- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Gastroesophageal Reflux Disease (GORD)- treatment of erosive reflux oesophagitis- long-term management of patients with healed oesophagitis to prevent relapse- symptomatic treatment of gastroesophageal reflux disease (GORD)In combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori and- healing of Helicobacter pylori associated duodenal ulcer and- prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcers
Patients requiring continued NSAID therapyHealing of gastric ulcers associated with NSAID therapy.Prevention of gastric and duodenal ulcers associated with NSAID therapy, in patients at risk.
Prolonged treatment after IV induced prevention of rebleeding of peptic ulcers.
Treatment of Zollinger Ellison Syndrome
Adolescents from the age of 12 years
Gastro-Oesophageal Reflux Disease (GORD)- treatment of erosive reflux oesophagitis - long-term management of patients with healed oesophagitis to prevent relapse - symptomatic treatment of gastro-oesophageal reflux disease (GORD) In combination with antibiotics in treatment of duodenal ulcer caused by Helicobacter pylori
Adults and adolescents from the age of 12 years
Gastroesophageal Reflux Disease (GORD)- treatment of erosive reflux oesophagitis40 mg once daily for 4 weeks.An additional 4 weeks treatment is recommended for patients in whom oesophagitis has not healed or who have persistent symptoms.- long-term management of patients with healed oesophagitis to prevent relapse20 mg once daily.- symptomatic treatment of gastroesophageal reflux disease (GORD)20 mg once daily in patients without oesophagitis. If symptom control has not been achieved after 4 weeks, the patient should be further investigated. Once symptoms have resolved, subsequent symptom control can be achieved using 20 mg once daily. In adults, an on demand regimen taking 20 mg once daily, when needed, can be used. In NSAID treated patients at risk of developing gastric and duodenal ulcers, subsequent symptom control using an on demand regimen is not recommended.
AdultsIn combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori and- healing of Helicobacter pylori associated duodenal ulcer and- prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcers.20 mg Emozul with 1 g amoxicillin and 500 mg clarithromycin, all twice daily for 7 days.
Patients requiring continued NSAID therapyHealing of gastric ulcers associated with NSAID therapy: The usual dose is 20 mg once daily. The treatment duration is 4-8 weeks.Prevention of gastric and duodenal ulcers associated with NSAID therapy in patients at risk: 20 mg once daily.
Prolonged treatment after IV induced prevention of rebleeding of peptic ulcers40 mg once daily for 4 weeks after IV induced prevention of rebleeding of peptic ulcers.
Treatment of Zollinger Ellison SyndromeThe recommended initial dosage is Emozul 40 mg twice daily. The dosage should then be individually adjusted and treatment continued as long as clinically indicated. Based on the clinical data available, the majority of patients can be controlled on doses between 80 to 160 mg esomeprazole daily. With doses above 80 mg daily, the dose should be divided and given twice daily.
Adolescents from the age of 12 yearsTreatment of duodenal ulcer caused by Helicobacter pyloriWhen selecting appropriate combination therapy, consideration should be given to official national, regional and local guidance regarding bacterial resistance, duration of treatment (most commonly 7 days but sometimes up to 14 days), and appropriate use of antibacterial agents. The treatment should be supervised by a specialist. The posology recommendation is:
|30 - 40 kg||Combination with two antibiotics: Emozul 20 mg, amoxicillin 750 mg and clarithromycin 7.5 mg/kg body weight are all administered together twice daily for one week.|
|> 40 kg||Combination with two antibiotics: Emozul 20 mg, amoxicillin 1 g and clarithromycin 500 mg are all administered together twice daily for one week.|
Children below the age of 12 yearsEmozul should not be used in children younger than 12 years since no data is available.
Patients with impaired renal functionDose adjustment is not required in patients with impaired renal function. Due to limited experience in patients with severe renal insufficiency, such patients should be treated with caution (see section 5.2).
Patients with impaired hepatic functionDose adjustment is not required in patients with mild to moderate liver impairment. For patients with severe liver impairment, a maximum dose of 20 mg Emozul should not be exceeded (see section 5.2).
Elderly patientsDose adjustment is not required in the elderly.Do not eat the desiccant capsule provided in the container.Method of administration The capsules should be swallowed whole with some water. The capsules should not be chewed or crushed.For patients who have difficulty in swallowing, the capsules can also be opened and the pellets mixed in half a glass of non-carbonated water. No other liquids should be used as the enteric coating may be dissolved. Drink the water with the pellets immediately or within 30 minutes. Rinse the glass with half a glass of water and drink. The pellets must not be chewed or crushed.For patients who cannot swallow, the capsules can be opened and pellets mixed in non-carbonated water and administered through a gastric tube. It is important that the appropriateness of the selected syringe and tube is carefully tested before use (see section 6.6).
Interference with laboratory testsIncreased CgA level may interfere with investigations for neuroendocrine tumours. To avoid this interference, esomeprazole treatment should be temporarily stopped for at least five days before CgA measurements.
HypomagnesaemiaSevere hypomagnesaemia has been reported in patients treated with PPIs like esomeprazole for at least three months, and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the PPI.For patients expected to be on prolonged treatment or who take PPIs with digoxin or drugs that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.
Special information about some of the ingredientsEmozul contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Effects of esomeprazole on the pharmacokinetics of other active substances
Medicinal products with pH dependent absorptionGastric acid suppression during treatment with esomeprazole and other PPIs might decrease or increase the absorption of medicinal products with a gastric pH dependent absorption. As with other medicinal products that decrease intragastric acidity, the absorption of medicinal products such as ketoconazole, itraconazole and erlotinib can decrease and the absorption of digoxin can increase during treatment with esomeprazole. Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10% (up to 30% in two out of ten subjects). Digoxin toxicity has been rarely reported. However, caution should be exercised when esomeprazole is given at high doses in elderly patients. Therapeutic drug monitoring of digoxin should then be reinforced.Omeprazole has been reported to interact with some protease inhibitors. The clinical importance and the mechanisms behind these reported interactions are not always known. Increased gastric pH during omeprazole treatment may change the absorption of the protease inhibitors. Other possible interaction mechanisms are via inhibition of CYP 2C19. For atazanavir and nelfinavir, decreased serum levels have been reported when given together with omeprazole and concomitant administration is not recommended. Co-administration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg to healthy volunteers resulted in a substantial reduction in atazanavir exposure (approximately 75% decrease in AUC, Cmax and Cmin). Increasing the atazanavir dose to 400 mg did not compensate for the impact of omeprazole on atazanavir exposure. The co-administration of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg to healthy volunteers resulted in a decrease of approximately 30% in the atazanavir exposure as compared with the exposure observed with atazanavir 300 mg/ritonavir 100 mg once daily without omeprazole 20 mg once daily. Co-administration of omeprazole (40 mg once daily) reduced mean nelfinavir AUC, Cmax and Cmin by 36-39 % and mean AUC, Cmax and Cmin for the pharmacologically active metabolite M8 was reduced by 75-92%. For saquinavir (with concomitant ritonavir), increased serum levels (80-100%) have been reported during concomitant omeprazole treatment (40 mg once daily). Treatment with omeprazole 20 mg once daily had no effect on the exposure of darunavir (with concomitant ritonavir) and amprenavir (with concomitant ritonavir). Treatment with esomeprazole 20 mg once daily had no effect on the exposure of amprenavir (with and without concomitant ritonavir). Treatment with omeprazole 40 mg once daily had no effect on the exposure of lopinavir (with concomitant ritonavir). Due to the similar pharmacodynamic effects and pharmacokinetic properties of omeprazole and esomeprazole, concomitant administration with esomeprazole and atazanavir is not recommended and concomitant administration with esomeprazole and nelfinavir is contraindicated.
Active substances metabolised by CYP2C19Esomeprazole inhibits CYP2C19, the major esomeprazole metabolising enzyme. Thus, when esomeprazole is combined with active substances metabolised by CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin etc., the plasma concentrations of these active substances may be increased and a dose reduction could be needed. This should be considered especially when prescribing esomeprazole for on demand therapy. Concomitant administration of 30 mg esomeprazole resulted in a 45% decrease in clearance of the CYP2C19 substrate diazepam. Concomitant administration of 40 mg esomeprazole resulted in a 13% increase in trough plasma levels of phenytoin in epileptic patients. It is recommended to monitor the plasma concentrations of phenytoin when treatment with esomeprazole is introduced or withdrawn. Omeprazole (40 mg once daily) increased voriconazole (a CYP2C19 substrate) Cmax and AUC by 15% and 41%, respectively.Concomitant administration of 40 mg esomeprazole to warfarin-treated patients in a clinical trial showed that coagulation times were within the accepted range. However, post-marketing, a few isolated cases of elevated INR of clinical significance have been reported during concomitant treatment. Monitoring is recommended when initiating and ending concomitant esomeprazole treatment during treatment with warfarin or other coumarine derivatives.Omeprazole as well as esomeprazole act as inhibitors of CYP2C19. Omeprazole, given in doses of 40 mg to healthy subjects in a cross-over study, increased Cmax and AUC for cilostazol by 18% and 26% respectively, and one of its active metabolites by 29% and 69% respectively.In healthy volunteers, concomitant administration of 40 mg esomeprazole resulted in a 32% increase in area under the plasma concentration-time curve (AUC) and a 31% prolongation of elimination half-life (t½) but no significant increase in peak plasma levels of cisapride. The slightly prolonged QTc interval observed after administration of cisapride alone, was not further prolonged when cisapride was given in combination with esomeprazole (see also section 4.4).Esomeprazole has been shown to have no clinically relevant effects on the pharmacokinetics of amoxicillin or quinidine.Studies evaluating concomitant administration of esomeprazole and either naproxen or rofecoxib did not identify any clinically relevant pharmacokinetic interactions during short-term studies.In a crossover clinical study, clopidogrel (300 mg loading dose followed by 75 mg/day) alone and with omeprazole (80 mg at the same time as clopidogrel) were administered for 5 days. The exposure to the active metabolite of clopidogrel was decreased by 46% (Day 1) and 42% (Day 5) when clopidogrel and omeprazole were administered together. Mean inhibition of platelet aggregation (IPA) was diminished by 47% (24 hours) and 30% (Day 5) when clopidogrel and omeprazole were administered together. In another study it was shown that administering clopidogrel and omeprazole at different times did not prevent their interaction that is likely to be driven by the inhibitory effect of omeprazole on CYP2C19. Inconsistent data on the clinical implications of this PK/PD interaction in terms of major cardiovascular events have been reported from observational and clinical studies.
Unknown mechanismWhen given together with PPIs, methotrexate levels have been reported to increase in some patients. In high-dose methotrexate administration a temporary withdrawal of esomeprazole may need to be considered.
Effects of other active substances on the pharmacokinetics of esomeprazoleEsomeprazole is metabolised by CYP2C19 and CYP3A4. Concomitant administration of esomeprazole and a CYP3A4 inhibitor, clarithromycin (500 mg b.i.d.), resulted in a doubling of the exposure (AUC) to esomeprazole. Concomitant administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP 3A4 may result in more than doubling of the esomeprazole exposure. The CYP2C19 and CYP3A4 inhibitor voriconazole increased omeprazole AUC by 280%. A dose adjustment of esomeprazole is not regularly required in either of these situations. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.Drugs known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St. John's wort) may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.
Blood and lymphatic system disordersRare: Leukopenia, thrombocytopeniaVery rare: Agranulocytosis, pancytopenia
Immune system disordersRare: Hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/shock
Metabolism and nutrition disordersUncommon: Peripheral oedemaRare: HyponatraemiaNot known: Hypomagnesaemia (See Special warnings and precautions for use (4.4)); severe hypomagnesaemia can correlate with hypocalcaemia
Psychiatric disordersUncommon: InsomniaRare: Agitation, confusion, depressionVery rare: Aggression, hallucinations
Nervous system disordersCommon: HeadacheUncommon: Dizziness, paraesthesia, somnolenceRare: Taste disturbance
Eye disordersRare: Blurred vision
Ear and labyrinth disordersUncommon: Vertigo
Respiratory, thoracic and mediastinal disordersRare: Bronchospasm
Gastrointestinal disordersCommon: Abdominal pain, constipation, diarrhoea, flatulence, nausea/vomitingUncommon: Dry mouthRare: Stomatitis, gastrointestinal candidiasisNot known: Microscopic colitis
Hepatobiliary disordersUncommon: Increased liver enzymesRare: Hepatitis with or without jaundiceVery rare: Hepatic failure, encephalopathy in patients with pre-existing liver disease
Skin and subcutaneous tissue disordersUncommon: Dermatitis, pruritus, rash, urticariaRare: Alopecia, photosensitivityVery rare: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN)
Musculoskeletal, connective tissue and bone disordersUncommon: Fracture of the hip, wrist or spine (see section 4.4)Rare: Arthralgia, myalgiaVery rare: Muscular weakness
Renal and urinary disordersVery rare: Interstitial nephritis
Reproductive system and breast disordersVery rare: Gynaecomastia
General disorders and administration site conditionsRare: Malaise, increased sweating
Reporting of suspected adverse reactionsReporting 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 http://yellowcard.mhra.gov.uk/
Mechanism of actionEsomeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the secretory canaliculi of the parietal cell, where it inhibits the enzyme H+K+-ATPase the acid pump and inhibits both basal and stimulated acid secretion.
