Consumer medicine information

Omnipaque Injection

Iohexol

BRAND INFORMATION

Brand name

Omnipaque (Intravascular, Oral and Body Cavities) 240 Solution for injection

Active ingredient

Iohexol

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Omnipaque Injection.

What is in this leaflet

This leaflet answers some common questions about OMNIPAQUE. It does not contain all the available information. It does not take the place of talking to your radiologist (the specialist doctor who does X-rays), doctor or pharmacist.

All preparations of this type have risks and benefits. Your radiologist and/or your doctor have weighed the risks of you receiving OMNIPAQUE against the benefits they expect it will have for you.

If you have any concerns about being given this preparation, ask your radiologist, doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What OMNIPAQUE is used for

OMNIPAQUE is one of a group of medicines known as “contrast media” for diagnostic use. OMNIPAQUE is used in X-ray examinations in many different parts of the body for adults and children. It can make it easier to find and see abnormalities, and improves the diagnostic information needed by the doctor.

Before you are given OMNIPAQUE

When you must not be given it

OMNIPAQUE should not be given to you if:

  1. You have ever had or are allergic to OMNIPAQUE, to any of the ingredients listed at the end of this leaflet (see Product description) or to any other contrast medium. Symptoms of an allergic reaction may include wheeziness, difficulty in breathing or tightness or pain in the chest, skin rash, swelling or itching.
  2. You have thyroid gland problems.
  3. You have had recent heart disease or problems with your heart.
  4. The expiry date on the pack has passed. If you use it after the expiry date, it may have no effect at all, or worse, an entirely unexpected effect.
  5. You have an infection or open wound near the site to be examined.
  6. You are pregnant or intend to become pregnant.

Before you are given it

You must tell your doctor if:

  1. You are pregnant, intend to become pregnant or breast-feeding or plan to breast-feed.
  2. You have, or have had, the following medical conditions:
  • Asthma
  • Allergies, for example hay fever or hives, or allergies to iodine-containing dyes, any medicines or any other substances, such as foods, preservatives or dyes.
  • Heart disease or problems with your heart.
  • An overactive thyroid gland or goitre (neck swelling of the thyroid gland).
  • Diabetes
  • Kidney and/or liver disease
  • Any disorder or injuries affecting your brain or nervous system, for example, stroke, bleeding inside the skull or brain tumours or tumours (or cancer) spreading to the brain, epilepsy, transient ischaemic attacks (mild strokes), or migraines
  • Alcoholism and/or addiction to, or dependence on drugs or medicines (there is an increased risk of seizure (fit)
  • Multiple myeloma (cancer of blood cells)
  • Phaeochromocytoma (a tumour which raises blood pressure)
  • Waldenström’s paraproteinemia [a disorder of the immunoglobulins (cells involved in the body's natural ability to fight disease)]
  • Myasthenia gravis (disease of the muscles causing drooping eyelids, double vision, difficulty in speaking and swallowing and sometimes muscle weakness in the arms or legs)
  • You are a diabetic

Taking other medicines

Tell the doctor if you are taking any other medicines,

including medicines you buy without a prescription from a pharmacy, supermarket or health food shop. Some medicines may interfere with OMNIPAQUE. These include:

  • Biguanides (eg metformin) a medicine for diabetes. Your doctor may ask you not to take biguanides for 48 hours before receiving an injection of OMNIPAQUE.
  • Interleukin-2.

These medicines may interact or affect the way OMNIPAQUE works. Check with your doctor or pharmacist if you are not sure whether you are taking biguanides or interleukin-2.

You should not eat or drink anything in the two hours before your examination with OMNIPAQUE. It is, however, important to drink plenty of water before the examination and after the examination.

How OMNIPAQUE is used

You will be given OMNIPAQUE before or during your X-ray examination. OMNIPAQUE will be injected by a qualified person. The amount injected can vary depending on the type of examination used, your age and your weight.

If you receive an overdose

An overdose may lead to serious effects on the kidneys. If you are given an overdose, your doctor will decide how to treat you.

While you are using OMNIPAQUE

After examination of the spinal canal (myelography), you will be asked to rest in bed in a sitting or semi-sitting position and to avoid bending down for the first few hours. It is not advisable to drive a vehicle or operate machinery for at least 24 hours following an intrathecal examination (myelography).

If you need to have a thyroid function test within the next 14 days after examination with OMNIPAQUE, please tell your doctor before the test is done.

If you have any blood or urine tests on the day of your examination with OMNIPAQUE, tell your doctor you are using OMNIPAQUE. OMNIPAQUE may affect the results of some laboratory tests.

Things to be careful of

Delayed reactions of iodine-containing dyes may occur.

Side effects

Usually, OMNIPAQUE does not cause any problems. It can, however, sometimes cause unwanted effects in some people. The most frequent effect is a mild sensation of warmth or pain during the injection. Although there is a risk that you might get an unwanted effect, your doctor will have chosen this treatment by considering these risks and the benefits for the examination.

If you get any of the following during or after the examination:

  • Wheeziness, difficulty in breathing or tightness or pain in the chest;
  • Skin rash, itching, swelling or other allergic symptoms;
  • Dizziness or feeling faint;

you should tell your doctor straight away.

