Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Bayer plc, 400 South Oak Way, Reading, RG2 6AD
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
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.
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.
Prior to administration of Primovist, it is recommended that all patients are screened for renal dysfunction by obtaining laboratory tests.
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). Patients undergoing liver transplantation are at particular risk since the incidence of acute renal failure is high in this group. As there is a possibility that NSF may occur with Primovist, it should therefore be avoided in patients with severe renal impairment and in patients in the perioperative liver transplantation period unless the diagnostic information is essential and not available with non-contrast enhanced MRI.
Haemodialysis shortly after Primovist administration 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.
As the renal clearance of gadoxetate may be impaired in the elderly, it is particularly important to screen patients aged 65 years and older for renal dysfunction.
Caution should be exercised when Primovist is administered to patients with severe cardiovascular problems because only limited data are available so far.
Primovist should not be used in patients with uncorrected hypokalemia.
Primovist should be used with special care in patients
Primovist may cause transient QT-prolongation in individual patients. (see section 5.3).
Allergy-like reactions, including shock, are known to be rare events after administration of gadolinium-based MRI contrast media. 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. Medication for the treatment of hypersensitivity reactions as well as preparedness for institution of emergency measures are necessary.
The risk of hypersensitivity reactions is higher in case of:
In patients with an allergic disposition (especially with a history of the above mentioned conditions) the decision to use Primovist must be made after particularly careful evaluation of the risk-benefit ratio.
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.
Intramuscular administration may cause local intolerance reactions including focal necrosis and must therefore be strictly avoided (see section 5.3).
After administration of gadoxetate disodium gadolinium can be retained in the brain and in other tissues of the body (bones, liver, kidneys, skin) and can cause dose-dependent increases in T1-weighted signal intensity in the brain, particularly in the dentate nucleus, globus pallidus, and thalamus. Clinical consequences are unknown. The possible diagnostic advantages of using gadoxetate disodium in patients who will require repeated scans should be weighed against the potential for deposition of gadolinium in the brain and other tissues.
This medicinal product contains 11.7 mg sodium per ml, equivalent to 0.585% of the WHO recommended maximum daily intake of 2 g sodium for an adult, (4.1% (82 mg) based on the amount given to a 70 kg person). The dosage is 0.1 ml/kg body weight.
As transport of gadoxetate to the liver may be mediated by OATP transporters it cannot be excluded that potent OATP inhibitors could cause drug interactions reducing the hepatic contrast effect. However, no clinical data have been presented to support that theory.
An interaction study in healthy subjects demonstrated that the co-administration of erythromycin did not influence efficacy and pharmacokinetics of Primovist. No further clinical interaction studies with other medicinal products have been performed.
Elevated levels of bilirubin or ferritin can reduce the hepatic contrast effect of Primovist (see section 5.1).
Serum iron determination using complexometric methods (e.g. Ferrocine complexation method) may result in false values for up to 24 hours after the examination with Primovist because of the free complexing agent contained in the contrast medium solution.
There are no data from the use of gadoxetate in pregnant women. Animal studies have shown reproductive toxicity at repeated high doses (see section 5.3). Primovist should not be used during pregnancy unless the clinical condition of the woman requires use of gadoxetate.
Gadolinium containing contrast agents are excreted into breast milk in very small amounts (see section 5.3). At clinical doses, no effects on the infant are anticipated due to the small amount excreted in milk and poor absorption from the gut. Continuing or discontinuing breast feeding for a period of 24 hours after administration of Primovist, should be at the discretion of the doctor and lactating mother.
Animal studies did not indicate impairment of fertility.
Primovist has no influence on the ability to drive and use machines.
The overall safety profile of Primovist is based on data from more than 1,900 patients in clinical trials, and from post-marketing surveillance.
The most frequently observed adverse drug reactions (≥0.5%) in patients receiving Primovist are nausea, headache, feeling hot, blood pressure increased, back pain and dizziness.
The most serious adverse drug reaction in patients receiving Primovist is anaphylactoid shock.
Delayed allergoid reactions (hours later up to several days) have been rarely observed.
Most of the undesirable effects were transient and of mild to moderate intensity.
The adverse drug reactions observed with Primovist are represented in the table below. They are classified according to System Organ Class (MedDRA version 12.1). The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions.
Adverse drug reactions from clinical trials are classified according to their frequencies. Frequency groupings are defined according to the following convention: common: ≥1/100 to <1/10; uncommon: ≥1/1,000 to <1/100; rare: ≥1/10,000 to <1/1,000. The adverse drug reactions identified only during post-marketing surveillance, and for which a frequency could not be estimated, are listed under ‘not known’.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Table 1. Adverse drug reactions reported in clinical trials or during post-marketing surveillance in patients treated with Primovist:
Not known: Hypersensitivity/anaphylactoid reaction (e.g. shock*, hypotension, pharyngolaryngeal edema, urticaria, face edema, rhinitis, conjunctivitis, abdominal pain, hypoesthesia, sneezing, cough, pallor)
Common: Headache
Uncommon: Vertigo, Dizziness, Dysgeusia, Paresthesia, Parosmia
Rare: Tremor, Akathisia
Not known: Restlessness
Rare: Bundle branch block, Palpitation
Not known: Tachycardia
Uncommon: Blood pressure increased, Flushing
Uncommon: Respiratory disorders (Dyspnea*, Respiratory distress)
Common: Nausea
Uncommon: Vomiting, Dry mouth
Rare: Oral discomfort, Salivary hypersecretion
Uncommon: Rash, Pruritus**
Rare: Maculopapular rash, Hyperhidrosis
Uncommon: Back pain
Uncommon: Chest pain, Injection site reactions (various kinds)***, Feeling hot, Chills, Fatigue, Feeling abnormal
Rare: Discomfort, Malaise
* Life-threatening and/or fatal cases have been reported. These reports originated from post-marketing experience.
** Pruritus (generalized pruritus, eye pruritus)
*** Injection site reactions (various kinds) comprise the following terms: Injection site extravasation, injection site burning, injection site coldness, injection site irritation, injection site pain
Laboratory changes such 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 protein, 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.
Cases of nephrogenic systemic fibrosis (NSF) have been reported with other gadolinium-containing contrast agents (see section 4.4).
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, www.mhra.gov.uk/yellowcard, or search for MHRA Yellow Card in the Google Play or Apple App Store.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
