Imaavy: Uses, Dosage & Side Effects

What Is Imaavy and What Is It Used For?

Imaavy contains the active substance gadopiclenol, a macrocyclic gadolinium chelate that functions as a paramagnetic contrast agent for magnetic resonance imaging (MRI). Gadolinium-based contrast agents (GBCAs) have been an essential component of diagnostic radiology for over three decades, enabling physicians to detect and characterize a wide range of pathological conditions that may not be clearly visible on non-contrast MRI scans. Imaavy represents a significant advancement in GBCA technology due to its uniquely high relaxivity, which is the measure of how effectively a contrast agent enhances MRI signal intensity.

Magnetic resonance imaging works by using powerful magnets and radiofrequency pulses to create detailed images of the body's internal structures. The contrast in MRI images depends on the relaxation properties of hydrogen protons in water molecules within different tissues. When a gadolinium-based contrast agent like Imaavy is injected intravenously, the gadolinium ions interact with nearby water protons and dramatically shorten their T1 (longitudinal) relaxation time. This shortening of T1 relaxation results in a brighter signal on T1-weighted MRI sequences, creating enhanced contrast between tissues that have taken up the contrast agent and those that have not.

What distinguishes Imaavy from earlier-generation GBCAs is its remarkably high relaxivity. Relaxivity (r1) is measured in units of mM^-1s^-1 and reflects the ability of a contrast agent to enhance the relaxation rate of water protons at a given concentration. Gadopiclenol has a relaxivity approximately twice that of conventional macrocyclic GBCAs such as gadobutrol, gadoterate, and gadoteridol at clinically relevant magnetic field strengths (1.5T and 3T). This means that an equivalent degree of MRI signal enhancement can be achieved with half the amount of gadolinium administered. The recommended dose of Imaavy is 0.05 mmol/kg body weight, compared to the standard 0.1 mmol/kg used with most other GBCAs. This dose reduction is clinically significant because it results in less total gadolinium being introduced into the patient's body during each MRI examination.

The high relaxivity of gadopiclenol is attributed to its unique molecular design. The gadolinium ion is chelated (bound) within a macrocyclic ligand that has been specifically engineered to optimize the interaction between the paramagnetic gadolinium center and surrounding water molecules. The macrocyclic structure also provides exceptional thermodynamic stability (high formation constant) and kinetic inertness (slow rate of gadolinium release), which are critical safety features. Macrocyclic chelates are generally considered to be more stable than linear chelates, and this stability is directly relevant to minimizing the release of free gadolinium ions in the body, which has been associated with adverse effects including nephrogenic systemic fibrosis (NSF) and tissue retention.

Imaavy is indicated for use in adults and children aged 2 years and older for contrast-enhanced MRI of the following:

• Central nervous system (CNS): Brain and spinal cord imaging to detect and characterize tumors (primary and metastatic), infections (abscesses, meningitis, encephalitis), inflammatory conditions (multiple sclerosis plaques, neurosarcoidosis), vascular malformations, and post-surgical changes. Contrast enhancement is particularly valuable for identifying lesions that disrupt the blood-brain barrier.
• Body imaging: Liver, kidney, musculoskeletal, and soft tissue imaging to detect and characterize focal lesions, including hepatocellular carcinoma, renal cell carcinoma, soft tissue sarcomas, and metastatic disease. Contrast-enhanced MRI can help differentiate benign from malignant lesions and assess treatment response.

Clinical trials evaluating gadopiclenol have demonstrated non-inferior diagnostic performance compared to standard-dose conventional GBCAs across multiple body regions. In pivotal phase III studies (PICTURE and PROMISE), blinded readers assessed lesion visualization, border delineation, internal morphology, and contrast enhancement in patients undergoing brain, spine, and body MRI. The results showed that gadopiclenol at 0.05 mmol/kg provided equivalent or superior image quality and diagnostic confidence compared to gadobutrol at 0.1 mmol/kg, despite delivering only half the gadolinium dose. These findings were consistent across 1.5T and 3T MRI systems.

Imaavy was authorized by the European Medicines Agency (EMA) and has gained regulatory approval in multiple countries worldwide. It is manufactured by Guerbet, a global leader in contrast media and medical imaging solutions. The introduction of Imaavy represents an important step toward reducing gadolinium exposure in medical imaging while maintaining the high diagnostic quality that clinicians and patients depend on.

What Should You Know Before Taking Imaavy?

Contraindications

The primary contraindication to Imaavy is known hypersensitivity (allergy) to gadopiclenol or to any of the excipients contained in the formulation. If you have previously experienced an allergic reaction to any gadolinium-based contrast agent, this must be reported to your healthcare provider before receiving Imaavy, as cross-reactivity between different GBCAs may occur. However, it should be noted that hypersensitivity to one GBCA does not necessarily predict an allergic reaction to another, and the decision to use a different GBCA after a previous reaction should be made on a case-by-case basis by a qualified physician.