Other unwanted effects which are unusual, but which may occur during or after the examination include:

  • Altered taste sensation in the mouth;
  • Abdominal discomfort;
  • Nausea, vomiting or diarrhoea;
  • Headache, dizziness, restlessness;
  • Chest pain, change in blood pressure or heart rate;
  • Blurred vision, auditory disturbance, confusion or a change in your sensation of touch;
  • Muscle weakness, numbness, spasms or seizures;
  • Difficulty in voiding;
  • Backache, pain in the arms and legs;
  • Swelling and tenderness of the salivary glands for up to approximately 10 days after the examination.
  • Flushing or feeling hot
  • Shortness of breath or coughing

These effects are often mild and of short duration. If they become severe or last for more than a few days, tell your doctor. Sometimes, medical treatment is necessary.

If you get any of the following during or after myelography:

  • Sensitivity to light
  • Neck stiffness
  • Muscle weakness or spasm

you should inform your doctor immediately.

Please tell your radiologist or doctor as soon as possible if you experience any other unwanted effects, or if you do not feel well after receiving an injection of OMNIPAQUE during the X-ray procedure or afterwards.

Product description

OMNIPAQUE is a sterile solution for injection which contains a substance called iohexol. The expiry date for OMNIPAQUE is printed on the label. The product should not be used after this date. OMNIPAQUE also contains the following inactive ingredients in small amounts:

trometamol, sodium calcium edetate, water for injection, hydrochloric acid and sodium hydroxide.

  • 180 mg I/mL:
    10mL glass vial, packs of 10* AUST R 12595
    15mL glass vial, packs of 10* AUST R 48215
    20mL glass vial, packs of 20* AUST R 48216
    10mL PPE ampoule, packs of 1* and 10* AUST R 76061
    15mL PPE ampoule, packs of 1* and 10* AUST R 76070
  • 240 mg I/mL:
    10mL glass vial, packs of 10* AUST R 12596
    10mL PPE ampoule, packs of 1* and 10* AUST R 76063
    15mL PPE ampoule, packs of 1* and 10* AUST R 76058
    20mL glass vial, packs of 25* AUST R 48217
    20mL PPE ampoule, packs of 1* and 10* AUST R 76072
    50mL glass and PPE* bottle, packs of 10 AUST R 39861
    50mL PPE ampoule, packs of 1* and 10* AUST R 76066
  • 300 mg I/mL:
    10mL glass vial, packs of 10* AUST R 15473
    10mL PPE ampoule, packs of 1* and 10* AUST R 76064
    20mL glass vial, packs of 10 AUST R 48220
    20mL PPE ampoule, packs of 1* and 10* AUST R 76071
    40mL PPE ampoule, packs of 1* and 10* AUST R 76059
    50mL glass and PPE* bottle, packs of 10 AUST R 39864
    50mL PPE ampoule, packs of 1* and 10* AUSTR 76068
    75mL glass bottle, packs of 10 AUST R 48243
    100mL glass and PPE* bottle, packs of 10 AUST R 48244
  • 350 mg I/mL:
    20mL glass vial, packs of 10 AUST R 39868
    20ml PPE ampoule, packs of 1* and 10* AUST R 76069
    40mL PPE ampoule, packs of 1* and 10* AUST R 76060
    50mL glass and PPE* bottle, packs of 10 AUST R 15474
    50mL PPE ampoule, packs of 1* and 10* AUST R 76065
    75mL glass bottle, packs of 10 AUST R 48225
    100mL glass and PPE* bottle, packs of 10 AUST R 48233
    125mL glass bottle packs of 10* AUST R 48234
    150mL glass and PPE bottle, packs of 10* AUST R 48236
    175mL glass and PPE bottle, packs of 10* AUST R 48238
    200mL glass and PPE* bottle, packs of 6 AUST R 48241

Storing the medicine

OMNIPAQUE should be stored below 30°C, protected from the light. Do not freeze.

Other information

Please ask your doctor, radiologist or nurse if you would like to know more or have any questions about OMNIPAQUE.

GE Healthcare Australia Pty Limited
32 Phillip St
Parramatta NSW 2150
PO Box 5079
Parramatta 2150
Phone: 1300 88 77 64
Fax: 1300 434 232

Revision Date of this Leaflet
November 2014

* Some presentations may not currently be available in Australia.

Omnipaque is a trademark of GE Healthcare.

GE and GE Monogram are trademarks of General Electric Company.

BRAND INFORMATION

Brand name

Omnipaque (Intravascular, Oral and Body Cavities) 240 Solution for injection

Active ingredient

Iohexol

Schedule

Unscheduled

 

1 Name of Medicine

Iohexol.

6.7 Physicochemical Properties

Chemical structure.


CAS number.

66108-95-0.
Iohexol (Omnipaque) Injection is the formulation of N,N'-bis(2,3-dihydroxypropyl)- 5-[N(2,3- dihydroxypropyl)acetamido]- 2,4,6-triiodoisophthalamide, which is a triiodinated, non-ionic water soluble contrast medium with a molecular weight of 821.14 (iodine content 46.4%).
The osmolality and viscosity values of Omnipaque are as follows (see Table 11):

2 Qualitative and Quantitative Composition

Omnipaque 180 mg I/mL, 240 mg I/mL, 300 mg I/mL, 350 mg I/mL Solution for Injection. See Table 1.
Omnipaque Solution for injection. Omnipaque is supplied ready to use as clear, colourless to pale yellow, sterile aqueous solutions.
Omnipaque at a concentration of 140 mg I/mL is isotonic to blood. Omnipaque contains no preservative. Each vial or bottle should be used only once and any residue discarded.

List of excipients.

