- 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
Adult patientsA single 70 mg loading dose should be administered on Day-1, followed by 50 mg daily thereafter. In patients weighing more than 80 kg, after the initial 70 mg loading dose, caspofungin 70 mg daily is recommended (see section 5.2). No dosage adjustment is necessary based on gender or race (see section 5.2).
Paediatric patients (12 months to 17 years)In paediatric patients (12 months to 17 years of age), dosing should be based on the patient's body surface area (see Instructions for Use in Paediatric Patients, Mosteller1 Formula). For all indications, a single 70-mg/m2 loading dose (not to exceed an actual dose of 70 mg) should be administered on Day 1, followed by 50 mg/m2 daily thereafter (not to exceed an actual dose of 70 mg daily). If the 50-mg/m2 daily dose is well tolerated but does not provide an adequate clinical response, the daily dose can be increased to 70 mg/m2 daily (not to exceed an actual daily dose of 70 mg). The safety and efficacy of caspofungin have not been sufficiently studied in clinical trials involving neonates and infants below 12 months of age. Caution is advised when treating this age group. Limited data suggest that caspofungin at 25 mg/m2 daily in neonates and infants (less than 3 months of age) and 50 mg/m2 daily in young children (3 to 11 months of age) can be considered (see section 5.2).
Duration of treatmentDuration of empirical therapy should be based on the patient's clinical response. Therapy should be continued until up to 72 hours after resolution of neutropaenia (ANC≥ 500). Patients found to have a fungal infection should be treated for a minimum of 14 days and treatment should continue for at least 7 days after both neutropaenia and clinical symptoms are resolved.Duration of treatment of invasive candidiasis should be based upon the patient's clinical and microbiological response. After signs and symptoms of invasive candidiasis have improved and cultures have become negative, a switch to oral antifungal therapy may be considered. In general, antifungal therapy should continue for at least 14 days after the last positive culture.Duration of treatment of invasive aspergillosis is determined on a case by case basis and should be based upon the severity of the patient's underlying disease, recovery from immunosuppression, and clinical response. In general, treatment should continue for at least 7 days after resolution of symptoms.The safety information on treatment durations longer than 4 weeks is limited. However, available data suggest that caspofungin continues to be well tolerated with longer courses of therapy (up to 162 days in adult patients and up to 87 days in paediatric patients).
Elderly patientsIn elderly patients (65 years of age or more), the area under the curve (AUC) is increased by approximately 30 %. However, no systematic dosage adjustment is required. There is limited treatment experience in patients 65 years of age and older (see section 5.2).
Renal impairmentNo dosage adjustment is necessary based on renal impairment (see section 5.2).
Hepatic impairmentFor adult patients with mild hepatic impairment (Child-Pugh score 5 to 6), no dosage adjustment is needed. For adult patients with moderate hepatic impairment (Child-Pugh score 7 to 9), caspofungin 35 mg daily is recommended based upon pharmacokinetic data. An initial 70 mg loading dose should be administered on Day-1. There is no clinical experience in adult patients with severe hepatic impairment (Child-Pugh score greater than 9) and in paediatric patients with any degree of hepatic impairment (see section 4.4).
Co-administration with inducers of metabolic enzymesLimited data suggest that an increase in the daily dose of caspofungin to 70 mg, following the 70 mg loading dose, should be considered when co-administering caspofungin in adult patients with certain inducers of metabolic enzymes (see section 4.5). When caspofungin is co-administered to paediatric patients (12 months to 17 years of age) with these same inducers of metabolic enzymes (see section 4.5), a caspofungin dose of 70-mg/m2 daily (not to exceed an actual daily dose of 70 mg) should be considered.
Method of administrationAfter reconstitution and dilution, the solution should be administered by slow intravenous infusion over approximately 1 hour. For reconstitution directions see section 6.6.Both 70 mg and 50 mg vials are available.Caspofungin should be given as a single daily infusion1 Mosteller RD: Simplified Calculation of Body Surface Area. N Engl J Med 1987 Oct 22;317(17):1098 (letter)
PregnancyThere are no or limited data from the use of caspofungin in pregnant women. Caspofungin should not be used during pregnancy unless clearly necessary. Animal studies have shown developmental toxicity (see section 5.3). Caspofungin has been shown to cross the placental barrier in animal studies.
