Clariscan (Gadoteric Acid)

What Is Clariscan and What Is It Used For?

Clariscan belongs to a group of medicines called contrast agents for magnetic resonance imaging (MRI). It contains the active substance gadoteric acid, a paramagnetic gadolinium chelate that works by altering the magnetic properties of nearby water molecules during an MRI scan. This shortens the T1 relaxation time of tissues, causing them to appear brighter on MRI images and dramatically improving the contrast between the area being examined and surrounding tissues.

Unlike X-ray contrast agents that use iodine, gadolinium-based contrast agents like Clariscan are specifically designed for use with MRI technology. They do not involve any ionizing radiation, making MRI with Clariscan a safe and highly effective diagnostic tool. Clariscan is classified as a macrocyclic agent, meaning the gadolinium ion is held within a cage-like molecular structure. This design provides exceptionally high thermodynamic stability (log K_therm = 25.6), which means the gadolinium remains tightly bound and is less likely to be released into the body compared to linear gadolinium agents.

Approved Indications

Clariscan is approved for use as a diagnostic tool in several types of MRI examinations. The specific indications vary by patient age group, as regulatory approvals reflect the available clinical evidence for each population:

In adults and children from birth to 18 years:

• Central nervous system (CNS) MRI: Enhanced imaging of the brain, spinal cord, and surrounding tissues to detect and characterize lesions such as tumors, inflammation, demyelinating disease, vascular malformations, and post-surgical changes.

In adults and children from 6 months to 18 years:

• Whole-body MRI: Enhanced imaging of organs and tissues throughout the body, including the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and musculoskeletal system, to detect and characterize focal lesions and abnormalities.

In adults only:

• Magnetic resonance angiography (MRA): Imaging of blood vessels to detect abnormalities such as narrowing (stenosis), blockages, or aneurysms. This indication covers all arteries except the coronary arteries.

How Clariscan Works

When Clariscan is injected intravenously, the gadoteric acid distributes throughout the extracellular fluid compartment of the body. Areas with increased blood supply or disrupted barriers (such as tumors, inflammation, or vascular abnormalities) accumulate more of the contrast agent than normal tissue. On MRI images, these areas appear significantly brighter, allowing radiologists to identify and characterize abnormalities with much greater precision than on unenhanced scans.

The contrast effect is temporary. Gadoteric acid does not undergo metabolism in the body and is eliminated unchanged through the kidneys by glomerular filtration. In patients with normal kidney function, approximately 94% of the dose is excreted within 24 hours, with a plasma elimination half-life of approximately 1.6 hours. This relatively rapid clearance contributes to the favorable safety profile of gadoteric acid compared to some other contrast agents.

What Should You Know Before Receiving Clariscan?

Contraindications

Clariscan must not be administered to patients who have a known allergy (hypersensitivity) to gadoteric acid or any of the other ingredients in the formulation (meglumine, tetraxetan/DOTA, or water for injections). It is also contraindicated in patients with a known allergy to any other gadolinium-containing contrast agent or MRI contrast medium.

If you have previously experienced an allergic reaction to any contrast agent, regardless of the imaging modality (MRI, CT, or other), it is essential to inform your doctor before the procedure. Even if the previous reaction was mild, there may be an increased risk of a more severe reaction with subsequent exposure.

Warnings and Precautions

Before receiving Clariscan, discuss the following conditions with your doctor or radiologist. Each of these factors may influence the decision to proceed with contrast administration or may require additional precautions:

• Previous hypersensitivity reaction: If you have ever had an allergic or anaphylactoid reaction to any contrast agent, your risk of reacting to Clariscan is increased. Your doctor will carefully weigh the benefits against the risks and may pre-medicate you with antihistamines and corticosteroids.
• Asthma: Patients with active asthma have a higher risk of bronchospasm and other hypersensitivity reactions during contrast administration.
• Other allergies: History of allergies such as shellfish allergy, hay fever, or urticaria (hives) may indicate an increased susceptibility to contrast reactions.
• Beta-blocker therapy: Patients taking beta-blockers (such as metoprolol, atenolol, or propranolol) may have an attenuated response to epinephrine if used to treat an anaphylactic reaction.
• Kidney impairment: Reduced kidney function affects the clearance of gadoteric acid and increases the risk of nephrogenic systemic fibrosis (NSF). Your doctor may order a blood test to check your kidney function before administering Clariscan.
• Liver transplantation: Patients who have recently undergone or are about to undergo liver transplantation are at particular risk due to the high incidence of acute kidney failure in this group.
• Seizure history or epilepsy: Gadolinium-based contrast agents may lower the seizure threshold in susceptible individuals.
• Severe cardiovascular disease: Patients with significant heart disease or vascular conditions require careful monitoring during and after contrast administration.

Risk of Serious Adverse Reactions

As with all MRI contrast agents, there is a risk of adverse reactions following Clariscan administration. Most side effects are mild and transient, but unpredictable and potentially life-threatening reactions can occur. Healthcare providers must be prepared to manage these events:

• Immediate reactions may occur within one hour of administration and can range from mild symptoms (nausea, urticaria) to severe anaphylaxis.
• Delayed reactions may develop up to seven days after administration and typically present as skin rashes or other mild symptoms.
• Patients with a history of previous contrast reactions are at significantly higher risk and should only receive Clariscan when the diagnostic benefit clearly outweighs the risk.

