Consumer medicine information

Omniscan Solution for injection

Gadodiamide

BRAND INFORMATION

Brand name

Omniscan Solution for injection

Active ingredient

Gadodiamide

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Omniscan Solution for injection.

What is in this leaflet

This leaflet tells you about OMNISCAN™. The information in this leaflet applies only to OMNISCAN.

This leaflet answers some common questions about OMNISCAN. It does not contain all the available information about the product and is not intended to replace discussions you may wish to have with your doctor, radiologist or other health professional.

All medicines have risks and benefits. Your doctors have weighed the risks of you being given this medicine against the benefits they expect it will have for you.

Please read this leaflet before you are given OMNISCAN.

If you have any questions, are not sure about anything or if you have any concerns about being given this medicine - ask your doctor, radiographer or nurse.

Keep this leaflet, you may need to read it again.

What OMNISCAN is used for

OMNISCAN is one of a group of medicines known as ‹contrast media› which are used in Magnetic Resonance Imaging (MRI) examinations.

OMNISCAN is used in MRI examinations of the brain or spine, as well as other parts of the body. OMNISCAN makes it easier to detect and locate changes and to improve the diagnostic information your radiologist needs.

OMNISCAN is intended for use in hospitals and radiology clinics only.

OMNISCAN is for use in adults, children and babies over 4 weeks of age.

How OMNISCAN works

MRI uses the magnetic properties of molecules in the body to “see” organs and other structures in the body and how they may have changed as a result of any condition you may have. OMNISCAN can greatly improve the clarity of the images the radiologist looks at to enable better, and more accurate, diagnosis of your condition.

What is in OMNISCAN

The name of your medicine is OMNISCAN. It contains an active substance known as gadodiamide.

OMNISCAN is a sterile, aqueous solution for injection, and contains 287 mg of gadodiamide per mL (equivalent to 0.5 mmol per mL).

Other ingredients are small amounts of caldiamide sodium and sodium hydroxide or hydrochloric acid (for pH adjustment), and water for injections.

Before being given OMNISCAN

If the answer to any of the following questions is YES, tell the doctor BEFORE you are given OMNISCAN.

  • Do you have an allergy or asthma?
  • Are you pregnant, or think you might be pregnant?
  • Have you ever had an allergic reaction to OMNISCAN, to any of its ingredients or to any other ‹contrast media›?
  • Do you suffer from any kidney problems or have reduced kidney function or are you undergoing dialysis?
  • Have you undergone liver transplantation or are you waiting to do so?
  • Are you currently taking any other medications that you have been prescribed by your doctor or bought yourself from a pharmacy?

How you will be given OMNISCAN

OMNISCAN will be injected into one of your veins usually as a single injection before or during your MRI examination. Occasionally, a second injection may be of additional diagnostic value.

The amount injected will depend upon your weight and what part of your body you are having examined. The usual dose is 0.2 mL/kg. Occasionally, a second dose of 0.4 mL/kg may be of additional diagnostic value. If you weigh more than 100 kg, you will normally receive 20 mL or, occasionally, a second dose of 40 mL.

During, and after, your examination

Usually, OMNISCAN does not cause any problems. It can, however, sometimes cause unwanted effects in some people. The most frequent effect is mild discomfort in the form of a sensation of warmth, cold, pressure or pain in the area around where the injection is given.

Although there is a risk that you might get an unwanted effect, your doctor will have chosen this ‹contrast medium› by considering these risks and the benefits of the examination.

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

  • wheeziness, difficulty in breathing or tightness, pain in the chest or heart palpitations
  • skin rash, lumps, itchy throat or spots
  • a decrease in the amount of urine you pass, or a change in its colour

- you should tell the doctor straight away.

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

  • a change in your sense of smell or taste
  • dizziness
  • throat irritation sneezing or coughing
  • headache
  • indigestion, nausea and/or vomiting, diarrhoea
  • weakness or drowsiness
  • cramps in arms, legs, other muscles or joint pain
  • tingling sensations
  • hearing or sight problems
  • anxiety, trembling, convulsions, shivering
  • fever
  • facial swelling

These effects are usually mild and of short duration. If they become severe, or last more than a few days, tell your doctor.

