Korjuny 10 mcg Concentrate for Solution for infusion

Korjuny is indicated for the intraperitoneal treatment of malignant ascites in adults with epithelial cellular adhesion molecule (EpCAM)-positive carcinomas, who are not eligible for further systemic anticancer therapy.

Korjuny must be administered under the supervision of a physician experienced in the use of anti-cancer medicinal products

EpCAM testing

EpCAM expression in the clinical studies was determined using a validated immunocytochemical assay applied to malignant ascites samples, with a positivity threshold of ≥ 400 EpCAM-positive cells per 10⁶ analysed ascites cells.

Where a CE-marked in vitro diagnostic device with the appropriate intended purpose is not available, alternative assays used in clinical practice should be validated and demonstrate appropriate analytical performance characteristics for this intended use.

Posology

Prior to the intraperitoneal infusion, medication for the prophylactic treatment of cytokine release symptoms, including analgesic, antipyretic and non-steroidal antiphlogistic medicinal products is recommended (see sections 4.4 and 5.1).

Side effects of catumaxomab treatment should be treated as medically indicated and according to the current standard of care.

Korjuny dosing schedule comprises the 4 intraperitoneal infusions listed in table 1.

Table 1 Korjuny dosing schedule

Patients should remain under close medical supervision for at least 24 hours after the first infusion of Korjuny. For the remaining doses, patients may be hospitalised for at least 6 hours or for a longer time after infusions of Korjuny at the discretion of the treating physician to safeguard patient safety.

The interval between the infusion days can be prolonged at the discretion of the treating physician if needed in order to minimise the risk of adverse reactions. The overall treatment period should not exceed 21 days.

Special populations

Hepatic impairment

No dose adjustment is needed for patients with mild to moderate hepatic impairment. Patients with severe hepatic impairment and/or with more than 70% of the liver metastasised and/or portal vein thrombosis/obstruction have not been investigated. Treatment of these patients with Korjuny should only be considered after a thorough evaluation of benefit/risk (see sections 4.4 and 5.2).

Renal impairment

No dose adjustment is needed for patients with mild renal impairment. Patients with moderate to severe renal impairment have not been studied. Treatment of these patients with Korjuny should only be considered after a thorough evaluation of benefit/risk (see sections 4.4 and 5.2).

Paediatric population

The safety and efficacy of Korjuny in children aged less than 18 years have not been established. No data are available.

Method of administration

Korjuny must be administered as an intraperitoneal infusion only.

Korjuny must not be administered by intraperitoneal bolus or by any other route of administration. For information on the perfusion system to be used see section 6.5.

Korjuny has to be administered as constant rate intraperitoneal infusion with an infusion time of at least 3 hours. In clinical studies infusion times of 3 hours and 6 hours were investigated. For the first of the 4 doses, an infusion time of 6 hours may be considered depending on the patient's health condition.

Precautions to be taken before administering the medicinal product

Before administration of Korjuny, the concentrate for solution for infusion is diluted in sodium chloride 9 mg/mL (0.9%) solution for injection. The diluted KORJUNY solution for infusion is administered intraperitoneally as constant rate infusion using an adequate pump system.

For instructions on dilution of the medicinal product before administration, see section 6.6.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Hypersensitivity to murine (rat and/or mouse) proteins.

Korjuny must not be administered as a bolus or by any route other than intraperitoneally.

Cytokine release related symptoms (CRS)

As release of pro-inflammatory and cytotoxic cytokines is initiated by the binding of catumaxomab to immune and tumour cells, cytokine release related clinical symptoms have been reported during and after catumaxomab administration, including events of fever, hypotension, gastrointestinal symptoms, headache, myalgia, arthralgia, tachycardia, chills, respiratory symptoms, skin symptoms, and fatigue.

Despite pre-medication (see sections 4.2 and 5.1), patients may experience CRS as described above with an intensity of up to grade 4, (see section 4.8). Patients should be counselled to seek immediate medical attention if signs or symptoms of CRS occur at any time. CRS should be treated as medically indicated and according to the current standard of care.

Systemic inflammatory response syndrome (SIRS)

Isolated incidence of SIRS (with concurrent fever, increased heart rate and respiratory rate, and abnormal leukocyte count) have been reported during and after treatment with catumaxomab. Patients should be counselled to seek immediate medical attention if signs or symptoms of SIRS occur at any time. SIRS should be treated as medically indicated and according to the current standard of care.

