Miradoscan (Solution) Instructions for Use

Marketing Authorization Holder

Pharmasintez-Tyumen, LLC (Russia)

ATC Code

V08CA03 (Gadodiamide)

Active Substance

Gadodiamide (Rec.INN registered by WHO)

Dosage Form

Miradoscan

Solution for intravenous administration 0.5 mmol/1 ml: fl. 10 ml, 15 ml or 20 ml 1 or 10 pcs

Dosage Form, Packaging, and Composition

Solution for intravenous administration transparent, colorless or slightly yellowish in color.

Excipients : caldiamide sodium – 12 mg, hydrochloric acid solution 1M or sodium hydroxide solution 1M – to pH 5.5-7.0, water for injections – to 1 ml.

10 ml – colorless glass bottles (1) – cardboard packs.
10 ml – colorless glass bottles (10) – cardboard packs.
15 ml – colorless glass bottles (1) – cardboard packs.
15 ml – colorless glass bottles (10) – cardboard packs.
20 ml – colorless glass bottles (1) – cardboard packs.
20 ml – colorless glass bottles (10) – cardboard packs.

Clinical-Pharmacological Group

Contrast diagnostic agent for magnetic resonance imaging

Pharmacotherapeutic Group

Contrast agents; magnetic resonance imaging contrast agents; paramagnetic contrast agents

Pharmacological Action

Contrast diagnostic non-ionic linear paramagnetic agent used for magnetic resonance imaging (MRI). It reduces the proton T₁ relaxation time, which leads to an increase in signal intensity and improved contrast during MRI.

In the field strength range from 0.15 Tesla to 1.5 Tesla, the relative image contrast does not depend on the applied field strength. It provides contrast enhancement and improved visualization of pathological structures or lesions in various parts of the body, including the CNS.

In cases of impaired blood-brain barrier (BBB) function, the administration of gadodiamide improves the visualization of pathological changes and foci with pathological vascularization (or processes leading to BBB damage) in the brain (intracranial lesions), spine and related tissues, as well as pathological foci in the chest, pelvic cavity and retroperitoneal space.

It also improves the definition of tumor boundaries, helping to establish the degree of invasiveness. Not all pathological processes result in signal enhancement; for example, some types of highly differentiated tumors or inactive multiple sclerosis plaques do not enhance sufficiently.

Thus, Gadodiamide can be used for the differential diagnosis of healthy and pathological tissues, for the detection of various pathological structures, and for differentiating tumor from tumor recurrence and scar tissue after treatment.

Pharmacokinetics

After intravenous administration, Gadodiamide is rapidly distributed in the extracellular fluid. The V_d is equivalent to the volume of extracellular fluid. The distribution half-life is approximately 4 min. No protein binding has been detected.

It does not penetrate the intact BBB.

The T_1/2 is about 70 min. It is almost completely excreted by the kidneys unchanged by glomerular filtration. At 4 hours after intravenous injection, 85% of the active substance is detected in the urine, and at 24 hours – 95-98%.

In patients with impaired renal function, the T_1/2 is prolonged in proportion to the degree of renal impairment. The contrast agent can be removed from the body by hemodialysis.

After the administration of gadolinium-containing contrast agents (GCCAs), trace amounts of gadolinium have been present for months or years in the brain, bones, skin and other organs.

Indications

For contrast enhancement during MRI of the brain and spinal cord in adults and children over 4 weeks of age.

For contrast enhancement during whole-body MRI in adults and children over 6 months of age, including MRI of the head and neck, MRI of the chest (including cardiac MRI), MRI of the extremities, MRI of the abdomen (pancreas and liver) and MRI of the pelvic organs (prostate and bladder), MRI of the retroperitoneal space (kidneys), breast MRI in women, MRI of the musculoskeletal system, magnetic resonance angiography in adults.

For contrast enhancement during cardiac MRI to assess coronary artery disease (CAD) through myocardial perfusion imaging (under stress/at rest and delayed enhancement imaging), for the detection and localization of CAD and differentiation of areas of ischemia and infarction in patients with known or suspected CAD.

ICD codes

Dosage Regimen

Administer as an intravenous bolus injection at a flow rate of approximately 10 ml per 15 seconds.

For adults and children over 2 years of age with a body weight up to 100 kg, the standard single dose is 0.1 mmol per kg of body weight.

For patients with a body weight exceeding 100 kg, the single dose is 10 mmol; do not exceed this maximum dose.

For pediatric patients aged 6 months to 2 years, use the same weight-based calculation of 0.1 mmol/kg for whole-body MRI.

For neonates and infants from 4 weeks to 6 months, use the same weight-based calculation of 0.1 mmol/kg for CNS and whole-body MRI.

