E-Z-Paque 96 % W/W Powder For Oral/Rectal Suspension
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
E-Z-Paque 96 % w/w powder for oral/rectal suspension
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Active Constituent:
Barium sulfate 96.3045 % w/w
Excipients with known effect:
Sorbitol (E420), 2 g per 100 g powder.
Approximately 224 mg sodium per 100 g powder.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Powder for oral/rectal suspension.
White powder.
4.1 Therapeutic indications
This medicinal product is for diagnostic use only.
E-Z-Paque is indicated for use as a positive contrast medium for radiographic visualisation of the gastro-intestinal tract.
The 177 g presentation is intended for oral administration and the 1200 g and 10 kg presentations for either oral or enema administration, in all cases following dispersion in water as directed.
E-Z-Paque is indicated in adults and children.
4.2 Posology and method of administration
Posology
E-Z-Paque is primarily intended for use in the upper gastro-intestinal tract but may also be administered by enema.
The administered dose of E-Z-Paque will depend on the patient in question, the route of administration and the section of the gastrointestinal tract to be viewed.
Adults: Single contrast of the oesophagus, stomach and duodenum - give orally 175 to 300 mL of suspension at 100 % w/v.
Small bowel - give orally 250 to 300 mL of suspension at 60 % w/v.
The actual administered dose should be determined from experience, by the radiologist.
Children: The dosage will be dependent on the size, age, health state and anatomic region to be imaged of the child. Individual requirements should be determined, from experience, by the radiologist.
Elderly: There are no special dosage recommendations. The dosage should be determined, from experience, by the radiologist.
Method of administration
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
4.3 Contraindications
Immune System Disorders
Hypersensitivity to barium sulfate or to any of the excipients listed in section 6.1
Gastrointestinal Disorders Patients with any of the following:
- a known or suspected perforation t of the gastrointestinal tract
- known or suspected tracheo-esophageal fistula (oral administration),
- gastrointestinal haemorrhage
- gastrointestinal ischemia
- megacolon or toxic megacolon
- necrotising entercolitis
- severe ileus
should not receive E-Z-Paque.
E-Z-Paque should not be used for infants with swallowing disorders.
Surgical and Medical Procedures
Barium sulfate should not be administered immediately after gastrointestinal surgery, including snare polypectomy or ‘hot’ colonic biopsy because of the potential for post-surgical or post-procedural leakage or the potential for gastrointestinal perforation. In case the patient has to undergo gastrointestinal surgery immediately after barium sulfate administration, caution should be exercised.
Injury, Poisoning and Procedural Complications
Barium Sulphate products should not be used during and up to four weeks after radiotherapy to the rectum or prostate. Do not use if there are new injuries or chemical burns of the gastrointestinal tract.
4.4 Special warnings and precautions for use
The product should be administered under the supervision of a physician.
Diagnostic procedures which involve the use of radiopaque contrast agents should be carried out under the direction of personnel with the requisite training and with a thorough knowledge of the particular procedure to be performed.
Barium Sulphate should not be administered in its dry form. The powder must be reconstituted, and some of the commercially prepared suspensions require further dilution, prior to administration.
Hypersensitivity
A history of bronchial asthma, atopy, as evidenced by hay fever and eczema, a family history of allergy, or a previous reaction to a contrast agent warrant special attention.
As stated in section 4.8, serious adverse reactions, including death, have been reported with the administration of barium sulfate formulations and are usually associated with the technique of administration, the underlying pathological condition and/or patient hypersensitivities. Anaphylactic and allergic reactions have been reported during double contrast examinations in which glucagon has been used. Rapid recognition, assessment, and diagnosis are crucial to the effective implementation of treatment. Imaging facilities should be staffed with well-trained personnel for the diagnosis and treatment of hypersensitivity reactions.
Barium sulfate preparations used as radiopaque media contain a number of additives to provide diagnostic properties and patient palatability. Allergic responses following the use of barium sulfate suspensions have been reported. Skin irritation, redness, inflammation and hives have been reported for infants and small children following spillage of barium sulfate suspension on their skin. These responses are thought to be caused by the flavors and/or preservatives used in the product.