Acute infections

In presence of factors interfering with the immune system, in particular acute infections, the administration of catumaxomab is not recommended. Patients should be monitored for signs and symptoms of infection, before and after Korjuny administration and treated appropriately.

Conditions affecting haemodynamic status of patients

Appropriate medical management of ascites drainage is a prerequisite for Korjuny treatment in order to assure stable circulatory and renal functions. This must at least include ascites drainage until stop of spontaneous flow or symptom relief.

Blood volume, blood protein, blood pressure, pulse and renal function should be assessed before each Korjuny infusion. Conditions such as hypovolaemia, hypoproteinaemia, hypotension, circulatory decompensation and acute renal impairment must be resolved prior to each Korjuny infusion.

Hepatic function

No dose adjustment is needed for patients with mild to moderate hepatic impairment. Transient elevations of liver parameters after catumaxomab infusions were observed in clinical studies which subsequently improved in the majority of patients shortly after completion of the last catumaxomab infusion. In rare cases, catumaxomab -drug induced liver injury (DILI) or hepatitis may occur, potentially leading to hepatic failure including fatal outcome. Patients treated with Korjuny should be closely monitored for signs of clinically significant elevated liver parameters.

Patients with severe hepatic impairment and/or with more than 70% of the liver volume involved by metastatic disease and/or portal vein thrombosis/obstruction have not been investigated. Treatment of these patients with catumaxomab should only be considered after a thorough evaluation of benefit/risk (see section 5.2).

Renal impairment

Catumaxomab is not eliminated via the renal pathway. Patients with moderate to severe renal impairment have not been investigated. Treatment of these patients with Korjuny should only be considered after a thorough evaluation of benefit/risk (see section 5.2).

Abdominal pain

Abdominal pain was commonly reported as an adverse reaction. This transient effect is considered partially a consequence of the intraperitoneal route of administration.

Monitoring

Adequate monitoring of the patient after end of Korjuny infusion is recommended with close medical supervision for at least 24 hours after the first infusion of Korjuny and for at least 6 hours after subsequent infusions.

Performance status and Body Mass Index (BMI)

In the pivotal study IP-REM-AC-01, patients with a Karnofsky performance score of < 60 and with a BMI of < 17 or > 40 kg/m² have not been investigated. Treating these patients with Korjuny is at the discretion of the treating physician.

Patient card

The prescriber must discuss the risks of Korjuny therapy with the patient. The patient should be provided with the patient card and instructed to carry it at all times. The patient card describes the common signs and symptoms of CRS and SIRS and provides instructions on when a patient should seek medical attention.

Excipient

This medicine contains 21.6 micrograms polysorbate 80 in each pre-filled syringe Korjuny 10 micrograms. Polysorbates may cause allergic reactions.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose unit, that is to say essentially 'sodium-free'. The amount of sodium administered per infusion is higher than that contained in the medicinal product due to the dilution of the concentrate with sodium chloride 9 mg/mL (0.9%) solution for injection. An additional 500 mL of sodium chloride 9 mg/mL (0.9%) solution for injection is given before each Korjuny administration and 250 mL of sodium chloride 9 mg/mL (0.9%) solution for injection is given in parallel with each Korjuny administration. See section 6.6.

No interaction studies have been performed.

Women of childbearing potential

Korjuny is not recommended in women of childbearing potential not using contraception.

Pregnancy

There are no or limited amount of data from the use of catumaxomab in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Korjuny is not recommended during pregnancy.

Breast-feeding

It is unknown whether catumaxomab/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Korjuny therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

No data on the effect of catumaxomab on fertility are available.

Korjuny has minor influence on the ability to drive and use machines.

Patients experiencing infusion-related symptoms should be advised not to drive and use machines until symptoms abate.

Summary of the safety profile

The most commonly reported adverse reactions were pyrexia (62%), abdominal pain (42%), nausea (41%), and vomiting (38%). The most serious adverse reactions are systemic inflammatory response syndrome and hepatic failure.

