Caprelsa (Vandetanib)

What Is Caprelsa and What Is It Used For?

Quick Answer: Caprelsa (vandetanib) is a targeted cancer medication that treats medullary thyroid cancer with RET mutations. It works by blocking the formation of new blood vessels in tumors and directly inhibiting cancer cell growth through multiple tyrosine kinase pathways.

Caprelsa contains the active substance vandetanib, which belongs to a class of medications called tyrosine kinase inhibitors (TKIs). It was developed specifically to target the molecular abnormalities that drive medullary thyroid cancer (MTC), a relatively rare form of thyroid malignancy that arises from the parafollicular C cells of the thyroid gland. MTC accounts for approximately 3–5% of all thyroid cancers and can occur in both hereditary and sporadic forms.

Vandetanib exerts its therapeutic effect through a multi-targeted mechanism of action. It selectively inhibits several key receptor tyrosine kinases that play critical roles in tumor biology. The primary targets include RET (Rearranged during Transfection), a proto-oncogene whose activating mutations are present in virtually all hereditary MTC cases and approximately 40–65% of sporadic MTC cases. Additionally, vandetanib inhibits vascular endothelial growth factor receptors (VEGFR-2 and VEGFR-3), which are essential for the formation of new blood vessels that supply tumors with nutrients and oxygen—a process known as angiogenesis. The drug also targets the epidermal growth factor receptor (EGFR), which contributes to cancer cell proliferation and survival.

By simultaneously blocking these pathways, vandetanib starves the tumor of its blood supply while directly interfering with cancer cell signaling, leading to reduced tumor growth and, in many cases, tumor shrinkage. In the landmark ZETA trial (a phase III randomized controlled trial published in the Journal of Clinical Oncology), vandetanib demonstrated a statistically significant improvement in progression-free survival compared to placebo in patients with advanced MTC, with a hazard ratio of 0.46 (p < 0.001).

Caprelsa is approved for the treatment of adults and children aged 5 years and older with symptomatic or progressive medullary thyroid cancer that has a confirmed RET mutation and is either unresectable (cannot be removed surgically) or metastatic (has spread to other parts of the body). In some regions, the indication is limited to locally advanced or metastatic disease, and prescribers must confirm RET mutation status before initiating treatment. Caprelsa was granted orphan drug status due to the rarity of medullary thyroid cancer, and in certain countries, it is available only through restricted distribution programs that include mandatory cardiac monitoring.

What Should You Know Before Taking Caprelsa?

Quick Answer: Caprelsa must not be used in patients with congenital long QT syndrome, those who are breastfeeding, or those taking certain medications that prolong the QT interval. Careful cardiac, electrolyte, and liver function monitoring is essential before and during treatment.

Contraindications

There are several situations in which Caprelsa must not be taken. Understanding these contraindications is critical for patient safety. You should not take Caprelsa if any of the following apply to you:

• Allergy to vandetanib or excipients: If you are allergic to vandetanib or any of the other ingredients in this medicine, you must not take it. Allergic reactions can range from skin rashes to more severe systemic reactions.
• Congenital long QT syndrome: If you have a hereditary heart condition known as congenital long QT syndrome (visible on an electrocardiogram), Caprelsa is strictly contraindicated because the drug itself prolongs the QT interval, which could lead to life-threatening cardiac arrhythmias such as torsades de pointes.
• Breastfeeding: Caprelsa must not be taken while breastfeeding, as the drug may pass into breast milk and harm the nursing infant.
• Concurrent use of certain medications: You must not take Caprelsa together with arsenic trioxide, cisapride, intravenous erythromycin, moxifloxacin, toremifene, mizolastine, or Class IA and Class III antiarrhythmic agents. These drugs also prolong the QT interval, and the combined effect with vandetanib could be fatal.

