Caspofungin Accord

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Caspofungin Accord 50 mg powder for concentrate for solution for infusion 
Caspofungin Accord 70 mg powder for concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Caspofungin Accord 50 mg powder for concentrate for solution for infusion 
Each vial contains 50 mg caspofungin (as acetate).  
 
Caspofungin Accord 70 mg powder for concentrate for solution for infusion 
Each vial contains 70 mg caspofungin (as acetate). 
 
For the full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM 
 
Powder for concentrate for solution for infusion. 
White to off-white, powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
 Treatment of invasive candidiasis in adult or paediatric patients. 
 Treatment of invasive aspergillosis in adult or paediatric patients who are refractory to or 

intolerant of amphotericin B, lipid formulations of amphotericin B and/or itraconazole. 
Refractoriness is defined as progression of infection or failure to improve after a minimum of 
7 days of prior therapeutic doses of effective antifungal therapy. 

 Empirical therapy for presumed fungal infections (such as Candida or Aspergillus) in febrile, 
neutropaenic adult or paediatric patients. 

 
4.2 Posology and method of administration 
 
Caspofungin should be initiated by a physician experienced in the management of invasive fungal 
infections. 
 
Posology 
 
Adult patients 
A 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).  
                                                      
1 Mosteller RD: Simplified Calculation of Body Surface Area. N Engl J Med 1987 Oct 22;317(17):1098 (letter) 



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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 treatment 
Duration 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 patients 
In 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 impairment 
No dosage adjustment is necessary based on renal impairment (see section 5.2). 
 
Hepatic impairment 
For adult patients with mild hepaticimpairment (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 enzymes 
Limited 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 administration 
After 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 infusion. 



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4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Anaphylaxis has been reported during administration of caspofungin. If this occurs, Caspofungin 
should be discontinued and appropriate treatment administered. Possibly histamine-mediated adverse 
reactions, including rash, facial swelling, angioedema, pruritus, sensation of warmth, or bronchospasm 
have been reported and may require discontinuation and/or administration of appropriate treatment.  
 
Limited data suggest that less common non-Candida yeasts and non-Aspergillus moulds are not 
covered by caspofungin. The efficacy of caspofungin against these fungal pathogens has not been 
established. 
 
Concomitant use of caspofungin with cyclosporin has been evaluated in healthy adult volunteers and 
in adult patients. Some healthy adult volunteers who received two 3 mg/kg doses of cyclosporin with 
caspofungin showed transient increases in alanine transaminase (ALT) and aspartate transaminase 
(AST) of less than or equal to 3-fold the upper limit of normal (ULN) that resolved with 
discontinuation of the treatment. In a retrospective study of 40 patients treated during marketed use 
with caspofungin and cyclosporin for 1 to 290 days (median 17.5 days), no serious hepatic adverse 
reactions were noted. These data suggest that caspofungin can be used in patients receiving 
cyclosporin when the potential benefit outweighs the potential risk. Close monitoring of liver enzymes 
should be considered if caspofungin and cyclosporin are used concomitantly. 
 
In adult patients with mild and moderate hepatic impairment, the AUC is increased about 20% and 
75 %, respectively. A reduction of the daily dose to 35 mg is recommended for adults with moderate 
hepatic impairment. There is no clinical experience in adults with severe hepatic impairment or in 
paediatric patients with any degree of hepatic impairment. A higher exposure than in moderate hepatic 
impairment is expected and caspofungin should be used with caution in these patients (see sections 4.2 
and 5.2). 
 
Laboratory abnormalities in liver function tests have been seen in healthy volunteers and adult and 
paediatric patients treated with caspofungin. In some adult and paediatric patients with serious 
underlying conditions who were receiving multiple concomitant medications with caspofungin, cases 
of clinically significant hepatic dysfunction, hepatitis and hepatic failure have been reported; a causal 
relationship to caspofungin has not been established. Patients who develop abnormal liver function 
tests during caspofungin therapy should be monitored for evidence of worsening hepatic function and 
the risk/benefit of continuing caspofungin therapy should be re-evaluated. 
 
This medicinal product contains sucrose. Patients with rare hereditary problems of fructose intolerance 
or sucrase–isomaltase insufficiency should not take this medicinal product (see section 2). 
 
Cases of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported 
after post-marketing use of caspofungin. Caution should apply in patients with history of allergic skin 
reaction (see section 4.8). 
 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Studies in vitro show that caspofungin is not an inhibitor of any enzyme in the cytochrome P450 
(CYP) system. In clinical studies, caspofungin did not induce the CYP3A4 metabolism of other 
substances. Caspofungin is not a substrate for P-glycoprotein and is a poor substrate for cytochrome 
P450 enzymes. However, caspofungin has been shown to interact with other medicinal products in 
pharmacological and clinical studies (see below). 
 



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In two clinical studies performed in healthy adult subjects, cyclosporin A (one 4 mg/kg dose or two 
3 mg/kg doses 12 hours apart) increased the AUC of caspofungin by approximately 35 %. These AUC 
increases are probably due to reduced uptake of caspofungin by the liver. Caspofungin did not increase 
the plasma levels of cyclosporin. There were transient increases in liver ALT and AST of less than or 
equal to 3-fold the upper limit of normal (ULN) when caspofungin and cyclosporin were 
co-administered, that resolved with discontinuation of the medicinal products. In a retrospective study 
of 40 patients treated during marketed use with caspofungin and cyclosporin for 1 to 290 days (median 
17.5 days), no serious hepatic adverse reactions were noted (see section 4.4). Close monitoring of liver 
enzymes should be considered if the two medicinal products are used concomitantly. 
 
Caspofungin reduced the trough concentration of tacrolimus by 26 % in healthy adult volunteers. For 
patients receiving both therapies, standard monitoring of tacrolimus blood concentrations and 
appropriate tacrolimus dosage adjustments are mandatory.  
 
Clinical studies in healthy adult volunteers show that the pharmacokinetics of caspofungin are not 
altered to a clinically relevant extent by itraconazole, amphotericin B, mycophenolate, nelfinavir, or 
tacrolimus. Caspofungin did not influence the pharmacokinetics of amphotericin B, itraconazole, 
rifampicin or mycophenolate mofetil. Although safety data are limited it appears that no special 
precautions are needed when amphotericin B, itraconazole, nelfinavir or mycophenolate mofetil are 
co-administered with caspofungin. 
 
