Summary of medicine characteristics - GEMCITABINE 2 G POWDER FOR SOLUTION FOR INFUSION
1 NAME OF THE MEDICINAL PRODUCT
Gemcitabine 2 g Powder for Solution for Infusion
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One vial contains gemcitabine hydrochloride, equivalent to 200 mg gemcitabine.
One vial contains gemcitabine hydrochloride, equivalent to 1 g gemcitabine.
One vial contains gemcitabine hydrochloride, equivalent to 2 g gemcitabine.
After reconstitution, the solution contains 38 mg/ml gemcitabine (as hydrochloride).
Excipient with known effect:
Gemcitabine 1g Powder for Solution for Infusion contains 29 mg sodium per vial.
Gemcitabine 2g Powder for Solution for Infusion contains 58.5 mg sodium per vial.
For a full list of excipients, see section 6.1.
Powder for solution for infusion (powder for infusion)
White to off-white plug or powder.
4.1 Therapeutic indications
Bladder Cancer:
Locally advanced or metastatic bladder cancer, in combination with cisplatin.
Pancreatic Cancer:
Locally advanced or metastatic adenocarcinoma of the pancreas.
Non-Small Cell Lung Cancer:
First-line treatment of patients with locally advanced or metastatic non-small cell lung cancer, in combination with cisplatin. Gemcitabine monotherapy can be considered in elderly patients or those with performance status 2.
Ovarian Cancer:
Locally advanced or metastatic epithelial ovarian carcinoma, in combination with carboplatin, in patients with relapsed disease following a recurrence-free interval of at least 6 months after platinum-based, first line therapy.
Breast Cancer:
Unresectable, locally recurrent or metastatic breast cancer, in combination with paclitaxel, in patients experiencing a relapse after adjuvant/neoadjuvant chemotherapy. The preceding chemotherapy should have included an anthracycline, unless clinically contraindicated.
4.2 Posology and method of administration
For intravenous infusion, following reconstitution. Upon reconstitution a colourless or slightly yellow solution is produced.
Gemcitabine should only be prescribed by a physician qualified in the use of anti-cancer chemotherapy.
Adults: The recommended dose for gemcitabine is 1000 mg/m2, given as a 30 minute infusion. The dose should be given on days 1, 8, and 15 of each 28 day cycle in combination with cisplatin. Cisplatin is given at a recommended dose of 70 mg/m2 on day 1 following gemcitabine, or day 2 of each 28 day cycle. This four week cycle is then repeated. Dosage reduction with each cycle or within a cycle may be applied, based upon the amount of toxicity experienced by the patient.
Adults: The recommended dose of gemcitabine is 1000 mg/m2, given by 30 minute intravenous infusion. This should be repeated once weekly for up to 7 weeks, followed by a one week rest period. Subsequent cycles should consist of gemcitabine infusions once weekly for 3 consecutive weeks out of every four weeks. Dosage reduction with each cycle or within a cycle may be applied, based upon the amount of toxicity experienced by the patient.
Adults: The recommended dose of gemcitabine is 1000 mg/m2, given by 30 minute intravenous infusion. This should be repeated once weekly for three weeks, followed by a one week rest period. This four-week cycle is then repeated. Dosage reduction with each cycle or within a cycle may be applied, based upon the amount of toxicity experienced by the patient.
Adults: The recommended dose of gemcitabine is 1250 mg/m2, given by 30 minute intravenous infusion, on days 1 and 8 of each 21 day cycle. Dosage reduction with each cycle or within a cycle may be applied, based upon the amount of toxicity experienced by the patient.
Cisplatin has been used at doses between 75–100 mg/m2 once every 3 weeks.
The recommended dose of gemcitabine, when used in combination with carboplatin, is 1000 mg/m2, given by 30 minute intravenous infusion on days 1 and 8 of each 21 day cycle. After gemcitabine, carboplatin will be given on day 1, consistent with a target Area Under Curve (AUC) of 4.0mg/ml/min. Dosage reduction with each cycle or within a cycle may be applied, based upon the amount of toxicity experienced by the patient.
Adults: It is recommended that gemcitabine is used together with paclitaxel according to the following procedure:
Paclitaxel (175 mg/m2) is intravenously infused over 3 hours on day 1, followed by gemcitabine (1250 mg/m2) intravenously infused for 30 minutes on days 1 and 8 of each 21 day treatment cycle. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient. The absolute granulocyte count should be at least 1.5 × 109/l before treatment with the gemcitabine + paclitaxel combination.