Tabulated list of adverse reactions

Adverse reactions are derived from an integrated safety analysis of 11 studies including 4 studies in patients with malignant ascites and 7 studies in patients with various other cancers. This includes data from the randomised, controlled main study period from pivotal study IP-REM-AC-01. Of 517 patients included in the analysis, 293 patients received catumaxomab intraperitoneally as 6‑hour infusion and 224 patients received catumaxomab intraperitoneally as 3‑hour infusion.

In Table 2, adverse reactions are listed by MedDRA system organ class. Frequency groupings are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100). Within each frequency grouping the adverse reactions are presented in the order of decreasing seriousness.

Table 2 Adverse reactions reported from patients receiving catumaxomab treatment

Description of selected adverse reactions

Cytokine release syndrome

Cytokine release syndrome (CRS), identified based on occurrence of hallmark symptoms for CRS (fever, hypotension, gastrointestinal symptoms, headache, myalgia, arthralgia, tachycardia, chills, respiratory symptoms, skin symptoms, and fatigue) in close temporal relationship (fever and at least 2 additional adverse reactions within a 4 day time window). At the time of the conduct of the pivotal study, 72% of catumaxomab exposed patients (ISS2) experienced at least one adverse event counted as hallmark symptoms of CRS during or within 1 day after a catumaxomab infusion. As the analysis was highly unspecific, data from the pivotal study were reanalysed according to an algorithm based on current CRS definitions and guidelines. Based on this re-analysis, 23% of patients treated with catumaxomab experienced CRS in the main study period or the crossover period of the pivotal clinical phase II/III study.

In the majority of cases, CRS was of CTCAE grade 1 or 2. Of 41 suspected CRS episodes, 3 were of grade 1, 27 were of grade 2, 10 were of grade 3, and 1 was of grade 4. Symptoms of cytokine release can be ameliorated or avoided by pre-medication (see sections 4.2 and 4.4).

Systemic inflammatory response syndrome (SIRS)

SIRS (with concurrent fever, increased heart rate and respiratory rate, and abnormal leukocyte count) was reported in 2 patients out of 203 patients exposed to catumaxomab in the pivotal study (157 in the main study period, 46 after crossover from control to catumaxomab). In both patients, SIRS was of Grade 4, required hospitalisation/prolongation of hospitalisation, and led to discontinuation of the treatment.

Abdominal pain

In 38.9% of patients in the main study period of the pivotal study, abdominal pain was reported as an adverse reaction, reaching grade 3 or higher in 8.9% of patients, but it resolved under symptomatic treatment.

Hepatic laboratory values

Transient increases in hepatic enzymes (alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase [ALP], gamma-glutamyl transferase [GGT]) and total bilirubin were commonly observed after the administration of catumaxomab. In general, the changes in laboratory parameters were not clinically relevant and mostly returned to baseline after end of treatment. In the pivotal clinical phase II/III study, 12 patients (5.6%) treated with catumaxomab experienced elevations of ALT of > 3 × upper limit of normal (ULN) in conjunction with bilirubin > 2 × ULN. In 2 of 12 patients, values continued to increase after end of infusion whereas in 10 of 12 patients, the increased values were reversible and showed a trend to improve shortly after the last catumaxomab infusion. Only in case of clinically relevant or persisting increase further diagnostics or therapy should be considered.

Duration of infusion

Data on a 3‑hour infusion duration of catumaxomab are available from studies in malignant ascites and studies in other oncological indications, mainly ovarian cancer and gastric cancer. The safety profile of catumaxomab using a 3 hour versus a 6‑hour infusion time is in general comparable with regards to nature, frequency and severity of adverse reactions. An increased frequency of some adverse reactions was seen in relation to 3‑hour administration including chills and hypotension (grades 1 or 2), diarrhoea (all grades) fatigue (grade 1 or 2), anaemia (all grades), and pleural effusion (grades 1 or 2).

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 at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Symptoms

Higher planned doses of catumaxomab were investigated in dose escalation studies, up to single treatment courses of catumaxomab 10-20-50-200-200 micrograms. Overall, effects observed with catumaxomab doses higher than the proposed dose were in line with known adverse reactions associated with catumaxomab administration and its mechanism of action. Laboratory values, notably changes in liver parameters, showed transient increases that were dose-dependent and showed tendency to accumulate.

