Thyrotropin Alfa - A Comprehensive Review

Overview:

Thyrotropin alfa is a form of TSH or human thyroid-stimulating hormone used to diagnose thyroid cancer. A genetically altered Chinese hamster ovary cell is used to synthesize Thyrotropin alfa. Thyrotropin alfa is a heterodimeric glycoprotein composed of

• Two noncovalently linked subunits.

• An alpha subunit residue of 92 amino acids comprises two N-linked glycosylation sites.

• A beta subunit of 118 residues comprises one N-linked glycosylation site.

It is used with or without radioactive iodine imaging to diagnose the presence of thyroglobulin (Tg) in thyroid cancer patients.

The Thyrotropin Alfa, amino acid sequence, is the same as human pituitary TSH (thyroid stimulating hormone). Thyrotropin alfa and the human pituitary TSH comprise a formulation of glycosylation variants. Thyrotropin alfa is sialylated but not sulfated. However, the pituitary TSH (thyroid stimulating hormone) comprises sialylated and sulfated forms.

Indications:

• Adjunctive testing tool for serum thyroglobulin diagnosis in well-differentiated thyroid cancer.

• It can be used with or without radioiodine imaging for follow-up in patients diagnosed with well-differentiated thyroid cancer who have undergone thyroidectomy.

Limitations of Use:

• Stimulated serum thyroglobulin levels are generally low and cannot be correlated with serum thyroglobulin levels after thyroid hormone withdrawal.

• There is a risk of missed diagnosis of thyroid cancer even after combining radioiodine imaging with thyrotropin-stimulated testing.

For Patients

What Is the Use of Thyrotropin Alfa?

Thyrotropin alfa is a form of TSH, or human thyroid-stimulating hormone, used to diagnose thyroid cancer. Adjunctive testing tool for serum thyroglobulin diagnosis in well-differentiated thyroid cancer. It can also be used with or without radioiodine imaging for follow-up in patients with well-differentiated thyroid cancer who have undergone thyroidectomy.

What Is the Composition of Thyrotropin Alfa?

This product is available in the following dosage forms:

• Powder for a solution.

Each vial of Thyrotropin alfa contains

• 1.1 milligrams of Thyrotropin alfa.

• 36 milligrams of mannitol.

• 5.1 milligrams of sodium phosphate.

• 2.4 milligrams of sodium chloride.

• Recombinant human thyroid stimulating hormone (TSH).

How Is the Thyrotropin Alfa Administered for Diagnosis?

Patients are instructed to inject Thyrotropin alfa intramuscularly into the buttocks only. Thyrotropin alfa must not be administered intravenously. The treatment regimen includes two doses of Thyrotropin alfa administered every 24 hours. The patients are advised to consume liquids and remain hydrated before treatment with Thyrotropin Alfa is started.

How Are the Appointments Scheduled?

If diagnostic scanning is required, the patient must be informed that radioiodine has to be taken 24 hours after the second Thyrotropin Alfa injection. The patients must return for scanning after 48 hours of radioiodine administration. If serum thyroglobulin testing is required, the patient should be informed that blood will be drawn 72 hours or later after the second Thyrotropin Alfa injection. Inform patients that if remnant ablation (an effective method to eliminate residual thyroid tissue) has to be done, radioiodine will be administered 24 hours after the second Thyrotropin alfa infection.

What Is the Dosage Administered for the Diagnosis of Thyroid Cancer?

Thyrotropin alfa is a lyophilized powder that contains 1.1 milligrams of Thyrotropin alfa for a single use after mixing with sterile water for injection.

It is supplied as

• Two vial kits contain two vials of lyophilized Thyrotropin alfa.

• A four-vial kit that contains two vials of lyophilized Thyrotropin alfa.

• Two vials of 10 milliliters of sterile water for injection.

Precautions:

• Pregnancy: Thyrotropic alpha has not been subjected to pregnancy category C animal reproduction studies. It is still unknown whether Thyrotropin alfa can affect reproductive capacity or lead to fetal harm when given to a pregnant woman. Thyrotropin alfa should be administered to pregnant women only if necessary.