Breast-feedingIt is unknown whether caspofungin is excreted in human milk. Available pharmacodynamic/ toxicological data in animals have shown excretion of caspofungin in milk. Women receiving caspofungin should not breast-feed.
FertilityFor caspofungin, there were no effects on fertility in studies conducted in male and female rats (see section 5.3). There are no clinical data for caspofungin to assess its impact on fertility.
Adult PatientsIn clinical studies, 1,865 adult individuals received single or multiple doses of caspofungin: 564 febrile neutropaenic patients (empirical therapy study), 382 patients with invasive candidiasis, 228 patients with invasive aspergillosis, 297 patients with localised Candida infections, and 394 individuals enrolled in Phase I studies. In the empirical therapy study patients had received chemotherapy for malignancy or had undergone haematopoietic stem-cell transplantation (including 39 allogeneic transplantations). In the studies involving patients with documented Candida infections, the majority of the patients with invasive Candida infections had serious underlying medical conditions (e.g., haematologic or other malignancy, recent major surgery, HIV) requiring multiple concomitant medications. Patients in the non-comparative Aspergillus study often had serious predisposing medical conditions (e.g., bone marrow or peripheral stem cell transplants, haematologic malignancy, solid tumours or organ transplants) requiring multiple concomitant medications. Phlebitis was a commonly reported local injection-site adverse reaction in all patient populations. Other local reactions included erythema, pain/tenderness, itching, discharge, and a burning sensation. Reported clinical and laboratory abnormalities among all adults treated with caspofungin (total 1,780) were typically mild and rarely led to discontinuation.The following adverse reactions were reported:
[Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥1/1,000 to <1/100)]
Blood and lymphatic system disorders:Common: haemoglobin decreased, haematocrit decreased, white blood cell count decreased Uncommon: anaemia, thrombocytopaenia, coagulopathy, leukopaenia, eosinophil count increased, platelet count decreased, platelet count increased, lymphocyte count decreased, white blood cell count increased, neutrophil count decreased
Metabolism and nutrition disorders:Common: hypokalemiaUncommon: fluid overload, hypomagnesaemia, anorexia, electrolyte imbalance, hyperglycaemia, hypocalcaemia, metabolic acidosis
Psychiatric disordersUncommon: anxiety, disorientation, insomnia
Nervous system disorders:Common: headacheUncommon: dizziness, dysgeusia, paraesthesia, somnolence, tremor, hypoaesthesia
Eye disorders:Uncommon: ocular icterus, vision blurred, eyelid oedema, lacrimation increased
Cardiac disorders:Uncommon: palpitations, tachycardia, arrhythmia, atrial fibrillation, cardiac failure congestive
Vascular disorders:Common: phlebitisUncommon: thrombophlebitis, flushing, hot flush, hypertension, hypotension
Respiratory, thoracic and mediastinal disorders:Common: dyspnoeaUncommon: nasal congestion, pharyngolaryngeal pain, tachypnoea, bronchospasm, cough, dyspnoea paroxysmal nocturnal, hypoxia, rales, wheezing
Gastrointestinal disorders:Common: nausea, diarrhoea, vomitingUncommon: abdominal pain, abdominal pain upper, dry mouth, dyspepsia, stomach discomfort, abdominal distension, ascites, constipation, dysphagia, flatulence
Hepatobiliary disorders:Common: elevated liver values (alanine aminotransferase, aspartate aminotranserase, blood alkaline phosphatase, bilirubin conjugated, blood bilirubin) Uncommon: cholestasis, hepatomegaly, hyperbilirubinaemia, jaundice, hepatic function abnormal, hepatotoxicity, liver disorder, gamma-glutamyltransferase increased
Skin and subcutaneous tissue disorders:Common: rash, pruritus, erythema, hyperhidrosis Uncommon: erythema multiforme, rash macular, rash maculo-papular, rash pruritic, urticaria, dermatitis allergic, pruritus generalised, rash erythematous, rash generalised, rash morbilliform, skin lesion
Musculoskeletal and connective tissue disordersCommon: arthralgiaUncommon: back pain, pain in extremity, bone pain, muscular weakness, myalgia
Renal and urinary disordersUncommon: renal failure, renal failure acute