Periodic physical examination and checks of renal and hepatic function should be made to detect non-haematological toxicity. Dosage reduction with each cycle or within a cycle may be applied, based upon the amount of toxicity experienced by the patient. In general, for severe (Grade 3 or 4) non-haematological toxicity, except nausea/vomiting, therapy with gemcitabine should be withheld or decreased depending on the judgement of the treating physician. Doses should be withheld until toxicity has been resolved.
For cisplatin, carboplatin, and paclitaxel dosage adjustment in combination therapy, please refer to the corresponding Summary of Product Characteristics.
Initiation of a cycle
For all indications, patients must be monitored before each dose for platelet and granulocyte counts. Patients should have an absolute granulocyte count of at least 1,500 (x106/l) and a platelet count of 100,000 (x106/l) prior to the administration of a cycle.
Within a cycle
Dose modifications of gemcitabine within a cycle should be performed according to the following tables:
| Dose modification of gemcitabine within a cycle for bladder cancer, pancreatic cancer, and NSCLC, given in monotherapy or in combination with cisplatin | |||
| Absolute Granulocyte Count (x 109/l) | Platelet Count (x 109/l) | % of Total Dose | |
| > 1 | and | >100 | 100 |
| 0.5–1 | or | 50–100 | 75 |
| < 0.5 | or | <50 | Withhold |
Withheld treatment will not be reinstated within a cycle before the absolute granulocyte count reaches at least 0.5(x 109/l) and the platelet count reaches 50 (x 109/l).
| Dose modification of gemcitabine within a cycle for ovarian cancer, given in combination with carboplatin | |||
| Absolute Granulocyte Count (x 109/l) | Platelet Count (x 109/1) | % of Total Dose | |
| >1.5 | and | >100 | 100 |
| 1–1.5 | or | 75–100 | 50 |
| <1 | or | <75 | Withhold |
Withheld treatment will not be reinstated within a cycle. Treatment will start on day 1 of the next cycle once the absolute granulocyte count reaches at least 1.5(x 109/l) and the platelet count reaches 100 (x 109/l)
| Dose modification of gemcitabine within a with | cycle for breast cancer, given in combination paclitaxel | ||
| Absolute Granulocyte Count (x 109/l) | Platelet Count (x 109/l) | % of Total Dose | |
| >1.2 | and | >75 | 100 |
| 1-<1.2 | or | 50–75 | 75 |
| 0.7-<1 | and | >50 | 50 |
| <0.7 | or | <50 | Withhold |
Withheld treatment will not be reinstated within a cycle. Treatment will start on day 1 of the next cycle once the absolute granulocyte count reaches at least 1.5 (x 109/l) and the platelet count reaches 100 (x 109/l).
Dose adjustment due to haematological toxicity in subsequent cycles, for all indications The gemcitabine dose should be reduced to 75% of the original cycle initiation dose, in the case of the following haematological toxicities:
Absolute granulocyte count < 0.5 × 109/l for more than 5 days
Absolute granulocyte count < 0.1 × 109/l for more than 3 days
Febrile neutropaenia
Platelets <25 × 109/l
Cycle delay of more than one week due to toxicity
Gemcitabine is tolerated well during infusion and may be administered ambulant. If extravasation occurs, generally the infusion must be stopped immediately and started again in another blood vessel. The patient should be monitored carefully after the administration.
For instructions on reconstitution, see section 6.6
Gemcitabine can suppress bone marrow function as manifested by leucopaenia, thrombocytopaenia, and anaemia.
Patients receiving gemcitabine should be monitored prior to each dose for platelet, leucocyte and granulocyte counts. Suspension or modification of therapy should be considered when drug-induced bone marrow depression is detected (see section 4.2). However, myelosuppression is short lived and usually does not result in dose reduction and rarely in discontinuation.
Peripheral blood counts may continue to deteriorate after gemcitabine administration has been stopped. In patients with impaired bone marrow function, the treatment should be started with caution. As with other cytotoxic treatments, the risk of cumulative bone-marrow suppression must be considered when gemcitabine treatment is given together with other chemotherapy.
Administration of gemcitabine to patients with concurrent liver metastases or a pre-existing medical history of hepatitis, alcoholism or cirrhosis of the liver may result in exacerbation of the underlying liver impairment.
Laboratory evaluation of renal and hepatic function (including virological tests) should be performed periodically.
Gemcitabine should be used with caution in patients with hepatic insufficiency or with impaired renal function as there is insufficient information from clinical studies to allow clear dose recommendation for this patient population (see section 4.2).
