IOHEXOL

The dosage depends on the type of investigation and the technique used. Usually the same iodine concentration and volume is used as for other iodinated X-ray contrast media in current use. Adequate hydration should be assured before and after administration as for other contrast media.

For intravenous, intra-arterial and intrathecal use, and use in body cavities. w. w. w. w. Phlebography (leg) 240 mg I/ml or 300 mg I/ml 20-100 ml/leg Digital subtraction angiography 140 mg I/ml Up to 3 ml per kg body weight Adults 300 mg I/ml or 350 mg I/ml 20 - 60 ml/inj.

w. w. CT enhancement Adults 140 mg I/ml or 240 mg I/ml or 300 mg I/ml or 350 mg I/ml 100 -400 ml 100-250 ml 100-200 ml 100-150 ml Guidelines for intra-arterial use: Indication Concentration Volume Comments Arteriographies Arch aortography 300 mg I/ml 30-40 ml/inj.

Selective cerebral 300 mg I/ml 5-10 ml/inj. Aortography 350 mg I/ml 40-60 ml/inj. Femoral 300 mg I/ml or 350 mg I/ml 30-50 ml/inj. Various 300 mg I/ml depending on type of examination Cardioangiography Adults Left ventricle and aortic root inj 350 mg I/ml 30-60 ml/inj.

Selective coronary arteriography 350 mg I/ml 4-8 ml/inj. ) Digital subtraction angiography Adults 140 mg I/ml or 240 mg I/ml or 300 mg I/ml 4 - 10 ml/inj. 1 - 15 ml/inj. 1 - 15 ml/inj. Children 140 mg I/ml Dependent upon age, weight and pathology Guidelines for intrathecal use: Indication Concentration Volume Comments Lumbar and thoracic myelography (lumbar injection) 240 mg I/ml 8 - 12 ml Cervical myelography (lumbar injection) 240 mg I/ml or 300 mg I/ml 10-12 ml 7 - 10 ml Cervical myelography (lateral cervical injection) 240 mg I/ml or 300 mg I/ml 6 - 10 ml 6 - 8 ml CT cisternography 240 mg I/ml 4 - 12 ml (lumbar injection) To minimize possible adverse reactions a total dose of 3 g iodine should not be exceeded.

5 - 2 ml Gastrointestinal studies 350 mg I/ml 10-20 ml For doses not possible using this product, there are other products available with Iohexol dosages lower than 300 mg I/ml 647 mg/ml. For elderly patients, patients with hepatic and/or renal impairments, the usual/proposed doses for adults can be used.

The listed frequencies are based on internal clinical documentation and published large scale studies, comprising more than 200,000 patients.

The frequencies of undesirable effects are defined as follows:

Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data). General (applies to all forms of use of iodinated radiological contrast media) Below are listed possible general side effects in relation with radiological procedures, which include the use of non-iodinated monomeric contrast media.

For side effects specific to mode of administration, please refer to these specific sections. Hypersensitivity reactions may occur irrespective of the dose and mode of administration And mild symptoms may represent the first signs of a serious anaphylactic reaction/shock.

Administration of the contrast medium must be discontinued immediately and, if necessary, specific therapy instituted via the vascular access. A transient increase in S-creatinine is common after iodinated radiological contrast media, contrast induced nephropathy may occur.

Iodism or ‘iodine mumps’ is a very rare complication of iodinated contrast media resulting in swelling and tenderness of the salivary glands for up to approximately 10 days after the examination.

Immune system disorders:

Rare: Hypersensitivity (may be life-threatening or fatal) including dyspnoea, rash, erythema, urticaria, pruritus, skin reaction, conjunctivitis, coughing, rhinitis, sneezing, vasculitis, angio oedema, laryngeal oedema, laryngospasm, bronchospasm or non-cardiogenic pulmonary oedema.

They may appear either immediately after the injection and may be indicative of the beginning of a state of shock. Hypersensitivity related skin reactions may appear up to a few days after the injection.

Very rare:

Anaphylactic/anaphylactoid reaction (may be life-threatening or fatal).

Not known:

Anaphylactic/anaphylactoid shock (may be life-threatening or fatal).

Nervous system disorders:

Uncommon: Headache Very rare: Dysgeusia (transient metallic taste), syncope vasovagal.

Cardiac disorders:

Rare: Bradycardia.