General disorders and administration site conditions:Common: pyrexia, chills, infusion-site pruritusUncommon: pain, catheter site pain, fatigue, feeling cold, feeling hot, infusion site erythema, infusion site induration, infusion site pain, infusion site swelling, injection site phlebitis, oedema peripheral, tenderness, chest discomfort, chest pain, face oedema, feeling of body temperature change, induration, infusion site extravasation, infusion site irritation, infusion site phlebitis, infusion site rash, infusion site urticaria, injection site erythema, injection site oedema, injection site pain, injection site swelling, malaise, oedema
Investigations:Common: blood potassium decreased, blood albumin decreased Uncommon: blood creatinine increased, red blood cells urine positive, protein total decreased, protein urine present, prothrombin time prolonged, prothrombin time shortened, blood sodium decreased, blood sodium increased, blood calcium decreased, blood calcium increased, blood chloride decreased, blood glucose increased, blood magnesium decreased, blood phosphorus decreased, blood phosphorus increased, blood urea increased, activated partial thromboplastin time prolonged, blood bicarbonate decreased, blood chloride increased, blood potassium increased, blood pressure increased, blood uric acid decreased, blood urine present, breath sounds abnormal, carbon dioxide decreased, immunosuppressant drug level increased, international normalised ratio increased, urinary casts, white blood cells urine positive, and pH urine increased. Caspofungin has also been evaluated at 150 mg daily (for up to 51 days) in 100 adult patients (see section 5.1). The study compared caspofungin at 50 mg daily (following a 70-mg loading dose on Day 1) versus 150 mg daily in the treatment of invasive candidiasis. In this group of patients, the safety of caspofungin at this higher dose appeared generally similar to patients receiving the 50-mg daily dose of caspofungin. The proportion of patients with a serious drug-related adverse reaction or a drug-related adverse reaction leading to caspofungin discontinuation was comparable in the 2 treatment groups.
Paediatric PatientsData from 5 clinical studies completed in 171 paediatric patients suggest that the overall incidence of clinical adverse experiences (26.3%; 95% CI -19.9, 33.6) is not worse than reported for adults treated with caspofungin (43.1%; 95% CI -40.0, 46.2). However, paediatric patients probably have a different adverse event profile compared to adult patients. The most common drug-related clinical adverse experiences reported in paediatric patients treated with caspofungin were pyrexia (11.7%), rash (4.7%) and headache (2.9%). The following adverse reactions were reported:
[Very common (≥ 1/10), Common (≥ 1/100 to <1/10)]
Blood and lymphatic system disorders:Common: eosinophil count increasedNervous system disorders: Common: headacheCardiac disorders:Common: tachycardiaVascular disorders: Common: flushing, hypotensionHepatobiliary disorders: Common: elevated liver enzyme levels (AST, ALT)Skin and subcutaneous tissue disorders: Common: rash, pruritusGeneral disorders and administration site conditions: Very common: feverCommon: chills, catheter site painInvestigations: Common: decreased potassium, hypomagnesaemia, increased glucose, decreased phosphorus, and increased phosphorus
Post-Marketing experience:The following post-marketing adverse reactions have been reported: Hepatobiliary disorders:Hepatic dysfunction, gamma-glutamyltransferase increased
General disorders and administration site conditions:Swelling and peripheral oedema
Investigations:Hypercalcaemia 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 the Yellow Card Scheme, website at www.mhra.gov.uk/yellowcard.
DistributionCaspofungin is extensively bound to albumin. The unbound fraction of caspofungin in plasma varies from 3.5 % in healthy volunteers to 7.6 % in patients with invasive candidiasis. Distribution plays the prominent role in caspofungin plasma pharmacokinetics and is the rate-controlling step in both the alpha- and beta-disposition phases. The distribution into tissues peaked at 1.5 to 2 days after dosing when 92 % of the dose was distributed into tissues. It is likely that only a small fraction of the caspofungin taken up into tissues later returns to plasma as parent compound. Therefore, elimination occurs in the absence of a distribution equilibrium, and a true estimate of the volume of distribution of caspofungin is currently impossible to obtain.
BiotransformationCaspofungin undergoes spontaneous degradation to an open ring compound. Further metabolism involves peptide hydrolysis and N-acetylation. Two intermediate products, formed during the degradation of caspofungin to this open ring compound, form covalent adducts to plasma proteins resulting in a low-level, irreversible binding to plasma proteins. In vitro studies show that caspofungin is not an inhibitor of cytochrome P450 enzymes 1A2, 2A6, 2C9, 2C19, 2D6 or 3A4. In clinical studies, caspofungin did not induce or inhibit the CYP3A4 metabolism of other medicinal products. Caspofungin is not a substrate for P-glycoprotein and is a poor substrate for cytochrome P450 enzymes.
EliminationThe elimination of caspofungin from plasma is slow with a clearance of 10-12 ml/min. Plasma concentrations of caspofungin decline in a polyphasic manner following single 1-hour intravenous infusions. A short alpha-phase occurs immediately post-infusion, followed by a beta-phase with a half-life of 9 to 11 hours. An additional gamma-phase also occurs with a half-life of 45 hours. Distribution, rather than excretion or biotransformation, is the dominant mechanism influencing plasma clearance. Approximately 75 % of a radioactive dose was recovered during 27 days: 41 % in urine and 34 % in faeces. There is little excretion or biotransformation of caspofungin during the first 30 hours after administration. Excretion is slow and the terminal half-life of radioactivity was 12 to 15 days. A small amount of caspofungin is excreted unchanged in urine (approximately 1.4 % of dose).Caspofungin displays moderate non-linear pharmacokinetics with increased accumulation as the dose is increased, and a dose dependency in the time to reach steady state upon multiple-dose administration.
Special populationsIncreased caspofungin exposure was seen in adult patients with renal impairment and mild liver impairment, in female subjects, and in the elderly. Generally the increase was modest and not large enough to warrant dosage adjustment. In adult patients with moderate liver impairment or in higher weight patients, a dosage adjustment may be necessary (see below).Weight: Weight was found to influence caspofungin pharmacokinetics in the population pharmacokinetic analysis in adult candidiasis patients. The plasma concentrations decrease with increasing weight. The average exposure in an adult patient weighing 80 kg was predicted to be about 23 % lower than in an adult patient weighing 60 kg (see section 4.2).Hepatic impairment: In adult patients with mild and moderate hepatic impairment, the AUC is increased about 20 and 75 %, respectively. There is no clinical experience in adult patients with severe hepatic impairment and in paediatric patients with any degree of hepatic impairment. In a multiple-dose study, a dose reduction of the daily dose to 35 mg in adult patients with moderate hepatic impairment has been shown to provide an AUC similar to that obtained in adult subjects with normal hepatic function receiving the standard regimen (see section 4.2).Renal impairment: In a clinical study of single 70 mg doses, caspofungin pharmacokinetics were similar in adult volunteers with mild renal impairment (creatinine clearance 50 to 80 ml/min) and control subjects. Moderate (creatinine clearance 31 to 49 ml/min), advanced (creatinine clearance 5 to 30 ml/min), and end-stage (creatinine clearance <10 ml/min and dialysis dependent) renal impairment moderately increased caspofungin plasma concentrations after single-dose administration (range: 30 to 49 % for AUC). However, in adult patients with invasive candidiasis, oesophageal candidiasis, or invasive aspergillosis who received multiple daily doses of caspofungin 50 mg, there was no significant effect of mild to advanced renal impairment on caspofungin concentrations. No dosage adjustment is necessary for patients with renal impairment. Caspofungin is not dialysable, thus supplementary dosing is not required following haemodialysis. Gender: Caspofungin plasma concentrations were on average 17-38 % higher in women than in men. Elderly: A modest increase in AUC (28 %) and C24h (32 %) was observed in elderly male subjects compared with young male subjects. In patients who were treated empirically or who had invasive candidiasis, a similar modest effect of age was seen in older patients relative to younger patients.Race: Patient pharmacokinetic data indicated that no clinically significant differences in the pharmacokinetics of caspofungin were seen among Caucasians, Blacks, Hispanics, and Mestizos.Paediatric Patients: In adolescents (ages 12 to 17 years) receiving caspofungin at 50 mg/m2 daily (maximum 70 mg daily), the caspofungin plasma AUC0-24hr was generally comparable to that seen in adults receiving caspofungin at 50 mg daily. All adolescents received doses >50 mg daily, and, in fact, 6 of 8 received the maximum dose of 70 mg/day. The caspofungin plasma concentrations in these adolescents were reduced relative to adults receiving 70 mg daily, the dose most often administered to adolescents.In children (ages 2 to 11 years) receiving caspofungin at 50 mg/m2 daily (maximum 70 mg daily), the caspofungin plasma AUC0-24hr after multiple doses was comparable to that seen in adults receiving caspofungin at 50 mg/day. In young children and toddlers (ages 12 to 23 months) receiving caspofungin at 50 mg/m2 daily (maximum 70 mg daily), the caspofungin plasma AUC0-24hr after multiple doses was comparable to that seen in adults receiving caspofungin at 50 mg daily and to that in older children (2 to 11 years of age) receiving the 50 mg/m2 daily dose. Overall, the available pharmacokinetic, efficacy, and safety data are limited in patients 3 to 10 months of age. Pharmacokinetic data from one 10-month old child receiving the 50 mg/m2 daily dose indicated an AUC0-24hr within the same range as that observed in older children and adults at the 50 mg/m2 and the 50 mg dose, respectively, while in one 6-month old child receiving the 50 mg/m2 dose, the AUC0-24hr was somewhat higher. In neonates and infants (<3 months) receiving caspofungin at 25 mg/m2 daily (corresponding mean daily dose of 2.1 mg/kg), caspofungin peak concentration (C1 hr) and caspofungin trough concentration (C24 hr) after multiple doses were comparable to that seen in adults receiving caspofungin at 50 mg daily. On Day 1, C1 hr was comparable and C24 hr modestly elevated (36 %) in these neonates and infants relative to adults. However, variability was seen in both C1 hr (Day 4 geometric mean 11.73 µg/ml, range 2.63 to 22.05 µg/ml) and C24 hr (Day 4 geometric mean 3.55 µg/ml, range 0.13 to 7.17 µg/ml). AUC0-24hr measurements were not performed in this study due to the sparse plasma sampling. Of note, the efficacy and safety of caspofungin have not been adequately studied in prospective clinical trials involving neonates and infants under 3 months of age.
Reconstitution of CANCIDASDO NOT USE ANY DILUENTS CONTAINING GLUCOSE, as CANCIDAS is not stable in diluents containing glucose. DO NOT MIX OR CO-INFUSE CANCIDAS WITH ANY OTHER MEDICINES, as there are no data available on the compatibility of CANCIDAS with other intravenous substances, additives, or medicinal products. Visually inspect the infusion solution for particulate matter or discolouration.Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
INSTRUCTIONS FOR USE IN ADULT PATIENTS
Step 1 Reconstitution of conventional vialsTo reconstitute the powder, bring the vial to room temperature and aseptically add 10.5 ml of water for injection. The concentrations of the reconstituted vials will be: 5.2 mg/ml (50 mg vial) or 7.2 mg/ml (70 mg vial).The white to off-white compact lyophilised powder will dissolve completely. Mix gently until a clear solution is obtained. Reconstituted solutions should be visually inspected for particulate matter or discolouration. This reconstituted solution may be stored for up to 24 hours at or below 25°C.
Step 2 Addition of reconstituted CANCIDAS to patient infusion solutionDiluents for the final solution for infusion are: sodium chloride solution for injection, or lactated Ringer's solution. The solution for infusion is prepared by aseptically adding the appropriate amount of reconstituted concentrate (as shown in the table below) to a 250 ml infusion bag or bottle. Reduced volume infusions in 100 ml may be used, when medically necessary, for 50 mg or 35 mg daily doses. Do not use if the solution is cloudy or has precipitated.