For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

See Section 2 Qualitative and Quantitative Composition.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Organic iodine compounds block x-rays as they pass through the body, thereby allowing body structures containing iodine to be delineated in contrast to those structures that do not contain iodine. Iohexol provides opacification of blood vessels and permits radiographic visualisation until sufficient haemodilution occurs or sufficient contrast material has left the site of injection.

Intravascular, oral and body cavity use.

For most of the haemodynamic, clinical chemical and coagulation parameters examined following intravenous injection of iohexol in healthy volunteers, no significant deviation from preinjection values has been found. The few changes observed in the laboratory parameters were minor and considered to be of no clinical importance.
A study was performed in 129 patients with diabetes and impaired renal function (serum creatinine levels from 115-308 micromol per litre) to compare a low osmolar (LOCM) and an isosmolar contrast medium (IOCM). Iohexol, as a representative of LOCM was compared to an IOCM in this high risk population. The results showed 26% of the patients experiencing a rise in serum creatinine of > 44.2 micromol per litre and 15% of patients with a rise of > 88.4 micromol per litre, which is in line with expected incidence of CIN.

Intrathecal use.

The initial concentration and volume of the medium, in conjunction with appropriate patient manipulation and the volume of CSF into which the medium is placed, will determine the extent of diagnostic contrast that can be achieved.
Following subarachnoid injection, Omnipaque will continue to provide good diagnostic contrast by conventional radiography for at least 30 minutes. Slow diffusion of iohexol takes place throughout the CSF as well as transfer into the circulation. At approximately 1 hour, contrast of diagnostic quality will not usually be available for conventional myelography. However, sufficient contrast for CT myelography will be available for several hours. If computed tomographic (CT) myelography is to follow, it should be deferred for several hours to allow the degree of contrast to decrease.
Following lumbar subarachnoid placement, irrespective of the position in which the patient is later maintained, slow upward diffusion of Omnipaque takes place throughout the CSF. CSF contrast enhancement for CT scanning may be expected in the thoracic region in about 1 hour, in the cervical region in about 2 hours, and in the basal cisterns in 3 to 4 hours after administration into the lumbar subarachnoid space.

Clinical trials.

Body cavities and oral use.

A number of clinical trials have been carried out administering Omnipaque into various body cavities including the oral route. There have been six studies using diluted Omnipaque orally through a feeding tube or rectally in infants and children as a contrast agent in the gastrointestinal tract with good results. This procedure is advantageous when barium sulphate is contraindicated. Excellent images are obtained. In double contrast arthrography, a randomised double blind study (n = 132) in patients with shoulder pain showed that image quality was good or excellent on CT examination in 96.1% of the group. Five studies have been carried out showing success in hysterosalpingography. There are four clinical studies using Omnipaque in endoscopic retrograde cholangiopancreatography (ERCP). It was found that LOWS (low osmolality water soluble) media (Omnipaque) reduce the frequency and severity of postprocedural pancreatitis compared with higher osmolality ionic contrast agents.
Efficacy for contrast agents is usually judged pragmatically by the adequacy of diagnostic information obtained. The primary outcome is the overall quality of visualisation and the secondary outcome includes good contrast opacity and satisfactory mucosal coating.

5.2 Pharmacokinetic Properties

Intravascular use.

87-99 per cent of the intravenously injected iohexol is excreted unchanged through the kidneys within 24 hours in patients with normal renal function. The maximum urinary concentration of iohexol appears within approximately 1 hour after injection. The elimination half-life is approximately 2 hours in patients with normal renal function. No metabolites have been detected. The protein binding of Omnipaque is so low (less than 2%), that it has no clinical relevance and can therefore be neglected.
Iohexol provides opacification of blood vessels and permits radiographic visualisation until sufficient haemodilution occurs or sufficient contrast material has left the site of injection.
Being a nonionic compound, iohexol yields solutions of lower osmolality than the conventional ionic contrast media. Intravenous or intra-arterial injection of iohexol causes less pain and sensation of heat than injection of conventional ionic media with similar iodine content. Iohexol solutions cause less cardiac and vascular disturbances on intravascular injection. The transit time of iohexol through the coronary vascular system is slightly increased compared with conventional ionic contrast media, probably due to the increased viscosity of iohexol at comparable iodine concentrations.
The period of maximum opacification of the renal vessels may begin as early as 30 seconds after IV injection. Urograms become apparent in about 1 to 3 minutes, with optimal contrast occurring between 5 to 15 minutes. In nephropathic conditions, particularly when excretory capacity has been altered, the rate of excretion may vary unpredictably, and opacification may be delayed after injection. Severe renal impairment may result in a lack of diagnostic opacification of the collecting system.
For most of the haemodynamic, clinical-chemical and coagulation parameters examined following intravenous administration of iohexol in healthy volunteers, no significant deviations from preinjection values have been found. The few changes observed in the laboratory parameters were minor and considered to be of no clinical importance.

Oral/ body cavity use.

For most body cavities, the injected iohexol is absorbed into the surrounding tissue and eliminated by the kidneys and bowel as described previously. Examinations of the uterus (hysterosalpingography) involve the most immediate drainage of contrast medium from the cavity upon conclusion of the radiographic procedure. Iohexol is well tolerated and readily absorbed if leakage into the peritoneal cavity occurs.
Visualisation of the joint spaces, uterus, fallopian tubes, peritoneal herniations, pancreatic and bile ducts can be accomplished by direct injection of contrast medium into the region to be studied. The use of appropriate Omnipaque concentrations assures diagnostic density.
Orally administered Omnipaque produces good visualisation of the gastrointestinal tract. Omnipaque is particularly useful when barium sulphate is contraindicated as in patients with suspected bowel perforation or those where aspiration of contrast medium is a possibility.