Concomitant radiotherapy (given together or <7 days apart): Toxicity has been reported (see section 4.5 for details and recommendations for use).
Live vaccinations
Yellow fever vaccine and other live attenuated vaccines are not recommended in patients treated with gemcitabine (see section 4.5).
Reports of posterior reversible encephalopathy syndrome (PRES) with potentially severe consequences have been reported in patients receiving gemcitabine as single agent or in combination with other chemotherapeutic agents. Acute hypertension and seizure activity were reported in most gemcitabine patients experiencing PRES, but other symptoms such as headache, lethargy, confusion and blindness could also be present. Diagnosis is optimally confirmed by magnetic resonance imaging (MRI). PRES was typically reversible with appropriate supportive measures. Gemcitabine should be permanently discontinued and supportive measures implemented, including blood pressure control and anti-seizure therapy, if PRES develops during therapy.
Due to the risk of cardiac and/or vascular disorders with gemcitabine, particular caution must be exercised with patients presenting a history of cardiovascular events.
Capillary leak syndrome
Capillary leak syndrome has been reported in patients receiving gemcitabine as single agent or in combination with other chemotherapeutic agents (see section 4.8). The condition is usually treatable if recognised early and managed appropriately, but fatal cases have been reported. The condition involves systemic capillary hyperpermeability during which fluid and proteins from the intravascular space leak into the interstitium. The clinical features include generalised oedema, weight gain, hypoalbuminaemia, severe hypotension, acute renal impairment and pulmonary oedema. Gemcitabine should be discontinued and supportive measures implemented if capillary leak syndrome develops during therapy. Capillary leak syndrome can occur in later cycles and has been associated in the literature with adult respiratory distress syndrome.
Pulmonary effects, sometimes severe (such as pulmonary oedema, interstitial pneumonitis, or adult respiratory distress syndrome (ARDS), have been reported in association with gemcitabine therapy. The aetiology of these effects is unknown. If such effects develop, consideration should be given to discontinuing gemcitabine therapy. Early use of supportive care measures may help ameliorate the condition.
Clinical findings consistent with the haemolytic uraemic syndrome (HUS) were rarely reported in patients receiving gemcitabine (see section 4.8). HUS is a life-threatening disease. Treatment should be discontinued at the first signs of any evidence of micro-angiopathic haemolytic anaemia, such as rapidly falling haemoglobin levels with concurrent thrombocytopenia, elevation of serum bilirubin, serum creatinine, blood urea nitrogen or lactate dehydrogenase (LDH). Renal failure may not be reversible with discontinuation of therapy, and dialysis may be required.
In fertility studies, gemcitabine caused hypospermatogenesis in male mice (see section 5.3). Therefore, men being treated with gemcitabine are advised not to father a child during and up to 6 months after treatment and to seek further advice regarding cryoconservation of sperm prior to treatment because of the possibility of infertility due to therapy with gemcitabine (see section 4.6).
Gemcitabine 200 mg Powder for Solution for Infusion
This medicinal product contains less than 1 mmol sodium (23 mg) per vial. Patients on low sodium diets can be informed that this medicinal product is essentially ‘sodium free’.
Gemcitabine 1 g Powder for Solution for Infusion
This medicinal product contains 29 mg sodium per vial, equivalent to 1.45% of the WHO maximum recommended daily intake (RDI) of 2 g sodium for an adult.
Gemcitabine 2 g Powder for Solution for Infusion
This medicinal product contains 58.5 mg sodium per vial, equivalent to 2.93% of the WHO maximum recommended daily intake (RDI) of 2 g sodium for an adult.
This medicinal product may be reconstituted with sodium-containing solutions (see section 6.6) and this should be considered in relation to the total sodium from all sources that will be administered to the patient.
4.5 Interaction with other medicinal products and other forms of interaction
No specific interaction studies have been performed (see section 5.2)
Radiotherapy
Concurrent (given together or < 7 days apart) – Toxicity associated with this multimodality therapy is dependent on many different factors, including dose of gemcitabine, frequency of gemcitabine administration, dose of radiation, radiotherapy planning technique, the target tissue, and target volume.