PREPARATION OF THE SOLUTION FOR INFUSION IN ADULTS
|DOSE*||Volume of reconstituted CANCIDAS for transfer to intravenous bag or bottle||Standard preparation(reconstituted CANCIDAS added to 250 ml) final concentration||Reduced volume infusion (reconstituted CANCIDAS added to 100 ml) final concentration|
|50 mg||10 ml||0.20 mg/ml||-|
|50 mg at reduced volume||10 ml||-||0.47 mg/ml|
|35 mg for moderate hepatic impairment (from one 50 mg vial)||7 ml||0.14 mg/ml||-|
|35 mg for moderate hepatic impairment (from one 50 mg vial) at reduced volume||7 ml||-||0.34 mg/ml|
|70 mg||10 ml||0.28 mg/ml||Not Recommended|
|70 mg (from two 50 mg vials)**||14 ml||0.28 mg/ml||Not Recommended|
|35 mg for moderate hepatic impairment (from one 70 mg vial)||5 ml||0.14 mg/ml||0.34 mg/ml|
INSTRUCTIONS FOR USE IN PAEDIATRIC PATIENTS
Calculation of Body Surface Area (BSA) for paediatric dosingBefore preparation of infusion, calculate the body surface area (BSA) of the patient using the following formula: (Mosteller Formula)Preparation of the 70 mg/m2 infusion for paediatric patients >3 months of age (using a 50-mg vial or a 70-mg vial)1. Determine the actual loading dose to be used in the paediatric patient by using the patient's BSA (as calculated above) and the following equation:BSA (m2) X 70 mg/m2 = Loading DoseThe maximum loading dose on Day 1 should not exceed 70 mg regardless of the patient's calculated dose.2. Equilibrate the refrigerated vial of CANCIDAS to room temperature.3. Aseptically add 10.5 ml of water for injection.a This reconstituted solution may be stored for up to 24 hours at or below 25°C.b This will give a final caspofungin concentration in the vial of 5.2 mg/ml (if using a 50-mg vial) or 7.2 mg/ml (if using a 70-mg vial).4. Remove the volume of medicinal product equal to the calculated loading dose (Step 1) from the vial. Aseptically transfer this volume (ml)c of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, or Lactated Ringers Injection. Alternatively, the volume (ml)c of reconstituted CANCIDAS can be added to a reduced volume of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection or Lactated Ringers Injection, not to exceed a final concentration of 0.5 mg/ml. This infusion solution must be used within 24 hours if stored at or below 25°C or within 48 hours if stored refrigerated at 2 to 8°C. Preparation of the 50 mg/m2 infusion for paediatric patients >3 months of age (using a 50-mg vial or a 70-mg vial)1. Determine the actual daily maintenance dose to be used in the paediatric patient by using the patient's BSA (as calculated above) and the following equation:BSA (m2) X 50 mg/m2 = Daily Maintenance DoseThe daily maintenance dose should not exceed 70 mg regardless of the patient's calculated dose.2. Equilibrate the refrigerated vial of CANCIDAS to room temperature.3. Aseptically add 10.5 ml of water for injection.a This reconstituted solution may be stored for up to 24 hours at or below 25°C.b This will give a final caspofungin concentration in the vial of 5.2 mg/ml (if using a 50-mg vial) or 7.2 mg/ml (if using a 70-mg vial).4. Remove the volume of medicinal product equal to the calculated daily maintenance dose (Step 1) from the vial. Aseptically transfer this volume (ml)c of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, or Lactated Ringers Injection. Alternatively, the volume (ml)c of reconstituted CANCIDAS can be added to a reduced volume of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection or Lactated Ringers Injection, not to exceed a final concentration of 0.5 mg/ml. This infusion solution must be used within 24 hours if stored at or below 25°C or within 48 hours if stored refrigerated at 2 to 8°C.
|Preparation notes: a. The white to off-white cake will dissolve completely. Mix gently until a clear solution is obtained.b. Visually inspect the reconstituted solution for particulate matter or discolouration during reconstitution and prior to infusion. Do not use if the solution is cloudy or has precipitated.c. CANCIDAS is formulated to provide the full labeled vial dose (50 mg or 70 mg) when 10 ml is withdrawn from the vial.|
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