Intrathecal use.

Following injection into the lumbar subarachnoid space, iohexol is absorbed from CSF into the bloodstream and is eliminated by renal excretion.
After lumbar administration of 10-15 mL iohexol at a concentration of 180 mg I/mL to 6 patients, a mean maximum serum concentration of 0.024 mg I/mL was observed after a mean of 2.2 hours. The mean half-life of the initial rapid distribution phase from blood was 34 minutes and for the slower elimination phase 3.4 hours.

5.3 Preclinical Safety Data

Iohexol has a very low acute intravenous toxicity in mice and rats. Animal studies have shown that iohexol has a very low protein binding, and is well tolerated by the kidneys. The cardiovascular and neurotoxicity are low. The histamine release ability and the anticoagulant activity have been shown to be less than for ionic contrast media.

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

This medicinal product is for diagnostic use only.

Intravascular.

Omnipaque is indicated in adults for angiography, excretory urography and contrast enhancement in computerised tomography. In children, Omnipaque is indicated for angiography and urography.

Oral/ body cavities.

Omnipaque is indicated in adults for arthrography, endoscopic retrograde pancreatography (ERP), endoscopic retrograde cholangiopancreatography (ERCP), herniography, hysterosalpingography, and in adults, children and premature babies for studies of the gastrointestinal tract.

Intrathecal.

Omnipaque is indicated for lumbar, thoracic, cervical and total columnar myelography and in computerised tomography of the CNS in adults and children.

4.3 Contraindications

General.

Hypersensitivity to the active substance or to any of the excipients.
History of serious reaction to Omnipaque.
Iodine containing radiographic contrast media, whether ionic or nonionic, should not be administered to patients with thyrotoxicosis, anuria or decompensated cardiac insufficiency. These agents are also contraindicated in certain specific procedures and situations such as carotid angiography during the progressive period of stroke; coronary arteriography in the first 4 weeks after myocardial infarction; and the presence of infection or open injury in or near the region to be examined.

Administration technique - intrathecal.

Do not administer with intrathecal corticosteroids.
Immediate repeat myelography, in the event of technical failure, is contraindicated because of overdosage considerations. (See Section 4.2 Dose and Method of Administration for interval recommendation.)

Hysterosalpingography.

The procedure should not be performed during the menstrual flow or when menstrual flow is imminent, nor should it be performed if infection is present in any portion of the genital tract, including the external genitalia. The procedure is contraindicated in pregnant women or for those in whom pregnancy is suspected. Its use is not advised for 6 months after termination of pregnancy or 30 days after conization or curettage.

4.4 Special Warnings and Precautions for Use

General.

Hydration.

Adequate hydration should be assured before and after contrast media administration. This applies especially to patients with multiple myeloma, diabetes mellitus, renal dysfunction, as well as to infants, small children and elderly patients. Young infants (age < 1 year) and especially neonates are susceptible to electrolyte disturbance and haemodynamic alterations.
Preventive measures include:
identification of high risk patients;
ensuring adequate hydration, if necessary by maintaining an I.V. infusion from before the procedure until the contrast medium has been cleared by the kidneys;
avoiding additional strain on the kidneys in the form of nephrotoxic drugs, oral cholecystographic agents, arterial clamping, renal arterial angioplasty, or major surgery, until the contrast medium has been cleared.
Postponing a repeat contrast medium examination until renal function returns to pre-examination levels.

Risk/ benefit should be considered when the following medical problems exist.

Hypersensitivity to iohexol.

A positive history of allergy, asthma, or untoward reactions to iodinated contrast media indicates a need for special caution. Premedication with corticosteroids or histamine H1 and H2 antagonists might be considered in these cases.
The risk of serious reactions in connection with use of Omnipaque is regarded as minor. However, iodinated contrast media may provoke anaphylactoid reactions or other manifestations of hypersensitivity. A course of action should therefore be planned in advance, with necessary drugs and equipment available for immediate treatment, should a serious reaction occur. It is advisable always to use an indwelling cannula or catheter for quick intravenous access throughout the entire X-ray procedure.

Contrast medium induced nephrotoxicity.

Contrast medium induced nephrotoxicity is a condition in which impaired renal function (an increase in serum creatinine by more than 25% or 44 micromol/L) occurs within three days following the intravascular administration of a contrast medium in the absence of an alternative aetiology. Dialysis has been used in the prevention of contrast medium induced nephropathy.

Prevention of nephropathy - haemodialysis.

Patients on haemodialysis may receive contrast media for radiological procedures. If clinically indicated, haemodialysis is an effective method for eliminating iodinated contrast medium from the body. Correlation of the time of contrast media injection with the haemodialysis session is unnecessary, because there is no evidence that haemodialysis protects patients with impaired renal function from contrast medium induced nephropathy. The patient should not be re-exposed to contrast media before the kidney function has returned to its previous function. If contrast medium is to be given again, the patient must be adequately hydrated.

Use in renal impairment.