After receiving Clariscan, you will be monitored by medical staff for at least 30 minutes. Emergency resuscitation equipment and trained personnel are always available at the imaging facility. A needle or intravenous line is kept in place throughout the procedure so that emergency medications can be administered immediately if needed.

Kidney Function and Nephrogenic Systemic Fibrosis

Nephrogenic systemic fibrosis (NSF) is a rare but serious condition that has been associated with the use of certain gadolinium-based contrast agents in patients with severe kidney impairment. NSF causes thickening and hardening of the skin, and can also affect soft tissues and internal organs. It has most frequently been reported in patients receiving linear (non-macrocyclic) gadolinium agents, though vigilance is maintained for all GBCAs.

A kidney function blood test is recommended for all patients before receiving Clariscan, and it is especially important for patients over 65 years of age, as renal function naturally declines with age. Clariscan should generally not be used in patients with:

• Severe renal impairment (GFR <30 ml/min/1.73m²)
• Acute kidney injury
• The perioperative period of liver transplantation

If Clariscan must be used in these high-risk patients after careful risk-benefit assessment, only a single dose should be given, and at least seven days should elapse before any repeat administration. Hemodialysis shortly after Clariscan administration may help remove the agent from the body, although there is no definitive evidence that this prevents NSF.

Pregnancy and Breastfeeding

Pregnancy: Gadoteric acid can cross the placenta. The effects on the developing fetus are not fully known. Clariscan should only be used during pregnancy if the physician considers it absolutely necessary and the diagnostic information cannot be obtained by other means. The American College of Radiology (ACR) recommends that GBCAs should only be administered to pregnant women when the potential benefit justifies the potential risk to the fetus.

Breastfeeding: Small amounts of gadoteric acid may pass into breast milk. If you are breastfeeding, discuss with your doctor whether to continue or to temporarily stop breastfeeding for 24 hours after receiving Clariscan. The decision should be made jointly based on individual circumstances. Current evidence suggests that the amount of GBCA excreted in breast milk and subsequently absorbed by the infant is very small, but a precautionary approach is generally recommended.

Driving and Operating Machinery

There are no specific studies on the effect of Clariscan on driving ability. However, some patients may experience dizziness, nausea, or low blood pressure after administration. If you feel unwell after the MRI examination, you should not drive or operate machinery until the symptoms have resolved. You are responsible for assessing your own fitness to drive after the procedure.

How Does Clariscan Interact with Other Drugs?

Clariscan is not metabolized by the liver and does not interact with the cytochrome P450 enzyme system, which significantly limits the potential for pharmacokinetic drug interactions. The agent is eliminated unchanged through the kidneys by glomerular filtration. No formal drug interaction studies have identified clinically significant pharmacokinetic interactions with other medications.

However, certain medications may be relevant in the context of contrast administration, primarily because they affect the management of potential hypersensitivity reactions or influence hemodynamic responses:

Food and Drink Interactions

Nausea and vomiting are known possible side effects of MRI contrast agents. To minimize the risk of aspiration in the event of vomiting, patients are generally advised to avoid eating for at least 2 hours before the MRI examination. Clear fluids are usually permitted and encouraged to ensure adequate hydration, which supports optimal kidney function and contrast clearance.

What Is the Correct Dosage of Clariscan?

Clariscan is always administered by trained healthcare professionals in a hospital, clinic, or radiology practice. You will never need to self-administer this medication. The doctor determines the appropriate dose based on your body weight, the type of MRI examination, and the specific clinical question being addressed. During administration, you will be monitored by medical staff, and an intravenous line is maintained throughout the procedure to allow rapid administration of emergency medications if necessary.

Adults

The infusion rate for standard MRI examinations is typically 3–5 ml/min. For angiographic procedures, higher injection rates up to 120 ml/min (2 ml/second) may be used to achieve optimal arterial-phase contrast enhancement. The choice of injection rate is determined by the radiologist based on the specific clinical protocol being used.

Children and Adolescents (0–18 years)

The use of Clariscan in pediatric patients requires careful consideration by the physician. The recommended dose for children is the same as for adults at 0.1 mmol/kg body weight (0.2 ml/kg), but the following restrictions apply:

Neonates and infants: Due to immature kidney function in neonates (up to 4 weeks) and infants (up to 1 year), Clariscan should only be used after careful consideration. The dose must not exceed 0.1 mmol/kg, only one dose should be given per examination, and the required dose should be administered by hand (not by power injector) to ensure accuracy. The choice of vial size should be appropriate for the small volumes required.

Elderly Patients (65 years and older)

No dose adjustment is necessary for elderly patients. However, a blood test to assess kidney function is recommended before administration, as renal clearance of gadoteric acid may be reduced with age. If kidney function is significantly impaired, the precautions for patients with renal impairment apply.