In patients with severely reduced renal function receiving OMNISCAN, a disease called nephrogenic systemic fibrosis (NSF) has rarely been observed, days to weeks after the examination. NSF causes discolouration and thickening of the skin. NSF may be painful and may result in reduced joint mobility, muscle weakness or impairment of the function of internal organs which may potentially be life threatening.

If you experience any other unwanted effects, please tell your doctor.

If you are given too much OMNISCAN (overdose)

As OMNISCAN will be given to you by a qualified person familiar with the procedure, overdosage is very unlikely to occur. But, in the event this happens, qualified personnel are available and know what to do to handle such an occurrence.

Other important information

OMNISCAN can affect the results of blood sample tests taken on the same day as your examination.

Please tell your doctor if you give a blood sample on the same day as you were given OMNISCAN.

If you are breast feeding

It is not known whether OMNISCAN passes into the breast milk. Just to be sure, do not give your baby any breast milk expressed in the first 24 hours after your examination.

Product Description

OMNISCAN is available in the following presentations:

Glass Vials;

5 mL (AUST R 62200)*
10 mL (AUST R 46378)*
15 mL (AUST R 47379)*
20 mL (AUST R 47380)*

Polypropylene Ampoules;

10 mL (AUST R 60112)*
15 mL (AUST R 60114)*
20 mL (AUST R 60113)*
40 mL (AUST R 72351)*
50 mL (AUST R 72352)*

Prefilled Syringes

10 mL (AUST R 74070)*
15 mL (AUST R 74069)*
20 mL (AUST R 74071)*

Storing the medicine

  • The expiry date is printed on the label. The product should not be used after this date.
  • OMNISCAN, in glass vials, polypropylene ampoules and prefilled syringes, is stored below 30°C (do not freeze) and protected from light.
  • The vial/ampoule/prefilled syringe is intended for one patient only. Any unused portions must be discarded.

Where to go for further information

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

Who supplies this medicine

GE Healthcare Australia Pty Limited
A.B.N. 32 001 408 402 32 Phillip St
Parramatta NSW 2150

Po Box 5079
Parramatta NSW 2150

Tel: 1300 88 77 64
Fax: 1300 434 232

Revision date of this leaflet

November 2014

* Australian Registration Number
Some presentations may not currently be available in Australia.

Omniscan is a trademark of GE Healthcare.

GE and GE Monogram are trademarks of General Electric Company.

BRAND INFORMATION

Brand name

Omniscan Solution for injection

Active ingredient

Gadodiamide

Schedule

Unscheduled

 

Name of the medicine

Gadodiamide.

Excipients.

Caldiamide sodium 12 mg/mL, water for injections; pH is adjusted between 6.0 and 7.0 with hydrochloric acid or sodium hydroxide. Omniscan contains no antimicrobial preservative.

Description

Chemical name: gadolinium,[5,8-bis(carboxymethyl)-11-[2-(methylamino)-2-oxoethyl]- 3-oxo-2,5,8,11-tetraazatridecan-13-oato(3-)]. Molecular formula: C16H26GdN5O8. MW: 573.66 (anhydrous).

Pertinent physicochemical data.

At 37°C the osmolality is 780 mOsmol/kg water. The viscosity at 20°C is 2.8 mPa.s and at 37°C is 1.9 mPa.s. The density at 20°C is 1.15 g/cm3. Omniscan has an osmolality 2.8 times that of plasma (285 mOsmol/kg water) at 37°C and is hypertonic under conditions of use.
Omniscan injection is the formulation of the gadolinium complex of diethylenetriamine penta-acetic acid bismethylamide, and is an injectable, nonionic extracellular enhancing agent for magnetic resonance imaging.

Pharmacology

The pharmacokinetics of intravenously administered Omniscan in normal subjects conforms to an open, two compartment model with mean distribution and elimination half-lives (reported as mean ± SD) of 3.7 ± 2.7 minutes and 77.8 ± 16 minutes, respectively. Gadodiamide is eliminated primarily in the urine with 95.4 ± 5.5% (mean ± SD) of the administered dose eliminated by 24 hours. There is no detectable biotransformation or decomposition of gadodiamide. The renal and plasma clearance rates of gadodiamide are nearly identical (1.7 and 1.8 mL/minute/kg, respectively), and are similar to that of substances excreted primarily by glomerular filtration.
In patients with impaired renal function GFR 18-43 mL/minute), the mean elimination half-life was 5.8 hours. Gadodiamide is cleared by routine haemodialysis, with 56% of the given dose eliminated during the first haemodialysis session and 72% during four sessions. Gadodiamide is also dialyzable by peritoneal dialysis with 76% of the given dose recovered over 22 days.
In magnetic resonance imaging, visualisation of normal and pathological brain and spinal tissue depends, in part, on variations in the radiofrequency signal intensity. These variations occur due to changes in proton density, alteration of the spin-lattice or longitudinal relaxation time (T1) and variation of the spin-spin or transverse relaxation time (T2). Omniscan is a paramagnetic agent with unpaired electron spins which generate a local magnetic field. As water protons move through this local magnetic field, the changes in magnetic field experienced by the protons reorient them with the main magnetic field more quickly than in the absence of a paramagnetic agent. Therefore, by increasing the relaxation rate, Omniscan decreases both the T1 and T2 relaxation times in tissues where it is distributed. At clinical doses the effect is primarily on the T1 relaxation time and produces an increase in signal intensity. Use of Omniscan provided contrast enhancement or facilitated visualisation of abnormal structures or lesions in 75% (266 of 353) of cases with abnormalities. In comparison with preinjection scans, Omniscan allowed visualisation of more or smaller lesions in 16% (50/306) of the cases. In 29/96 of the cases, Omniscan revealed lesions where no lesions were detected prior to Omniscan administration.
Current evidence suggests that gadolinium accumulates in the brain after repeated administrations of Gadolinium-based contrast agents (GBCAs) although the exact mechanism of gadolinium passage into the brain has not been established.

Clinical Trials

The efficacy of gadodiamide in CNS and whole body imaging of adults and children aged over 6 months of age has been demonstrated in clinical trials.

CNS (central nervous system), children less than 6 months of age.

A total of 7 clinical studies, including 363 patients, have been performed to document the use of gadodiamide injection in paediatric patients undergoing MRI examination of the CNS. Six of these clinical studies included both children and adolescents. The remaining study was designed specifically to demonstrate the safety and effectiveness of Omniscan for the enhancement of magnetic resonance images of intracranial and spinal lesions in infants and neonates less than 6 months of age.
In this last study, 61 children below 6 months of age undergoing MRI were included in an open, nonrandomised clinical trial conducted at three centres. Forty patients were recruited to receive gadodiamide injection at a dose of 0.1 mmol/kg in the Omniscan group (group A) and 21 patients requiring plain MRI examination without contrast were the control group (plain MRI, group B). No patients were withdrawn, however, 2 of the children included were older than 6 months and their data excluded from all analyses. In group A, 16 patients were female and 23 male and in group B, 7 were female and 13 male. There were no relevant differences between the two groups regarding age, weight and height. Group A included 8 patients with mass lesions, 7 each with convulsive disorders and hydrocephalus, 6 with infections, 3 with congenital anomalies and 2 each with metabolic disease and hypoxia. Group B included 11 patients with congenital anomalies, 3 with hypoxia, 2 with vascular diseases, one each with convulsive disorders, hydrocephalus and metabolic disease and one with periventricular leukomalacia. In the comparison of precontrast and postcontrast evaluation of the images neither the number of patients with lesions nor the number of lesions in each patient was found to be different. Both the onsite investigator and the independent reader found the quality of lesion delineation to be improved by the injection of contrast medium. There was a discrepancy between investigators in the evaluation of contrast enhancement in the pathological area of interest and was probably due to a different interpretation of the area of interest. In no case was a lesion obscured after administration of the contrast medium. For all patients, the postcontrast images contained at least as much diagnostic information as the precontrast images. No serious or significant adverse event occurred. Gadodiamide injection at a dose of 0.1 mmol/kg was shown to be safe, well tolerated and effective in MRI examination of children under 6 months.

Indications

Omniscan is indicated for use in adults and children, including infants and neonates less than 6 months of age for the enhancement of magnetic resonance images of intracranial and spinal lesions where there is an abnormal blood brain barrier or abnormal vascularity, and;
whole body imaging for adults and children over 6 months of age.

Contraindications

Use of Omniscan (gadodiamide) is contraindicated in patients with acute or chronic severe renal insufficiency (a glomerular filtration rate < 30 mL/minute/1.73 m2).
Patients with renal insufficiency of any severity due to the hepatorenal syndrome or in the perioperative liver transplantation period.
Omniscan is contraindicated in patients with acute kidney injury and in neonates up to 4 weeks of age.
Omniscan should not be used in patients with known hypersensitivity to Omniscan or its constituents.

Precautions

Prior to administration of Omniscan, all patients should be screened for renal dysfunction by obtaining laboratory tests.

Patients with renal impairment.

Because of the lack of information on repeated administration, Omniscan injections should not be repeated unless the interval between injections is at least 7 days.

Neonates and infants.

Omniscan is contraindicated in neonates up to 4 weeks of age. Due to immature renal function in infants up to 1 year of age, Omniscan should only be used in these patients after careful consideration.
The accepted safety considerations and procedures which are required for MRI are applicable when Omniscan is used for contrast enhancement. Administration of contrast media should be performed by qualified personnel familiar with the procedure, and an appropriate technique should be utilised.

Accumulation of gadolinium in the brain.

The current evidence suggests that gadolinium accumulates in the brain after multiple administrations of GBCAs. Increased signal intensity on non-contrast Tl weighted images of the brain has been observed after multiple administrations of GBCAs in patients with normal renal function. Gadolinium has been detected in brain tissue after multiple exposures to GBCAs, particularly in the dentate nucleus and globus pallidus. The evidence suggests that gadolinium accumulation is higher after repeat administration of linear than after repeat administration of macrocyclic agents. The clinical significance of gadolinium accumulation in the brain is presently unknown. In order to minimize potential risks associated with gadolinium accumulation in the brain, it is recommended to use the lowest effective dose and perform a careful benefit risk assessment before administering repeated doses.
The possibility of a reaction including serious, life threatening, fatal, anaphylactoid or cardiovascular or other idiosyncratic reactions should always be considered, especially in those patients with known clinical hypersensitivity or a history of asthma or other allergic respiratory disorders. A course of action should, therefore, be planned in advance, with the necessary drugs and equipment available for immediate treatment should a serious reaction occur.

Central nervous system disorders.

In patients suffering from epilepsy or brain lesions the likelihood of convulsions during the examination may be increased. Precautions are necessary when examining these patients (e.g. monitoring of the patient) and the equipment and medicinal products needed for the rapid treatment of possible convulsions should be available.

Severe renal impairment and liver transplant patients.

There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of gadodiamide and some other gadolinium containing contrast agents in patients with severe renal impairment and those who have had or are undergoing liver transplantation. NSF is a debilitating and sometimes fatal disease affecting the skin, muscle and internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering an Omniscan (gadodiamide) injection, do not exceed the dose recommended. Allow sufficient time for elimination of the agent prior to any readministration. Transitory changes in serum iron (within the normal range in the majority of cases) have been observed in some patients after administration of Omniscan. The clinical significance of this, if any, is not known but all patients in whom this effect was observed remained asymptomatic.
Omniscan interferes with serum calcium measurements with some colorimetric (complexometric) methods commonly used in hospitals. It may also interfere with determinations of other electrolytes (e.g. iron). Thus it is recommended that such methods not be used for 12-24 hours after administration of Omniscan. If such measurements are necessary, the use of other methods is recommended.
Diagnostic procedures involving the use of contrast agents should be conducted under the supervision of a physician with the prerequisite training and a thorough knowledge of the procedure to be performed. If Omniscan is drawn into a disposable syringe it should be used immediately. If nondisposable equipment is used, scrupulous care should be taken to prevent residual contamination with traces of cleansing agents.
Data on the safety of repeated injections are not available. If the physician determines that sequential or repeat examinations are required, a suitable interval of time between administrations should be observed to allow for clearance of the drug from the body.

Carcinogenesis, mutagenesis, impairment of fertility.

The results of three in vitro and one in vivo short-term genotoxicity assays were negative. No long-term studies have been performed to evaluate the carcinogenic potential of Omniscan. Omniscan had no effect on the fertility and general reproductive performance of rats or in teratology studies in rats and rabbits at doses that did not cause maternal toxicity.

Use in pregnancy.

(Category B3)
No effects of Omniscan on reproductive performance were seen in rats at doses up to 1.0 mmol/kg. In rabbits, there was an increased incidence of litters with skeletal or visceral abnormalities at doses up to 0.5 and 1.0 mmol/kg. However, these effects are possibly attributable to maternal toxicity rather than a direct effect of the drug. There are no adequate and well controlled studies of Omniscan in pregnant women. Omniscan should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Use in lactation.

It is not known whether Omniscan is excreted in human milk. Breastfeeding should be discontinued prior to administration and should not be recommenced until at least 24 hours after the administration of Omniscan. Available data in animals have shown excretion of gadodiamide in milk. A risk to the suckling child cannot be excluded.

Use in children.

The safety and effectiveness of Omniscan have been established for whole body magnetic resonance imaging in children from 6 months of age. The safety and effectiveness in infants and neonates have been established in the evaluation of lesions within the brain and spine.
There is no experience with Omniscan in children below 6 months of age with severe hepatic or renal disease, with premature infants below 4 weeks or those with a postconceptional age of less than 30 weeks.

Use in elderly patients.

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.

Effects on ability to drive and use machines.

None known.

Interactions

None known.

Drug incompatibilities.

Omniscan should not be directly mixed with other drugs. A separate syringe and needle should be used.

Laboratory test findings.

Asymptomatic transitory increases in serum iron and bilirubin have been reported in patients receiving Omniscan.

Adverse Effects

Discomfort with a general sensation of warmth, coolness or a sensation of local pressure or pain at the injection site were commonly (≥ 1% and < 10%) observed in clinical studies. Dizziness, nausea, headache and a perverted sense of taste or smell were reported less frequently, but also in ≥ 1% of patients. Uncommon (≥ 0.1% and ≤ 1%) reactions included vomiting, somnolence, paraesthesia or allergy-like symptoms such as urticaria, itching, irritation in the throat and bronchospasm. Anaphylactoid reactions have occurred. The majority of adverse reactions in clinical studies were of mild intensity.
The following adverse reactions occurred in less than 1% of the patients, and were considered to be possibly related or of unknown relationship to Omniscan.

Body as a whole.

Body pain, fatigue, malaise, fever, anaphylactoid reaction.

Cardiovascular.

Warmth, chest pain, hypotension (syncope), tachycardia, flushing.

Digestive.

Melaena, dyspepsia, vomiting, diarrhoea, abdominal pain.

Musculoskeletal.

Arthralgia.

Nervous system.

Anxiety, paraesthesia, tinnitus, somnolence, lightheadedness, trembling, ataxia, personality disorder, convulsions, transient parosmia.

Respiratory.

Rhinitis, dyspnoea.

Skin and appendages.

Urticaria, pruritus, flushing, rash, face oedema, angioedema.

Special senses.

Visual disturbances.

Respiratory, thoracic and mediastinal disorders.

