Iopromide

In patients with acute kidney failure or severe chronic kidney disease biguanide elimination can be reduced leading to accumulation and the development of lactic acidosis. As the application of iopromide can lead to renal impairment or an aggravation of renal impairment, patients treated with metformin may be at an increased risk of developing lactic acidosis, especially those with prior renal impairment. Based on measurements of kidney function, the need for an interruption in the metformin administration should be considered.

Diagnosis and treatment of thyroid disorders with thyrotropic radioisotopes may be impeded for up to several weeks after administration of Ultravist due to reduced radioisotope uptake.

The intravascular injection of iopromide may precipitate pulmonary oedema in patients with heart failure.

Since iopromide is excreted almost exclusively in an unchanged form via the kidneys, the elimination of iopromide is prolonged in patients with renal impairment. In order to reduce the risk of additional contrast media-induced renal impairment in patients with pre-existing renal impairment, the minimum possible dose should be used in these patients.

Patients with CNS disorders may be at increased risk to have neurological complications in relationship to iopromide administration. Neurological complications are more frequent in cerebral angiography and related procedures.

Caution should be exercised in situations in which there may be a reduced seizure threshold, such as a previous history of seizures and the use of certain concomitant medication.

Factors which increase blood-brain barrier permeability facilitate the passage of the contrast medium into cerebral tissue, possibly leading to CNS reactions.

Patients with pheochromocytoma may be at an increased risk to develop a hypertensive crisis.

Patients with significant cardiac disease or severe coronary artery disease are at an increased risk of developing clinically relevant haemodynamic changes and arrhythmia.

Caution must also be exercised in alcoholics because of the possibility of a reduced seizure threshold.

The use of certain concomitant medication may reduce the seizure threshold, thus increasing the risk of a contrast medium related reaction.

The administration of iopromide may aggravate the symptoms of myasthenia gravis.

Previous treatment (up to several weeks) with interleukin-2 is associated with an increased risk for delayed reactions to iopromide.

Adequate and well-controlled studies in pregnant women have not been conducted. It has not been sufficiently demonstrated that non ionic contrast media are safe for use in pregnant patients. Since, wherever possible, radiation exposure should be avoided during pregnancy, the benefits of any X-ray examination – with or without contrast media – should be carefully weighed against the possible risk.

Animal studies do not indicate harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development following diagnostic application of iopromide in humans.

Safety of iopromide for nursed infants has not been investigated. Contrast media are poorly excreted in human breast milk. Harm to the nursed infant is not likely.

No data available.

Summary of the safety profile

The overall safety profile of iopromide is based on data obtained in pre-marketing studies in more than 3,900 patients and post-marketing studies in more than 74,000 patients, as well as data from spontaneous reporting and the literature. The most frequently observed adverse drug reactions (≥4%) in patients receiving iopromide are headache, nausea and vasodilatation.

The most serious adverse drug reactions in patients receiving iopromide are anaphylactoid shock, respiratory arrest, bronchospasm, laryngeal edema, pharyngeal edema, asthma, coma, cerebral infarction, stroke, brain edema, convulsion, arrhythmia, cardiac arrest, myocardial ischemia, myocardial infarction, cardiac failure, bradycardia, cyanosis, hypotension, shock, dyspnea, pulmonary edema, respiratory insufficiency and aspiration.

List of adverse reactions

The adverse drug reactions observed with iopromide are represented below. They are classified according to System Organ Class (MedDRA version 13.0). 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’.

Immune system disorders

Uncommon: Hypersensitivity/Anaphylactoid reactions (Anaphylactoid shock§*, Respiratory arrest§*, Bronchospasm*, Laryngeal*/Pharyngeal*/Face edema, Tongue edema§, Laryngeal/Pharyngeal spasm§, Asthma§*, Conjunctivitis§, Lacrimation§, Sneezing, Cough, Mucosal edema, Rhinitis§, Hoarseness§, Throat irritation§, Urticaria, Pruritus, Angioedema)

Endocrine disorders

Not Known: Thyrotoxic crisis, Thyroid disorder

Psychiatric disorders

Rare: Anxiety

Nervous system disorders

Common: Dizziness, Headache, Dysgeusia

Uncommon: Vasovagal reactions, Confused state, Restlessness, Paraesthesia/Hypoaesthesia, Somnolence

Not Known: Coma*, Cerebral ischaemia/infarction*, Stroke*, Brain edema^a*, Convulsion*, Transient cortical blindness^a, Loss of consciousness, Agitation, Amnesia, Tremor, Speech disorders, Paresis/Paralysis

Eye disorders

Common: Blurred/Disturbed vision

Ear and labyrinth disorders

Not Known: Hearing disorders

Cardiac disorders

Common: Chest pain/discomfort

Uncommon: Arrhythmia

Rare: Palpitations, Cardiac arrest*, Myocardial ischaemia*

Not Known: Myocardial infarction*, Cardiac failure*, Bradycardia*, Tachycardia, Cyanosis*

Vascular disorders

Common: Hypertension, Vasodilatation

Uncommon: Hypotension*

Not Known: Shock*, Thromboembolic events^a, Vasospasm^a

Respiratory thoracic and mediastinal disorders

Uncommon: Dyspnea*

Not Known: Pulmonary edema*, Respiratory insufficiency*, Aspiration*

Gastrointestinal disorders

Common: Vomiting, Nausea

Uncommon: Abdominal Pain

Not Known: Dysphagia, Salivary gland enlargement, Diarrhoea

Skin and subcutaneous tissue disorders

Not Known: Bullous conditions (e.g. StevensJohnson’s or Lyell syndrome), Rash, Erythema, Hyperhydrosis

Musculoskeletal, connective tissue and bone disorders

Not Known: Compartment syndrome in case of extravasationa)

Renal and urinary disorders

Not Known: Renal impairment^a, Acute renal failure^a

General disorders and administration site conditions

Common: Pain, Injection site reactions (various kinds e.g. pain, warmth§, edema§, inflammation§ and soft tissue injury§ in case of extravasation), Feeling hot

Uncommon: Edema

Not Known: Malaise, Chills, Pallor

Investigations

Not Known: Body temperature fluctuation

* life-threatening and/or fatal cases have been reported
^a intravascular use only
^§ identified only during post-marketing surveillance (frequency not known)

In addition to the adverse drug reactions (ADRs) listed above, the following ADRs have been reported with intrathecal use: Chemical meningitis and meningism at an unknown frequency.

In addition to the ADRs listed above, the following ADRs have been reported with use for ERCP: Elevation of pancreatic enzyme levels and pancreatitis at an unknown frequency. The majority of the reactions after myelography or use in body cavities occur some hours after the administration.

Description of selected adverse reactions

Based on experience with other non-ionic contrast media, the following undesirable effects may occur with intrathecal use in addition to the undesirable effects listed above:

Psychosis, neuralgia, paraplegia, aseptic meningitis, back pain, pain in extremities, micturition disorder, EEG Abnormal.