Vascular disorders:

Very rare: Hypertension, hypotension.

Gastrointestinal disorders:

Uncommon: Nausea.

Rare:

Vomiting, abdominal pain.

Very rare:

Diarrhoea.

Not known:

Salivary gland enlargement.

General disorders and administration siteconditions:

Common: Feeling hot Uncommon: Hyperhidrosis, cold feeling, vasovagal reactions.

Rare:

Pyrexia.

Very rare:

Shivering (chills). Intravascular use (Intra-arterial and Intravenous use) Please first read the section labelled ‘General’. Below, only undesirable events during intravascular use of non- ionic monomer contrast media are described. The nature of the undesirable effects specifically seen during intraarterial use depends on the site of injection and dose given.

Selective arteriographies and other procedures in which the contrast medium reaches a particular organ in high concentrations may be accompanied by complications in that particular organ.

Blood and lymphatic system disorders:

Not known: Thrombocytopenia.

Endocrine disorders:

Not known: Thyrotoxicosis, transient hypothyroidism.

Psychiatric disorders:

Not known: Confusion, agitation, restlessness, anxiety.

Nervous system disorders:

Rare: Dizziness, paresis, paralysis, photophobia, somnolence.

Very rare:

Seizures, disturbance in consciousness, cerebrovascular accident, stupor, sensory abnormalities (including hypoaesthesia), paraesthesia, tremor.

Not known:

Transient motor dysfunction (including speech disorder, aphasia and dysarthria), transient contrast induced encephalopathy (including transient memory loss, disorientation, coma, retrograde amnesia, hemiparesis, disorientation and brain oedema).

Eye disorders:

Rare: Visual impairment (including diplopia and blurred vision) photophobia.

Not known:

Transient cortical blindness.

Ear and labyrinth disorders:

Not known: Transient hearing loss.

Cardiac disorders:

Rare: Arrhythmia (including bradycardia, tachycardia).

Very rare:

Myocardial infarction, chest pain.

Not known:

Severe cardiac complications (including cardiac arrest, cardio-respiratory arrest), cardiac failure, spasm of the coronary arteries, cyanosis.

Vascular disorders:

Very rare: Flushing.

Not known:

Shock, arterial spasm, thrombophlebitis, venous thrombosis.

Respiratory, thoracic and mediastinal disorders:

Common: Transient changes in respiratory rate, respiratory distress Rare: Cough, respiratory arrest.

Very rare:

Dyspnoea.

Not known:

Severe respiratory symptoms and signs, pulmonary oedema, acute respiratory distress syndrome, bronchospasm, laryngospasm, apnoea, aspiration, asthmatic attack.

Gastrointestinal disorders:

Rare: Diarrhoea.

Not known:

Aggravation of pancreatitis.

Skin and subcutaneous tissue disorders:

Rare: Rash, pruritus, urticaria.

Not known:

Angioedema, bullous dermatitis, Stevens-Johnson syndrome, erythema multiformae, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms, induced psoriasis flare-up, erythema, drug eruption, skin exfoliation.

Musculoskeletal and connective tissue disorders:

Not known: Arthralgia, muscular weakness, musculoskeletal spasm, back pain.

Renal and urinary disorders:

Uncommon: Acute kidney injury.

Not known:

Blood creatinine increased.

General disorders and administration site conditions:

Uncommon: Pain and discomfort.

Rare:

Asthenic conditions (including malaise, fatigue).

Not known:

Administration site reactions, including extravasation.

Injury, poisoning and procedural complications:

Not known: Iodism. Intrathecal use Please first read the section ‘General’. Below, only undesirable event with frequency during intrathecal use of nonionic monomer contrast media are described. Undesirable effects following intrathecal use may be delayed and present some hours or even days after the procedure.

The […]

Special precautions for using non-ionic monomeric contrast media in general Hypersensitivity A positive history of allergy, asthma or untoward reactions to iodinated contrast media indicates the need for special caution. Any application of contrast media should, therefore, be preceded by a detailed medical history, in patients with allergic diathesis and in patients with known hypersensitivity reactions a very strict indication is required.

Premedication with corticosteroids or histamine H1 and H2 antagonists might be considered in patients at risk for intolerance, they may however not prevent anaphylactic shock, they may actually mask initial symptoms. In patients with bronchial asthma especially the risk of bronchospasm is increased.