Dyspnoea, coughing bronchospasm, respiratory distress, throat irritation, sneezing.

General disorders and administration site conditions.

Chest pain, fever, shivering.
In patients with pre-existing severe renal insufficiency: rare acute kidney injury and increase in blood creatinine (frequency: not known) have been reported.
Cases of nephrogenic systemic fibrosis (NSF) have been reported with Omniscan.
In very rare cases convulsions have been observed after the administration of Omniscan, as is the case for other paramagnetic MR contrast media. However, a causal relationship seems to be questionable.
Two cases of transient elevated liver enzymes have been reported. However, in both cases concomitant medication known to cause abnormal results for liver function tests was taken. A causal relationship to Omniscan could therefore not be established.
Single cases of relapse of multiple sclerosis, encephalopathy and hallucinations have been reported.
Transient renal failure was observed in one patient who received an X-ray contrast medium for myelography 22 hours prior to the injection of Omniscan. The causality for the reaction has not been established.

Dosage and Administration

Omniscan is to be administered by intravenous injection. No special preparation of the patient is required. Omniscan should be drawn into the syringe immediately before use. For use in a single patient only and any unused portion must be discarded. For intravenous use. The required dose should be administered as a single intravenous injection. To ensure complete injection of the contrast medium, the injection should be followed by a 5 mL sodium chloride 0.9% (normal saline flush). Unless otherwise specified, the imaging procedure should be completed within 1 hour of administration of Omniscan. Parenteral products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit. Do not use the solution if it is discoloured or if particulate matter is present.
The lowest effective dose should be used.

Dosage for CNS (central nervous system) MRI.

Adults and children (including neonates and infants).

The recommended dosage of Omniscan is 0.2 mL/kg bodyweight (0.1 mmol/kg bodyweight) up to 100 kg. Above 100 kg bodyweight, 20 mL is usually sufficient to provide diagnostically adequate contrast. The required dose should be administered as a bolus intravenous injection.

Adults only.

When brain metastases are suspected, a dosage of 0.6 mL/kg bodyweight (0.3 mmol/kg bodyweight) can be administered up to 100 kg. Above 100 kg bodyweight, a total dose of up to 60 mL is recommended. In patients with equivocal scans after administration of the 0.2 mL/kg bodyweight injection, a second bolus injection of 0.4 mL/kg bodyweight (0.2 mmol/kg bodyweight) may be administered within 25 minutes of the first injection in patients up to 100 kg bodyweight. In patients with equivocal scans above 100 kg bodyweight, a second bolus injection of 40 mL may be administered.

Dosage for whole body MRI.

Adults.

The recommended dosage is usually 0.2 mL/kg bodyweight (0.1 mmol/kg bodyweight) up to 100 kg bodyweight. Above 100 kg bodyweight, 20 mL is usually sufficient to provide diagnostically adequate contrast.

Dosage for children from 6 months of age.

The recommended dosage is 0.2 mL/kg bodyweight (0.1 mmol/kg bodyweight).
See Table 1.

Overdosage

Clinical consequences of overdosage have not been reported and acute symptoms of toxicity are unlikely in patients with normal renal function. Treatment is symptomatic. There is no antidote for this contrast medium. In patients with delayed elimination due to renal insufficiency and in patients who have received excessive doses, the contrast medium can be eliminated by haemodialysis.

Presentation

Solution for injection, 287 mg/mL (0.5 mol/L) (sterile, aqueous, clear, colourless to slightly yellow), 5 mL, 10 mL, 15 mL*, 20 mL: 10's (glass vial); 10 mL, 15 mL, 20 mL, 40 mL, 50 mL: 10's (polypropylene ampoule*); 10 mL, 15 mL, 20 mL*: 10's (prefilled syringe).
*Not currently marketed in Australia.

Storage

Omniscan Injection in glass vials, polypropylene ampoules and prefilled syringes should be stored below 30°C and protected from light. Do not freeze.

Poison Schedule

Unscheduled.