Treatment

No antidote for catumaxomab is available. In case of overdose, symptomatic treatment should be initiated at the physician's discretion.

Pharmacotherapeutic group: Antineoplastic agents, other monoclonal antibodies and antibody drug conjugates, ATC code: L01FX03

Mechanism of action

Catumaxomab is a trifunctional rat-mouse hybrid monoclonal antibody that is specifically directed against the epithelial cell adhesion molecule (EpCAM) and the CD3 antigen.

The EpCAM antigen is expressed on most cancers especially carcinomas. CD3 is expressed on mature T-cells as a component of the T-cell receptor. A third functional binding site in the Fc-region of catumaxomab enables interaction with accessory immune cells via Fc-gamma receptors. Due to catumaxomab's binding properties, tumour cells, T-cells and accessory immune cells come in close proximity. Thereby, a concerted immunoreaction against tumour cells is induced which includes different mechanisms of action such as T-cell activation, T-cell mediated killing via the granzyme / perforin system, antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and phagocytosis. This results in destruction of tumour cells in the peritoneal cavity, thereby eliminating a major cause of malignant ascites.

Pharmacodynamic effects

The anti-tumour activity of catumaxomab has been demonstrated in vitro and in vivo. Effective catumaxomab-mediated killing of tumour cells in vitro was observed for target cells with low and high expression of the EpCAM antigen, independent of the primary tumour type. The in vivo anti-tumour activity of catumaxomab was confirmed in an immunologically compromised mouse model of ovarian carcinoma, where tumour development was delayed by an intraperitoneal treatment with catumaxomab and human peripheral blood mononuclear cells.

Clinical efficacy

The efficacy of catumaxomab was evaluated in one phase II/III clinical study. Patients of non-Caucasian origin have not been included in this clinical study.

IP-REM-AC-01

A pivotal, two-arm, randomised, open-label, phase II/III clinical study in 258 patients with symptomatic malignant ascites due to EpCAM-positive carcinomas of whom 170 were randomised to catumaxomab treatment. Presence of EpCAM-positive cells in ascites fluid was determined using an immunohistochemistry (IHC) assay. Patients were eligible for enrolment if ascites fluid contained ≥ 400 EpCAM- positive cells/10⁶ analysed ascites cells. This study compared paracentesis plus catumaxomab versus paracentesis alone (control).

Catumaxomab was applied in patients where standard therapy was not available or no longer feasible and who had a Karnofsky performance status of at least 60. Catumaxomab was administered as four intraperitoneal infusions with increased doses of 10, 20, 50 and 150 micrograms on day 0, 3, 7 and 10, respectively. On infusion days (Days 0, 3, 7, 10), patients remained hospitalised for at least 24 h (see section 4.2).

Among patients randomised (n=258), 79% of patients were female (100% in the ovarian cancer stratum, 59% in the non-ovarian cancer stratum). Mean age was 58.5 years in the ovarian cancer stratum and 58.8 years in the non-ovarian cancer stratum. Caucasians accounted for 99% of patients overall. The most frequent cancer types in the non-ovarian cancer stratum was gastric cancer (51%), followed by breast cancer (10%); other cancer types (colon, pancreas, lung, endometrium, others) were individually present in < 10% of patients in the non-ovarian cancer stratum.

In this study, the primary efficacy endpoint was puncture-free survival in the randomised, controlled main study period, which was a composite endpoint defined as the time to first need for therapeutic ascites puncture or death, whichever occurred first. The results for puncture-free survival are presented in Table 3. Kaplan Meier estimates for puncture-free survival are given in Figure 1.

Table 3 Efficacy results (puncture-free survival) of study IP-REM-AC-01

Patients who completed the study at the scheduled study end without therapeutic puncture were censored at the date of the scheduled study end. Patients who discontinued the study after randomisation but before the endpoint of puncture or death were censored at the date of premature discontinuation.

HR: Hazard ratio, PuFS: puncture-free survival

Figure 1 Kaplan-Meier estimates of puncture-free survival in study IP‑REM‑AC‑01

Compared with paracentesis alone (control), treatment with paracentesis and catumaxomab in patients with malignant ascites due to EpCAM-positive carcinomas prolonged puncture-free survival from 11 to 48 days in ovarian cancer patients and from 14 to 30 days in non-ovarian cancer patients.