Acute and delayed hypersensitivity reactions, including anaphylaxis, have been reported with gadolinium-based contrast agents as a class. These reactions can range from mild (urticaria, pruritus, rhinitis) to severe (bronchospasm, laryngeal edema, cardiovascular collapse) and can occur immediately during or shortly after injection, or may be delayed for hours to days. Emergency resuscitation equipment and trained personnel should always be available during the administration of any GBCA.

Warnings and Precautions

Before receiving Imaavy, discuss the following with your healthcare provider:

• Renal impairment: Patients with impaired kidney function are at increased risk for nephrogenic systemic fibrosis (NSF), a rare but serious condition that causes hardening and thickening of the skin, joints, and internal organs. NSF has been almost exclusively associated with linear GBCAs in patients with severe renal failure; the risk with macrocyclic agents such as Imaavy is considered very low. Nevertheless, renal function (estimated glomerular filtration rate, eGFR) should be assessed before administration in patients with known or suspected kidney disease, including those over 65 years of age, patients with diabetes, and those with a history of renal disease.
• History of allergic reactions: Patients with a history of asthma, allergies (including allergic reactions to contrast media), or other hypersensitivity reactions may be at increased risk of allergic reactions to GBCAs. Pre-medication with antihistamines and/or corticosteroids may be considered in patients with a history of prior GBCA reactions, although this approach does not guarantee prevention of a reaction.
• Seizure disorders: As with other GBCAs, there have been rare reports of seizures following administration. Patients with epilepsy or other conditions that lower the seizure threshold should be closely monitored.
• Cardiac conditions: Patients with significant cardiovascular disease should be monitored during and after administration, as hypersensitivity reactions can have cardiovascular manifestations.

Pregnancy and Breastfeeding

Imaavy should not be used during pregnancy unless the clinical situation warrants it and no alternative unenhanced imaging modality can provide the necessary diagnostic information. Gadolinium-based contrast agents cross the placenta and enter the fetal circulation. While gadopiclenol has not been shown to cause fetal harm in animal reproduction studies at clinically relevant doses, there are no adequate and well-controlled studies in pregnant women. The American College of Radiology (ACR) and the European Society of Urogenital Radiology (ESUR) both recommend that gadolinium-based contrast agents should be avoided during pregnancy whenever possible. If MRI contrast is deemed necessary during pregnancy, the decision should involve careful consideration of the potential benefits and risks by the referring physician and radiologist.

It is not known whether gadopiclenol is excreted in human breast milk. As a precautionary measure, some guidelines historically recommended temporarily discontinuing breastfeeding for 24 hours after receiving a GBCA. However, both the ACR and the American College of Obstetricians and Gynecologists (ACOG) now state that the amount of GBCA excreted into breast milk is extremely small (less than 0.04% of the administered dose), and of this amount, less than 1% is expected to be absorbed from the infant's gastrointestinal tract. Based on this evidence, continuation of breastfeeding after gadolinium administration is considered safe. Nonetheless, if the mother is concerned, she may choose to express and discard breast milk for 24 hours after receiving the contrast agent.

Children and Adolescents

Imaavy is approved for use in children aged 2 years and older. The safety and efficacy of gadopiclenol in pediatric patients have been evaluated in clinical studies, and the pharmacokinetics in children are similar to those in adults when dosed on a per-kilogram basis. The recommended pediatric dose is the same as for adults (0.05 mmol/kg body weight, equivalent to 0.1 mL/kg of the 185 mg/mL solution). Imaavy has not been studied in neonates and infants under 2 years of age, and its use in this population is not recommended due to the immaturity of renal function and the potential for increased gadolinium retention.

Elderly Patients

No dose adjustment is required for elderly patients with normal renal function. However, since renal function tends to decline with age, it is recommended that eGFR be assessed before administration in patients aged 65 years and older. Elderly patients may also be at increased risk for dehydration, which can further impair renal function and potentially increase the risk of adverse effects. Adequate hydration before and after the procedure is recommended.

How Does Imaavy Interact with Other Drugs?

Gadopiclenol, the active ingredient in Imaavy, is a highly stable macrocyclic gadolinium chelate that does not undergo hepatic metabolism. It is eliminated from the body almost exclusively through glomerular filtration in the kidneys in an unchanged form, with minimal protein binding and no interaction with cytochrome P450 (CYP) enzymes, transporters, or other drug-metabolizing systems. Formal drug interaction studies have not identified any clinically meaningful pharmacokinetic interactions between gadopiclenol and commonly used medications.