To prevent acute renal failure following contrast media administration, special care should be exercised in patients with pre-existing renal impairment and diabetes mellitus as they are at risk.
To prevent lactic acidosis, serum creatinine level should be measured in diabetic patients treated with metformin prior to intravascular administration of iodinated contrast medium. Normal serum creatinine / renal function: Administration of metformin should be stopped at the time of administration of contrast medium and not resumed for 48 hours or until renal function/ serum creatinine is normal. Abnormal serum creatinine/ renal function: Metformin should be stopped and the contrast medium examination delayed for 48 hours. Metformin should only be restarted if renal function/ serum creatinine is unchanged. In emergency cases where renal function is abnormal or unknown, the physician should evaluate the risk/ benefit of the contrast medium examination, and precautions should be implemented: Metformin should be stopped, patient hydrated, renal function monitored and patient observed for symptoms of lactic acidosis.

Use in hepatic impairment.

A potential risk of transient hepatic dysfunction exists. Particular care is required in patients with severe disturbance of both renal and hepatic function as they may have significantly delayed contrast medium clearance.

Use in the elderly.

No data available.

Paediatric use.

Infants.

Thyroid function in infants exposed to iodinated contrast media (ICM) should be evaluated and monitored. Decreased levels of thyroxine (T4) and triiodothyronine (T3) and increased level of thyroid stimulating hormone (TSH) were reported after exposure to ICM in infants, especially preterm infants, which remained for up to a few weeks or more than a month. Thyroid function in infants exposed to ICM should therefore be evaluated and monitored until thyroid function is normalised. Some patients were treated for hypothyroidism.

Severe cardiovascular disease or congestive heart failure.

Care should also be taken in patients with serious cardiac disease and/or pulmonary hypertension as they may develop haemodynamic changes or arrhythmias.

History of seizures.

General.

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

Intrathecal use.

A few patients have experienced a temporary hearing loss or even deafness after myelography, which is believed to be due to a drop in spinal fluid pressure by the lumbar puncture per se. This also applies to elderly patients who are at increased risk of cerebral pathology. Discontinue medications that may lower the seizure threshold at least 48 hours before iohexol administration and do not resume for at least 24 hours postprocedure. Patients on anticonvulsant medication should be maintained on that therapy.

Severe thyrotoxicosis.

Iodinated contrast media should not be administered to patients with thyrotoxicosis (see Section 4.3 Contraindications). Special care should be exercised in patients with hyperthyroidism. Patients with multinodular goiter may be at risk of developing hyperthyroidism following injection of iodinated contrast media. One should also be aware of the possibility of inducing transient hypothyroidism in premature infants receiving contrast media.

Multiple myeloma.

Patients with paraproteinemias (myelomatosis and Waldenström's macroglobulinemia) and sickle cell disease are also at risk.

Known or suspected phaeochromocytoma.

The administration of iodinated contrast media may aggravate the symptoms of myasthenia gravis. In patients with phaeochromocytoma undergoing interventional procedures, alpha blockers should be given as prophylaxis to avoid a hypertensive crisis.

Precautions related to administration technique.

General.

Risk of procedure related thrombosis and embolism.

Nonionic contrast media have less effect on the coagulation system in vitro, compared with ionic contrast media. When performing vascular catheterisation procedures, one should pay meticulous attention to the angiographic technique and flush the catheter frequently (e.g. with heparinised saline) so as to minimise the risk of procedure related thrombosis and embolism.

Extravasation.

Extravasation of contrast media may on rare occasions give rise to local pain, and oedema, which usually recedes without sequelae. However, inflammation and even tissue necrosis have been seen. Elevating and cooling the affected site is recommended as routine measures. Surgical decompression may be necessary in cases of compartment syndrome.

Observation time.

After contrast medium administration the patient should be observed for at least 30 minutes, since the majority of serious side effects occur within this time. However, delayed reactions may occur.

Intrathecal use.

Following myelography the patient should rest with the head and thorax elevated by 20° for one hour. Thereafter, he/she may ambulate carefully but bending down must be avoided. The head and thorax should be kept elevated for the first 6 hours if remaining in bed. Patients suspected of having a low seizure threshold should be observed during this period.
Outpatients should not be completely alone for the first 24 hours. It is advisable that patients do not drive vehicles or use machinery during the 24 hours following intrathecal examination.
Care is required in patient management to prevent inadvertent intracranial entry of a large bolus dose of the contrast medium. Prophylactic anticonvulsant treatment should be considered in patients with evidence of inadvertent intracranial entry of a large bolus of the medium, since there is an increased risk of seizure in such cases.

Other.

General.

Other precautions which apply to the various radiographic contrast medium procedures are the same for Omnipaque as they are for all other nonionic contrast media. The risk of the procedure itself should be carefully evaluated in each patient. Such precautions include the following.

Vascular, oral and body cavity use.

Cerebral angiography.

Use with caution in patients with extreme senility, advanced atherosclerosis or severe hypotension.
The procedure may be hazardous in subarachnoid haemorrhage and in migraine (because of ischaemic complications).

Peripheral angiography.

Pulsation should be present in the artery to be injected.
In thromboangiitis obliterans (Buerger's disease) or ischaemia associated with ascending infection, angiography should be performed with extreme caution, if at all.

Cardioangiography.

Caution is advised in the administration of large volumes to patients with incipient heart failure because of the possibility of aggravating the pre-existing condition. Hypotension should be corrected promptly since it may induce serious arrhythmias.
Caution is advised with dosage in patients with right ventricular failure, pulmonary hypertension, or stenotic pulmonary vascular beds because of the haemodynamic changes which may occur after injection into the right heart outflow tract.

Urography.

It is advisable to allow an interval of at least 48 hours before repeating excretory urography.
Dehydration should be avoided in the elderly, particularly those with polyuria, oliguria, advanced vascular disease or pre-existing dehydration.
Myelomatosis (see above).