Flush the intravenous line with 0.9% sodium chloride solution immediately after injection to ensure complete delivery of the contrast medium.

Initiate the MRI scanning procedure shortly after administration, as the optimal contrast enhancement is typically observed during the first post-injection hour.

Calculate the exact volume to be administered based on the patient’s body weight and the preparation’s concentration of 0.5 mmol/ml.

Inspect the solution visually for particulate matter and discoloration prior to administration; use only if the solution is clear, colorless to slightly yellow, and the container is undamaged.

Do not use automatic power injectors without ensuring the device’s pressure limit is set appropriately for the vial and intravenous line used.

Maintain an interval of at least 7 days between repeated administrations due to the lack of data on more frequent use.

Adverse Reactions

Immune system disorders uncommon – allergic reactions on the skin and mucous membranes, hypersensitivity; frequency unknown anaphylactic/anaphylactoid reactions*.

Psychiatric disorders rare – anxiety.

Nervous system disorders common – headache; uncommon – dizziness, paresthesia, transient change in taste sensations; rare – convulsions, tremor, drowsiness, transient change in smell.

Eye disorders rare – visual impairment.

Cardiac disorders frequency unknown – tachycardia.

Vascular disorders uncommon – skin redness.

Respiratory, thoracic and mediastinal disorders rare – dyspnea, cough; frequency unknown – bronchospasm, breathing disorder, throat irritation, sneezing.

Gastrointestinal disorders common – nausea; uncommon – vomiting, diarrhea.

Skin and subcutaneous tissue disorders uncommon – itching; rare – edema, including facial edema and angioedema, urticaria, rash; frequency unknown – nephrogenic systemic fibrosis, skin induration**.

Musculoskeletal and connective tissue disorders rare – arthralgia.

Renal and urinary disorders rare – acute renal failure.

Local reactions common – transient sensation of heat, cold or fullness at the injection site, transient painful sensations at the injection site.

General disorders and administration site conditions rare – chest pain, fever, chills.

Contraindications

Hypersensitivity to gadodiamide; severe renal impairment (GFR<30 ml/min/1.73 m²), acute renal failure, in the perioperative period of liver transplantation, newborns under 4 weeks of age.

With caution

Anemia (sickle cell, hemolytic), hemoglobinopathy, hepatic insufficiency, patients with renal impairment (GFR 30-59 ml/min/1.73 m²), allergy, bronchial asthma, epilepsy, brain diseases, history of adverse reactions to the administration of a radiocontrast agent (except for allergic reactions).

Use in Pregnancy and Lactation

There is no experience with the use in women during pregnancy. GCCAs cross the placental barrier. They affect the fetus and lead to the accumulation of gadolinium.

Clinical data on the association between GCCAs and adverse fetal outcomes are limited and inconclusive. Gadodiamide should not be used for the examination of pregnant women, except in cases where contrast-enhanced MRI is prescribed by a doctor due to necessity and the potential benefit of this examination outweighs the possible risk to the fetus.

Animal studies have shown reproductive toxicity of the drug when administered repeatedly in high doses.

It is not known whether Gadodiamide is excreted in human breast milk. Available data from animal studies show excretion of gadodiamide in breast milk. A risk to the breastfed child cannot be excluded. Breastfeeding should be discontinued for 24 hours after administration of the drug containing Gadodiamide.

Use in Hepatic Impairment

Contraindication: in the perioperative period of liver transplantation.

With caution: hepatic insufficiency.

Use in Renal Impairment

Contraindication: severe renal impairment (GFR<30 ml/min/1.73 m²), acute renal failure.

With caution: patients with renal impairment (GFR 30-59 ml/min/1.73 m²).

Pediatric Use

Contraindicated in newborns under 4 weeks of age.

Geriatric Use

Since elderly patients may have slowed renal clearance of gadodiamide, it is particularly important to examine patients over 65 years of age for the presence of renal impairment.

Special Precautions

It is necessary to observe the usual precautions when performing MRI, such as excluding patients with pacemakers and ferromagnetic implants.

As with the use of other intravenous contrast agents, the use of gadodiamide may be accompanied by the occurrence of allergic reactions and other manifestations of idiosyncrasy, which may manifest in the form of cardiovascular, respiratory and skin reactions, up to shock. Most of these reactions develop within half an hour after the administration of the contrast agent. As with the use of any other contrast agents of this class, in rare cases, delayed reactions may occur (after several hours or days).

In case of a hypersensitivity reaction, the administration of the contrast agent should be stopped immediately.

In emergency cases, for the provision of emergency care, equipment for intubation and artificial ventilation must be available.

The risk of hypersensitivity reactions is increased in patients with a predisposition to allergic reactions; in patients with bronchial asthma, in whom the risk of bronchospasm is especially high; in patients with a history of severe adverse reactions to contrast agents.