Despite the absence of formal drug interactions, certain clinical considerations are important when Imaavy is administered in conjunction with other medications. Drugs that affect renal function can indirectly influence the elimination of gadopiclenol and potentially increase the duration of gadolinium exposure in the body. This is particularly relevant for patients who are already receiving nephrotoxic medications.

Important Clinical Considerations

Although Imaavy does not have direct pharmacokinetic drug interactions, the concomitant use of nephrotoxic drugs warrants particular attention. Drugs such as aminoglycosides, amphotericin B, ciclosporin, and high-dose NSAIDs can impair renal function and thereby delay the excretion of gadopiclenol. In patients receiving these medications, it is advisable to assess renal function (eGFR) before administering Imaavy and to ensure adequate hydration before and after the procedure.

Patients taking beta-blockers deserve special consideration because beta-blockade can make anaphylactic reactions more severe and more difficult to treat. Epinephrine (adrenaline), the first-line treatment for anaphylaxis, may be less effective in patients on beta-blockers due to competitive antagonism at beta-adrenergic receptors. Healthcare facilities should have glucagon available as an alternative for managing anaphylaxis in beta-blocked patients.

Interaction with Diagnostic Tests

Gadolinium-based contrast agents can interfere with certain laboratory tests. Iron assays using complexometric methods (colorimetric tests) may be falsely decreased for up to 24 hours after GBCA administration. This is due to the chelate structure of the gadolinium complex potentially interfering with the reagents used in these assays. If serum iron testing is needed, it should ideally be performed before the MRI examination or delayed for at least 24 hours afterward. Standard ferritin assays and other common blood tests are generally not affected.

What Is the Correct Dosage of Imaavy?

Imaavy is administered exclusively by healthcare professionals in clinical settings equipped for MRI procedures. The dose is calculated based on the patient's body weight and is given as a single intravenous bolus injection, typically at a rate of approximately 1–2 mL per second, followed by a saline flush. The optimal timing of MRI scanning after injection depends on the type of imaging being performed and the clinical question being addressed.

Adults

For adult patients, the recommended dose of Imaavy is 0.1 mL/kg body weight (equivalent to 0.05 mmol/kg or 18.5 mg gadopiclenol per kg). For a 70 kg patient, this corresponds to 7 mL of the 185 mg/mL solution. The injection should be administered as a single intravenous bolus at a rate of 1–2 mL per second, followed by a flush of at least 5 mL of 0.9% sodium chloride (normal saline) to ensure complete delivery of the contrast agent. Only one dose should be administered per MRI examination. If a repeat examination is required, a minimum interval of 7 days between administrations is recommended to allow for adequate renal clearance.

Children

In children aged 2 years and older, the recommended dose is the same as for adults on a per-kilogram basis (0.1 mL/kg body weight). The injection rate may be adjusted according to the size of the venous access and the child's weight. For very young children, the injection may be administered by hand (manual injection) rather than by power injector to allow better control of the injection rate. Imaavy has not been studied in children under 2 years of age, and its use in this age group is not recommended due to the immaturity of the developing kidneys and the potential for prolonged gadolinium retention.

Elderly

No dose adjustment is required for elderly patients with normal renal function. However, since age-related decline in renal function is common, eGFR should be assessed before administration in patients aged 65 years and older. If renal function is significantly impaired, the general precautions for patients with renal impairment apply. Adequate hydration before and after the MRI procedure is particularly important in elderly patients who may be more susceptible to dehydration.

Missed Dose

The concept of a missed dose does not apply to Imaavy in the traditional sense, as it is a single-use contrast agent administered during a specific MRI examination, not a medication taken on a regular schedule. If an MRI examination is postponed or cancelled, no action is required regarding the contrast agent. The procedure will simply be rescheduled, and Imaavy will be administered at the time of the rescheduled examination.

Overdose

No cases of clinically significant overdose with gadopiclenol have been reported in clinical trials. In the event of accidental overdose, the patient should be closely monitored for signs and symptoms of adverse reactions, with particular attention to renal function, cardiovascular status, and potential allergic reactions. Gadopiclenol is dialyzable, meaning it can be removed from the body through hemodialysis. However, there is no evidence that hemodialysis is useful for the prevention of nephrogenic systemic fibrosis (NSF) in patients who have received an overdose. Treatment of overdose is supportive and symptomatic.

What Are the Side Effects of Imaavy?

Like all gadolinium-based contrast agents, Imaavy can cause side effects, although not everyone experiences them. The overall safety profile of gadopiclenol in clinical trials has been favorable, with the majority of adverse reactions being mild to moderate in severity and self-limiting. In the pivotal phase III clinical trials (PICTURE and PROMISE), the incidence of adverse events with gadopiclenol was comparable to that observed with the comparator GBCA (gadobutrol).