• Breastfeeding: It is uncertain whether the Thyrotropin alpha is excreted in human milk. Thyrotropin alfa must be cautiously administered to a nursing woman because many drugs are excreted in human milk.

• Pediatrics: The effectiveness and safety have not been established in pediatric patients.

• Geriatric: Data from controlled trials do not indicate any difference in the safety and efficacy of Thyrotropin alfa in patients less than or above 65 years.

• Renal Impairment: Prolonged elevation of TSH levels is observed in dialysis-dependent end-stage renal disease (ESRD) patients since Thyrotropin alfa elimination is significantly slower.

• Side Effects: The medicine may lead to some unwanted and desired effects. Usually, all the side effects are not observed in one patient. However, certain side effects might be observed, requiring immediate medical attention. Inform the healthcare professional if the following side effects are observed.

Common side effects include

• Frequent urge to urinate.

• Inability to move the arms or legs.

• Paralysis of one side of the body.

• Stomach discomfort.

Rare side effects include

• Faintness.

• The feeling of warmth.

• Burning, numbness, prickling, "pins and needles" feeling.

• Diarrhea.

• Lack or loss of strength.

• Stuffy or runny nose.

• Trouble sleeping.

• Unusual tiredness or weakness.

• Vomiting.

• Skin rash or hives.

• Itching, swelling, or redness at the injection site.

• Loss of vision.

• Redness of the face, arms, or neck.

• Tightness of the throat.

Some side effects might not require medical attention, which may resolve during treatment as the body adjusts to this medication. Further, the health care provider informs the patients about ways to reduce or prevent these side effects. A healthcare professional must be consulted if these side effects worsen or bother the patient.

What Should Be Done in the Case of an Overdose?

In the case of an overdose emergency, help must be sought immediately. The following symptoms are observed in the case of an overdose:

• Blurred vision.

• Chest pain.

• Dizziness, faintness, or lightheadedness on getting up suddenly from a sitting or lying position.

• Increased sweating.

• Fast or irregular heartbeat.

• Irritability.

• Nervousness.

• Nausea.

• Sweating.

Other Important Information:

• The effects of this medication may increase due to the slower removal of the medicine from the body.

• The patient must know the risks and benefits of this medication before administering it.

• A nurse or healthcare professional administers this medicine in a medical setting. It is administered as a shot into a muscle in the buttocks.

• The patient is advised to drink extra fluids before treatment with this medication is initiated.

• The patient must receive two doses of this medicine. After the second dose, the doctor might perform some essential tests.

• The doctor usually instructs the patient specifically before initiating the treatment. The patient must ask the doctor if these instructions are not given or understood.

For Doctors

Indications:

• Adjunctive testing tool for serum thyroglobulin diagnosis in well-differentiated thyroid cancer.

• It can be used with or without radioiodine imaging for follow-up in patients diagnosed with well-differentiated thyroid cancer who have undergone thyroidectomy.

Limitations of Use:

• Stimulated serum thyroglobulin levels are generally low and cannot be correlated with serum thyroglobulin levels after thyroid hormone withdrawal.

• There is a risk of a missed diagnosis of thyroid cancer even after combining radioiodine imaging with thyrotropin-stimulated testing.

What Are the Pharmacological Aspects of Thyrotropin Alpha?

Mechanism of Action:

Thyrotropin is a hormone secreted by the pituitary and stimulates the thyroid gland to produce thyroid hormone. The binding of thyrotropin alfa to TSH receptors on normal thyroid epithelial cells or issues of well-differentiated thyroid cancer stimulates iodine uptake, synthesis, and secretion of the following:

• Thyroglobulin (Tg).

• Triiodothyronine (T3).

• Thyroxine (T4).

Thyroglobulin is a tumor marker that is detected in blood samples. The thyroid-stimulating hormone (TSH) activates the thyroid cells to increase radioiodine uptake and allow the detection or killing of thyroid cells. TSH activation further leads to thyroglobulin release by thyroid cells.

Pharmacokinetics:

• Mean Peak Serum TSH Concentrations: 116 ± 38 mU/L achieved between 3 to 24 hours (median of 10 hours).

• The Mean Apparent Elimination Half-Life: 25 ± 10 hours.

