Primovist^® (Solution) Instructions for Use

Marketing Authorization Holder

Bayer, AG (Germany)

ATC Code

V08CA10 (Gadoxetic acid)

Active Substance

Gadoxetic acid (Rec.INN registered by WHO)

Dosage Form

Primovist®

Solution for intravenous administration 0.25 mmol/ml: vials 5 ml, 7.5 ml or 10 ml 1, 5 or 10 pcs.; syringes 5 ml, 7.5 ml or 10 ml 1, 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous administration from colorless to light yellow or brownish, or slightly brownish-yellow, or slightly greenish-yellow, transparent, free from mechanical inclusions.

Excipients: gadoxetic acid trisodium salt – 1 mg, trometamol – 1.211 mg, hydrochloric acid 3.6% – 8.4 mg, sodium hydroxide – 0.264 mg, water for injections – 901.195 mg.

5 ml – vials of colorless glass (1) – cardboard packs^×.
5 ml – vials of colorless glass (5) – cardboard packs^×.
5 ml – vials of colorless glass (10) – cardboard packs^×.
7.5 ml – vials of colorless glass (1) – cardboard packs^×.
7.5 ml – vials of colorless glass (5) – cardboard packs^×.
7.5 ml – vials of colorless glass (10) – cardboard packs^×.
10 ml – vials of colorless glass (1) – cardboard packs^×.
10 ml – vials of colorless glass (5) – cardboard packs^×.
10 ml – vials of colorless glass (10) – cardboard packs^×.
5 ml – syringes of colorless glass (1) – PVC containers (1) – cardboard packs^×.
5 ml – syringes of colorless glass (5) – PVC containers (1) – cardboard packs^×.
5 ml – syringes of colorless glass (10) – PVC containers (1) – cardboard packs^×.
7.5 ml – syringes of colorless glass (1) – PVC containers (1) – cardboard packs^×.
7.5 ml – syringes of colorless glass (5) – PVC containers (1) – cardboard packs^×.
7.5 ml – syringes of colorless glass (10) – PVC containers (1) – cardboard packs^×.
10 ml – syringes of colorless glass (1) – PVC containers (1) – cardboard packs^×.
10 ml – syringes of colorless glass (5) – PVC containers (1) – cardboard packs^×.
10 ml – syringes of colorless glass (10) – PVC containers (1) – cardboard packs^×.
5 ml – syringes of colorless cycloolefin polymer (1) – PVC containers (1) – cardboard packs^×.
5 ml – syringes of colorless cycloolefin polymer (5) – PVC containers (1) – cardboard packs^×.
5 ml – syringes of colorless cycloolefin polymer (10) – PVC containers (1) – cardboard packs^×.
7.5 ml – syringes of colorless cycloolefin polymer (1) – PVC containers (1) – cardboard packs^×.
7.5 ml – syringes of colorless cycloolefin polymer (5) – PVC containers (1) – cardboard packs^×.
7.5 ml – syringes of colorless cycloolefin polymer (10) – PVC containers (1) – cardboard packs^×.
10 ml – syringes of colorless cycloolefin polymer (1) – PVC containers (1) – cardboard packs^×.
10 ml – syringes of colorless cycloolefin polymer (5) – PVC containers (1) – cardboard packs^×.
10 ml – syringes of colorless cycloolefin polymer (10) – PVC containers (1) – cardboard packs^×.

^× with first opening control.

Clinical-Pharmacological Group

Contrast diagnostic agent for magnetic resonance imaging

Pharmacotherapeutic Group

Contrast agent for NMR

Pharmacological Action

Contrast diagnostic paramagnetic ionic agent, it is a stable chelate compound of Gd-EOB-DTPA (gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid).

Due to its paramagnetic properties, it provides enhancement of image contrast during MRI and facilitates the visualization of abnormal structures in the examined organs and tissues.

Pharmacokinetics

After intravenous administration, the active substance rapidly diffuses into the extracellular space.

Seven days after administration, less than 1% of the dose is detected in the bodies of rats and dogs.

High concentrations were found in the kidneys and liver.

The active substance does not penetrate the blood-brain barrier and penetrates the placental barrier to a small extent.