The following side effects have been reported in clinical trials and post-marketing surveillance. They are organized by frequency according to the standard medical classification: very common (affects more than 1 in 10 people), common (1 in 10 to 1 in 100), uncommon (1 in 100 to 1 in 1,000), and rare (less than 1 in 1,000).

The most frequently observed side effect in clinical trials was injection site pain, reported in approximately 2–3% of patients. Headache and nausea were each reported in approximately 1–2% of patients. These symptoms typically resolved spontaneously within minutes to hours after the MRI examination without requiring specific treatment.

Gadolinium Retention

An important area of ongoing research concerns the retention of trace amounts of gadolinium in body tissues after the administration of GBCAs. Studies have demonstrated that detectable levels of gadolinium can persist in the brain (particularly the dentate nucleus and globus pallidus), bones, and skin for months to years after GBCA administration, even in patients with normal renal function. Macrocyclic GBCAs like Imaavy are associated with significantly lower levels of tissue retention compared to linear GBCAs, which is attributed to their greater thermodynamic stability and kinetic inertness.

To date, no adverse clinical effects have been definitively linked to gadolinium retention at the levels observed with macrocyclic agents. However, the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have recommended that GBCAs should be used at the lowest dose necessary for adequate diagnostic imaging, which aligns with the dose-reduction advantage of Imaavy. The regulatory agencies also recommend that repeated GBCA administrations be minimized when possible, and that macrocyclic agents be preferred over linear agents when a GBCA is needed.

How Should You Store Imaavy?

Imaavy is supplied as a clear, colorless to slightly yellow solution for injection in single-dose vials and pre-filled syringes. Proper storage is essential to maintain the integrity and efficacy of the product. The following storage guidelines should be followed:

• Temperature: Store below 25°C (77°F). Do not freeze. If the product has been accidentally frozen, it should be discarded and not used. Freezing can alter the physicochemical properties of the solution and potentially compromise the stability of the gadolinium chelate.
• Light protection: Keep the vial or pre-filled syringe in the original outer carton to protect from light until immediately before use. Prolonged exposure to light may degrade the product.
• Shelf life: The shelf life of Imaavy is 3 years from the date of manufacture when stored according to the recommended conditions. Do not use the product after the expiry date printed on the label and carton.
• After opening: Imaavy is a single-dose product and does not contain preservatives. Any unused portion of the solution remaining in the vial or syringe after injection must be discarded. The product should be used immediately after opening. If the solution appears discolored, cloudy, or contains particulate matter, it should not be used.
• Disposal: Any unused product or waste material should be disposed of in accordance with local requirements for contrast media and pharmaceutical waste. Gadolinium-containing waste should be handled according to institutional protocols for potentially hazardous materials.

As Imaavy is administered in clinical settings by healthcare professionals, patients typically do not handle the product directly. However, understanding storage requirements helps ensure that any questions about the product's integrity can be addressed before the MRI examination. Healthcare facilities should maintain a record of storage temperatures and ensure that contrast media are stored within the specified conditions as part of their quality assurance programs.

What Does Imaavy Contain?

Each milliliter of Imaavy solution for injection contains 185 mg of gadopiclenol, which corresponds to 0.5 mmol of gadolinium per milliliter. Gadopiclenol is a macrocyclic gadolinium chelate with the chemical formula C₂₂H₂₇GdN₅O₉. The gadolinium ion (Gd³⁺) is firmly bound within the macrocyclic ligand, forming a highly stable complex that is critical for the product's safety profile. The stability constants (both thermodynamic and kinetic) of gadopiclenol are among the highest in the class of GBCAs.

The excipients (inactive ingredients) in Imaavy are:

• Trometamol (tromethamine): A buffer used to maintain the pH of the solution within the optimal range for both stability and patient comfort during injection. Trometamol helps ensure that the product remains within a physiologically acceptable pH range (approximately pH 7).
• Hydrochloric acid and/or sodium hydroxide: Used for pH adjustment during the manufacturing process to achieve the target pH of the final product.
• Water for injections: The solvent used as the base for the solution, meeting pharmacopoeial standards for sterile, pyrogen-free water suitable for parenteral administration.

Imaavy is an iso-osmolar to slightly hyperosmolar solution with a viscosity that allows for comfortable injection through standard intravenous catheters and power injectors. The osmolality of the 185 mg/mL solution is approximately 820 mOsm/kg, and its viscosity at 37°C is approximately 2.0 mPa·s, which is lower than most conventional GBCAs at their standard concentrations. These physicochemical properties contribute to good injectability and patient comfort.

Imaavy is available in the following presentation sizes:

• Single-dose vials: 7.5 mL, 15 mL, and 30 mL
• Pre-filled syringes: 7.5 mL and 15 mL

The product does not contain preservatives, which is why it is designed for single-use only. Any unused portion must be discarded after the injection is administered.