Warnings and Precautions

Before starting treatment and throughout the course of therapy, it is important to discuss the following conditions and situations with your doctor:

• Photosensitivity: Some patients taking vandetanib develop increased sensitivity to sunlight, which may result in severe sunburn. You should consistently use broad-spectrum sunscreen (SPF 30+) and wear protective clothing when outdoors.
• Hypertension (high blood pressure): Caprelsa can cause or worsen high blood pressure. Your doctor will monitor your blood pressure regularly and may prescribe antihypertensive medication if needed.
• Aneurysm or artery dissection: Inform your doctor if you have had or currently have an aneurysm (enlargement and weakening of a blood vessel wall) or a dissection (tear in the artery wall), as vandetanib may affect vascular integrity.
• Surgical procedures: Because Caprelsa can impair wound healing, your doctor may temporarily discontinue treatment before major surgery and resume it once adequate wound healing has been confirmed.
• Skeletal complications: If you are taking medications to prevent bone complications from thyroid cancer or osteoporosis (such as bisphosphonates or denosumab), discuss this with your doctor, as there is a risk of osteonecrosis of the jaw.
• Kidney problems: Patients with impaired renal function may require dose adjustments, as vandetanib clearance is affected by kidney function. Close monitoring is recommended.
• Severe cutaneous adverse reactions (SCAR): Rare but potentially life-threatening skin reactions, including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported. If you develop widespread skin rash with blisters, peeling skin, or sores in your mouth, throat, or eyes, stop taking Caprelsa immediately and seek emergency medical attention.

Required Monitoring

Your doctor or nurse will perform regular tests to monitor your safety during Caprelsa treatment. These include blood tests to check levels of potassium, calcium, magnesium, and thyroid-stimulating hormone (TSH), as well as ECG tests to assess the electrical activity of your heart. The monitoring schedule typically follows this pattern:

• Before starting Caprelsa (baseline)
• At 1, 3, and 6 weeks after starting treatment
• At 12 weeks after starting treatment
• Every 3 months thereafter
• Whenever the dose of Caprelsa is changed
• Whenever a new medication that may affect the heart is started

Pregnancy and Breastfeeding

Caprelsa may cause harm to a developing fetus. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine. Your physician will carefully weigh the potential benefits against the risks of treatment during pregnancy.

Women of childbearing potential must use effective contraception during treatment with Caprelsa and for at least four months after the last dose. Men with female partners of childbearing potential must also use effective contraception during treatment and for at least four months after the last dose. Breastfeeding is contraindicated during treatment to protect the infant from potential exposure to vandetanib.

Use in Children

Caprelsa is approved for use in children aged 5 years and older with RET-mutant medullary thyroid cancer. It should not be given to children under 5 years of age. In pediatric patients, the dose is calculated based on body surface area (height and weight), and the total daily dose must not exceed 300 mg. Treatment in children may involve daily dosing, every-other-day dosing, or a repeating 7-day schedule as determined by the prescribing physician.

Driving and Operating Machinery

Exercise caution when driving or operating machinery while taking Caprelsa. The medication may cause fatigue, weakness, and blurred vision, all of which can impair your ability to safely perform these activities. If you experience these symptoms, avoid driving until they resolve.

How Does Caprelsa Interact with Other Drugs?

Quick Answer: Caprelsa interacts with many medications, particularly those that prolong the QT interval or affect liver enzymes. Several drug combinations are strictly contraindicated, and many others require careful monitoring or dose adjustment.

Vandetanib is metabolized by the liver through the CYP3A4 enzyme system and is also a substrate of various drug transporters. Many commonly used medications can either increase or decrease vandetanib blood levels, or may combine with vandetanib to increase the risk of serious cardiac side effects. It is essential to inform your doctor about all medications you are taking, including prescription drugs, over-the-counter medicines, herbal products, and dietary supplements.

Contraindicated Combinations

The following medications must never be taken together with Caprelsa due to the risk of dangerous QT prolongation and potentially fatal heart rhythm disturbances:

Significant Interactions Requiring Monitoring

The following medications may interact significantly with Caprelsa and require careful monitoring or dose adjustment by your healthcare provider:

What Is the Correct Dosage of Caprelsa?

Quick Answer: The standard adult dose of Caprelsa is 300 mg once daily by mouth, with or without food. Doses may be reduced to 200 mg or 100 mg based on tolerability. Pediatric dosing is calculated by body surface area.

Always take Caprelsa exactly as your doctor has prescribed. Do not change the dose without medical advice. Consistent timing of your daily dose helps maintain stable drug levels in your blood, which is important for both efficacy and safety.

Adults

Children (5 years and older)

Elderly Patients

Patients with Kidney Impairment

Difficulty Swallowing

If you have difficulty swallowing the tablet, you may dissolve it in water using the following method:

1. Place the tablet in half a glass of still (non-carbonated) water. Do not use other liquids.
2. Stir until the tablet is completely dissolved. This may take approximately 10 minutes.
3. Drink the solution immediately.
4. Rinse the glass with another half glass of water and drink it to ensure you have received the full dose.