The risk of serious reactions in connection with use of Iohexol is regarded as minor. However iodinated contrast media may provoke serious, life-threatening, fatal anaphylactic/anaphylactoid reactions or other manifestations of hypersensitivity.

Independent of quantity and route of administration, symptoms such as angio-oedema, conjunctivitis, coughing, pruritus, rhinitis, sneezing and urticaria may be indicative of a serious anaphylactoid reaction requiring treatment. A course of action should therefore be planned in advance, with necessary drugs and equipment, medical experience and skilled personnel available for immediate treatment, should a serious reaction occur.

In imminent state of shock, administration of the contrast medium must be terminated immediately and - if necessary - specific intravenous treatment must be initiated. It is advisable always to use an indwelling cannula or catheter for quick intravenous access throughout the entire X-ray procedure.

Patients using beta-adrenergic blocking agents, particularly asthmatic patients, may have a lower threshold for bronchospasm and are less responsive to treatment with beta agonists and adrenaline, which may necessitate the use of higher doses.

These patients may also exhibit atypical symptoms of anaphylaxis. These could be misconstrued as a vagal reaction. Usually, hypersensitivity reactions become manifest as minor respiratory or cutaneous symptoms such as mild difficulties of breathing, skin reddening(erythema), urticaria, pruritus or facial oedema.

Severe reactions such as angioedema, subglottis oedema, bronchial spasms and shock are rare. These reactions usually occur within one hour following application of the contrast medium. In rare cases, hypersensitivity may occur (after hours or days), but these cases are rarely life threatening, and mainly affect the skin.

Hydration Adequate hydration should be assured before and after contrast media administration. If necessary, the patient should be hydrated intravenously until excretion of the contrast medium is complete. This applies especially to patients with dys- and paraproteinaemias like multiple myeloma, diabetes mellitus, renal dysfunction, hyperuricaemia as well as to infants, small children, elderly patients and patients in bad general condition.

In patients at risk the water and electrolyte metabolism must be controlled and symptoms of a dropping serum calcium level must be taken care of. Due to the risk of dehydration, induced by diuretics, at first water and electrolyte rehydration is necessary to limit the risk of acute kidney injury.

Cardio-circulatory reactions Care should also be taken in patients with serious cardiac disease /cardio-circulatory disease and pulmonary hypertension as they may develop haemodynamic changes or arrhythmias. 8). Patients with cardiac insufficiency, severe coronary heart disease, instable angina pectoris, valvular diseases, previous myocardial infarction, coronary bypass and pulmonary hypertension are especially predisposed for cardiac reactions.

In elderly patients and patients with pre-existing cardiac diseases, reactions with ischemic changes in the ECG and arrhythmia occur more frequently. In patients with cardiac insufficiency intravasal injection of contrast media can induce pulmonary oedema.

CNS disturbances Patients with acute cerebral pathology, tumours or a history of epilepsy are predisposed for seizures and merit particular care. Also alcoholics and drug addicts have an increased risk for seizures and neurological reactions.

8). Contrast encephalopathy may manifest with symptoms and signs of neurological dysfunction such as headache, visual disturbance, cortical blindness, confusion, seizures, loss of coordination, hemiparesis, aphasia, unconsciousness, coma and cerebral oedema.

Symptoms usually occur within minutes to hours after administration of iohexol, and generally resolve within days. Factors which increase blood-brain barrier permeability will ease the transfer of contrast media to brain tissue and may lead to possible CNS reactions for instance encephalopathy.

Caution is advised in intravascular application to patients with acute cerebral infarction or acute intracranial bleeding as well as in patients with diseases causing disturbance of the blood-brain barrier, and in patients with cerebral oedema, acute demyelinisation or advanced cerebral atherosclerosis.

If contrast encephalophy is suspected, administration of iohexol should be discontinued and appropriate medical management should be initiated. Neurological symptoms caused by metastases, degenerative or inflammatory processes can be aggravated by application of contrast media.

Patients with symptomatic cerebrovascular disease, previous stroke or frequent transitory ischemic attacks are at increased risk for contrast medium-induced neurological complications following intra-arterial injection. Intra- arterial injection of contrast media may induce vasospasms with resulting in cerebral ischemic phenomena.

A […]

1. • Manifest thyrotoxicosis. There are no clear, absolute contraindications for the use of non-ionic uro-angiographic contrast media.