Arthrography.

Strict aseptic technique is required to prevent infection.
Fluoroscopic control should be used to ensure proper needle placement, prevent extracapsular injection and prevent dilution of contrast medium.
Undue pressure should not be exerted during injection.

Hysterosalpingography.

In patients with carcinoma or in those in whom the condition is suspected, use caution to avoid possible spreading of the lesion by the procedure.

Effects on laboratory tests.

All iodinated contrast media may interfere with tests on thyroid function, thus the iodine-binding capacity of the thyroid may be reduced for up to several weeks.
High concentrations of contrast media in serum and urine can interfere with laboratory tests for bilirubin, proteins or inorganic substances (e.g. iron, copper, calcium and phosphate). These substances should therefore not be assayed on the day of examination.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Use of contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin (see Section 4.4 Special Warnings and Precautions for Use).
Patients treated with interleukin-2 less than two weeks previously have been associated with an increased risk of delayed reactions (flu-like symptoms or skin reactions).
Patients using beta-blockers may present with atypical symptoms of anaphylaxis which may be misinterpreted as a vagal reaction.
All iodinated contrast media may interfere with tests on thyroid function, thus the iodine binding capacity of the thyroid may be reduced for up to several weeks.
High concentrations of contrast media in serum and urine can interfere with laboratory tests for bilirubin, proteins or inorganic substances (e.g. iron, copper, calcium and phosphate). These substances should therefore not be assayed on the day of examination.
Although no incompatibility has been found, Omnipaque should not be directly mixed with other drugs. A separate syringe should be used and the injection needle should be flushed between administrations of Omnipaque and other drugs.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
The safety of Omnipaque for use in pregnancy has not been established. Teratogenicity studies have been performed in rats and rabbits at doses up to 4 g I/kg and 2.5 g I/kg, respectively. No evidence of harm to the embryo or foetus, or of impaired fertility has been demonstrated due to Omnipaque.
Since, whenever possible, radiation exposure should be avoided during pregnancy, the benefits of an X-ray examination, with or without contrast media, should be weighed against the possible risk. Omnipaque should not be used in pregnancy unless the benefit outweighs the risk and it is considered essential by the physician. Also see Section 4.4 Special Warnings and Precautions for Use, Paediatric use.
Infants born to women who received iodinated contrast media while pregnant should have testing for hypothyroidism in the neonatal period. Some patients were treated for hypothyroidism. Also see Section 4.4 Special Warnings and Precautions for Use, Paediatric use.
Approximately 0.5% of the weight adjusted maternal dose is excreted in breast milk during 24 hours after injection of iohexol. Nursing may be continued normally when iodinated contrast media are given to the mother.
Also see Paediatric use.

4.8 Adverse Effects (Undesirable Effects)

General.

Below are listed possible general side effects in relation with radiographic procedures, which include the use of Omnipaque. For side effects specific to mode of administration, please refer to these specific sections.
Serious reactions as well as fatalities are only seen on very rare occasions.
Hypersensitivity reactions usually present as respiratory or cutaneous symptoms like dyspnoea, rash, erythema, urticaria, pruritus, skin reaction, angioneurotic oedema, laryngeal oedema, bronchospasm or pulmonary oedema. They may appear either immediately after the injection or up to a few days later.
Hypersensitivity reactions may occur irrespectively of the dose and mode of administration and mild symptoms may represent the first signs of a serious anaphylactoid reaction/shock. Administration of the contrast medium must be discontinued immediately and, if necessary, specific therapy instituted via the vascular access. Patients using beta-blockers may present with atypical symptoms of hypersensitivity, which may be misinterpreted as a vagal reaction.
An undesirable effect is said to be: very frequent if its frequency is ≥ 10%; common if its frequency is between ≥ 1% and < 10%; uncommon if its frequency is between ≥ 0.1% and < 1%; rare if its frequency is between ≥ 0.01% and < 0.1%; very rare if its frequency is < 0.01%.
Reactions, for which no frequency rate can be provided due to lack of clinical data, have been entered with 'Not known'.
The listed frequencies are based on internal clinical documentation and published large scale studies, comprising more than 90,000 patients. See Table 7.

Intravascular use (intra-arterial and intravenous use).

Please first read the section labelled 'General'. In Table 8, only undesirable events with frequency during intra-vascular use of Omnipaque are described.
The nature of the undesirable effects specifically seen during intra-arterial 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.
A transient increase in serum creatinine is common, but usually of no clinical relevance.

Use in body cavities.

Please first read the section labelled 'General'. In Table 9, only undesirable events with frequency during use of Omnipaque in body cavities are described.

Intrathecal use.

Please first read the section labelled 'General'. In Table 10, only undesirable events 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 frequency is similar to lumbar puncture alone.
Headache, nausea, vomiting or dizziness may largely be attributed to pressure loss in the subarachnoid space resulting from leakage at the puncture site. Excessive removal of cerebrospinal fluid should be avoided in order to minimise pressure loss.

Reporting suspected adverse events.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

General.