Known hypersensitivity or allergy to latex is a contraindication for the use of balloon retention enema tips containing latex.
Because of reported anaphylactoid reactions to latex, the use of non-latex gloves during the procedure should be considered.
Perforation
In patients with a serious stenosis at any level of the gastro-intestinal tract, especially if it is distal to the stomach, and in the presence of conditions and ailments that increase the risk of perforation such as known gastrointestinal fistulae and carcinomas, inflammatory intestinal disease, diverticulitis and diverticulosis and amoebiasis, careful consideration of the risks and benefits of the administration of a barium sulfate suspension is required.
Care must be taken during insertion of the enema tip into the patient and when using a retention balloon, particularly in the newborn, the elderly and in patients with recto-sigmoidal strictures, inflammatory bowel disease, rectal neoplasm or radiation therapy. Enema tip forceful, too deep insertion or balloon inflation may cause tearing or perforation of the rectum.
Insertion of an enema tip should be performed only after digital examination by qualified medical personnel. When balloon retention tips are used, care should be taken to avoid over inflation of the balloon, since overfilling or asymmetrical filling may cause displacement of the tip. Such a displacement can lead to rectal perforation or barium sulfate granulomas.
Inflation of the balloon should be done under fluoroscopic control by qualified medical personnel. Do not unnecessarily move the enema tip once inserted. A specially designed enema tip is required for a barium sulfate suspension examination of a colostomy patient. Intubation of an enteroclysis catheter should be done by qualified medical personnel.
Aspiration
For patients who are prone to aspiration (the newborn, elderly and stroke patients), it is recommended that the procedure starts with a small ingested volume.
Vomiting following oral administration of barium sulfate may lead to aspiration pneumonitis. Oral administration of barium sulfate suspension by an infant sucking a bottle and administration of large quantities by catheter are reported to be likely to result in aspiration into the tracheobronchial tree. Cardiopulmonary arrest leading to fatality has been reported in infants following aspiration. Aspiration of smaller amounts may cause respiratory tract inflammation and pneumonia.
Ingestion of barium is not recommended in patients with a history of food aspiration. If barium procedures are required in these patients or in patients in whom integrity of the swallowing mechanism may be compromised, proceed with caution. If this product is aspirated into the larynx, further administration should be immediately discontinued.
Obstruction/Fluid Overload
Barium Sulphate suspensions, after oral administration, have been reported to cause obstruction of the small bowel (impaction) in pediatric patients with cystic fibrosis.
Barium sulfate suspensions have been reported to cause fluid overload due to water absorption.
Children and patients with impaired renal function are the most susceptible to water intoxication, as are children with Hirschsprung’s Disease.
It is suggested to not fill the entire colon when evaluating a child with Hirschsprung’s Disease; use only the amount of fluid necessary for the diagnosis.
Preparatory enemas in patients with Hirschsprung’s Disease should be avoided.
Intravasation
Barium sulfate may also intravasate into the venous drainage of the large bowel and enter the circulation as a "barium embolus". This complication occurs rarely, but can lead to potentially fatal complications, including systemic and pulmonary embolism, disseminated intravascular coagulation, septicaemia and prolonged severe hypotension. It is more likely to occur in elderly patients, due to thinning of the rectal wall and vaginal thinning with age, and in those with colorectal disease, when intraluminal pressure overcomes the resistance of the colonic wall affected by colitis, diverticulitis or intestinal obstruction. The diagnosis should be considered in any patient who collapses during or shortly after barium enema, and in those who become suddenly unwell in the hours following the procedure This complication may be prevented by ensuring correct placement of the rectal catheter and by reducing the use of balloon catheters.
Misplacement of the rectal catheter in the vagina can lead to intravasation: correct rectal catheter placement should be confirmed prior to enema administration.
Constipation or Diarrhoea
E-Z-Paque should be used with care if the patient is dehydrated, suffers from any condition or is on any other treatment that can cause constipation, or if the patient has history of constipation. In this situation a mild bulk laxative should be administered following completion of the X-ray examination. Increased intake of liquids is recommended after oral or rectal administration of barium sulfate to prevent severe constipation and the risk of impaction.
Conversely, since E-Z-Paque contains sorbitol, administration may have a mild laxative effect. The calorific value of sorbitol is 2.6 kcal/g.
Other Possible Complications
Care must be taken during an enema procedure as vasovagal reactions, syncopal episodes, cardiac dysrhythmia and other cardiovascular side effects can occur during barium enemas.
All plastic/rubber accessories are disposable, single-use devices that must not be reused or left in the body cavity for an extended period of time.
Apprehensive patients may develop weakness, pallor, tinnitus, diaphoresis and bradycardia following the administration of any diagnostic agent. Such reactions are usually unpredictable and are best treated by having the patient lie flat for an additional 10 - 30 minutes under observation.
Patient preparation for diagnostic gastrointestinal examinations frequently requires cathartics and a liquid diet. The various preparations can result in water loss for the patient. Patients should be rehydrated quickly following a barium sulfate suspension examination of the gastrointestinal tract. In patients with reduced colon motility, saline cathartics may be required after the barium sulfate suspension enema. Saline cathartics are recommended on a routine basis in patients with a history of constipation unless clinically contraindicated.
Baroliths
Baroliths consist of inspissated barium associated with faeces. They are often asymptomatic, but may be associated with abdominal pain, appendicitis, bowel obstruction, or perforation. Patients who are elderly, with impaired gastrointestinal motility, colon obstruction, electrolyte imbalance, dehydration or on a low residue diet may be at risk of developing baroliths. To reduce this risk, adequate hydration should be maintained during and in the days following barium sulfate procedure. The use of laxatives (especially in case of constipation) should be considered.
Hereditary Fructose Intolerance
E-Z-Paque contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not use this medicine. Therefore, it should only be used in babies and small children after consultation with the doctor, due to the possibility of unknown hereditary fructose intolerance.
Patients on a Controlled Sodium Diet
E-Z-Paque contains sodium among the excipients. Care should be taken in patients on a controlled sodium diet, especially in the cases of repeated administration.
Children, Elderly and Debilitated Patients
As with any barium sulfate preparation, care should be taken when administering E-Z-Paque to children, the elderly or the debilitated. It should be used cautiously in patients with pre-existing heart disease. As bacteraemia may occur during a barium enema, IV antibiotic cover is recommended for patients with prosthetic heart valves.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
Barium sulfate is biologically inert and there are no known interactions with other medicinal products. However, the presence of barium sulfate formulations in the gastrointestinal tract may alter the absorption of therapeutic agents taken concomitantly. In order to minimise any potential change in absorption, the separate administration of barium sulfate from that of other medicines should be considered.
Other examinations of the same area of the gastrointestinal tract with another contrast agent may be complicated by the presence of barium sulfate (residue) in the gastrointestinal tract up to several days following the examination with barium contrast media.
4.6 Fertility, pregnancy and lactation
Pregnancy
Although this product is not contraindicated in pregnancy, we would like to point out that radiographic procedures may damage the foetus, particularly during the first trimester of pregnancy. Any examination should only be carried out after careful consideration of the benefit/risk of the procedure.
Fertility
Following oral or rectal administration, barium sulfate is absorbed systemically in negligible amounts. Though barium sulfate is pharmacologically inert, no studies of its mutagenic or teratogenic potential are available.
Breastfeeding
Since the absorption of barium sulfate is negligible, its use is not contraindicated during breastfeeding.
4.7 Effects on ability to drive and use machines
E-Z-Paque has negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Undesirable effects may occur during or after a procedure with barium sulfate.
Skin and subcutaneous disorders together with immune system disorders, reflecting allergic reactions either to barium sulfate or the product excipients, are among the most commonly reported effects; for example urticaria, erythema and rash.
Gastrointestinal disorders are also one of the most frequently reported class of undesirable effects; for example diarrhoea, nausea, abdominal pain/distention, constipation.
