recombinant human thyroid stimulating hormone, is a heterodimeric glycoprotein comprised of two non-covalently 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 TSH. Thyrotropin alfa is synthesized in a genetically modified Chinese hamster ovary cell line. Both thyrotropin alfa and naturally occurring human pituitary TSH are synthesized as a mixture of glycosylation variants. Unlike pituitary TSH, which is secreted as a mixture of sialylated and sulfated forms, thyrotropin alfa is sialylated but not sulfated. 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 thyrotropin alfa activity by measuring the luciferase response. The specific activity of thyrotropin alfa is determined relative to an internal Genzyme reference standard that was calibrated against the World Health Organization (WHO) human TSH reference standard. THYROGEN (thyrotropin alfa) for injection is a sterile, white to off-white lyophilized powder in a single-dose vial for intramuscular use after reconstitution . Each single-dose vial provides 0.9 mg of thyrotropin alfa, and contains mannitol (36 mg); sodium chloride (2.4 mg);sodium phosphate dibasic, heptahydrate (3.7 mg); and sodium phosphate monobasic, monohydrate (1.4 mg). After reconstitution with 1.2 mL of Sterile Water for Injection, USP, the concentration is 0.9 mg/mL with a deliverable volume of 1 mL (0.9 mg) and a pH of approximately 6.5 to 7.5.

What Is Thyrotropin Alfa Used For?

1 INDICATIONS AND USAGE THYROGEN ® is a thyroid stimulating hormone indicated for: Adjunctive Diagnostic Tool for Well-Differentiated Thyroid Cancer: 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. ( 1.1 ) Limitations of Use : THYROGEN-stimulated Tg levels are generally lower than, and do not correlate with Tg levels after thyroid hormone withdrawal. Even when THYROGEN-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. Adjunct for Thyroid Remnant Ablation in Well-Differentiated Thyroid Cancer: 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. ( 1.2 ) Limitations of Use : The effect of THYROGEN on thyroid cancer recurrence greater than 5 years post-remnant ablation has not been evaluated. 1.1 Adjunctive Diagnostic Tool for Well-Differentiated Thyroid Cancer THYROGEN ® is 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. Limitations of Use : THYROGEN-stimulated Tg levels are generally lower than, and do not correlate with, Tg levels after thyroid hormone withdrawal [see Clinical Studies (14.1) ] . Even when THYROGEN-stimulated Tg testing is performed in combination with radioiodine imaging, there remains a risk of missing a diagnosis of thyroid cancer or of underestimating the extent of disease. Anti-Tg antibodies may confound the Tg assay and render Tg levels uninterpretable [see Clinical Studies (14.1) ] . Therefore, in such cases, even with a negative or low-stage THYROGEN radioiodine scan, consideration should be given to further evaluating patients. 1.2 Adjunct for Thyroid Remnant Ablation in Well-Differentiated Thyroid Cancer THYROGEN 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. Limitations of Use : The effect of THYROGEN on thyroid cancer recurrence greater than five years post-remnant ablation has not been evaluated [see Clinical Studies (14.2) ] .

Dosage and Administration

2 DOSAGE AND ADMINISTRATION THYROGEN should be used by physicians knowledgeable in the management of patients with thyroid cancer. ( 2.1 ) A two-injection regimen is recommended: THYROGEN 0.9 mg is administered intramuscularly, followed by a second 0.9 mg intramuscular injection 24 hours later. ( 2.1 ) 2.1 Recommended Dosage THYROGEN should be used by physicians knowledgeable in the management of patients with thyroid cancer. THYROGEN is indicated as a two-injection regimen. The recommended dosage of THYROGEN is a 0.9 mg intramuscular injection to the buttock followed by a second 0.9 mg intramuscular injection to the buttock 24 hours later. THYROGEN should be administered intramuscularly only. THYROGEN should not be administered intravenously. Pretreatment with glucocorticoids should be considered for patients in whom tumor expansion may compromise vital anatomic structures [see Warnings and Precautions (5.3) ] . Routine measurement of serum TSH levels is not recommended after THYROGEN use. 2.2 Reconstitution, Preparation, and Administration of THYROGEN The supplied lyophilized powder must be reconstituted with Sterile Water for Injection, USP. THYROGEN should be prepared, and administered in the following manner: Reconstitute each 0.9 mg vial of THYROGEN with 1.2 mL of Sterile Water for Injection, USP to yield a single-dose solution containing 0.9 mg/mL of thyrotropin alfa that delivers 1 mL (0.9 mg). Gently swirl the contents of the vial until all the material is dissolved. Do not shake the solution. Visually inspect the reconstituted solution for particulate matter and discoloration prior to administration. The reconstituted THYROGEN solution should be clear and colorless. Do not use if the solution has particulate matter or is cloudy or discolored. Withdraw 1 mL of the reconstituted THYROGEN solution (0.9 mg of thyrotropin alfa) and inject intramuscularly in the buttocks. Discard any unused portions. The reconstituted THYROGEN solution must be injected within 3 hours unless refrigerated. If necessary, the reconstituted solution can be stored refrigerated at a temperature between 2°C and 8°C (36°F to 46°F) for up to 24 hours, while avoiding microbial contamination. Do not mix with other substances. 2.3 Timing of Serum Thyroglobulin Testing Following THYROGEN Administration For serum thyroglobulin testing, the serum sample should be obtained 72 hours after the final injection of THYROGEN [see Clinical Studies (14.1) ] . 2.4 Timing for Remnant Ablation and Diagnostic Scanning Following THYROGEN Administration Oral radioiodine should be given 24 hours after the second injection of THYROGEN in both remnant ablation and diagnostic scanning. The activity of 131 I is carefully selected at the discretion of the nuclear medicine physician. Diagnostic scanning should be performed 48 hours after the radioiodine administration.

