Prohance (Solution) Instructions for Use

Marketing Authorization Holder

Bracco Suisse SA (Switzerland)

Manufactured By

Bipso, GmbH (Germany)

Labeled By

FAMAR ITALIA, S.p.A. (Italy)

ATC Code

V08CA04 (Gadoteridol)

Active Substance

Gadoteridol (Rec.INN registered by WHO)

Dosage Form

Prohance

Solution for intravenous administration 279.3 mg/ml: 10 ml, 15 ml, or 20 ml fl. 1 pc.

Dosage Form, Packaging, and Composition

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

Clinical-Pharmacological Group

Contrast diagnostic agent for magnetic resonance imaging

Pharmacotherapeutic Group

Contrast agent for MRI

Pharmacological Action

Diagnostic agent. Non-ionic paramagnetic contrast medium for magnetic resonance imaging (MRI). When localized in a magnetic field, Gadoteridol shortens the longitudinal (T1) relaxation time of water protons in the tissues of the examined areas. In recommended doses, the effect is observed with the greatest sensitivity in T1-weighted image sequences.

Gadoteridol does not cross the intact blood-brain barrier (BBB), and thus does not accumulate in the intact brain or in pathological foci with an intact BBB, such as cysts, formed postoperative scars, etc. However, damage to the BBB or normal vascularization allows gadoteridol to penetrate into such pathological foci as neoplasms, abscesses, and subacute infarctions.

Pharmacokinetics

The pharmacokinetics of gadoteridol after intravenous administration to healthy subjects follows a two-compartment open model with distribution and elimination half-lives (T_1/2) of approximately 0.20±0.04 h and 1.57±0.08 h, respectively.

Gadoteridol is eliminated exclusively by the kidneys, with 94.4±4.8% of the administered dose excreted within 24 hours after injection. No detectable biotransformation or decomposition of gadoteridol was found.

The essentially identical renal and plasma clearance rates of gadoteridol (1.41±0.33 ml/min/kg and 1.50±0.35 ml/min/kg, respectively) demonstrate the absence of elimination-kinetic changes of gadoteridol during its passage through the kidneys, as well as the actual excretion of gadoteridol by the kidneys. The volume of distribution (V_d) of gadoteridol (204±58 ml/kg) is identical to the volume of extracellular fluid, and its clearance is similar to the clearance of substances undergoing glomerular filtration.

Indications

For MRI – to visualize foci with impaired blood supply to the brain and spinal cord and surrounding tissues, as well as foci with a disrupted BBB.

For whole-body MRI, including the head, neck, liver, breasts, musculoskeletal system, and soft tissues.

ICD codes

Dosage Regimen

Administered intravenously at a dose of 0.1 mmol/kg.

For adult patients with suspected brain metastases or other pathological foci with less contrast accumulation, the recommended dose is 0.3 mmol/kg.

The benefit/risk should be carefully assessed when using gadoteridol in children aged 6 months to 1 year due to the incompletely developed excretory system in children of this age. The dose should not exceed 0.1 mmol/kg, and the use of more than one dose during a single examination is not recommended. Re-administration is possible only after more than 7 days.

Adverse Reactions

Immune system disorders: uncommon – anaphylactic/anaphylactoid reactions.

Psychiatric disorders: rare – anxiety.

Nervous system disorders: uncommon – headache, paresthesia, dizziness, taste alteration; rare – decreased mental capacity, epileptiform seizures, coordination impairment; unknown – loss of consciousness, vasovagal reactions.

Eye disorders: uncommon – increased lacrimation.

Ear and labyrinth disorders: rare – tinnitus.

Cardiac and vascular disorders: uncommon – decreased blood pressure, sensation of “flushing”; rare – tachycardia; unknown – increased R-R interval.

Respiratory, thoracic and mediastinal disorders: rare – laryngospasm, wheezing, dyspnea, rhinitis, cough, chest pain; unknown – pulmonary edema, respiratory arrest.

Gastrointestinal disorders: common – nausea; uncommon – dry mouth, vomiting; rare – abdominal pain, tongue swelling and/or itching, gingivitis, diarrhea, increased salivation, difficulty swallowing.

Skin and subcutaneous tissue disorders: uncommon – pruritus, skin rash, increased sweating.

Allergic reactions: uncommon – urticaria; rare – facial edema.

Musculoskeletal and connective tissue disorders: rare – muscle stiffness.

Renal and urinary disorders: unknown – acute renal failure.

General disorders and administration site conditions: common – pain at the injection site, asthenia; rare – hyperthermia.

Contraindications

Children under 18 years of age for whole-body MRI and children under 6 months of age for all other indications; hypersensitivity to gadoteridol or other contrast agents containing gadolinium.

Use in Pregnancy and Lactation

Gadoteridol should not be used in pregnant women, except in cases where the intended benefit to the mother outweighs the potential risk to the fetus, and such an examination is prescribed by a doctor due to absolute necessity.

There are no data on the excretion of gadoteridol into breast milk. Therefore, if it is necessary to perform the examination during breastfeeding, breastfeeding should be discontinued before administration of the drug and not resumed for at least 24 hours after the examination.

Use in Hepatic Impairment

The drug is approved for use in hepatic impairment.

Pediatric Use

Contraindicated for use under 18 years of age for whole-body MRI and under 6 months of age for all other indications.

Special Precautions

Use with caution: in children aged 6 months to 2 years for all indications except whole-body MRI; since Gadoteridol is eliminated by the kidneys, it should be used with caution in patients with renal impairment (GFR <30 ml/min/1.73 m²); in patients with acute renal failure against the background of hepatorenal syndrome; in patients in the perioperative period of liver transplantation; in patients with epilepsy; in patients with cardiovascular diseases; in patients with circulatory disorders, with disorders of the central nervous system; in patients with a history of allergic diseases.

Gadoteridol should be used only by specialists with clinical experience in performing MRI.

When using drugs containing gadolinium, it is necessary to consider the possibility of accumulation of the active substance in the brain and other organs, 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.

There are reports of nephrogenic systemic fibrosis associated with the use of gadolinium-containing contrast agents in patients with severe renal impairment (GFR < 30 ml/min/1.73 m²). In patients on hemodialysis, it can be used briefly to remove gadoteridol from the body. However, for patients who have not previously undergone hemodialysis, it is not justified to initiate it to prevent or treat nephrogenic systemic fibrosis.

Since anaphylactic reactions have been reported after the administration of gadoteridol, special attention should be paid to the availability of drugs and appropriate equipment for emergency measures. The risk of developing hypersensitivity reactions is higher in cases of: previous reaction to a contrast agent; bronchial asthma; history of allergic diseases (bronchial asthma, hay fever). Most of these reactions develop within 0.5-1 hour after administration. However, in rare cases, delayed reactions may develop.

It should be taken into account that patients taking beta-blockers may be resistant to the treatment of hypersensitivity reactions with drugs that have beta-agonistic action.

In patients predisposed to developing allergic reactions, the decision to use gadoteridol should be made only after a careful assessment of the risk/benefit ratio.

After a diagnostic procedure using gadoteridol, monitoring of the patient’s condition is recommended.

MRI with contrast agents containing other gadolinium chelate complexes should not be performed within 7 hours after the use of gadoteridol.

When administering the contrast agent in patients with epilepsy, CNS lesions, or a history of seizures, a decrease in the seizure threshold may be observed. Patient monitoring is necessary.

The physician should have medications necessary for the rapid relief of seizures available.

Effect on ability to drive vehicles and operate machinery

Given the possibility of adverse reactions in the form of dizziness, such activities should be avoided for 24 hours after the administration of gadoteridol.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.