Within the table below, clinically significant adverse reactions are listed if they have been reported during post approval use of all barium sulfate formulations. Their frequency is not known, therefore relative reporting rate (for example, less commonly) compared to overall reporting for barium sulfate is used.
|
MedDRA System |
Adverse events | |
|
Organ Class |
Clinical Trials |
Post-marketing Surveillance |
|
Rare (>1/10,000 to | ||
|
<1/1,000) | ||
|
Infections and infestations |
Appendicitis, Bacteraemia. Less commonly other infections have been reported including rare cases of Abscess intestinal, Liver abscess, Peritoneal infection and Pneumonia | |
|
Blood and the lymphatic system disorders |
Lymphadenopathy | |
|
Immune system disorders |
Hypersensitivity presenting with a wide range of signs and symptoms including skin and subcutaneous reactions such as urticaria, pruritus, rash, erythema and facial swelling. Potential hypersensitivity associated respiratory signs and symptoms including dyspnoea, pharyngeal oedema and throat tightness have been reported. Anaphylactic reaction and anaphylactic shock have been reported less commonly. | |
|
Metabolism and nutrition disorders |
Infrequent cases of Hyperglycaemia have been reported in diabetic patients | |
|
Psychiatric disorders |
Agitation, Confusional state, Nervousness and related symptoms have been reported during the administration of barium sulfate | |
|
Nervous system disorders |
Loss of consciousness, Syncope, Syncope vasovagal, Dizziness, Burning sensation, Headache, Dysarthria, Hypotonia | |
|
Eye disorders |
Eye disorders, including Eye swelling, usually associated with allergic reactions have been reported | |
|
Ear and labyrinth disorders |
Tinnitus | |
|
Cardiac disorders |
Bradycardia, Cyanosis, Tachycardia | |
|
Vascular disorders |
Hypotension, Pallor, Vasodilatation | |
|
Respiratory, |
Bronchospasm, Dyspnoea, Laryngeal |
|
thoracic and mediastinal disorders |
oedema, Pharyngeal oedema and pain, Throat irritation or tightness, Cough. When administered orally, Aspiration, Pneumonia aspiration. | |
|
Gastrointestinal disorders |
Abdominal pain Nausea; Vomiting |
Gastrointestinal signs and symptoms are widely reported, it is not always possible to differentiate between preexisting medical conditions and procedural complications. Events reported include: Intestinal ischemia, Constipation and in severe cases gastrointestinal blockage; Gastrointestinal inflammation, ulceration or perforation; Abdominal discomfort abdominal distension; Diarrhoea; Colitis ulcerative may be aggravated; Retching; Flatulence; Swollen tongue |
|
Skin and subcutaneous tissue disorders |
Skin reactions are varied and most likely to be associated with allergic reactions. Reports include: Erythema, Dermatitis Contact, Excessive granulation tissue, Hyperhidrosis, Periorbital oedema, Pruritus, Rash, Swelling face, Urticaria | |
|
Renal and urinary disorders |
Dysuria | |
|
General disorders and administration site conditions |
Malaise, Pain, Swelling, Asthenia, Pyrexia, Face oedema | |
|
Investigations |
Electrocardiogram abnormal | |
|
Injury and poisoning |
Intravasation by barium sulfate, associated with pre-existing bowel disease or diverticulitis, has been reported rarely. Barium impaction. |
More rarely and depending on the route of administration, i.e. oral or rectal, the following procedural complications have been reported:
Infections (e.g. peritonitis) subsequent to existing or new gastrointestinal perforation. Complications include adhesions and granuloma.
Subsequent to existing or procedural gastrointestinal trauma, intravasation of barium sulfate with rare subsequent venous emboli formation, including the hepatic portal vein, vena cava and pulmonary embolism that may be fatal in approx 50% of cases.
Following oral administration, aspiration, with pulmonary complications, may occur and may be fatal in rare cases.
Please see section 4.4 for measures to be taken to avoid these adverse reactions, and actions to take if such adverse reactions occur.