After completion of the main study period, patients were further observed until the end of their lifetime to assess overall survival. Patients receiving paracentesis (control) could cross over to paracentesis and catumaxomab after completion of the main study period; nevertheless, these patients were counted as control patients despite the crossover. There was no worsening in overall survival in patients receiving paracentesis and catumaxomab relative to patients receiving paracentesis (Table 4).

Table 4 Overall survival of study IP-REM-AC-01

¹ Crossover patients were counted as control patients despite crossing over to paracentesis and catumaxomab treatment; this were 45 of 88 (51%) patients in the control arm.

Immunogenicity

The induction of anti-catumaxomab antibodies is an intrinsic effect of murine monoclonal antibodies. Data on catumaxomab derived from the pivotal study show that < 10% of patients were anti-catumaxomab antibodies positive before the 4^th infusion.

Anti-catumaxomab antibodies were present in 95% of patients one month after the last catumaxomab infusion.

Paediatric population

The Licensing Authority has waived the obligation to submit the results of studies with Korjuny in all subsets of the paediatric population in the treatment of malignant ascites (see section 4.2 for information on paediatric use).

Pharmacokinetics of catumaxomab during and after four intraperitoneal infusions of 10, 20, 50 and 150 micrograms catumaxomab as 6‑hour infusion were investigated in a dedicated study in 13 patients with symptomatic malignant ascites due to EpCAM-positive carcinomas.

Catumaxomab was detectable in ascites fluid and in plasma. The concentrations increased with the number of infusions and the doses applied in most patients. Plasma levels tended to decline after achieving a maximum after each dose.

Absorption

Catumaxomab is administered via the intraperitoneal route and therefore is immediately available at the targeted site of malignant cells in the peritoneal cavity.

Distribution

Upon intraperitoneal infusion, catumaxomab distributes in ascites fluid as the site of action. Mean and median C_max for ascites fluid were 7122 and 3270 pg/mL, respectively.

After intraperitoneal administration and binding to target cells in the peritoneal cavity, residual catumaxomab reaches systemic circulation in intact form. The geometric mean plasma C_max was 0.5 ng/ml (range 0 to 2.3), and the geometric mean plasma AUC was 1.7 day* ng/ml (range < LLOQ (lower limit of quantification) to 13.5).

The variability between subjects in ascites and plasma catumaxomab levels was high, due to varying ascites volume and malignant cell burden in the peritoneal cavity.

Metabolism and elimination

The metabolism and elimination of catumaxomab is similar to endogenous IgG i.e. primarily via proteolytic catabolism throughout the body; it does not rely primarily on elimination through the kidneys and liver.

For systemic catumaxomab, i.e. residual (not target-bound) catumaxomab that reached the circulation from the peritoneal cavity, geometric mean apparent terminal plasma elimination half-life (t_1/2) was 2.5 days (range 0.7 to 17.5).

Special populations

No studies have been conducted.

Administration of catumaxomab in animal models did not result in any signs of abnormal or product related acute toxicity or signs of local intolerance at the injection/infusion site. However, these findings are of limited value due to the high species-specificity of catumaxomab.

Repeated-dose toxicity, genotoxicity, carcinogenicity, reproductive and developmental toxicity studies have not been performed.

Sodium citrate (E331)

Citric acid monohydrate (E330)

Polysorbate 80 (E433)

Water for injections

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

3 years

After dilution

The prepared solution for infusion is physically and chemically stable for 48 hours at 2 °C to 8 °C and for 24 hours at a temperature not above 25 °C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

Store in a refrigerator (2 °C - 8 °C).

Do not freeze.

Store in the original package in order to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

Pre-filled syringe (type I glass, siliconised) with plunger stopper (bromobutyl rubber) and luer lock system (polypropylene siliconised and polycarbonate), with tip cap (bromobutyl rubber). A cannula is enclosed.

Korjuny 10 micrograms concentrate for solution for infusion

The pre-filled syringe contains 0.1 mL concentrate for solution and is packed in a carton with a blue colour code.

Pack size: 3 pre-filled syringes and 5 cannulas

Not all pack sizes may be marketed.

The pre-filled syringe is for single use only.

Material and equipment required for dilution and administration of Korjuny:
• sodium chloride 9 mg/mL (0.9%) solution for injection
• 50 mL polypropylene syringes
• cap for 50 mL polypropylene syringes
• polyethylene perfusion tubing with an inner diameter of 1 mm and a length of 150 cm
• polycarbonate infusion valves / Y connections
• polyurethane silicon-coated catheters
• precision perfusion pump

Dilution prior to administration

Korjuny should be prepared by a healthcare professional using appropriate aseptic technique.

The outer surface of the pre-filled syringe is not sterile.

• The volume of sodium chloride 9 mg/mL (0.9%) solution for injection listed in Table 5 is extracted with a 50 mL syringe.
• An additional air buffer of at least 3 mL is included in the 50 mL syringe.
• The Korjuny pre-filled syringe(s) of the required strength listed in Table 5 below are visually inspected for any foreign particulates or discolouration.
• With the pre-filled syringe tip pointing up, the tip cap is gently removed. Do not twist off or rotate the cap.
• The enclosed cannula is attached to the pre-filled syringe and the cannula shield removed. A new cannula must be used for each syringe.
• The cannula is inserted through the 50 mL syringe opening so that the cannula is immersed in the sodium chloride 9 mg/mL (0.9%) solution for injection (Figure 2).
 Do not administer the Korjuny pre-filled syringe directly to a patient.
• The entire content of the pre-filled syringe is injected into the sodium chloride 9 mg/mL (0.9%) solution for injection.
• The plunger rod must not be drawn back to rinse the pre-filled syringe, to avoid contamination and to ensure that the correct volume is ejected.
• Based on Table 5, the previous steps are repeated to inject the required number of pre-filled syringes into the 50 mL syringe.
• The 50 mL syringe is closed with a cap and shaken gently to mix the solution.
• After removing the cap, any air bubbles are eliminated from the 50 mL syringe.
• The red peelable sticker, which is provided inside the carton lid, displaying the text “Diluted Korjuny. Intraperitoneal use only.” must be attached to the 50 mL syringe. This is a precautionary measure to ensure Korjuny is intraperitoneally infused only.
• The 50 mL syringe is inserted in the infusion pump.

Table 5 Number of pre-filled syringes and volumes required for preparation of Korjuny solution for intraperitoneal infusion

Method of administration

The catheter for intraperitoneal administration is placed under ultrasound guidance by a doctor experienced in intraperitoneal administration. The catheter is used for ascites drainage, and administration of diluted Korjuny solution for infusion and sodium chloride 9 mg/mL (0.9%) solution for injection. It is recommended that the catheter remains in the abdominal cavity during the entire treatment period. It can be removed based on the judgement of the treating physician on the day after the last infusion.

Prior to each Korjuny administration, the ascites fluid must be drained until cessation of spontaneous flow or symptom relief (see section 4.4). Subsequently, prior to each Korjuny administration, 500 mL sodium chloride 9 mg/mL (0.9%) solution for injection shall be infused to support distribution of the antibody in the abdominal cavity.

Diluted Korjuny solution for infusion is intraperitoneally administered over an infusion time of at least 3 hours via a constant infusion pump system, as follows:
• The connected perfusion tubing equipment of the infusion pump is prefilled with the diluted Korjuny solution for infusion.
• The perfusion tubing is connected to the Y connection.
• Parallel to each Korjuny administration, 250 mL sodium chloride 9 mg/mL (0.9%) solution for injection is infused via an infusion valve / Y connection in the perfusion lead of the catheter.
• The pump speed is adjusted according to the volume to be administered and the scheduled infusion time of at least 3 hours.
• When the 50 mL syringe containing the diluted Korjuny solution for infusion is empty, it is replaced with a 50 mL syringe containing 20 mL sodium chloride 9 mg/mL (0.9%) solution for injection, to clear the dead volume in the perfusion lead (approximately 2 mL), under unchanged conditions. The remaining sodium chloride 9 mg/mL (0.9%) solution for injection can be discarded.
• The catheter is kept closed until the next infusion.
• The day after the last infusion, a drainage of ascites is performed until cessation of spontaneous flow. Subsequently, the catheter can be removed.

Disposal

No special requirements.