Rifampicin caused a 60 % increase in AUC and 170 % increase in trough concentration of 
caspofungin on the first day of co-administration when both medicinal products were initiated together 
in healthy adult volunteers. Caspofungin trough levels gradually decreased upon repeated 
administration. After two weeks’ administration rifampicin had limited effect on AUC, but trough 
levels were 30 % lower than in adult subjects who received caspofungin alone. The mechanism of 
interaction could possibly be due to an initial inhibition and subsequent induction of transport proteins. 
A similar effect could be expected for other medicinal products that induce metabolic enzymes. 
Limited data from population pharmacokinetics studies indicate that concomitant use of caspofungin 
with the inducers efavirenz, nevirapine, rifampicin, dexamethasone, phenytoin, or carbamazepine may 
result in a decrease in caspofungin AUC. When co-administering inducers of metabolic enzymes, an 
increase in the daily dose of caspofungin to 70 mg, following the 70 mg loading dose, should be 
considered in adult patients (see section 4.2). 
 
All adult drug-drug interaction studies described above were conducted at a 50 or 70 mg daily 
caspofungin dose. The interaction of higher doses of caspofungin with other medicinal products has 
not been formally studied. 
 
In paediatric patients, results from regression analyses of pharmacokinetic data suggest that 
co-administration of dexamethasone with caspofungin may result in clinically meaningful reductions 
in caspofungin trough concentrations. This finding may indicate that paediatric patients will have 
similar reductions with inducers as seen in adults. When caspofungin is co-administered to paediatric 
patients (12 months to 17 years of age) with inducers of drug clearance, such as rifampicin, efavirenz, 
nevirapine, phenytoin, dexamethasone, or carbamazepine, a caspofungin dose of 70-mg/m2 daily (not 
to exceed an actual daily dose of 70 mg) should be considered. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There 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-feeding 
It 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. 



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Fertility 
For 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.  
 
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. 
 
4.8 Undesirable effects 
 
Hypersensitivity reactions (anaphylaxis and possibly histamine-mediated adverse reactions) have been 
reported (see section 4.4). 
 
Also reported in patients with invasive aspergillosis were pulmonary oedema, adult respiratory distress 
syndrome (ARDS), and radiographic infiltrates. 
 
Adult patients 
In 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 hematopoietic 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. 
 
Tabulated list of adverse reactions 
 
The following adverse reactions were reportedduring clinical studies and/or post-marketing use: 
 

System Organ 
Class 

Common 
(≥1/100 to 
<1/10) 

Uncommon (≥1/1,000 to <1/100) Not known 
(cannot be 
estimated 
from 
available 
data) 

Blood and 
lymphatic system 
disorders 

haemoglobin 
decreased, 
haematocrit 
decreased, white 
blood cell count 
decreased 

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 

hypokalemia fluid overload, hypomagnesaemia, 
anorexia, electrolyte imbalance, 
hyperglycaemia, hypocalcaemia, metabolic 
acidosis 

 

Psychiatric  anxiety, disorientation, insomnia  



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disorders 
Nervous system 
disorders 

headache dizziness, dysgeusia, paraesthesia, 
somnolence, tremor, hypoaesthesia 

 

Eye disorders  ocular icterus, vision blurred, eyelid 
oedema, lacrimation increased 

 

Cardiac disorders  palpitations, tachycardia, arrhythmia, atrial 
fibrillation, cardiac failure congestive 

 

Vascular 
disorders 

phlebitis thrombophlebitis, flushing, hot flush, 
hypertension, hypotension 

 

Respiratory, 
thoracic and 
mediastinal 
disorders 

dyspnoea nasal congestion, pharyngolaryngeal pain, 
tachypnoea, bronchospasm, cough, 
dyspnoea paroxysmal nocturnal, hypoxia, 
rales, wheezing 

 

Gastrointestinal 
disorders 

nausea, 
diarrhoea, 
vomiting 

abdominal pain, abdominal pain upper, dry 
mouth, dyspepsia, stomach discomfort, 
abdominal distension, ascites, constipation, 
dysphagia, flatulence 

 

Hepatobiliary 
disorders 

elevated liver 
values (alanine 
aminotransferase, 
aspartate 
aminotranserase, 
blood alkaline 
phosphatase, 
bilirubin 
conjugated, 
blood bilirubin) 

cholestasis, hepatomegaly, 
hyperbilirubinaemia, jaundice, hepatic 
function abnormal, hepatotoxicity, liver 
disorder, gamma-glutamyltransferase 
increased 

 

Skin and 
subcutaneous 
tissue disorders 

rash, pruritus, 
erythema, 
hyperhidrosis 

erythema multiforme, rash macular, rash 
maculo-papular, rash pruritic, urticaria, 
dermatitis allergic, pruritus generalised, 
rash erythematous, rash generalised, rash 
morbilliform, skin lesion 

Toxic 
epidermal 
necrolysis and 
Stevens-
Johnson 
syndrome (see 
section 4.4) 

Musculoskeletal 
and connective 
tissue disorders 

arthralgia back pain, pain in extremity, bone pain, 
muscular weakness, myalgia 

 

Renal and urinary 
disorders 

 renal failure, renal failure acute  

General disorders 
and 
administration site 
conditions 

pyrexia, chills, 
infusion-site 
pruritus 

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 blood potassium 
decreased, blood 
albumin 
decreased 

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 

 



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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 Patients 
Data 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%). 
 
Tabulated list of adverse reactions 
 
The following adverse reactions were reported: 
 
System Organ Class Very 

common 
(≥1/10) 

Common (≥1/100 to <1/10) 

Blood and lymphatic system 
disorders 

 eosinophil count increased 

Nervous system disorders  headache 
Cardiac disorders  tachycardia 
Vascular disorders  flushing, hypotension 
Hepatobiliary disorders  elevated liver enzyme levels (AST, ALT) 
Skin and subcutaneous 
tissue disorders 

 rash, pruritus 

General disorders and 
administration site 
conditions 

fever chills, catheter site pain 

Investigations  decreased potassium, hypomagnesemia, increased 
glucose, decreased phosphorus, and increased 
phosphorus 

 
 



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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 national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Inadvertent administration of up to 400 mg of caspofungin in one day has been reported. These 
occurrences did not result in clinically important adverse reactions. Caspofungin is not dialysable. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: antimycotics for systemic use, ATC code: J02AX04 
 
Mechanism of action 
Caspofungin acetate is a semi-synthetic lipopeptide (echinocandin) compound synthesised from a 
fermentation product of Glarea lozoyensis. Caspofungin acetate inhibits the synthesis of 
beta (1,3)-D-glucan, an essential component of the cell wall of many filamentous fungi and yeast. 
Beta (1,3)-D-glucan is not present in mammalian cells. 
 
Fungicidal activity with caspofungin has been demonstrated against Candida yeasts. Studies in vitro 
and in vivo demonstrate that exposure of Aspergillus to caspofungin results in lysis and death of 
hyphal apical tips and branch points where cell growth and division occur. 
 