Very rare cases of death associated with barium sulfate administration have been reported in the literature. The majority of the deaths relate to procedural complications usually caused by failure to follow generally accepted radiological practice. Some cases had a history indicating that barium sulfate administration was highly unlikely to be a primary or even secondary causative factor in patient fatality.
Paediatric patients
The type of adverse reactions is similar in children and adults.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme - Website: www.mhra.gov.uk/yellowcard
4.9 Overdose
Barium sulfate is non-toxic and absorbed systemically in negligible amounts.
Repeated use within a very short period of time has led to abdominal cramps, nausea, vomiting, diarrhoea, and constipation. These symptoms are transitory in nature and may be allowed to resolve without medical intervention or may be treated according to currently accepted standards of care.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: X-ray contrast media, barium sulfate with suspending agents, ATC code: V08BA01
The active constituent of E-Z-Paque, barium sulfate, is inert and has no pharmacological action. It serves only as a radiopaque substance to opacify the gastro-intestinal tract during X-ray examinations.
5.2 Pharmacokinetic properties
Under physiological conditions, barium sulfate passes through the gastrointestinal tract in an unchanged form and is absorbed only in small, pharmacologically insignificant amounts.
5.3 Preclinical safety data
There are no preclinical data of relevance to the prescriber which are additional to that already included elsewhere in the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sorbitol (E420)
Sodium citrate (E331)
Pectin (E440)
Sodium carrageenan (E407)
Bentonite Tragacanth (E413)
Citric acid (E330)
Simeticone Strawberry flavour Xanthan gum (E415)
Polyoxyethylene glyceryl mono-oleate Propylene glycol Saccharin sodium (E954)
Vanilla flavour
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
Three years.
E-Z-Paque should be administered immediately following reconstitution and must not be stored.
6.4 Special precautions for storage
Store below 25 °C. Store in the original package.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
6.5 Nature and contents of container
E-Z-Paque is presented in three pack sizes as follows:
Unit dose bottle (containing 177g E-Z-Paque) composed of a high density polyethylene (HDPE) with a polypropylene screw lid having a liner of three-ply co-extruded material (a foamed, low density polyethylene core between two solid layers of low density polyethylene). Polyethylene bottle with polypropylene lid containing 177 g of product. Polyethylene jug with polypropylene screw cap containing 1200 g of product. Polyethylene bag inside a polyethylene bucket with a polypropylene lid containing 10 kg of product.
6.6 Special precautions for disposal and other handling
Adults: E-Z-Paque should be suspended over the density range 60 to 100 % w/v. Reconstitution information for use of E-Z-Paque is provided below.
For pack size 177 g:
Add water to approximately 2.5 cm above barium level. Secure lid, invert bottle and shake vigorously. Add more water to desired % w/v line on bottle.
Replace lid and shake for 30 seconds.
Important : Always re-shake just prior to administration to the patient. Do not store reconstituted product.
For pack size 1200 g:
Add required amount of water, secure cap and invert jug, tapping base to loosen powder. Shake vigorously. Reshake just prior to use.
Add 900 mL water to give 1200 mL suspension at 100 % w/v.
Add 1400 mL water to give 1700 mL suspension at 70 % w/v.
Add water to neck of jug and shake, then top up with more water and shake again to give 2000 mL suspension at 60 % w/v.
Important: Always re-shake just prior to administration to the patient. Do not store reconstituted product.
For pack size 10 kg:
To one level scoop (275 g) add the following amounts of water:
- For 60 % w/v add 370 mL water. Approximate yield 440 mL suspension.
- For 70 % w/v add 305 mL water. Approximate yield 380 mL suspension.
- For 100 % w/v add 190 mL water. Approximate yield 265 mL suspension.
On addition of water shake vigorously. Reshake just prior to use. Do not store reconstituted product.
Any unused, opened product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Bracco Imaging spa Via Egidio Folli 50 20134 Milano Italy
8 MARKETING AUTHORISATION NUMBER(S)
PL 12032/0020
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
29th April 1994
10 DATE OF REVISION OF THE TEXT
26/09/2016