Before using gadodiamide, all patients should undergo laboratory tests to assess renal function.

Cases of nephrogenic systemic fibrosis associated with the use of gadodiamide and some other gadolinium-containing contrast agents have been reported in patients with acute or chronic renal failure (GFR <30 ml/min/1.73m²) and/or acute kidney injury. Gadodiamide is contraindicated in such patients.

Patients who have undergone liver transplantation are at particularly high risk, as the incidence of acute renal failure in this group of patients is especially high. Therefore, Gadodiamide is contraindicated in patients with acute renal failure, in patients in the perioperative period of liver transplantation, as well as in newborns.

The risk of developing nephrogenic systemic fibrosis in patients with moderate renal impairment (GFR 30-59 ml/min/1.73 m²) is unknown, so Gadodiamide in such patients should be used only after a careful risk-benefit assessment.

Due to lack of information on repeated use, the interval between administrations of gadodiamide should be at least 7 days.

After the use of gadodiamide, hemodialysis can be used to remove it from the body. There is no convincing data to support initiating hemodialysis for the prevention or treatment of nephrogenic systemic fibrosis in patients who are not already on hemodialysis.

Trace amounts of gadolinium can accumulate in the brain (particularly in the dentate nucleus and globus pallidus), as well as in other tissues and remain there for months and years after the administration of GCCAs.

Concentrations detected in the skin and bones exceed the concentration of gadolinium in the brain. Preclinical data indicate that after repeated administration of linear GCCAs, gadolinium accumulates in larger quantities than after repeated administration of macrocyclic GCCAs.

An increase in signal intensity on T₁-weighted images of the brain was observed after multiple administrations of GCCAs even in patients with normal renal function. The clinical significance of gadolinium accumulation in the brain is unknown.

There are a small number of reports of pathological skin changes, including the development of gadolinium-associated plaques in patients with normal renal function. There have been post-marketing reports of adverse events affecting several organ systems in patients with normal renal function. A causal relationship with gadolinium has not been established. These reactions include: weakness, asthenia, pain syndromes. As well as various groups of symptoms from the nervous system, skin, musculoskeletal system.

Although the clinical consequences of gadolinium accumulation in patients with normal renal function have not been established, a number of patients may be at increased risk. These include patients requiring repeated contrast administration, pregnant women and children.

To minimize the potential risks associated with gadolinium accumulation, it is recommended to use the lowest effective dose of the drug and perform a thorough risk/benefit assessment before re-administering the drug. Use only as a second-line drug. When it is not possible to use macrocyclic gadolinium-containing drugs.

In patients taking beta-blockers, the manifestations of anaphylaxis when using gadodiamide may be atypical and mistakenly taken for vagal reactions.

Hypersensitivity reactions in this group of patients may be more severe. Also, in patients with severe heart disease (e.g., severe heart failure, CAD), more severe cardiovascular reactions may be observed.

In patients suffering from epilepsy or brain diseases, the risk of developing seizures may be increased, as has been occasionally observed with the use of other drugs in this class. When conducting studies in such patients, precautions should be taken (e.g., monitor the patient). Equipment and medications necessary for emergency therapy should be available in case of seizures.

When using gadolinium-containing drugs, the possibility of accumulation of the active substance in the brain and other organs must be taken into account, and therefore they should be used only in cases of extreme necessity, when alternative diagnostic methods are not possible, and in the minimum possible doses that allow obtaining the necessary image.

Use in pediatrics

Gadodiamide is contraindicated for use in newborns under 4 weeks of age. Due to the immaturity of renal function in infants under 1 year of age, Gadodiamide in such patients should be used only after a careful case assessment.

There is no experience with the use of gadodiamide in infants younger than 6 months with severe hepatic or renal impairment, as well as in preterm newborns younger than 4 weeks or with a gestational age of less than 30 weeks.

Gadolinium accumulates in the brains of children, and its amount and distribution are similar to those in adult patients. The developing brain of a child may be more susceptible to potential side effects due to gadolinium exposure.

Elderly patients

Since elderly patients may have slowed renal clearance of gadodiamide, it is particularly important to examine patients over 65 years of age for the presence of renal impairment.

Effect on the ability to drive vehicles and mechanisms

No studies on the effect on the ability to drive vehicles and mechanisms have been conducted. It is not recommended to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions for 24 hours after the study.

Drug Interactions

It may affect the results of measuring plasma calcium concentration when using conventional complexometric (colorimetric) methods. It may also distort the results of measuring other electrolytes (e.g., iron), so the use of these methods is not recommended in the first 12-24 hours after administration of the drug containing Gadodiamide.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.