Pre-clinical and clinical studies have shown that gemcitabine has radiosensitising activity. In a single trial, where gemcitabine at a dose of 1,000 mg/m2 was administered concurrently for up to 6 consecutive weeks with therapeutic thoracic radiation to patients with non-small cell lung cancer, significant toxicity in the form of severe, and potentially life threatening mucositis, especially oesophagitis, and pneumonitis was observed, particularly in patients receiving large volumes of radiotherapy [median treatment volumes 4,795 cm3]. Studies done subsequently have suggested that it is feasible to administer gemcitabine at lower doses with concurrent radiotherapy with predictable toxicity, such as a phase II study in non-small cell lung cancer, where thoracic radiation doses of 66 Gy were applied concomitantly with an administration with gemcitabine (600 mg/m2, four times) and cisplatin (80 mg/m2 twice) during 6 weeks. The optimum regimen for safe administration of gemcitabine with therapeutic doses of radiation has not yet been determined in all tumour types.
Non-concurrent (given >7 days apart) – Available information does not indicate any enhanced toxicity when gemcitabine is administered more than 7 days before or after radiation, other than radiation recall. Data suggest that gemcitabine can be started after the acute effects of radiation have resolved or at least one week after radiation.
Radiation injury has been reported on targeted tissues (e.g. oesophagitis, colitis, and pneumonitis) in association with both concurrent and non-concurrent use of gemcitabine.
Others
Yellow fever and other live attenuated vaccines are not recommended due to the risk of systemic, possibly fatal, disease, particularly in immunosuppressed patients.
4.6 Fertility, pregnancy and lactation
There are no adequate data from the use of gemcitabine in pregnant patients. Studies in animals have shown reproductive toxicity (see section 5.3). Based on results from animal studies and the mechanism of action of gemcitabine, this substance should not be used during pregnancy, unless clearly necessary. Women should be advised not to become pregnant during treatment with gemcitabine and to warn their attending physician immediately, should this occur.
It is not known whether gemcitabine is excreted in human milk and adverse events on the suckling child cannot be excluded. Breast-feeding must be discontinued during gemcitabine therapy.
In fertility studies, gemcitabine caused hypospermatogenesis in male mice (see section 5.3). Therefore, men being treated with gemcitabine are advised not to father a child during and up to 6 months after treatment and to seek further advice regarding cryoconservation of sperm prior to treatment because of the possibility of infertility due to therapy with gemcitabine.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed. However, gemcitabine has been reported to cause mild to moderate somnolence, especially in combination with alcohol consumption. Patients should be cautioned against driving or operating machinery until it is established that they do not become somnolent.
4.8 Undesirable effects
The most commonly reported adverse reactions associated with gemcitabine treatment include: nausea, with or without vomiting, and raised liver transaminases ( (AST/ ALT) and alkaline phosphatase, reported in approximately 60% of patients; proteinuria and haematuria reported in approximately 50% of patients; dyspnoea reported in 10–40% of patients (highest incidence in lung cancer patients); allergic skin rashes occurring in approximately 25% of patients, and are associated with itching in 10% of patients.
The frequency and severity of the adverse reactions are affected by the dose, infusion rate, and intervals between doses (see section 4.4). Dose-limiting adverse reactions are reductions in thrombocyte, leucocyte, and granulocyte counts (see section 4.2).
Clinical trial data
Frequencies are defined as: Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
| System Organ Class | Frequency Grouping |
| Infections and infestations | Common: Infections Not known: Sepsis |