Missed Dose

If you forget to take a dose, the action you should take depends on how long until your next scheduled dose:

• 12 hours or more until the next dose: Take the missed dose as soon as you remember, then take the next dose at the regular time.
• Less than 12 hours until the next dose: Skip the missed dose entirely and take the next dose at the regular time.

Never take a double dose to make up for a missed one. Taking two doses at once can significantly increase the risk of side effects, particularly QT prolongation.

Overdose

If you take more Caprelsa than prescribed, contact your doctor immediately or go to the nearest hospital emergency department. Symptoms of overdose may include severe nausea, diarrhea, rash, and potentially dangerous changes in heart rhythm. There is no specific antidote for vandetanib overdose; treatment is supportive and based on symptoms. Due to the long half-life of vandetanib (approximately 19 days), adverse effects from overdose may persist for an extended period.

What Are the Side Effects of Caprelsa?

Quick Answer: Like all medicines, Caprelsa can cause side effects, though not everyone experiences them. The most common are diarrhea, skin rash, nausea, high blood pressure, and fatigue. Some side effects, such as QT prolongation, severe skin reactions, and interstitial lung disease, require immediate medical attention.

Side effects are categorized below by their frequency of occurrence. If you experience any side effects, inform your doctor, as dose adjustments or additional medications may help manage them. Some side effects are serious and require immediate medical attention.

Side Effects Detected by Laboratory Tests

Some side effects can only be identified through blood tests and other laboratory investigations ordered by your doctor. These include:

• Altered heart rhythm: QT prolongation detected on ECG. Your doctor may reduce the dose or stop treatment.
• Liver or pancreatic abnormalities: Elevated enzyme levels detected in blood tests. These usually do not cause symptoms but require monitoring.
• Decreased blood calcium: Your doctor may need to adjust thyroid hormone replacement therapy.
• Decreased blood potassium: May contribute to cardiac rhythm disturbances and requires correction.
• Increased blood calcium or glucose: May require monitoring and management.
• Decreased blood sodium: May cause symptoms of weakness or confusion if severe.
• Hypothyroidism: Reduced thyroid function requiring hormone replacement adjustment.
• Polycythemia: Elevated red blood cell counts.
• Protein or blood in urine: Detected on urinalysis, indicating possible kidney involvement.

How Should You Store Caprelsa?

Quick Answer: Store Caprelsa below 30°C (86°F) in its original packaging. Keep it out of reach of children and do not use it after the expiration date.

Proper storage of Caprelsa is important to ensure the medication remains effective and safe to use. Follow these storage guidelines carefully:

• Temperature: Store at or below 30°C (86°F). Do not freeze.
• Packaging: Keep the tablets in the original blister packaging until you are ready to take them. This protects the medication from moisture and light.
• Keep out of reach of children: Store this medication in a secure location where children cannot access it.
• Expiration date: Do not use Caprelsa after the expiration date printed on the blister pack and carton (marked as EXP). The expiration date refers to the last day of the indicated month.
• Disposal: Do not dispose of medications in household waste or down the drain. Ask your pharmacist about proper disposal methods to protect the environment.

What Does Caprelsa Contain?

Quick Answer: Each Caprelsa tablet contains vandetanib (100 mg or 300 mg) as the active ingredient, along with inactive ingredients including calcium hydrogen phosphate dihydrate, microcrystalline cellulose, and a film coating.

Understanding the composition of your medication is important, especially if you have allergies or sensitivities to certain ingredients. Caprelsa contains the following:

Active Ingredient

Vandetanib – each film-coated tablet contains either 100 mg or 300 mg of vandetanib.

Inactive Ingredients (Excipients)

• Tablet core: Calcium hydrogen phosphate dihydrate, microcrystalline cellulose, crospovidone (type A), povidone (K29–32), magnesium stearate
• Film coating: Hypromellose, macrogol, titanium dioxide (E171)

Appearance and Packaging

Caprelsa 100 mg: White, round film-coated tablet marked “Z100” on one side.

Caprelsa 300 mg: White, oval film-coated tablet marked “Z300” on one side.

Caprelsa is supplied in blister packs containing 30 tablets. The medication is manufactured by Genzyme Ireland Ltd. and Sanofi Winthrop Industrie, and is marketed by Sanofi B.V.