• TSH Clearance: The organ responsible for men's clearance is unknown. However, pituitary-derived TSH studies suggest the involvement of the liver and kidneys.

What Are the Adverse Reactions?

The most common adverse effects of Thyrotropin Alfa include

• Nausea.

• Headache.

The patients must be advised to seek immediate medical attention if they experience severe symptoms.

What Are the Associated Warnings?

Thyrotropin Alfa-Induced Hyperthyroidism: The following patients are at higher risk of Thyrotropin alfa-induced hyperthyroidism:

• The elderly.

• Patients with a history of heart disease.

Thyrotropin alfa may lead to a temporary (7 to 14 days) but consequential rise in serum thyroid hormone concentration when administered to patients with functional thyroid cancer metastases. Deaths have been reported in non-thyroidectomized patients and distant metastatic thyroid cancer patients where death within 24 hours after administration of Thyrotropin alfa was documented. The patient must be observed after the administration of Thyrotropin alpha to avoid severe consequences.

Stroke: Post-marketing data suggest that neurological findings and radiologically-confirmed strokes were reported within 72 hours of administration of Thyrotropin alfa in patients without known central nervous system metastases. Most patients were young women taking oral contraceptives or having other stroke risk factors, like smoking or migraine headaches. However, the correlation between stroke and Thyrotropin Alfa is still unclear. Patients are advised to consume an adequate amount of liquid and to be properly hydrated before treatment with Thyrotropin Alfa is initiated.

Sudden Rapid Tumor Enlargement: Following treatment with Thyrotropin alpha, a sudden and painful enlargement of residual thyroid tissue or distant metastases can be seen. This may cause the following acute symptoms:

• Acute hemiplegia (paralysis affecting one side of the body).

• Hemiparesis (weakness or inability of one side of the body to function).

• Vision loss one to three days after the administration of Thyrotropin alfa.

Other adverse effects include

• Laryngeal edema.

• Pain at the site of distant metastasis.

• Respiratory distress.

Pretreatment with glucocorticoids should be considered in patients where tumor expansion can disrupt the surrounding vital structures.

Clinical Trials

In clinical trials, the observed adverse reaction rates cannot be compared directly to those in trials of another drug. They may not indicate the actual rates in practice because these clinical trials are carried out under various conditions.

A study including six clinical trials of thyrotropin alpha was conducted on 481 thyroid cancer patients, out of which four trials were for diagnostic use and two for ablation (procedure for atrial fibrillation treatment). In clinical trials, the mean age of patients was 46.1 years, and they had undergone a near-total thyroidectomy. In most patients, two intramuscular injections of 0.9 mg of Thyrotropin alfa were administered every 24 hours.

The diagnosis of thyroid cancer was as follows:

• Papillary (69.2 %).

• Papillary or follicular (15.6 %).

• Follicular (12.9 %).

• Hurthle cell (2.3 %).

Drug Interactions:

Certain medications must not be used together. In some cases, it might be necessary to use two medicines together, even if there are chances of interaction. In such cases, the doctor might change the dose or take other necessary precautions. The healthcare professional must be informed about any prescribed or nonprescribed (over-the-counter) medication.

Other Interactions:

Certain medicines are not to be administered at or around the time of eating or eaten with certain types of food since interactions might occur. The use of alcohol or tobacco with some medicines may also lead to interactions. The healthcare professional should know the medicine the patient takes with food, alcohol, or tobacco.

Other Medical Problems:

The administration of this medication may be affected by other medical problems.

The doctor must be informed if the following medical problems are present:

• Heart disease.

• Metastatic thyroid cancer (cancer that has already spread to different body parts).

• Migraine headaches.

• Nerve problems.

• Patients who did not undergo surgery to remove thyroid gland or residual thyroid tissue.

• Stroke.

• End-stage kidney disease.

• Patients undergoing dialysis.

Other Important Information

Before administering Thyrotropin Alfa, the patients must be counseled to seek help immediately for neurological symptoms seen after administering the drug.

Patients should be informed about

• Severe consequences of Thyrotropin alfa-induced hyperthyroidism.

• Hospitalization for the administration of Thyrotropin Alfa.

• Post-administrative observation.