| Blood and lymphatic system disorders | Very common: Leucopenia (Neutropaenia grade 3 =19.3% ; grade 4 =6%) Thrombocytopaenia Anaemia Bone marrow suppression is usually mild to moderate and mostly affects the granulocyte count (see section 4.2) Common: Febrile neutropenia Very rare: Thrombocytosis Thrombotic microangiopathy |
| Immune system disorders | Very Rare: Anaphylactoid reaction |
| Metabolism and nutrition disorders | Common: Anorexia |
| Nervous system disorders | Common: Headache Insomnia Somnolence Uncommon Cerebrovascular accident |
| System Organ Class | Frequency Grouping |
| Very rare Posterior reversible encephalopathy syndrome (see section 4.4) | |
| Cardiac disorders | Uncommon: Arrhythmias, predominantly supraventricular in nature Heart failure Rare: Myocardial infarct |
| Vascular disorders | Rare: Clinical signs of peripheral vasculitis and gangrene Hypotension Very Rare Capillary leak syndrome (see section 4.4) |
| Respiratory, thoracic and mediastinal disorders | Very common: Dyspnoea -usually mild and passes rapidly without treatment Common: Cough Rhinitis Uncommon: Interstitial pneumonitis (see section 4.4) Bronchospasm – usually mild and transient but may require parenteral treatment Rare: Pulmonary oedema Adult respiratory distress syndrome (see section 4.4) Not known: Pulmonary eosinophilia |
| Gastrointestinal disorders | Very common: Vomiting Nausea Common: Diarrhoea Stomatitis & ulceration of the mouth Constipation |
| System Organ Class | Frequency Grouping |
| Very rare: Ischaemic colitis | |
| Hepatobiliary disorders | Very common: Elevation of liver transaminases (ASTand ALT) and alkaline phosphatase Common: Increased bilirubin Uncommon: Serious hepatotoxicity, including liver failure and death Rare: Increased gamma glutamyl transferase (GGT) |
| Skin and subcutaneous tissue disorders | Very common: Allergic skin rash frequently associated with pruritus Alopecia Common: Itching Sweating Rare: Severe skin reactions, including desquamation and bullous skin eruptions Ulceration Vesicle and sore formation Scaling Very rare: Toxic epidermal necrolysis Stevens-Johnson Syndrome Not known: Pseudocellulitis |
| Musculoskeletal and connective tissue disorders | Common: Back pain Myalgia |
| Renal and urinary disorders | Very common: |
| System Organ Class | Frequency Grouping |
| Haematuria Mild proteinurea Uncommon: Renal failure (see section 4.4) Haemolytic uraemic syndrome (see section 4.4) | |
| General disorders and administration site conditions | Very common: Influenza-like symptoms -the most common symptoms are fever, headache, chills, myalgia, asthenia, and anorexia. Cough, rhinitis, malaise, perspiration and sleeping difficulties have also been reported. Oedema/peripheral oedema – including facial oedema. Oedema is usually reversible after stopping treatment Common: Fever Asthenia Chills Rare: Injection site reactions -mainly mild in nature |
| Injury, poisoning, and procedural complications | Rare: Radiation toxicity (see section 4.5) Radiation recall |
The frequency of grade 3 and 4 haematological toxicities, particularly neutropaenia, increases when gemcitabine is used in combination with paclitaxel. However, the increase in these adverse reactions is not associated with an increased incidence of infections or haemorrhagic events. Fatigue and febrile neutropaenia occur more frequently when gemcitabine is used in combination with paclitaxel. Fatigue, which is not associated with anaemia, usually resolves after the first cycle.
Grade 3 and 4 Adverse Events. Paclitaxel versus gemcitabine plus paclitaxel:
| Number (%) of Patients | ||||
| Paclitaxel Arm (n= 259) | Gemcitabine plus Paclitaxel Arm (n= 262) | |||
| Grade 3 | Grade 4 | Grade 3 | Grade 4 | |
| Laboratory | ||||
| Anaemia | 5(1.9) | 1 (0.4) | 15 (5.7) | 3 (1.1) |
| Thrombocytopaenia | 0 | 0 | 14 (5.3) | 1 (0.4) |
| Neutropaenia | 11 (4.2) | 17 (6.6) | 82 (31.3) | 45 (17.2) |
| Non-laboratory | ||||
| Febrile neutropenia | 3 (1.2) | 0 | 12 (4.6) | 1 (0.4) |
| F atigue | 3 (1.2) | 1 (0.4) | 15 (5.7) | 2 (0.8) |
| Diarrhoea | 5 (1.9) | 0 | 8(3.1) | 0 |
| Motor neuropathy | 2 (0.8) | 0 | 6 (2.3) | 1 (0.4) |
| Sensory neuropathy | 9 (3.5) | 0 | 14 (5.3) | 1 (0.4) |
* Grade 4 neutropenia lasting for more than 7 days occurred in 12.6% of patients in the combination arm and 5.0% of patients in the paclitaxel arm.