Administration of contrast media should be performed by qualified personnel familiar with the procedure and an appropriate technique should be utilised.
As in all diagnostic procedures, the lowest dose of Omnipaque necessary to obtain adequate visualisation should be used. Most procedures do not require the use of either the maximum volume or the highest concentration of Omnipaque. The combination of volume and concentration of Omnipaque to be used should be carefully individualised accounting for factors such as age, bodyweight, size of the vessel and the rate of blood flow within the vessel. Other factors such as anticipated pathology, degree and extent of opacification required, structure(s) or area to be examined, disease process affecting the patient, and equipment and technique to be employed should be considered.
The dosage varies depending on the type of examination and the technique used. Adequate hydration should be assured before and after administration as with other contrast media.
Patients will tolerate a contrast medium better if the contrast medium is warmed to body temperature which lowers the viscosity.
Omnipaque should be inspected visually for particulate matter, discolouration and the integrity of the container prior to administration. Omnipaque should only be used if clear and within the normal colourless to pale yellow range. Do not use if particulate matter or discolouration are present.

Intravascular use.

Generally recommended doses are contained in Tables 2 and 3.

Administration instructions for body cavities/oral use.

1. Arthrography.

The amount of Omnipaque injected is dependent on the size of the joint to be examined and the technique employed. Lower volumes of contrast medium are usually injected for knee and shoulder arthrography when double contrast examinations using 15 mL to 100 mL of air are performed.
The following concentrations and volumes are recommended for normal adult knee, shoulder and temporomandibular joints but should serve as guidelines since joints may require more or less contrast medium for optimal visualisation.

Knee.

Omnipaque 240: 5 mL to 15 mL.
Omnipaque 300: 5 mL to 15 mL.
Omnipaque 350: 5 mL to 10 mL.

Shoulder.

Omnipaque 300: 10 mL.
Omnipaque 240: 3 mL.

Temporomandibular.

Omnipaque 300: 0.5 mL to 1.0 mL.
Lower volumes recommended for double contrast examinations; higher volumes recommended for single contrast examinations. Passive or active manipulation is used to disperse the medium throughout the joint space.

2. Oral use.

Adults.

The recommended dosage of undiluted Omnipaque 350 at a concentration of 350 mg I/mL for oral pass through examination of the gastrointestinal tract in adults is 50 mL to 100 mL depending on the nature of the examination and the size of the patient.
Omnipaque diluted to concentrations from 6 mg I/mL to 9 mg I/mL and administered orally in conjunction with Omnipaque 300 at a concentration of 300 mg I/mL administered intravenously is indicated in adults for use in contrast enhanced computed tomography of the abdomen. Dilute oral plus intravenous Omnipaque may be useful when unenhanced imaging does not provide sufficient delineation between normal loops of the bowel and adjacent organs or areas of suspected pathology.
The recommended oral dosage of Omnipaque dilute to concentrations of 6 mg I/mL to 9 mg I/mL for contrast enhanced computed tomography of the abdomen in adults is 500 mL to 1000 mL. Smaller administered volumes are needed as the concentration of the final solution is increased. In conjunction with dilute oral administration, the recommended dosage of Omnipaque 300 administered intravenously is 100 mL to 150 mL. The oral dose is administered about 20 to 40 minutes prior to the intravenous dose and image acquisition.

Children.

The dosage of undiluted Omnipaque 300 at a concentration of 300 mg I/mL, Omnipaque 240 at a concentration of 240 mg I/mL or Omnipaque 180 at a concentration of 180 mg I/mL for oral pass through examination of the gastrointestinal tract is dependent on the nature of the examination and the size of the patient. Based on clinical experience, it is recommended that Omnipaque 180 be used in children less than 3 months of age. Omnipaque 180, Omnipaque 240 or Omnipaque 300 may be used in children 3 months of age and older. The recommended does for oral use in children is 2-4 mL/kg. The estimated total volumes based on this dosage are shown in Table 4.
When given rectally, larger volumes may be used.
Omnipaque diluted to concentrations from 9-21 mg I/mL administered orally in conjunction with Omnipaque 240 at a concentration of 240 mg I/mL or Omnipaque 300 at a concentration of 300 mg I/mL administered intravenously is indicated in children for use in contrast enhanced computed tomography of the abdomen. The recommended dose is 15-20 mL/kg up to a maximum volume of 750 mL. Smaller administered volumes are needed as the concentration of the final solution is increased. The total oral dose in grams of iodine should generally not exceed 5 g for children less than 3 years of age and 10 g for children from 3 to 18 years of age. The oral dosage may be given all at once or over a period of 30 to 45 minutes if there is difficulty consuming the required volume.
In conjunction with dilute oral administration the recommended dosage of Omnipaque 240 and Omnipaque 300 is 2.0 mL/kg when administered intravenously with a range of 1.0 mL/kg to 2.0 mL/kg. Dosage for infants and children should be administered in proportion to age and bodyweight. The total intravenously administered dose should not exceed 3 mL/kg. The oral dose is administered about 30 to 60 minutes prior to the intravenous dose and image acquisition.

Intrathecal use.

To minimise possible adverse reactions a total dose of 3 g iodine should not be exceeded. As in all diagnostic procedures, the minimum concentration and volume to produce adequate visualisation should be used.
To avoid excessive mixing with CSF and consequent dilution of contrast, as well as premature dispersion upwards, injection must be made slowly.
Depending on the estimated volume of Omnipaque which may be required for the procedure, a small amount of CSF may be removed to minimise the distension of the subarachnoid spaces.
The needle may be removed immediately following injection since it is not necessary to remove Omnipaque after injection into the subarachnoid space.
An interval of 48 hours should be allowed before repeat examination.
Direct intracisternal or ventricular administration for standard radiography (without computerized tomographic enhancement) is not recommended.

Adults.

The usual recommended total doses of Omnipaque are shown in Table 5.

Infants and children.