Effect on gastric acid secretionAfter oral dosing with esomeprazole 20 mg and 40 mg the onset of effect occurs within one hour. After repeated administration with 20 mg esomeprazole once daily for five days, mean peak acid output after pentagastrin stimulation is decreased 90% when measured 6-7 hours after dosing on day five.After five days of oral dosing with 20 mg and 40 mg of esomeprazole, intragastric pH above 4 was maintained for a mean time of 13 hours and 17 hours, respectively over 24 hours in symptomatic GORD patients. The proportion of patients maintaining an intragastric pH above 4 for at least 8, 12 and 16 hours respectively were for esomeprazole 20 mg 76%, 54% and 24%. Corresponding proportions for esomeprazole 40 mg were 97%, 92% and 56%.Using AUC as a surrogate parameter for plasma concentration, a relationship between inhibition of acid secretion and exposure has been shown.
Therapeutic effects of acid inhibitionHealing of reflux oesophagitis with esomeprazole 40 mg occurs in approximately 78% of patients after four weeks, and in 93% after eight weeks.One week treatment with esomeprazole 20 mg b.i.d. and appropriate antibiotics, results in successful eradication of H. pylori in approximately 90% of patients.After eradication treatment for one week there is no need for subsequent monotherapy with antisecretory active substances for effective ulcer healing and symptom resolution in uncomplicated duodenal ulcers.In a randomized, double blind, placebo-controlled clinical study, patients with endoscopically confirmed peptic ulcer bleeding characterised as Forrest Ia, Ib, IIa or IIb (9%, 43%, 38% and 10% respectively) were randomized to receive esomeprazole solution for infusion (n=375) or placebo (n=389). Following endoscopic hemostasis, patients received either 80 mg esomeprazole as an intravenous infusion over 30 minutes followed by a continuous infusion of 8 mg per hour or placebo for 72 hours. After the initial 72 hour period, all patients received open-label 40 mg oral esomeprazole for 27 days for acid suppression The occurrence of rebleeding within 3 days was 5.9% in the esomeprazole treated group compared to 10.3% for the placebo group. At 30 days post-treatment, the occurrence of rebleeding in the esomeprazole treated versus the placebo treated group 7.7% vs 13.6%.
Other effects related to acid inhibitionDuring treatment with antisecretory active substances serum gastrin increases in response to the decreased acid secretion. Chromogranin A (CgA) also increases due to decreased gastric acidity.An increased number of ECL cells (enterochromaffin-like cells), possibly related to the increased serum gastrin levels, have been observed in some patients during long term treatment with esomeprazole.During long-term treatment with antisecretory active substances gastric glandular cysts have been reported to occur at a somewhat increased frequency. These changes are a physiological consequence of pronounced inhibition of acid secretion, are benign and appear to be reversible.Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter and in hospitalised patients, possibly also Clostridium difficile.In two studies with ranitidine as an active comparator, esomeprazole showed better effect in healing of gastric ulcers in patients using NSAIDs, including COX-2 selective NSAIDs.In two studies with placebo as comparator, esomeprazole showed better effect in the prevention of gastric and duodenal ulcers in patients using NSAIDs (aged >60 and/or with previous ulcer), including COX-2 selective NSAIDs.
Paediatric populationIn a study in paediatric GORD patients (<1 to 17 years of age) receiving long-term PPI treatment, 61% of the children developed minor degrees of ECL cell hyperplasia with no known clinical significance and with no development of atrophic gastritis or carcinoid tumours.
Absorption and distributionEsomeprazole is acid labile and is administered orally as enteric-coated granules. In vivo conversion to the R-isomer is negligible. Absorption of esomeprazole is rapid, with peak plasma levels occurring approximately 1-2 hours after dose. The absolute bioavailability is 64% after a single dose of 40 mg and increases to 89% after repeated once-daily administration. For 20 mg esomeprazole the corresponding values are 50% and 68% respectively.The apparent volume of distribution at steady state in healthy subjects is approximately 0.22 l/kg body weight. Esomeprazole is 97% plasma protein bound.Food intake both delays and decreases the absorption of esomeprazole although this has no significant influence on the effect of esomeprazole on intragastric acidity.