Patients with Kidney or Liver Impairment

For patients with mild to moderate kidney impairment (GFR ≥30 ml/min/1.73m²), the standard adult dose applies. For patients with severe kidney impairment (GFR <30 ml/min/1.73m²) or those in the perioperative phase of liver transplantation, Clariscan should only be used after careful risk-benefit assessment and when the diagnostic information is essential and cannot be obtained without contrast. In these cases:

• The dose must not exceed 0.1 mmol/kg
• Only one dose should be administered per examination
• At least 7 days must pass before any repeat injection

Overdose

Overdose with Clariscan is highly unlikely because the medication is administered by trained medical professionals in a controlled clinical environment. No case of clinically significant overdose has been reported with gadoteric acid. Should an overdose occur, the patient would be monitored for any adverse effects, and gadoteric acid can be removed from the body by hemodialysis if necessary. The high thermodynamic stability of the macrocyclic chelate means that even at higher-than-intended doses, the risk of free gadolinium release remains low.

What Are the Side Effects of Clariscan?

Like all medicines, Clariscan can cause side effects, although not everyone experiences them. After receiving the injection, you will be monitored by medical staff for at least 30 minutes. Most side effects appear shortly after administration, but some delayed reactions may occur up to seven days after the injection.

There is a small risk of allergic reactions to Clariscan. These reactions can range from mild skin symptoms to severe anaphylaxis, which is a life-threatening emergency. If you notice any of the following symptoms after receiving Clariscan, inform medical staff immediately:

• Swelling of the face, mouth, or throat that makes it difficult to swallow or breathe
• Swelling of the hands or feet
• Feeling faint (low blood pressure)
• Difficulty breathing, wheezing, or coughing
• Itching, hives, or skin rash
• Runny nose, sneezing, or irritated eyes

Nephrogenic Systemic Fibrosis (NSF)

Cases of nephrogenic systemic fibrosis (NSF) have been reported in association with gadolinium-based contrast agents, primarily in patients who received gadoteric acid together with other gadolinium-containing agents. NSF causes progressive thickening and hardening of the skin, and may also affect muscles, joints, and internal organs. If you notice any changes in the color or thickness of your skin anywhere on your body in the weeks following your MRI examination, contact the doctor who performed the study immediately.

It is important to note that macrocyclic agents like Clariscan have a substantially lower association with NSF compared to linear gadolinium agents. The European Medicines Agency (EMA) has classified macrocyclic GBCAs as having the lowest risk of NSF among all gadolinium-based contrast agents.

Reporting Side Effects

Reporting suspected adverse reactions after authorization of a medicine is important for ongoing safety monitoring. If you experience any side effects after receiving Clariscan, including those not listed above, you should report them to your doctor and to your national pharmacovigilance authority (for example, the FDA MedWatch program in the United States, the MHRA Yellow Card Scheme in the United Kingdom, or the EMA EudraVigilance system in Europe).

How Should Clariscan Be Stored?

As Clariscan is administered in a medical facility, storage is handled by healthcare professionals. You will not need to store this medication at home. However, the following storage guidelines apply to the facility:

• Vials and bottles: No special storage conditions required. Store at room temperature.
• Pre-filled syringes: Do not freeze. Store at room temperature.
• Keep out of sight and reach of children.
• Do not use after the expiration date (EXP) printed on the packaging. The expiration date refers to the last day of that month.
• Chemical and physical stability has been demonstrated for 48 hours at 30°C.
• From a microbiological standpoint, the product should be used immediately after opening. If not used immediately, storage should not exceed 24 hours at 2–8°C under controlled aseptic conditions.

Clariscan is for single use only. Any unused product remaining in the vial, syringe, or injection system must be discarded after the examination. The solution should be visually inspected before use; only clear solutions free from visible particles should be administered. Unused medicine and waste should be disposed of in accordance with local regulations for pharmaceutical waste.

What Does Clariscan Contain?

Active Ingredient

The active substance in Clariscan is gadoteric acid, present as its meglumine salt. Each milliliter of the solution for injection contains 279.32 mg of gadoteric acid, which corresponds to 0.5 mmol of gadoteric acid. Gadoteric acid is a macrocyclic ionic gadolinium chelate with the chemical name gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd-DOTA).

Inactive Ingredients (Excipients)

• Meglumine — a glucamine derivative used as a counterion for the gadoteric acid complex
• Tetraxetan (DOTA) — free chelating agent present in small excess to ensure no free gadolinium ions are released
• Water for injections — the vehicle for the solution

Appearance and Packaging

Clariscan is a clear, colorless to slightly yellow solution for intravenous injection. It is available in the following presentations:

• Glass vials (Type 1, transparent): 5 ml, 10 ml, 15 ml, and 20 ml
• Pre-filled syringes: 10 ml, 15 ml, and 20 ml
• Glass bottles (Type 1, transparent) and plastic bottles: 50 ml and 100 ml

All presentations are available in single packs or multipacks of 10. Not all pack sizes may be marketed in all countries. The removable tracking label on the syringes, vials, or bottles should be affixed to the patient record to allow accurate documentation of the gadolinium-containing contrast agent used, including the product name, batch number, and dose administered.