Pharmacodynamic effects 
Caspofungin has in vitro activity against Aspergillus species (Aspergillus fumigatus [N = 75], 
Aspergillus flavus [N = 111], Aspergillus niger [N = 31], Aspergillus nidulans [N = 8], Aspergillus 
terreus [N = 52], and Aspergillus candidus [N = 3]). Caspofungin also has in vitro activity against 
Candida species (Candida albicans [N = 1,032], Candida dubliniensis [N = 100], Candida glabrata 
[N = 151], Candida guilliermondii [N = 67], Candida kefyr [N = 62], Candida krusei [N = 147], 
Candida lipolytica [N = 20], Candida lusitaniae [N = 80], Candida parapsilosis [N = 215], Candida 
rugosa [N = 1], and Candida tropicalis [N = 258]), including isolates with multiple resistance 
transport mutations and those with acquired or intrinsic resistance to fluconazole, amphotericin B, and 
5-flucytosine. Susceptibility testing was performed according to a modification of both the Clinical 
and Laboratory Standards Institute (CLSI, formerly known as the National Committee for Clinical 
Laboratory Standards [NCCLS]) method M38-A2 (for Aspergillus species) and method M27-A3 (for 
Candida species).  
Standardised techniques for susceptibility testing have been established for yeasts by EUCAST.  
EUCAST breakpoints have not yet been established for caspofungin, due to significant 
inter-laboratory variation in MIC ranges for caspofungin. In lieu of breakpoints, Candida isolates that 
are susceptible to anidulafungin as well as micafungin should be considered susceptible to 
caspofungin. Similarly, C. parapsilosis isolates intermediate to anidulafungin and micafungin can be 
regarded intermediate to caspofungin. 
 
Mechanism of resistance 
 Isolates  of Candida with reduced susceptibility to caspofungin have been identified in a small number 
of patients during treatment (MICs for caspofungin >2 mg/L (4- to 30-fold MIC increases) have been 
reported using standardized MIC testing techniques approved by the CLSI). The mechanism of 
resistance identified  is FKS1 and/or  FKS2  (for C. glabrata)  gene mutations. These cases have been 
associated with poor clinical outcomes.  
Development of in vitro resistance to caspofungin by Aspergillus species has been identified. In 
limited clinical experience, resistance to caspofungin in patients with invasive aspergillosis has been 
observed. The mechanism of resistance has not been established. The incidence of resistance to 



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caspofungin by various clinical isolates of Aspergillus is rare. Caspofungin resistance in Candida has 
been observed but the incidence may differ by species or region. 
Clinical efficacy and safety 
Invasive Candidiasis in Adult Patients: Two hundred thirty-nine patients were enrolled in an initial 
study to compare caspofungin and amphotericin B for the treatment of invasive candidiasis. Twenty-
four patients had neutropaenia. The most frequent diagnoses were bloodstream infections 
(candidaemia) (77 %, n=186) and Candida peritonitis (8 %, n=19); patients with Candida 
endocarditis, osteomyelitis, or meningitis were excluded from this study. Caspofungin 50 mg once 
daily was administered following a 70 mg loading dose, while amphotericin B was administered at 0.6 
to 0.7 mg/kg/day to non-neutropaenic patients or 0.7 to 1.0 mg/kg/day to neutropaenic patients. The 
mean duration of intravenous therapy was 11.9 days, with a range of 1 to 28 days. A favourable 
response required both symptom resolution and microbiological clearance of the Candida infection. 
Two hundred twenty-four patients were included in the primary efficacy analysis (MITT analysis) of 
response at the end of IV study therapy; favourable response rates for the treatment of invasive 
candidiasis were comparable for caspofungin (73 % [80/109]) and amphotericin B (62 % [71/115]) [% 
difference 12.7 (95.6 % CI -0.7, 26.0)]. Among patients with candidaemia, favourable response rates 
at the end of IV study therapy were comparable for caspofungin (72 % [66/92]) and amphotericin B 
(63 % [59/94]) in the primary efficacy analysis (MITT analysis) [% difference 10.0 (95.0 % CI -4.5, 
24.5)]. Data in patients with non-blood sites of infection were more limited. Favourable response rates 
in neutropaenic patients were 7/14 (50 %) in the caspofungin group and 4/10 (40 %) in the 
amphotericin B group. These limited data are supported by the outcome of the empirical therapy 
study. 
 
In a second study, patients with invasive candidiasis received daily doses of caspofungin at 50 mg/day 
(following a 70-mg loading dose on Day 1) or caspofungin at 150 mg/day (see section 4.8). In this 
study, the caspofungin dose was administered over 2 hours (instead of the routine 1-hour 
administration). The study excluded patients with suspected Candida endocarditis, meningitis, or 
osteomyelitis. As this was a primary therapy study, patients who were refractory to prior antifungal 
agents were also excluded. The number of neutropenic patients enrolled in this study was also limited 
(8.0 %). Efficacy was a secondary endpoint in this study. Patients who met the entry criteria and 
received one or more doses of caspofungin study therapy were included in the efficacy analysis. The 
favourable overall response rates at the end of caspofungin therapy were similar in the 2 treatment 
groups: 72 % (73/102) and 78 % (74/95) for the caspofungin 50-mg and 150-mg treatment groups, 
respectively (difference 6.3 % [95 % CI -5.9, 18.4]). 
 
Invasive Aspergillosis in Adult Patients: Sixty-nine adult patients (age 18-80) with invasive 
aspergillosis were enrolled in an open-label, non-comparative study to evaluate the safety, tolerability, 
and efficacy of caspofungin. Patients had to be either refractory to (disease progression or failure to 
improve with other antifungal therapies given for at least 7 days) (84 % of the enrolled patients) or 
intolerant of (16 % of enrolled patients) other standard antifungal therapies. Most patients had 
underlying conditions (haematologic malignancy [N = 24], allogeneic bone marrow transplant or stem 
cell transplant [N = 18], organ transplant [N = 8], solid tumour [N = 3], or other conditions [N = 10]). 
Stringent definitions, modelled after the Mycoses Study Group Criteria, were used for diagnosis of 
invasive aspergillosis and for response to therapy (favourable response required clinically significant 
improvement in radiographs as well as in signs and symptoms). The mean duration of therapy was 
33.7 days, with a range of 1 to 162 days. An independent expert panel determined that 41 % (26/63) of 
patients receiving at least one dose of caspofungin had a favourable response. For those patients who 
received more than 7 days of therapy with caspofungin, 50 % (26/52) had a favourable response. The 
favourable response rates for patients who were either refractory to or intolerant of previous therapies 
were 36 % (19/53) and 70 % (7/10), respectively. Although the doses of prior antifungal therapies in 
5 patients enrolled as refractory were lower than those often administered for invasive aspergillosis, 
the favourable response rate during therapy with caspofungin was similar in these patients to that seen 
in the remaining refractory patients (2/5 versus 17/48, respectively). The response rates among 
patients with pulmonary disease and extrapulmonary disease were 47 % (21/45) and 28 % (5/18), 
respectively. Among patients with extrapulmonary disease, 2 of 8 patients who also had definite, 
probable, or possible CNS involvement had a favourable response. 
 