Metabolism and excretionEsomeprazole is completely metabolised by the cytochrome P450 system (CYP). The major part of the metabolism of esomeprazole is dependent on the polymorphic CYP2C19, responsible for the formation of the hydroxy- and desmethyl metabolites of esomeprazole. The remaining part is dependent on another specific isoform, CYP3A4, responsible for the formation of esomeprazole sulphone, the main metabolite in plasma.The parameters below reflect mainly the pharmacokinetics in individuals with a functional CYP2C19 enzyme, extensive metabolisers.Total plasma clearance is about 17 l/h after a single dose and about 9 l/h after repeated administration. The plasma elimination half-life is about 1.3 hours after repeated once-daily dosing. The pharmacokinetics of esomeprazole has been studied in doses up to 40 mg b.i.d. The area under the plasma concentration-time curve increases with repeated administration of esomeprazole. This increase is dose-dependent and results in a more than dose proportional increase in AUC after repeated administration. This time - and dose-dependency is due to a decrease of first pass metabolism and systemic clearance probably caused by an inhibition of the CYP2C19 enzyme by esomeprazole and/or its sulphone metabolite. Esomeprazole is completely eliminated from plasma between doses with no tendency for accumulation during once-daily administration.The major metabolites of esomeprazole have no effect on gastric acid secretion. Almost 80% of an oral dose of esomeprazole is excreted as metabolites in the urine, the remainder in the faeces. Less than 1% of the parent compound is found in urine.
Special patient populationsApproximately 2.9 ± 1.5% of the population lack a functional CYP2C19 enzyme and are called poor metabolisers. In these individuals the metabolism of esomeprazole is probably mainly catalysed by CYP3A4. After repeated once-daily administration of 40 mg esomeprazole, the mean area under the plasma concentration-time curve was approximately 100% higher in poor metabolisers than in subjects having a functional CYP2C19 enzyme (extensive metabolisers). Mean peak plasma concentrations were increased by about 60%.These findings have no implications for the posology of esomeprazole.The metabolism of esomeprazole is not significantly changed in elderly subjects (71-80 years of age).Following a single dose of 40 mg esomeprazole the mean area under the plasma concentration-time curve is approximately 30% higher in females than in males. No gender difference is seen after repeated once-daily administration. These findings have no implications for the posology of esomeprazole.
Impaired organ functionThe metabolism of esomeprazole in patients with mild to moderate liver dysfunction may be impaired. The metabolic rate is decreased in patients with severe liver dysfunction resulting in a doubling of the area under the plasma concentration-time curve of esomeprazole. Therefore, a maximum of 20 mg should not be exceeded in patients with severe dysfunction. Esomeprazole or its major metabolites do not show any tendency to accumulate with once-daily dosing.No studies have been performed in patients with decreased renal function. Since the kidney is responsible for the excretion of the metabolites of esomeprazole but not for the elimination of the parent compound, the metabolism of esomeprazole is not expected to be changed in patients with impaired renal function.
Adolescents 12-18 years:Following repeated dose administration of 20 mg and 40 mg esomeprazole, the total exposure (AUC) and the time to reach maximum plasma concentration (tmax) in 12 to18 year-olds was similar to that in adults for both esomeprazole doses.
Pellets in the capsule core:Sugar spheres (sucrose and maize starch)Povidone K30Sodium laurilsulfatePoly(vinyl alcohol)Titanium dioxide (E171)Macrogol Talc (E553b)Magnesium carbonate, heavyPolysorbate 80 (E433)Methacrylic acid ethyl acrylate copolymer (1:1) dispersion 30 per cent
Capsule shell:Gelatin (E441)Titanium dioxide (E171)Red iron oxide (E172)
Blister pack consisting of OPA/Al/PE + DES film/Al foilThis medicinal product does not require any special temperature storage conditions. Store in the original package in order to protect from moisture.
Blister pack consisting of OPA/Al/PVC/Al foilDo not store 30°C. Store in the original package in order to protect from moisture.
HDPE containerThis medicinal product does not require any special temperature storage conditions. Keep the container tightly closed in order to protect from moisture.
Administration through gastric tube1. Open the capsule and empty the pellets into an appropriate syringe and fill the syringe with approximately 25 ml water and approximately 5 ml air.For some tubes, dispersion in 50 ml water is needed to prevent the pellets from clogging the tube.2. Immediately shake the syringe to evenly distribute the granules throughout the suspension.3. Hold the syringe with the tip up and check that the tip has not clogged.4. Attach the syringe to the tube whilst maintaining the above position.5. Shake the syringe and position it with the tip pointing down. Immediately inject 5 10 ml into the tube. Invert the syringe after injection and shake (the syringe must be held with the tip pointing up to avoid clogging of the tip)6. Turn the syringe with the tip down and immediately inject another 5 10 ml into the tube. Repeat this procedure until the syringe is empty.7. Fill the syringe with 25 ml of water and 5 ml of air and repeat step 5 if necessary to wash down any sediment left in the syringe. For some tubes, 50 ml water is needed.
Consilient Health Ltd
No. 1 Church Road, Richmond upon Thames, Surrey, TW9 2QE, UK
+44(0)20 3751 1889
+44(0) 20 3751 1888