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The most common adverse reactions (>5%) reported in clinical trials were nausea and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at 800-745-4447 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to THYROGEN in 481 thyroid cancer patients who participated in a total of 6 clinical trials of THYROGEN: 4 trials for diagnostic use and 2 trials for ablation. In clinical trials, patients had undergone near-total thyroidectomy and had a mean age of 46.1 years. Thyroid cancer diagnosis was as follows: papillary (69.2%), follicular (12.9%), Hurthle cell (2.3%) and papillary/follicular (15.6%). Most patients received 2 intramuscular injections of 0.9 mg of THYROGEN injection gin 24 hours apart [see Clinical Studies (14.1 , 14.2) ] . The safety profile of patients who have undergone thyroidectomy and received THYROGEN as adjunctive treatment for radioiodine ablation of thyroid tissue remnants for well-differentiated thyroid cancer did not differ from that of patients who received THYROGEN for diagnostic purposes. Reactions reported in ≥1% of patients in the combined trials are summarized in Table 1. In some studies, an individual patient may have participated in both THYROGEN and thyroid hormone withdrawal [see Clinical Studies (14.1 , 14.2) ] . Table 1: Summary of Adverse Reactions by THYROGEN and Thyroid Hormone Withdrawal in Pooled Clinical Trials (≥1% of Patients in any Phase) THYROGEN Thyroid Hormone Withdrawal (N=481) (N=418) Preferred Term n (%) n (%) Nausea 53 (11) 2 (<1) Headache 29 (6) 0 Fatigue 11 (2) 2 (<1) Vomiting 11 (2) 0 Dizziness 9 (2) 0 (0.0) Asthenia 5 (1) 1 (<1) 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of THYROGEN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Transient (<48 hours) influenza-like symptoms, including fever (>100°F/38°C), chills/shivering, myalgia/arthralgia, fatigue/asthenia/malaise, headache, and chills. Hypersensitivity including urticaria, rash, pruritus, flushing, and respiratory signs and symptoms. Injection site reactions, including pain, erythema, bruising, and pruritus.

Contraindications

4 CONTRAINDICATIONS If THYROGEN is administered with radioiodine, the contraindications to radioiodine also apply to this combination regimen. Refer to the radioiodine prescribing information for a list of contraindications for radioiodine. If THYROGEN is administered with radioiodine, the contraindications to radioiodine also apply to this combination regimen. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary THYROGEN may be used in combination with radioiodine (RAI). If THYROGEN is administered with RAI, the combination regimen is contraindicated in pregnant women because fetal exposure to RAI can lead to neonatal hypothyroidism, which in some cases is severe and irreversible. Refer to the RAI prescribing information for more information on use during pregnancy. Available data from case reports and postmarketing experience with THYROGEN use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with THYROGEN. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Overdosage

10 OVERDOSAGE In clinical trials of THYROGEN, three patients experienced symptoms after receiving THYROGEN doses higher than those recommended. Two patients had nausea after a 2.7 mg IM dose (3 times the recommended dose), and in one of these patients, the event was accompanied by weakness, dizziness and headache. Another patient experienced nausea, vomiting and hot flashes after a 3.6 mg IM dose (4 times the recommended dose). There is no specific therapy for THYROGEN overdose. Supportive care is recommended.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING THYROGEN (thyrotropin alfa) for injection is as a sterile white to off-white lyophilized powder in a single-dose vial. Each carton (NDC 58468-0030-2) contains two 0.9 mg single-dose vials of THYROGEN (NDC 58468-0030-1). Store THYROGEN refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.