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Empirical Therapy in Febrile, Neutropaenic Adult Patients: A total of 1,111 patients with persistent 
fever and neutropaenia were enrolled in a clinical study and treated with either caspofungin 50 mg 
once daily following a 70 mg loading dose or liposomal amphotericin B 3.0 mg/kg/day. Eligible 
patients had received chemotherapy for malignancy or had undergone hematopoietic stem-cell 
transplantation, and presented with neutropaenia (<500 cells/mm3 for 96 hours) and fever (>38.0°C) 
not responding to ≥96 hours of parenteral antibacterial therapy. Patients were to be treated until up to 
72 hours after resolution of neutropaenia, with a maximum duration of 28 days. However, patients 
found to have a documented fungal infection could be treated longer. If the drug was well tolerated but 
the patient’s fever persisted and clinical condition deteriorated after 5 days of therapy, the dosage of 
study drug could be increased to 70 mg/day of caspofungin (13.3 % of patients treated) or to 
5.0 mg/kg/day of liposomal amphotericin B (14.3 % of patients treated). There were 1,095 patients 
included in the primary Modified Intention-To-Treat (MITT) efficacy analysis of overall favourable 
response; caspofungin (33.9 %) was as effective as liposomal amphotericin B (33.7 %) [% difference 
0.2 (95.2 % CI –5.6, 6.0)]. An overall favourable response required meeting each of 5 criteria: 
(1) successful treatment of any baseline fungal infection (caspofungin 51.9 % [14/27], liposomal 
amphotericin B 25.9 % [7/27]), (2) no breakthrough fungal infections during administration of study 
drug or within 7 days after completion of treatment (caspofungin 94.8 % [527/556], liposomal 
amphotericin B 95.5 % [515/539]), (3) survival for 7 days after completion of study therapy 
(caspofungin 92.6 % [515/556], liposomal amphotericin B 89.2 % [481/539]), (4) no discontinuation 
from the study drug because of drug-related toxicity or lack of efficacy (caspofungin 89.7 % 
[499/556], liposomal amphotericin B 85.5 % [461/539]), and (5) resolution of fever during the period 
of neutropaenia (caspofungin 41.2 % [229/556], liposomal amphotericin B 41.4 % [223/539]). 
Response rates to caspofungin and liposomal amphotericin B for baseline infections caused by 
Aspergillus species were, respectively, 41.7 % (5/12) and 8.3 % (1/12), and by Candida species were 
66.7 % (8/12) and 41.7 % (5/12). Patients in the caspofungin group experienced breakthrough 
infections due to the following uncommon yeasts and moulds: Trichosporon species (1), Fusarium 
species (1), Mucor species (1), and Rhizopus species (1). 
 
Paediatric population 
The safety and efficacy of caspofungin was evaluated in paediatric patients 3 months to 17 years of 
age in two prospective, multicentre clinical trials. The study design, diagnostic criteria, and criteria for 
efficacy assessment were similar to the corresponding studies in adult patients (see section 5.1).  
 
The first study, which enrolled 82 patients between 2 to 17 years of age, was a randomized, double-
blind study comparing caspofungin (50 mg/m2 IV once daily following a 70-mg/m2 loading dose on 
Day 1 [not to exceed 70 mg daily]) to liposomal amphotericin B (3 mg/kg IV daily) in a 2:1 treatment 
fashion (56 on caspofungin, 26 on liposomal amphotericin B) as empirical therapy in paediatric 
patients with persistent fever and neutropenia. The overall success rates in the MITT analysis results, 
adjusted by risk strata, were as follows: 46.6 % (26/56) for caspofungin and 32.2 % (8/25) for 
liposomal amphotericin B.  
 
The second study was a prospective, open-label, non-comparative study estimating the safety and 
efficacy of caspofungin in paediatric patients (ages 6 months to 17 years) with invasive candidiasis, 
esophageal candidiasis, and invasive aspergillosis (as salvage therapy). Forty-nine patients were 
enrolled and received caspofungin at 50 mg/m2 IV once daily following a 70-mg/m2 loading dose on 
Day 1 (not to exceed 70 mg daily), of whom 48 were included in the MITT analysis. Of these, 37 had 
invasive candidiasis, 10 had invasive aspergillosis, and 1 patient had esophageal candidiasis. The 
favourable response rate, by indication, at the end of caspofungin therapy was as follows in the MITT 
analysis: 81 % (30/37) in invasive candidiasis, 50 % (5/10) in invasive aspergillosis, and 100 % (1/1) 
in esophageal candidiasis. 
 
In a double-blind, randomized (2:1) comparator-controlled study safety, tolerability and efficacy of 
caspofungin (2 mg/kg/d intravenously, infused over 2 hours) vs amphotericin B deoxycholate 
(1 mg/kg/d) was evaluated in neonates and infants less than 3 months of age with (culture-confirmed) 
invasive candidiasis. Due to poor enrolment, the study was terminated early and only 51 patients were 
randomized. The proportion of patients with fungal-free survival at 2 weeks post-therapy in the 
caspofungin treatment group (71.0 %) was similar to that seen in the amphotericin B deoxycholate 



12 

treatment group (68.8 %). Based on this study, no posology recommendations for neonates and infants 
can be made. 
 
5.2 Pharmacokinetic properties 
 
Distribution 
Caspofungin 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. 
 
Biotransformation 
Caspofungin 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. 
 
Elimination 
The 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 populations 
Increased 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 



13 

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 AUC0-24 hr 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 AUC0-24 hr 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 AUC0-24 hr 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 AUC0-24 hr 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 AUC0-24 hr 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). AUC0-24 hr 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. 
 



14 

5.3 Preclinical safety data 
 
Repeated dose toxicity studies in rats and monkeys using doses up to 7-8 mg/kg given intravenously 
showed injection site reactions in rats and monkeys, signs of histamine release in rats, and evidence of 
adverse effects directed at the liver in monkeys. Developmental toxicity studies in rats showed that 
caspofungin caused decreases in foetal body weights and an increase in the incidence of incomplete 
ossification of vertebra, sternebra, and skull bone at doses of 5 mg/kg that were coupled to adverse 
maternal effects such as signs of histamine release in pregnant rats. An increase in the incidence of 
cervical ribs was also noted. Caspofungin was negative in in vitro assays for potential genotoxicity as 
well as in the in vivo mouse bone marrow chromosomal test. No long-term studies in animals have 
been performed to evaluate the carcinogenic potential. For caspofungin, there were no effects on 
fertility in studies conducted in male and female rats up to 5 mg/kg/day. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sucrose 
Mannitol 
Succinic acid 
Sodium hydroxide (to adjust the pH) 
 
6.2 Incompatibilities 
 
Do not mix with diluents containing glucose, as Caspofungin Accord is not stable in diluents 
containing glucose. In the absence of compatibility studies, this medicinal product must not be mixed 
with other medicinal products. 
 
6.3 Shelf life 
 
2 years 
 
Reconstituted concentrate: should be used immediately. Stability data have shown that the concentrate 
for solution for infusion can be stored for up to 24 hours when the vial is stored at 25°C or less and 
reconstituted with water for injections. 
 
Diluted patient infusion solution: should be used immediately. Stability data have shown that the 
product can be used within 24 hours when stored at 25°C or less, or within 48 hours when the 
intravenous infusion bag (bottle) is stored refrigerated (2 to 8°C) and diluted with sodium chloride 
solution 9 mg/mL (0.9 %), 4.5 mg/mL (0.45 %), or 2.25 mg/mL (0.225 %) for infusion, or lactated 
Ringer’s solution. 
 
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 to 8°C, unless reconstitution and dilution have taken 
place in controlled validated aseptic conditions. 
 
6.4 Special precautions for storage 
 
Unopened vials: store in a refrigerator 2°C - 8°C). 
 
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Caspofungin Accord 50 mg powder for concentrate for solution for infusion  



15 

10 mL Type I clear glass vial with bromobutyl rubber stopper and red aluminium seal with transparent 
plastic flip off button. 
 
Caspofungin Accord 70 mg powder for concentrate for solution for infusion  
10 mL Type I clear glass vial with bromobutyl rubber stopper and orange aluminium seal with 
transparent plastic flip off button. 
 
Supplied in packs of 1 vial. 
 
6.6 Special precautions for disposal  
 
Reconstitution of Caspofungin Accord 
DO NOT USE ANY DILUENTS CONTAINING GLUCOSE, as Caspofungin Accord is not stable in 
diluents containing glucose. DO NOT MIX OR CO-INFUSE CASPOFUNGIN ACCORD WITH 
ANY OTHER MEDICINES, as there are no data available on the compatibility of Caspofungin 
Accord 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 (Caspofungin Accord 50 mg) 
 
Step 1 Reconstitution of conventional vials  
To 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. 
 
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 Caspofungin Accord to patient infusion solution  
Diluents for the final solution for infusion are: sodium chloride solution for injection 9 mg/mL or 
lactated Ringer’s solution should be used. 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.  
 



16 

PREPARATION OF THE SOLUTION FOR INFUSION IN ADULTS 
 
DOSE* Volume of recon- 

stituted 
Caspofungin 
Accord for 
transfer to 
intravenous bag or 
bottle 

Standard preparation 
(reconstituted 
Caspofungin Accord 
added to 250 mL) final 
concentration 

Reduced volume 
infusion  
(reconstituted 
Caspofungin Accord 
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 

* 10.5 mL should be used for reconstitution of all vials. 
 

INSTRUCTIONS FOR USE IN ADULT PATIENTS (Caspofungin Accord 70 mg) 
 
Step 1 Reconstitution of conventional vials 
To 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 7.2 mg/mL. 
 
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 Caspofungin Accord to patient infusion solution 
Diluents for the final solution for infusion are: sodium chloride solution for injection 9 mg/mL or 
lactated Ringer’s solution should be used. 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 
Caspofungin Accord 
for transfer to 
intravenous bag or 
bottle 

Standard preparation 
(reconstituted 
Caspofungin Accord 
added to 250 mL) final 
concentration 

Reduced volume 
infusion 
(reconstituted 
Caspofungin Accord 
added to 100 mL) final 
concentration 

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 

* 10.5 mL should be used for reconstitution of all vials. 
** If 70 mg vial is not available, the 70 mg dose can be prepared from two 50 mg vials 
 



17 

INSTRUCTIONS FOR USE IN PAEDIATRIC PATIENTS (Caspofungin Accord 50 mg) 
 
Calculation of Body Surface Area (BSA) for paediatric dosing 
Before 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) 
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 Dose 
The maximum loading dose on Day 1 should not exceed 70 mg regardless of the patient's 
calculated dose. 

2. Equilibrate the refrigerated vial of Caspofungin Accord 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.  

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 Caspofungin Accord to an IV bag 
(or bottle) containing 250 mL of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride solution for 
infusion, or Lactated Ringers solution for infusion. Alternatively, the volume (mL)c of 
reconstituted Caspofungin Accord can be added to a reduced volume of 0.9 %, 0.45 %, or 
0.225 % Sodium Chloride solution for infusion or Lactated Ringers solution for infusion, 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) 
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 Dose 
The daily maintenance dose should not exceed 70 mg regardless of the patient's calculated dose. 

2. Equilibrate the refrigerated vial of Caspofungin Accord 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. 

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 Caspofungin 
Accord to an IV bag (or bottle) containing 250 mL of 0.9 %, 0.45 %, or 0.225 % Sodium 
Chloride solution for infusion, or Lactated Ringers solution for infusion. Alternatively, the 
volume (mL)c of reconstituted Caspofungin Accord can be added to a reduced volume of 0.9 %, 
0.45 %, or 0.225 % Sodium Chloride solution for infusion or Lactated Ringers solution for 
infusion, 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. Caspofungin Accord is formulated to provide the full labeled vial dose (50 mg) when 10 mL is 

withdrawn from the vial. 
 

INSTRUCTIONS FOR USE IN PAEDIATRIC PATIENTS (Caspofungin Accord 70 mg) 



18 

 
Calculation of Body Surface Area (BSA) for paediatric dosing 
Before 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 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 Dose 
The maximum loading dose on Day 1 should not exceed 70 mg regardless of the patient's 
calculated dose. 

2. Equilibrate the refrigerated vial of Caspofungin Accord 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 
7.2 mg/mL. 

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 Caspofungin Accord to an IV bag 
(or bottle) containing 250 mL of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride solution for 
infusion or Lactated Ringers solution for infusion. Alternatively, the volume (mL)c of 
reconstituted Caspofungin Accord can be added to a reduced volume of 0.9 %, 0.45 %, or 
0.225 % Sodium Chloride solution for infusion or Lactated Ringers solution for infusion, 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 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 Dose 
The daily maintenance dose should not exceed 70 mg regardless of the patient's calculated dose. 