Omnipaque 180 mg I/mL is recommended for the examination of the lumbar, thoracic and cervical regions in children by lumbar injection and is slightly hypertonic to CSF. The usual recommended total doses for myelography (by lumbar injection) are given in Table 6, depending largely on patient age.
Avoid rapid dispersion of the medium. (To avoid excessive mixing with cerebrospinal fluid (CSF) and consequent dilution of iohexol solution, injection should be made slowly over 1 to 2 minutes.)
If repeat examinations are desired, a suitable interval of time between administrations is needed to allow for normal clearance of the drug from the body. An interval of at least 48 hours should be allowed before repeat examination; however, 5 to 7 days is recommended whenever possible.

4.7 Effects on Ability to Drive and Use Machines

None known after intravascular use.
It is not advisable to drive a car or use machines during the first 24 hours following intrathecal examination.

4.9 Overdose

Intravascular use.

Preclinical data indicate a high safety margin for Omnipaque and no fixed upper dose level has been established for routine intravascular use. Symptomatic overdosing is unlikely unless the patient has received an excess of 2000 mg I/kg bodyweight over a limited period of time.
The duration of the procedure is important for the renal tolerability of high doses of contrast media (t½ approx. 2 hours). Accidental overdosing is most likely following complex angiographic procedures in children, particularly when multiple injections of contrast medium with high concentration are given.
In cases of overdose, any resulting water or electrolyte imbalance must be corrected. Renal function should be monitored for the next three days. If needed, haemodialysis may be used for clearance of excessive contrast medium. There is no specific antidote.

Intrathecal use.

Clinical consequences of overdosage with Omnipaque have not been reported. However, based on experience with other nonionic myelographic media, physicians should be alert to a potential increase in the frequency and severity of CNS mediated reactions. Even use of the recommended dose can produce effects tantamount to overdosage if incorrect management of the patient during or immediately following the procedure permits inadvertent early intracranial entry of a large portion of the medium.
The maximum recommended dose of Omnipaque by intrathecal administration is 3 g of iodine.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

Unscheduled.

6 Pharmaceutical Particulars

6.1 List of Excipients

Trometamol, sodium calcium edetate, hydrochloric acid (pH adjustment), water for injections.
The pH of the product is 6.8-7.6.

6.2 Incompatibilities

Although no incompatibility has been found, Omnipaque should not be directly mixed with other drugs. A separate syringe should be used and the injection needle should be flushed between administrations of Omnipaque and other drugs. Also see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

Glass vials: 3 years in all climatic zones.
Polypropylene bottles: 3 years climatic zones I and II.
In climatic zones III and IV the shelf-life is shorter, depending on volume and storage conditions.

6.4 Special Precautions for Storage

Omnipaque Injection should be stored below 30°C and protected from light. Do not freeze.
The product in glass containers and in polypropylene bottles may be stored at 37°C for up to one month prior to use in a contrast agent warmer utilising circulating warm air. 10, 15 and 20 mL polypropylene ampoules may be stored at 37°C for up to one week prior to use.

6.5 Nature and Contents of Container

Glass vials and bottles: The product is filled in injection vials (10, 15, 20 mL) and infusion bottles (40, 50, 75, 100, 200 and 500 mL). Both containers are made of colourless highly resistant borosilicate glass (Ph. Eur. Type I), closed with halobutyl rubber stoppers (Ph. Eur. Type I), and sealed with combined "flip off seal/tear off seal - flat plast disc".
Polypropylene bottles: The product is filled in polypropylene bottles. The bottles of 10, 15, 20, 40 and 50 mL are rigid stand-up bottles with a twist-off top.
The bottles of 50, 75, 100, 150, 175, 200 and 500 mL are closed with halobutyl rubber stoppers (Ph. Eur. Type I), and supplied with a plastic screw cap, which is provided with a tamper proof ring.

*Presentations.

180 mg I/mL: 10 mL glass vial, packs of 10.
15 mL glass vial, packs of 10.
20 mL glass vial, packs of 20.
10 mL PPE ampoule, packs of 10.
15 mL PPE ampoule, packs of 10.
240 mg I/mL: 10 mL glass vial, packs of 10.
10 mL PPE ampoule, packs of 10.
15 mL PPE ampoule, packs of 10.
20 mL glass vial, packs of 25.
20 mL PPE ampoule, packs of 10.
50 mL glass and PPE bottle, packs of 10.
50 mL PPE ampoule, packs of 10.
300 mg I/mL: 10 mL glass vial, packs of 10.
10 mL PPE ampoule, packs of 10.
20 mL glass vial, packs of 10 and 25.
20 mL PPE ampoule, packs of 10.
40 mL PPE ampoule, packs of 10.
50 mL glass and PPE bottle, packs of 10.
50 mL PPE ampoule, packs of 10.
75 mL glass and PPE bottle, packs of 10.
100 mL glass and PPE bottle, packs of 10.
350 mg I/mL: 20 mL glass vial, packs of 10 and 25.
20 mL PPE ampoule, packs of 10.
40 mL PPE ampoule, packs of 10.
50 mL glass and PPE bottle, packs of 10.
50 mL PPE ampoule, packs of 10.
75 mL glass and PPE bottle, packs of 10.
100 mL glass and PPE bottle, packs of 10.
125 mL glass bottle packs of 10.
150 mL glass and PPE bottle, packs of 10.
175 mL glass and PPE bottle, packs of 10.
200 mL glass and PPE bottle, packs of 6.
*Not all Presentations may be available in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes