Gadofosveset

Use of gadofosveset should be avoided in patients with severe renal impairment (GFR <30 ml/min/1.73 m²) and in patients in the perioperative liver transplantation period unless the diagnostic information is essential and not available with non-contrast enhanced magnetic resonance imaging (MRI). If use of gadofosveset cannot be avoided, the dose should not exceed 0.03 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, gadofosveset injections should not be repeated unless the interval between injections is at least 7 days.

In rabbits, an increased number of early resorptions and a slight but significant increase in the number of foetal anomalies (in particular hydrocephalus and malrotated limbs) were observed at doses at which no or slight maternal toxicity was observed (exposure was 2 and 5 times the expected human exposure, respectively). In an animal study, it was shown that less than 1% of the dose of gadofosveset administered enters breast milk.

Hypersensitivity warning

The possibility of a reaction, including serious, life-threatening, fatal, anaphylactoid, or cardiovascular reactions, or other idiosyncratic reactions should always be considered especially in those patients with a known clinical hypersensitivity, previous reaction of contrast media, a history of asthma, or other allergic disorders. Experience with other contrast media shows that the risk of hypersensitivity reactions is higher in those patients. Delayed reactions may occur (after hours to days).

Caution should also be exercised in the following case:

Hypersensitivity reactions: If hypersensitivity reactions occur, administration of the contrast medium must be discontinued immediately and – if necessary – specific therapy instituted via a venous access. It is therefore advisable to use a flexible indwelling cannula for intravenous contrast medium administration. Due to the possibility of severe hypersensitivity reactions after intravenous contrast administration, preparedness for institution of emergency measures is necessary, e.g., appropriate medicinal products, an endotracheal tube, and a respirator should be at hand.

Since gadofosveset is cleared from the body primarily by urinary excretion, caution should be exercised in patients with impaired renal function.

Prior to administration of gadofosveset, 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 <30 ml/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 gadofosveset, 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 gadofosveset administration may be useful at removing gadofosveset 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.

There are no data from the use of gadofosveset in pregnant women. Animal studies have shown reproductive toxicity at repeated high doses. Gadofosveset should not be used during pregnancy unless the clinical condition of the woman requires use of the medicinal product.

Gadolinium containing contrast agents are excreted into breast milk in very small amounts. 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 breast-feeding or discontinuing gadofosveset for a period of 24 hours after administration should be at the discretion of the physician and breast-feeding mother.

No studies on the effects on the ability to drive and use machine have been performed. Uncommonly, dizziness or vision problems may occur with this medicine. If a patient experiences these effects he/she should not drive or use machines.

The most common adverse reactions were pruritus, paresthesia, headache, nausea, vasodilatation, burning sensation and dysgeusia. Most of the adverse reactions were mild to moderate in intensity. Most of the adverse reactions (80%) occurred within 2 hours. Delayed reactions (after hours to days) may occur.

Clinical trial data

Based on clinical trial experience in more than 1,800 patients, the following adverse reactions have been observed.

The list below reports adverse reactions by MedDRA system organ classes (MedDRA SOCs). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Common (≥1/100), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000)

Infections and infestations

Uncommon: Nasopharyngitis

Rare: Cellulitis, Urinary tract infection

Immune system disorders

Uncommon: Hypersensitivity

Metabolism and nutrition disorders

Uncommon: Hyperglycaemia, Electrolyte imbalance (incl. Hypocalcemia)

Rare: Hyperkalemia, Hypokalemia, Hypernatremia, Appetite decreased

Psychiatric disorders

Uncommon: Anxiety, Confusion

Rare: Hallucination, Abnormal dreams

Nervous system disorders

Common: Headache, Paraesthesia, Dysgeusia, Burning sensation

Uncommon: Dizziness (excl. Vertigo), Tremor, Hypoesthesia, Parosmia, Ageusia, Muscle contractions involuntary

Eye disorders

Uncommon: Vision abnormal, Lacrimation increased

Rare: Abnormal sensation in eye, Asthenopia

Ear and labyrinth disorders

Rare: Ear pain

Cardiac disorders

Uncommon: Atrioventricular block first degree, Electrocardiogram QT prolonged, Tachycardia, Electrocardiogram abnormal

Rare: Cardiac flutter, Myocardial ischaemia, Bradycardia, Atrial fibrillation, Palpitations, Electrocardiogram ST segment depression, Electrocardiogram T wave amplitude decreased

Vascular disorders

Common: Vasodilatation (incl. Flushing)

Uncommon: Phlebitis, Hypertension, Peripheral coldness

Rare: Anaphylactoid reaction, Hypotension, Arteriosclerosis

Respiratory, thoracic and mediastinal disorders

Uncommon: Dyspnea, Cough

Rare: Respiratory depression

Gastrointestinal disorders

Common: Nausea

Uncommon: Vomiting, Retching, Diarrhea, Abdominal pain, Pharyngolaryngeal pain, Abdominal discomfort, Flatulence, Hypoesthesia lips, Salivary hypersecretion, Dyspepsia, Dry mouth, Pruritus ani

Skin and subcutaneous tissue disorders

Common: Pruritus

Uncommon: Urticaria, Rash, Erythema, Sweating increased

Rare: Swelling face, Clamminess

Musculoskeletal and connective tissue disorders

Uncommon: Pain in limb, Neck pain, Muscle cramps, Muscle spasms

Rare: Muscle tightness, Sensation of heaviness

Renal and urinary disorders

Uncommon: Haematuria, Microalbuminuria, Glycosuria

Rare: Micturition urgency, Renal pain, Urinary frequency

Reproductive system and breast disorders

Uncommon: Genital pruritus, Genital burning sensation

Rare: Pelvic pain

General disorders and administration site conditions

Common: Feeling cold

Uncommon: Pain, Chest pain, Groin pain, Fatigue, Feeling abnormal, Feeling hot, Injection site pain, Injection site erythema, Injection site coldness

Rare: Pyrexia, Rigors, Weakness, Chest pressure sensation, Injection site thrombosis, Injection site bruising, Injection site inflammation, Injection site burning, Injection site extravasation, Injection site haemorrhage, Injection site pruritus, Sensation of pressure

Injury, poisoning and procedural complications

Rare: Phantom limb pain

Cases of nephrogenic systemic fibrosis (NSF) have been reported with other gadolinium-containing contrast agents.

As with other intravenous contrast agents, this medicinal product can be associated with anaphylactoid/hypersensitivity reactions characterised by cutaneous, respiratory and/or cardiovascular manifestations which may lead to shock.