2. Equilibrate the refrigerated vial of Caspofungin Accord 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 
7.2 mg/mL. 

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 Caspofungin 
Accord to an IV bag (or bottle) containing 250 mL of 0.9 %, 0.45 %, or 0.225 % Sodium 
Chloride solution for infusion or Lactated Ringers solution for infusion. Alternatively, the 
volume (mL)c of reconstituted Caspofungin Accord can be added to a reduced volume of 0.9 %, 
0.45 %, or 0.225 % Sodium Chloride solution for infusion or Lactated Ringers solution for 
infusion, 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. Caspofungin Accord is formulated to provide the full labeled vial dose (70 mg) when 10 mL is 

withdrawn from the vial. 
 
 



19 

7. MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
50 mg: EU/1/15/1081/001 
70 mg: EU/1/15/1081/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorization: 11 February 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu. 
 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 

RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



21 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Accord Healthcare Limited 
Sage House, 319 Pinner Road 
North Harrow, Middlesex, HA1 4HF 
United Kingdom 
 
Xellia Pharmaceuticals ApS 
Dalslandsgade 11, København S, 
2300, Denmark 
 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2) 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
 Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
 Risk Management Plan (RMP) 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any subsequent updates of 
the RMP. 
 
An updated RMP should be submitted: 
 At the request of the European Medicines Agency; 
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 
 



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Caspofungin Accord 50 mg powder for concentrate for solution for infusion 
caspofungin  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains: 50 mg caspofungin (as acetate) 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sucrose, mannitol, succinic acid and sodium hydroxide. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion. 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use after reconstitution and dilution. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
 
 



25 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1081/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
[Justification for not including Braille accepted] 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN:



26 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Caspofungin Accord 50 mg powder for concentrate  
caspofungin  
IV use 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Accord 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



27 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Caspofungin Accord 70 mg powder for concentrate for solution for infusion 
caspofungin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains: 70 mg caspofungin(as acetate). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sucrose, mannitol, succinic acid, and sodium hydroxide. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion. 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use after reconstitution and dilution. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
 
 



28 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1081/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
[Justification for not including Braille accepted] 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



29 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Caspofungin Accord 70 mg powder for concentrate  
caspofungin 
IV use 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Accord 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT  
 
 
6. OTHER 
 



30 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



31 

Package leaflet: Information for the user 
 

Caspofungin Accord 50 mg powder for concentrate for solution for infusion  
Caspofungin Accord 70 mg powder for concentrate for solution for infusion 

caspofungin  
 

Read all of this leaflet carefully before you or your child are given this medicine because it 
contains important information for you.  
 Keep this leaflet. You may need to read it again. 
 If you have any further questions, ask your doctor, nurse or pharmacist. 
 If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Caspofungin Accord is and what it is used for 
2. What you need to know before you are given Caspofungin Accord 
3. How to use Caspofungin Accord 
4. Possible side effects 
5. How to store Caspofungin Accord 
6. Contents of the pack and other information 
 
 
1. What Caspofungin Accord is and what it is used for 
 
What Caspofungin Accord is 
Caspofungin Accord contains a medicine called caspofungin. This belongs to a group of medicines 
called anti-fungals.  
 
What Caspofungin Accord is used for 
Caspofungin Accord is used to treat the following infections in children, adolescents and adults: 
 serious fungal infections in your tissues or organs (called ‘invasive candidiasis’). This infection 

is caused by fungal (yeast) cells called Candida.  
People who might get this type of infection include those who have just had an operation or 
those whose immune systems are weak. Fever and chills that do not respond to an antibiotic are 
the most common signs of this type of infection. 

 fungal infections in your nose, nasal sinuses or lungs (called ‘invasive aspergillosis’) if other 
anti-fungal treatments have not worked or have caused side effects. This infection is caused by a 
mould called Aspergillus.  
People who might get this type of infection include those having chemotherapy, those who have 
had a transplant and those whose immune systems are weak. 

 suspected fungal infections if you have a fever and a low white cell count that have not 
improved on  treatment with an antibiotic. People who are at risk of getting a fungal infection 
include those who have just had an operation or those whose immune systems are weak.  

 
How Caspofungin Accord works 
Caspofungin Accord makes fungal cells fragile and stops the fungus from growing properly. This 
stops the infection from spreading and gives the body’s natural defences a chance to completely get rid 
of the infection.  
 
 
2. What you need to know before you are given Caspofungin Accord 
 
Do not use Caspofungin Accord 
 

 -if you are allergic to caspofungin or any of the other ingredients of this medicine (listed in 
section 6). 



32 

If you are not sure, talk to your doctor, nurse or pharmacist before you are given your medicine. 
 
Warnings and precautions 
Talk to your doctor, nurse or pharmacist before you are given Caspofungin Accord if: 
 you are allergic to any other medicines 
 you have ever had liver problems - you might need a different dose of this medicine 
 you are already taking cyclosporin (used to help prevent organ transplant rejection or to 

suppress your immune system) - as your doctor may need to run extra blood tests during your 
treatment. 

 if you have ever had any other medical problem.  
 
If any of the above applies to you (or you are not sure), talk to your doctor, nurse or pharmacist before 
you are given Caspofungin Accord. 
 
Caspofungin Accord  may also cause Serious Cutaneous Adverse Reactions such as Stevens-Johnson 
Syndrome (SJS) and toxic epidermal necrolysis (TEN). 
 
Other medicines and Caspofungin Accord 
Please tell your doctor, nurse or pharmacist if you are taking, have recently taken or might take any 
other medicines. This includes medicines obtained without a prescription, including herbal medicines. 
This is because Caspofungin Accord can affect the way some other medicines work. Also some other 
medicines can affect the way Caspofungin Accord works.  
 
Tell your doctor, nurse or pharmacist if you are taking any of the following medicines: 
 cyclosporin or tacrolimus (used to help prevent organ transplant rejection or to suppress your 

immune system) as your doctor may need to run extra blood tests during your treatment 
 some HIV medicines such as efavirenz or nevirapine 
 phenytoin or carbamazepine (used for the treatment of seizures)  
 dexamethasone (a steroid) 
 rifampicin (an antibiotic). 
 
If any of the above apply to you (or you are not sure), talk to your doctor, nurse or pharmacist before 
you are given Caspofungin Accord.  
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding ,think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 
 Caspofungin Accord has not been studied in pregnant women. It should be used in pregnancy 

only if the potential benefit justifies the potential risk to the unborn baby.  
 Women given Caspofungin Accord should not breast-feed. 
 