Combination use in bladder cancer
Grade 3 and 4 Adverse Events. MVAC versus gemcitabine plus cisplatin:
| Number (%) of Patients | ||||
| MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) Arm (n= 196) | Gemcitabine plus cisplatin Arm (n= 200) | |||
| Grade 3 | Grade 4 | Grade 3 | Grade 4 | |
| Laboratory | ||||
| Anaemia | 30 (16) | 4 (2) | 47 (24) | 7 (4) |
| Thrombocytopaenia | 15 (8) | 25 (13) | 57 (29) | 57 (29) |
| Non-laboratory | ||||
| Nausea and vomiting | 37 (19) | 3 (2) | 44 (22) | 0 (0) |
| Diarrhoea | 15 (8) | 1 (1) | 6 (3) | 0 (0) |
| Infection | 19 (10) | 10 (5) | 4 (2) | 1 (1) |
| Stomatitis | 34 (18) | 8 (4) | 2 (1) | 0 (0) |
Combination use in ovarian cancer
Grade 3 and 4 Adverse Events. Carboplatin versus gemcitabine plus carboplatin:
| Number (%) of Patients | ||||
| Carboplatin Arm (n= 174) | Gemcitabine plus carboplatin Arm (n= 175) | |||
| Grade 3 | Grade 4 | Grade 3 | Grade 4 | |
| Laboratory | ||||
| Anaemia | 10 (5.7) | 4 (2.3) | 39 (22.3) | 9 (5.1) |
| Neutropaenia | 19 (10.9) | 2 (1.1) | 73 (41.7) | 50 (28.6) |
| Thrombocytopaenia | 18 (10.3) | 2 (1.1) | 53 (30.3) | 8 (4.6) |
| Leucopaenia | 11 (6.3) | 1 (0.6) | 84 (48.0) | 9 (5.1) |
| Non-laboratory | ||||
| Haemorrhage | 0 (0.0) | 0 (0.0) | 3 (1.8) | (0.0) |
| Febrile neutropaenia | 0 (0.0) | 0 (0.0) | 2 (1.1) | (0.0) |
| Infection without neutropaenia | 0 (0) | 0 (0.0) | (0.0) | 1 (0.6) |
Sensory neuropathy was also more frequent in the combination arm than with single agent carboplatin.
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.
4.9 Overdose
There is no known antidote for overdose of gemcitabine. Single doses of up to 5.7 g/m2 have been administered as intravenous infusions over 30 minutes every other week, with clinically acceptable toxicity. In the event of suspected overdose, the patient should be monitored with appropriate blood counts and should receive supportive therapy as necessary.
5 PHARMACOLOGICAL PROPERTIES
6 PHARMACEUTICAL PARTICULARS
For single use only
This medicinal product has only been shown to be compatible with sodium chloride 9 mg/ml (0.9%) solution for injection. Accordingly, only this diluent should be used for reconstitution. Compatibility with other active
substances has not been studied. Therefore, it is not recommended to mix this medicinal product with other active substances when reconstituted.
Reconstitution at concentrations greater than 38 mg/ml may result in incomplete dissolution, and should be avoided.
To reconstitute, slowly add the appropriate volume of sodium chloride 9 mg/ml (0.9%) solution for injection (as stated in the table below) and shake to dissolve.
| Presentation | Volume of sodium chloride 9 mg/ml (0.9%) solution for injection to be added | Displacement volume | Final concentration |
| 200 mg | 5 ml | 0.26 ml | 38 mg/ml |
| 1 g | 25 ml | 1.3 ml | 38 mg/ml |
| 2 g | 50 ml | 2.6 ml | 38 mg/ml |
The appropriate amount of medicinal product may be further diluted with sodium chloride 9 mg/ml (0.9%) solution for injection.
Parenteral medicinal products should be inspected visually for particulate matter and discolouration, prior to administration, whenever solution and container permit.
Any unused solution should be discarded as described below.
Local guidelines on safe preparation and handling of cytotoxic medicinal products must be adhered to. Cytotoxic preparations should not be handled by pregnant staff. The preparation of injectable solutions of cytotoxic agents must be carried out by trained specialist personnel with knowledge of the medicines used. This should be performed in a designated area. The work surface should be covered with disposable plastic-backed absorbent paper.
Suitable eye protection, disposable gloves, face mask and disposable apron should be worn. Precautions should be taken to avoid the medicinal product accidentally coming into contact with the eyes. If accidental contamination occurs, the eye should be washed with water thoroughly and immediately.
Syringes and infusion sets should be assembled carefully to avoid leakage (use of Luer lock fittings is recommended). Large bore needles are recommended to minimise pressure and the possible formation of aerosols. The latter may also be reduced by the use of a venting needle.
Actual spillage or leakage should be mopped up wearing protective gloves. Excreta and vomit must be handled with care.
Adequate care and precaution should be taken in the disposal of items used to reconstitute this medicinal product. Any unused dry product or contaminated materials should be placed in a high-risk waste bag. Sharp objects (needles, syringes, vials, etc) should be placed in a suitable rigid container. Personnel concerned with the collection and disposal of this waste should be aware of the hazard involved. Waste material should be destroyed by incineration. Any unused product or waste material should be disposed of in accordance with local requirements.