Primovist^® Short Product Information

Primovist 0.25 mmol/mL solution for injection.

Composition: 1 mL solution for injection contains 181.43 mg gadoxetic acid, Gd-EOB-DTPA disodium, equivalent to 0.25 mmol Gd-EOB-DTPA disodium.

Indications: Primovist is indicated for the detection of focal liver lesions and provides information on the character of lesions in T1-weighted magnetic resonance imaging (MRI). This medical product is for diagnostic use only.

Contraindications: Hypersensitivity to the active substance or to any of the excipients.

Undesirable effects: During the clinical development phase the overall incidence of adverse reactions which were classified as related was below 5 %. Most of the undesirable effects were transient and of mild to moderate intensity. No individual adverse reaction reached a frequency greater than 1/100 • Nervous system disorders headache, dizziness, paresthesia, taste disturbance, vertigo, akathisia, tremor, parosmia • Cardiac disorders bundle branch block, palpitation • Vascular disorders flushing, hypertension • Respiratory, thoracic and mediastinal disorders dyspnea, respiratory distress
• Gastrointestinal disorders vomiting, nausea, dry mouth, oral discomfort, salivary hypersecretion • Skin and subcutaneous tissue disorders rash, pruritus, maculopapular rash, hyperhidrosis
• General disorders and administration site conditions chest pain, injection site reactions, feeling hot, chills, discomfort fatigue,malaise, feeling abnormal. Laboratory changes as elevated serum iron, elevated bilirubin, increases in liver transaminases, decrease of hemoglobin, elevation of amylase, leucocyturia, hyperglycemia, elevated urine albumin, hyponatremia, elevated inorganic phosphate, decrease of serum proteine, leucocytosis, hypokalemia, elevated LDH were reported in clinical trials. ECGs were regularly monitored during clinical studies and transient QT prolongation was observed in some patients without any associated adverse clinical events. In very rare cases anaphylactoid reactions leading to shock may occur.

Precautions: General information The usual safety precautions for MRI must be observed, e.g. exclusion of cardiac pacemakers and ferromagnetic implants. Diagnostic procedures that involve the use of contrast agents should be carried out under the direction of a physician with the prerequisite training and a thorough knowledge of the procedure to be performed. The patient should refrain from eating for two hours prior to examination to reduce the risk of aspiration, as nausea and vomiting are known possible adverse reactions. Whenever possible, the contrast agent should be administered with the patient lying down. After the injection, the patient should be kept under observation for at least 30 minutes, since experience with contrast media shows that the majority of undesirable effects occur within this time. Caution should be exercised in patients with severe renal impairment due to reduced elimination capacity of Gd-EOB-DTPA. Patients with renal impairment: There have been reports of Nephrogenic Systemic Fibrosis (NSF) associated with use of some gadolinium-containing contrast agents in patients with

• acute or chronic severe renal impairment (GFR< 30ml/min /1.73 m2) or
• acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period.

As there is a possibility that NSF may occur with Primovist, it should therefore only be used in these patients after careful risk/benefit assessment and if the diagnostic information is essential and not available with non-contrast enhanced magnetic resonance imaging (MRI).

All patients should be screened, in particular patients over the age of 65, for renal dysfunction by obtaining a history and/or laboratory tests.

Haemodialysis shortly after Primovist administration in patients currently receiving haemodialysis may be useful at removing Primovist from the body.

There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in patients not already undergoing haemodialysis.

Caution should be exercised in patients with severe renal impairment due to reduced elimination capacity of Gd-EOB-DTPA.Caution should be exercised when Primovist is administered to patients with severe cardiovascular problems because only limited data are available so far. It cannot be excluded that Gd-EOB-DTPA may cause torsade de points arrhythmias in an individual patient. Hypersensitivity Allergy-like reactions, including shock, are known to be rare events after administration of gadolinium-based MRI contrast media. Patients with a history of allergic/allergoid reactions or bronchial asthma might be at higher risk for severe reactions. Most of these reactions occur within half an hour after administration of contrast media. However, as with other contrast media of this class, delayed reactions may occur after hours to days in rare cases. Adequate measures for resuscitation should be made readily available prior to administration of contrast agents. Hypersensitivity reactions can be more intense in patients on beta-blockers, particularly in the presence of bronchial asthma. It should be considered that patients on beta-blockers may be refractory to standard treatment of hypersensitivity reactions with beta-agonists. If hypersensitivity reactions occur, injection of the contrast medium must be discontinued immediately. Local intolerance Intramuscular administration may cause local intolerance reactions including focal necrosis and should therefore be strictly avoided.

Date of preparation of the text: October 2007. Please note! For current prescribing information refer to the package insert and/or contact your local BSP organisation. Bayer Pharma AG, 13342 Berlin, Germany. Adverse reactions can be reported to GPV.CaseProcessing@bayerhealthcare.com