Driving and using machines 
There is no information to suggest that Caspofungin Accord affects your ability to drive or operate 
machinery. 
 
 

3. How to use Caspofungin Accord 
 
Caspofungin Accord will always be prepared and given to you by a healthcare professional. 
You will be given Caspofungin Accord: 
 once each day 
 by slow injection into a vein (intravenous infusion)  
 over about 1 hour.  
 
Your doctor will determine the duration of your treatment and how much Caspofungin Accord you 
will be given each day. Your doctor will monitor how well the medicine works for you. If you weigh 
more than 80 kg, you may need a different dose. 



33 

 
Children and adolescents 
The dose for children and adolescents may differ from the adult dose. 
 
If you have been given more Caspofungin Accord than you should 
 
Your doctor will decide how much Caspofungin Accord you need and for how long each day. If you 
are worried that you may have been given too much Caspofungin Accord, tell your doctor or nurse 
straight away. 
 
If you have any further questions on the use of this medicine, ask your doctor, nurse or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
 

Tell your doctor or nurse straight away if you notice any of the following side effects – you may 
need urgent medical treatment: 
 rash, itching, feeling warm, swelling of your face, lips or throat or difficulty breathing - you 

may be having a histamine reaction to the medicine. 
 difficulty breathing with wheezing or a rash that gets worse - you may be having an allergic 

reaction to the medicine. 
 cough, serious breathing difficulties - if you are an adult and have invasive aspergillosis you 

may be experiencing a serious respiratory problem that could result in respiratory failure.  
 rash, skin peeling, mucous membrane sores, hives, large areas of peeling skin. 
 
As with any prescription medicine, some side effects may be serious. Ask your doctor for more 
information.  
 
Other side effects in adults include 
 
Common (may affect up to 1 in 10 people): 
 Decreased haemoglobin (decreased oxygen carrying substance in the blood), decreased white 

blood cells 
 Decreased blood albumin (a type of protein) in your blood, decreased potassium or low 

potassium levels in the blood 
 Headache 
 Inflammation of the vein 
 Shortness of breath 
 Diarrhoea, nausea or vomiting 
 Changes in some laboratory blood tests (including increased values of some liver tests) 
 Itching, rash, skin redness or sweating more than usual  
 Joint pain 
 Chills, fever 
 Itching at the injection site. 
 
Uncommon (may affect up to 1 in 100 people): 
 Changes in some laboratory blood tests (including disease of blood clotting, platelets, red blood 

cells and white blood cells) 
 Loss of appetite, increase in amount of body fluid,  imbalance of salt in the body, high sugar 

level in the blood, low calcium level in the blood, increase calcium level in the blood, low 
magnesium level in the blood, increase in acid level in the blood  

 Disorientation, feeling nervous, being unable to sleep  
 Feeling dizzy, decreased feeling or sensitivity (especially in the skin), shaking, feeling sleepy, 

change in the way things taste, tingling or numbness 



34 

 Blurred vision, increase in tears, swollen eyelid, yellowing of the whites of the eyes 
 Sensation of fast or irregular heart beats, rapid heart beat, irregular heart beat, abnormal heart 

rhythm, heart failure 
 Flushing, hot flush, high blood pressure, low blood pressure, redness along a vein which is 

extremely tender when touched 
 Tightening of the bands of muscle around the airways resulting in wheezing or coughing, fast 

breathing rate, shortness of breath that wakes you up, shortage of oxygen in the blood, abnormal 
breath sounds, crackling sounds in the lungs, wheezing, nasal congestion, cough, throat pain 

 Belly pain, upper belly pain, bloating, constipation, difficulty swallowing, dry mouth, 
indigestion, passing gas, stomach discomfort, swelling due to build-up of fluid around the belly 

 Decreased flow of bile, enlarged liver, yellowing of the skin and/or whites of the eyes, liver 
injury caused by a drug or chemical, liver disorder 

 Abnormal skin tissue, generalised itching, hives, rash of varying appearance, abnormal skin, red 
often itchy spots on your arms and legs and sometimes on the face and the rest of the body  

 Back pain, pain in an arm or leg, bone pain, muscle pain, muscle weakness 
 Loss of kidney function, sudden loss of kidney function 
 Catheter site pain, injection site complaints (redness, hard lump, pain, swelling, irritation, rash, 

hives, leaking of fluid from the catheter into the tissue), inflammation of vein at injection site 
 Increased blood pressure and alterations in some laboratory blood tests (including kidney 

electrolyte and clotting tests), increased levels of the medicines you are taking that weaken the 
immune system 

 Chest discomfort, chest pain, feeling of body temperature change, generally feeling unwell, 
general pain, swelling of the face, swelling of the ankles, hands or feet, swelling, tenderness, 
feeling tired. 

 
Side effects in children and adolescents  
 
Very common (may affect more than 1 in 10 people): 
 Fever 
Common (may affect up to 1 in 10 people): 
 Headache 
 Fast heart beat 
 Flushing, low blood pressure 
 Changes in some laboratory blood tests (increased values of some liver tests) 
 Itching, rash 
 Catheter site pain 
 Chills 
 Changes in some laboratory blood tests. 
 
 
 
Reporting of side effects  
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Caspofungin Accord 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and the vial . The expiry 
date refers to the last day of that month. 
 
Store in a refrigerator (2C to 8C). 



35 

 
Once Caspofungin Accord has been prepared, it should be used straight away. This is because it does 
not contain any ingredients to stop the growth of bacteria. Only a trained healthcare professional who 
has read the complete directions should prepare the medicine (please see below “Instructions of how 
to reconstitute and dilute Caspofungin Accord”). 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Caspofungin Accord contains 
 The active substance is caspofungin. Each vial of Caspofungin Accord contains 50 mg or 70 mg 

of caspofungin (as acetate).  
 The other ingredients are sucrose, mannitol, succinic acid and sodium hydroxide (please see 

section 2. What you need to know before you are given Caspofungin Accord). 
 
What Caspofungin Accord looks like and contents of the pack 
Caspofungin Accord powder for concentrate for solution for infusion is a white to off-white powder.  
 
Each pack contains one vial of powder. 
 
