OPTIRAY

Adults:

Recommended dosage schedule Procedure Dosage Maximum Total Dose Peripheral angiography 10-90 ml 250 ml Venography 50-100 ml 250 ml Left ventriculography 30-50 ml 250 ml Coronary arteriography 1-10 ml 250 ml Visceral angiography 12-60 ml 250 ml Aortography 10-80 ml 250 ml Renal angiography 6-15 ml 250 ml Urography 50-75 ml 150 ml Procedure Dosage Maximum Total Dose Head CT 50-150 ml 150 ml Body CT 25-150 ml 150 ml IA-DSA 5-80 ml 250 ml IV-DSA 30-50 ml 250 ml Elderly: Dosage as for adults.

Where poor demonstration is to be expected, the dosage can be increased to the maximum.

Paediatric population:

The safety and efficacy of Optiray 350 in children have not been established. The medicinal product should therefore not be used in children aged up to 18 years, until further data becomes available. For cerebral, peripheral and visceral angiography and for intravenous urography Optiray 300 may be used in children.

It is recommended that intravascularly administered iodinated contrast agents are warmed up to body temperature prior to injection. As with all radiopaque contrast agents, the lowest dose necessary to obtain adequate visualisation should be used.

Appropriate resuscitation equipment should be available.

8. The reason has not yet been clarified. According to the literature an increased or delayed occurrence of these reactions within a period of 2 weeks was observed after administration of Interleukin. Diuretics In case of diuretic-induced dehydration, patients are at increased risk of acute renal failure when using iodinated contrast media.

Close monitoring is required to ensure adequate hydration before administration of ioversol. The lowest necessary dose of ioversol consistent with a diagnostic result should be used. Vasopressors The arterial injection of an X-ray contrast medium should never be made following the administration of vasopressors, since they strongly potentiate neurologic effects.

Oral cholecystographic agents Renal toxicity has been reported in single patients with liver dysfunction, who were given oral cholecystographic agents followed by intravascular contrast agents. Administration of any intravascular X-ray contrast agent should therefore be postponed in patients who have recently received a cholecystographic contrast agent.

6 Fertility, pregnancy and lactation Pregnancy Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. There are, however, no adequate and well controlled studies in pregnant women.

It is not known whether ioversol crosses the placental barrier or reaches foetal tissues. However, many injectable contrast agents cross the placental barrier in humans and appear to enter foetal tissue passively. Because animal teratology studies are not always predictive of human response, caution should be exercised when prescribing to pregnant women.

Since any X-ray investigation during pregnancy may involve a potential risk, the risk/benefit ratio should be carefully weighed. If a better and safer alternative is available, an X-ray investigation involving X-ray contrast media should be avoided.

Ioversol contains iodine which may induce foetal dysthyroidism if the examination takes place after more than 14 weeks of amenorrhoea. Thyroid function of neonates should be closely monitored during the first week of life if iodinated contrast was administered to the mother during pregnancy.

It is recommended that thyroid function be monitored again at 2 weeks of age. Breast-feeding It is not known whether ioversol is excreted in human breast milk. However, many injectable contrast agents are excreted unchanged in breast milk to an amount of approximately 1 % of the given dose.

Although it has not been established that adverse events occur to nursing infants, caution should be exercised when intravascular X-ray contrast media are administered to nursing women because of potential adverse events, and consideration should be given to discontinuing nursing for one day.

Fertility Animal studies did not indicate direct or indirect harmful effects with respect to fertility in humans. There are, however, no adequate and well controlled clinical studies on fertility. 7 Effects on ability to drive and use machines There is no known effect on the ability to drive and operate machines.

However, because of the risk of early reactions driving or operating machinery is not advisable for 1 hour post injection. 8 Undesirable effects Frequencies for adverse drug reactions are defined as follows: Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1000 to <1/100) Rare (≥1/10,000 to <1/1000) Very rare (<1/10,000) Not known (cannot be estimated from the available data) a.

Summary of the safety profile Adverse reactions following the use of Optiray formulations are generally independent of the dose administered. Usually, they are mild to moderate, of short duration and resolve spontaneously (without treatment).

However, even mild adverse reactions may be the first indication of a serious, generalized reaction that can occur rarely after iodinated contrast media. Such serious reactions may be life-threatening and fatal, and usually affect the cardiovascular system.

Most adverse drug reactions to Optiray formulations occur within minutes after administration, however contrast related hypersensitivity reactions may occur with a delay of some hours up to several days. b. Tabulated summary of adverse reactions From clinical studies, mild discomfort, including sensation of heat or cold, pain during the injection, and/or transient taste perversion, was noted in 10% to 50% of patients.

1%). 1% of the patients. The following adverse reactions have been collected after Optiray administration from clinical trials and post-market experience, including post-market surveys.

Infections and infestations:

Rare rhinitis Immune system disorders: Very rare anaphylactoid (hypersensitivity) reaction Not known anaphylactic shock Endocrine disorders: Not known hypothyroidism* Psychiatric disorders: Very rare confusional state; agitation; anxiety Nervous system disorders: Uncommon dizziness; dysgeusia; headache; paraesthesia Rare syncope; tremor Very rare loss of consciousness; paralysis; speech disorders; somnolence; stupor; aphasia; dysphasia; hypoaesthesia Not known seizure; contrast-induced encephalopathy; amnesia; dyskinesia Eye disorders: Rare vision blurred; eye swelling; periorbital oedema Very rare conjunctivitis allergic (including eye irritation, ocular hyperaemia,lacrimation increased, conjunctival oedema) Not known blindness transient Ear and labyrinth disorders: Rare vertigo Very rare tinnitus Cardiac disorders: Rare tachycardia Very rare heart block; arrhythmia; angina pectoris; bradycardia; atrial fibrillation; electrocardiogram abnormal Not known cardiac arrest; ventricular fibrillation; arteriospasm; coronary extrasystoles; palpitations […]

General comments Serious or fatal reactions have been associated with the administration of iodinated X-ray contrast media. It is important to be prepared to treat any contrast medium reaction. Diagnostic procedures, which involve the use of iodinated intravascular agents, should be performed under the direction of personnel skilled and experienced in the particular procedure to be performed.

A fully equipped emergency cart, or equivalent supplies and equipment, and personnel competent in recognising and treating adverse reactions of all types should always be available. Since severe delayed reactions have been known to occur, the patient should be observed and emergency facilities and competent personnel should be available for at least 30 to 60 minutes after administration.

Hypersensitivity The patient should also be informed that allergic reactions may develop up to several days post administration; in such case, a physician should be consulted immediately. The occurrence of severe idiosyncratic reactions has prompted the use of several pre- testing methods.

However, pre-testing with a small dose of contrast agent administered cannot be relied upon to predict severe reactions and may itself be hazardous to the patient, as it may elicit an adverse reaction. It is suggested that a thorough medical history with emphasis on allergy and hypersensitivity, prior to the injection of any contrast medium, may be more accurate than pre-testing in predicting potential adverse reactions.

3). Appropriate resuscitation measures should be immediately available. Pre-medication with antihistamines and corticosteroids to avoid or minimise allergic reactions should be considered. Reports indicate that such pre-treatment does not prevent serious life-threatening reactions, but may reduce both their incidence and severity.

g. nausea, vomiting, dyspnoea, erythema, urticaria and hypotension. A higher incidence of such reactions has been observed in patients with a history of bronchial asthma, previous intolerance reactions to other contrast media, or any history of allergy or hypersensitivity.

3). Severe cutaneous adverse reactions (SCAR) SCAR may develop from 1 hour to several weeks after intravascular contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS).

Reaction severity may increase and time to onset may decrease with repeat administration of a contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering Optiray to patients with a history of a severe cutaneous adverse reaction to Optiray.

Coagulation disorders The anticoagulant effect of non-ionic X-ray contrast media has been shown, in vitro, to be less than that of conventional ionic agents at comparable concentrations. Similar results were found in some in vivo studies.

g. frequent flushing of standard angiographic catheters and avoiding prolonged contact of blood with the contrast agent in syringes and catheters. 3). Cardiovascular diseases In angiographic procedures, the possibility of dislodging plaque or damaging or perforating the vessel wall should be considered during catheter manipulation and contrast medium injection.

Test injections to ensure proper catheter placement are recommended. Angiography should be avoided whenever possible in patients with homocystinuria due to an increased risk of thrombosis and embolism. Patients with congestive heart failure should be observed for several hours following the procedure to detect delayed haemodynamic disturbances, which may be associated with a transitory increase in the circulating osmotic load.

Thromboembolic disorders In patients with advanced atherosclerosis, serious hypertension, cardiac decompensation, senility, preceding cerebral thrombosis or embolism, special caution should be exercised. Cardiovascular reactions as bradycardia, rising or falling of blood pressure may occur more often.

Central nervous system disorders Serious neurologic events have been observed following direct injection into cerebral arteries or vessels supplying the spinal cord or in angiocardiography, due to inadvertent filling of the carotids.

A cause-effect relationship to the contrast medium has not been established, since the patient's pre-existing condition and procedural techniques are causative factors in themselves. 8). Contrast- induced 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 ioversol and generally resolve within days. g. encephalopathy. If contrast encephalopathy is suspected, appropriate […]

1. Manifest hyperthyroidism.