It is excreted equally by the kidneys and with bile.

T_1/2 is about 1 hour.

The total plasma clearance is about 250 ml/min, renal clearance is about 120 ml/min.

In patients with severe renal impairment, T_1/2 slightly increases; in severe renal failure (when hemodialysis is required), T_1/2 increases significantly.

Indications

To enhance contrast during MRI for the detection of focal lesions in the liver in adults.

ICD codes

Dosage Regimen

It is necessary to observe the usual rules adopted for patients with a cardiac pacemaker and a ferromagnetic implant.

Patients should refrain from eating for 2 hours before the examination to reduce the risk of aspiration, as nausea and vomiting are known side effects of all contrast agents.

During the administration of the contrast agent, the patient should be in a lying position.

It is administered by intravenous bolus injection. The recommended dose is 25 µmol/kg of body weight.

Adverse Reactions

From the central nervous system headache, dizziness, paresthesia, akathisia, tremor, agitation.

From the cardiovascular system symptoms of vasodilation, bundle branch block, palpitation, arterial hypertension, tachycardia.

From the digestive system nausea, abdominal pain, vomiting, dry mouth, increased salivation.

From the sensory organs taste perversion, parosmia.

From the respiratory system dyspnea.

Dermatological reactions skin itching, rash, maculopapular rash, increased sweating.

Allergic reactions very rarely – anaphylactoid reactions, anaphylactic shock.

From the body as a whole chills, pain, back and chest pain, asthenia, general malaise, weakness, thermosensitivity.

Other less than 1% – reversible (within 1-4 days) increase in serum iron and bilirubin content.

Contraindications

Hypersensitivity to gadoxetic acid.

Use in Pregnancy and Lactation

If it is necessary to use the drug during pregnancy, the expected benefit of therapy for the mother and the potential risk to the fetus should be carefully weighed.

It is not known whether the active substance is excreted in human breast milk.

Use in Renal Impairment

There are data on the development of nephrogenic systemic fibrosis after the use of gadolinium-containing contrast agents in patients with severe renal impairment and in patients with acute renal failure of any severity due to hepatorenal syndrome or in the perioperative period during liver transplantation. Given this, in cases of renal impairment, gadoxetic acid should be used only after thorough examination and assessment of the benefit-risk ratio for the patient.

Pediatric Use

There is no clinical experience of use in children and adolescents under 18 years of age.

Special Precautions

The risk of developing severe allergic reactions, up to anaphylactic shock, is increased with a history of allergic reactions to any allergens, especially to previously used contrast agents; with bronchial asthma and other allergic diseases.

Most of these reactions develop within 30 minutes after administration, but delayed effects (from several hours to a day) are also possible.

After the administration of gadoxetic acid, manifestations of idiosyncrasy from the cardiovascular, respiratory systems and skin reactions are also possible.

Given this, it is recommended to monitor the patient’s condition for at least 30 minutes after the procedure.

In case of hypersensitivity reactions, the administration of the contrast agent should be stopped immediately and emergency therapy should be carried out.

Do not allow intramuscular administration, as local intolerance reactions, including tissue necrosis, are possible.

Caution is required when using in patients with severe cardiovascular diseases, as clinical data for this category of patients are limited.

In clinical studies, transient prolongation of the QT interval was observed in some cases without any adverse reactions.

There are data on the development of nephrogenic systemic fibrosis after the use of gadolinium-containing contrast agents in patients with severe renal impairment and in patients with acute renal failure of any severity due to hepatorenal syndrome or in the perioperative period during liver transplantation.

Given this, in cases of renal impairment, gadoxetic acid should be used only after thorough examination and assessment of the benefit-risk ratio for the patient.

There is no clinical experience of use in children and adolescents under 18 years of age.

Drug Interactions

Anionic drugs that are predominantly excreted in bile (such as rifampicin) may compete with gadoxetic acid for biliary excretion. Experimental studies have shown that rifamycin antibiotics block the hepatic uptake of gadoxetic acid, leading to a decrease in its contrast properties.

With increased concentrations of bilirubin or ferritin, the contrast properties of gadoxetic acid are reduced.

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.