Marketing Authorisation Holder and Manufacturer 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
Manufacturer 
Accord Healthcare Limited 
Sage House, 319 Pinner Road, North Harrow, Middlesex, HA1 4HF 
United Kingdom 
 
 
Xellia Pharmaceuticals ApS 
Dalslandsgade 11, København S, 
2300, Denmark 
 
 
This leaflet was last revised in  
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 



36 

 
 
The following information is intended for medical or healthcare professionals only: 
 
Instructions of how to reconstitute and dilute Caspofungin Accord: 
 
Reconstitution of Caspofungin Accord 
DO NOT USE ANY DILUENTS CONTAINING GLUCOSE as CASPOFUNGIN ACCORD is not 
stable in diluents containing glucose. DO NOT MIX OR CO-INFUSE Caspofungin Accord WITH 
ANY OTHER MEDICINES, as there are no data available on the compatibility of Caspofungin 
Accord with other intravenous substances, additives, or medicinal products. Visually inspect the 
infusion solution for particulate matter or discolouration. 
 

INSTRUCTIONS FOR USE IN ADULT PATIENTS (Caspofungin Accord 50 mg) 
 
Step 1 Reconstitution of conventional vials  
To 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. 
 
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 Caspofungin Accord to patient infusion solution  
Diluents for the final solution for infusion are: sodium chloride solution for injection 9 mg/mL, or 
lactated Ringer’s solution should be used. 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 recon- 

stituted 
Caspofungin 
Accord for 
transfer to 
intravenous bag or 
bottle 

Standard preparation 
(reconstituted 
Caspofungin Accord 
added to 250 mL) final 
concentration 

Reduced volume 
infusion  
(reconstituted 
Caspofungin Accord 
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 

* 10.5 mL should be used for reconstitution of all vials 
 

INSTRUCTIONS FOR USE IN ADULT PATIENTS (Caspofungin Accord 70 mg) 
 
Step 1 Reconstitution of conventional vials 
To 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 7.2 mg/mL. 
 



37 

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 Caspofungin Accord to patient infusion solution 
Diluents for the final solution for infusion are: sodium chloride solution for injection 9 mg/mL 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 
Caspofungin Accord 
for transfer to 
intravenous bag or 
bottle 

Standard preparation 
(reconstituted 
Caspofungin Accord 
added to 250 mL) final 
concentration 

Reduced volume 
infusion 
(reconstituted 
Caspofungin Accord 
added to 100 mL) final 
concentration 

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 

* 10.5 mL should be used for reconstitution of all vials. 
** If 70 mg vial is not available, the 70 mg dose can be prepared from two 50 mg vials 
 

INSTRUCTIONS FOR USE IN PAEDIATRIC PATIENTS (Caspofungin Accord 50 mg) 
 

Calculation of Body Surface Area (BSA) for paediatric dosing 
Before preparation of infusion, calculate the body surface area (BSA) of the patient using the 
following formula: (Mosteller2 Formula) 

 
 
Preparation of the 70 mg/m2 infusion for paediatric patients >3 months of age (using a 50-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 Dose 
The maximum loading dose on Day 1 should not exceed 70 mg regardless of the patient's 
calculated dose. 

2. Equilibrate the refrigerated vial of Caspofungin Accord 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. 

4. Remove the volume of medicine equal to the calculated loading dose (Step 1) from the vial. 
Aseptically transfer this volume (mL)c of reconstituted Caspofungin Accord to an IV bag (or 
bottle) containing 250 mL of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride solution for infusion, 
or Lactated Ringers solution for infusion. Alternatively, the volume (mL)c of reconstituted 
Caspofungin Accord can be added to a reduced volume of 0.9 %, 0.45 %, or 0.225 % Sodium 
Chloride solution for infusion or Lactated Ringers solution for infusion, not to exceed a final 

                                                      
2 Mosteller RD: Simplified Calculation of Body Surface Area. N Engl J Med 1987 Oct 22;317(17): 1098 (letter) 



38 

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) 
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 Dose 
The daily maintenance dose should not exceed 70 mg regardless of the patient's calculated dose. 

2. Equilibrate the refrigerated vial of Caspofungin Accord 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. 

4. Remove the volume of medicine equal to the calculated daily maintenance dose (Step 1) from 
the vial. Aseptically transfer this volume (mL)c of reconstituted Caspofungin Accord to an IV 
bag (or bottle) containing 250 mL of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride solution for 
infusion, or Lactated Ringers solution for infusion. Alternatively, the volume (mL)c of 
reconstituted Caspofungin Accord can be added to a reduced volume of 0.9 %, 0.45 %, or 
0.225 % Sodium Chloride solution for infusion or Lactated Ringers solution for infusion, 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 discoloration during 
reconstitution and prior to infusion. Do not use if the solution is cloudy or has precipitated. 

 

c Caspofungin Accord is formulated to provide the full labeled vial dose (50 mg) when 10 mL is 
withdrawn from the vial. 

 

 
INSTRUCTIONS FOR USE IN PAEDIATRIC PATIENTS (Caspofungin Accord 70 mg) 

 
Calculation of Body Surface Area (BSA) for paediatric dosing 
Before preparation of infusion, calculate the body surface area (BSA) of the patient using the 
following formula: (Mosteller3 Formula) 

 
 
Preparation of the 70 mg/m2 infusion for paediatric patients > 3 months of age (using 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 Dose 
The maximum loading dose on Day 1 should not exceed 70 mg regardless of the patient's 
calculated dose. 

2. Equilibrate the refrigerated vial of Caspofungin Accord 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 
7.2 mg/mL. 

4. Remove the volume of medicine equal to the calculated loading dose (Step 1) from the vial. 
Aseptically transfer this volume (mL)c of reconstituted Caspofungin Accord to an IV bag (or 
bottle) containing 250 mL of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride solution for infusion 
or Lactated Ringers solution for infusion. Alternatively, the volume (mL)c of reconstituted 

                                                      
3 Mosteller RD: Simplified Calculation of Body Surface Area. N Engl J Med 1987 Oct 22;317(17): 1098 (letter) 



39 

Caspofungin Accord can be added to a reduced volume of 0.9 %, 0.45 %, or 0.225 % Sodium 
Chloride solution for infusion or Lactated Ringers solution for infusion, 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 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 Dose 
The daily maintenance dose should not exceed 70 mg regardless of the patient's calculated dose. 

2. Equilibrate the refrigerated vial of Caspofungin Accord 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 
7.2 mg/mL. 

4. Remove the volume of medicine equal to the calculated daily maintenance dose (Step 1) from 
the vial. Aseptically transfer this volume (mL)c of reconstituted Caspofungin Accord to an IV 
bag (or bottle) containing 250 mL of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride solution for 
infusion or Lactated Ringers solution for infusion. Alternatively, the volume (mL)c of 
reconstituted Caspofungin Accord can be added to a reduced volume of 0.9 %, 0.45 %, or 
0.225 % Sodium Chloride solution for infusion or Lactated Ringers solution for infusion, 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. Caspofungin Accord is formulated to provide the full labelled vial dose (70 mg) when 10 mL is 
withdrawn from the vial. 

 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET