Cubicin

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

 



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1. NAME OF THE MEDICINAL PRODUCT

Cubicin 350 mg powder for solution for injection or infusion
Cubicin 500 mg powder for solution for injection or infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Cubicin 350 mg powder for solution for injection or infusion
Each vial contains 350 mg daptomycin.
One ml provides 50 mg of daptomycin after reconstitution with 7 ml of sodium chloride 9 mg/ml 
(0.9 %) solution.

Cubicin 500 mg powder for solution for injection or infusion
Each vial contains 500 mg daptomycin.
One ml provides 50 mg of daptomycin after reconstitution with 10 ml of sodium chloride 9 mg/ml 
(0.9 %) solution.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder for solution for injection or infusion
A pale yellow to light brown lyophilised cake or powder.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Cubicin is indicated for the treatment of the following infections (see sections 4.4 and 5.1).
- Adult and paediatric (1 to 17 years of age) patients with complicated skin and soft-tissue 

infections (cSSTI).
- Adult patients with right-sided infective endocarditis (RIE) due to Staphylococcus aureus. It is 

recommended that the decision to use daptomycin should take into account the antibacterial 
susceptibility of the organism and should be based on expert advice. See sections 4.4 and 5.1.

- Adult and paediatric (1 to 17 years of age) patients with Staphylococcus aureus bacteraemia 
(SAB). In adults, use in bacteraemia should be associated with RIE or with cSSTI, while in 
paediatric patients, use in bacteraemia should be associated with cSSTI.

Daptomycin is active against Gram positive bacteria only (see section 5.1). In mixed infections where 
Gram negative and/or certain types of anaerobic bacteria are suspected, Cubicin should be 
co-administered with appropriate antibacterial agent(s).

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

Clinical studies in patients employed infusion of daptomycin over at least 30 minutes. There is no 
clinical experience in patients with the administration of daptomycin as an injection over 2 minutes. 
This mode of administration was only studied in healthy subjects. However, when compared with the 
same doses given as intravenous infusions over 30 minutes there were no clinically important 
differences in the pharmacokinetics and safety profile of daptomycin (see also sections 4.8 and 5.2).

 



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Posology

Adults
- cSSTI without concurrent SAB: Cubicin 4 mg/kg is administered once every 24 hours for 

7-14 days or until the infection is resolved (see section 5.1).
- cSSTI with concurrent SAB: Cubicin 6 mg/kg is administered once every 24 hours. See below 

for dose adjustments in patients with renal impairment. The duration of therapy may need to be 
longer than 14 days in accordance with the perceived risk of complications in the individual 
patient.

- Known or suspected RIE due to Staphylococcus aureus: Cubicin 6 mg/kg is administered once 
every 24 hours. See below for dose adjustments in patients with renal impairment. The duration 
of therapy should be in accordance with available official recommendations.

Cubicin is administered intravenously in 0.9 % sodium chloride (see section 6.6). Cubicin should not 
be used more frequently than once a day.

Creatine phosphokinase (CPK) levels must be measured at baseline and at regular intervals (at least 
weekly) during treatment (see section 4.4).

Renal impairment
Daptomycin is eliminated primarily by the kidney.

Due to limited clinical experience (see table and footnotes below) Cubicin should only be used in 
adult patients with any degree of renal impairment (CrCl < 80 ml/min) when it is considered that the 
expected clinical benefit outweighs the potential risk. The response to treatment, renal function and 
creatine phosphokinase (CPK) levels should be closely monitored in all patients with any degree of 
renal impairment (see also sections 4.4 and 5.2). The dosage regimen for Cubicin in paediatric 
patients with renal impairment has not been established.

Dose adjustments in adult patients with renal impairment by indication and creatinine clearance

Indication for use Creatinine clearance Dose recommendation Comments
cSSTI without SAB

 30 ml/min
4 mg/kg once daily See section 5.1

< 30 ml/min 4 mg/kg every 48 hours (1, 2)

RIE or cSSTI 
associated with 
SAB

 30 ml/min
6 mg/kg once daily See section 5.1

< 30 ml/min
6 mg/kg every 48 hours (1, 2)

cSSTI = complicated skin and soft-tissue infections; SAB = S. aureus bacteraemia 
(1) The safety and efficacy of the dose interval adjustment have not been evaluated in controlled 
clinical trials and the recommendation is based on pharmacokinetic studies and modelling results (see 
sections 4.4 and 5.2).
(2) The same dose adjustments, which are based on pharmacokinetic data in volunteers including PK 
modelling results, are recommended for adult patients on haemodialysis (HD) or continuous 
ambulatory peritoneal dialysis (CAPD). Whenever possible, Cubicin should be administered 
following the completion of dialysis on dialysis days (see section 5.2).

 



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Hepatic impairment
No dose adjustment is necessary when administering Cubicin to patients with mild or moderate 
hepatic impairment (Child-Pugh Class B) (see section 5.2). No data are available in patients with 
severe hepatic impairment (Child-Pugh Class C). Therefore caution should be exercised if Cubicin is 
given to such patients.

Elderly patients
The recommended doses should be used in elderly patients except those with severe renal impairment
(see above and section 4.4).

Paediatric population (1 to 17 years of age)
The recommended dosage regimens for paediatric patients based on age and indication are shown 
below.

Age Group

Indication

cSSTI without SAB cSSTI associated with SAB

Dosage Regimen
Duration of 

Therapy
Dosage Regimen

Duration of 
Therapy

12 to 17
years

5 mg/kg once every 
24 hours infused over

30 minutes

Up to 14 days

7 mg/kg once every 
24 hours infused over 

30 minutes

(1)

7 to 11 
years

7 mg/kg once every 
24 hours infused over

30 minutes

9 mg/kg once every
24 hours infused over 

30 minutes

2 to 6 years
9 mg/kg once every 

24 hours infused over
60 minutes

12 mg/kg once every 
24 hours infused over 

60 minutes

1 to < 2
years

10 mg/kg once every 
24 hours infused over

60 minutes

12 mg/kg once every 
24 hours infused over 

60 minutes

cSSTI = complicated skin and soft-tissue infections; SAB = S. aureus bacteraemia; 
(1) Minimum duration of Cubicin for paediatric SAB should be in accordance with the perceived risk 
of complications in the individual patient. The duration of Cubicin may need to be longer than 
14 days in accordance with the perceived risk of complications in the individual patient. In the
paediatric SAB study, the mean duration of IV Cubicin was 12 days, with a range of 1 to 44 days. The 
duration of therapy should be in accordance with available official recommendations.

Cubicin is administered intravenously in 0.9 % sodium chloride (see section 6.6). Cubicin should not 
be used more frequently than once a day.

Creatine phosphokinase (CPK) levels must be measured at baseline and at regular intervals (at least 
weekly) during treatment (see section 4.4).

Paediatric patients below the age of one year should not be given Cubicin due to the risk of potential 
effects on muscular, neuromuscular and/or nervous systems (either peripheral and/or central) that
were observed in neonatal dogs (see section 5.3).

Method of administration
In adults, Cubicin is given by intravenous infusion (see section 6.6) and administered over a 
30-minute period or by intravenous injection (see section 6.6) and administered over a 2-minute 
period.

In paediatric patients aged 7 to 17 years, Cubicin is given by intravenous infusion over a 30-minute 
period (see section 6.6). In paediatric patients aged 1 to 6 years, Cubicin is given by intravenous 

 



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infusion over a 60-minute period (see section 6.6).

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

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

General
If a focus of infection other than cSSTI or RIE is identified after initiation of Cubicin therapy 
consideration should be given to instituting alternative antibacterial therapy that has been 
demonstrated to be efficacious in the treatment of the specific type of infection(s) present.

Anaphylaxis/hypersensitivity reactions
Anaphylaxis/hypersensitivity reactions have been reported with Cubicin. If an allergic reaction to 
Cubicin occurs, discontinue use and institute appropriate therapy.

Pneumonia
It has been demonstrated in clinical studies that Cubicin is not effective in the treatment of 
pneumonia. Cubicin is therefore not indicated for the treatment of pneumonia.

RIE due to Staphylococcus aureus
Clinical data on the use of Cubicin to treat RIE due to Staphylococcus aureus are limited to 19 adult
patients (see “Clinical efficacy in adults” in section 5.1). The safety and efficacy of Cubicin in 
children and adolescents aged below 18 years with right-sided infective endocarditis (RIE) due to 
Staphylococcus aureus have not been established.
The efficacy of Cubicin in patients with prosthetic valve infections or with left-sided infective 
endocarditis due to Staphylococcus aureus has not been demonstrated.

Deep-seated infections
Patients with deep-seated infections should receive any required surgical interventions (e.g. 
debridement, removal of prosthetic devices, valve replacement surgery) without delay.

Enterococcal infections
There is insufficient evidence to be able to draw any conclusions regarding the possible clinical 
efficacy of Cubicin against infections due to enterococci, including Enterococcus faecalis and 
Enterococcus faecium. In addition, dose regimens of daptomycin that might be appropriate for the 
treatment of enterococcal infections, with or without bacteraemia, have not been identified. Failures 
with daptomycin in the treatment of enterococcal infections that were mostly accompanied by 
bacteraemia have been reported. In some instances treatment failure has been associated with the 
selection of organisms with reduced susceptibility or frank resistance to daptomycin (see section 5.1).

Non-susceptible micro-organisms
The use of antibacterials may promote the overgrowth of non-susceptible micro-organisms. If 
superinfection occurs during therapy, appropriate measures should be taken.

Clostridioides difficile-associated diarrhoea
Clostridioides difficile-associated diarrhoea (CDAD) has been reported with Cubicin (see 
section 4.8). If CDAD is suspected or confirmed, Cubicin may need to be discontinued and 
appropriate treatment instituted as clinically indicated.

Drug/laboratory test interactions
False prolongation of prothrombin time (PT) and elevation of international normalised ratio (INR) 

 



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have been observed when certain recombinant thromboplastin reagents are utilised for the assay (see 
also section 4.5).

Creatine phosphokinase and myopathy
Increases in plasma creatine phosphokinase (CPK; MM isoenzyme) levels associated with muscular 
pains and/or weakness and cases of myositis, myoglobinaemia and rhabdomyolysis have been 
reported during therapy with Cubicin (see also sections 4.5, 4.8 and 5.3). In clinical studies, marked 
increases in plasma CPK to > 5x Upper Limit of Normal (ULN) without muscle symptoms occurred 
more commonly in Cubicin-treated patients (1.9 %) than in those that received comparators (0.5 %). 
Therefore, it is recommended that:
 Plasma CPK should be measured at baseline and at regular intervals (at least once weekly)

during therapy in all patients.
 CPK should be measured more frequently (e.g. every 2-3 days at least during the first two 

weeks of treatment) in patients who are at higher risk of developing myopathy. For example, 
patients with any degree of renal impairment (creatinine clearance < 80 ml/min; see also
section 4.2), including those on haemodialysis or CAPD, and patients taking other medicinal 
products known to be associated with myopathy (e.g. HMG-CoA reductase inhibitors, fibrates 
and ciclosporin).

 It cannot be ruled out that those patients with CPK greater than 5 times upper limit of normal at 
baseline may be at increased risk of further increases during daptomycin therapy. This should 
be taken into account when initiating daptomycin therapy and, if daptomycin is given, these 
patients should be monitored more frequently than once weekly.

 Cubicin should not be administered to patients who are taking other medicinal products 
associated with myopathy unless it is considered that the benefit to the patient outweighs the 
risk.

 Patients should be reviewed regularly while on therapy for any signs or symptoms that might 
represent myopathy.

 Any patient that develops unexplained muscle pain, tenderness, weakness or cramps should 
have CPK levels monitored every 2 days. Cubicin should be discontinued in the presence of 
unexplained muscle symptoms if the CPK level reaches greater than 5 times upper limit of 
normal.

Peripheral neuropathy
Patients who develop signs or symptoms that might represent a peripheral neuropathy during therapy 
with Cubicin should be investigated and consideration should be given to discontinuation of 
daptomycin (see sections 4.8 and 5.3).

Paediatric population
Paediatric patients below the age of one year should not be given Cubicin due to the risk of potential 
effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) that 
were observed in neonatal dogs (see section 5.3).

Eosinophilic pneumonia
Eosinophilic pneumonia has been reported in patients receiving Cubicin (see section 4.8). In most 
reported cases associated with Cubicin, patients developed fever, dyspnoea with hypoxic respiratory 
insufficiency, and diffuse pulmonary infiltrates or organising pneumonia. The majority of cases 
occurred after more than 2 weeks of treatment with Cubicin and improved when Cubicin was 
discontinued and steroid therapy was initiated. Recurrence of eosinophilic pneumonia upon re-
exposure has been reported. Patients who develop these signs and symptoms while receiving Cubicin 
should undergo prompt medical evaluation, including, if appropriate, bronchoalveolar lavage, to 
exclude other causes (e.g. bacterial infection, fungal infection, parasites, other medicinal products).
Cubicin should be discontinued immediately and treatment with systemic steroids should be initiated 
when appropriate.

 



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Severe cutaneous adverse reactions
Severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic 
symptoms (DRESS) and vesiculobullous rash with or without mucous membrane involvement 
(Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN)), which could be 
life-threatening or fatal, have been reported with daptomycin (see section 4.8). At the time of 
prescription, patients should be advised of the signs and symptoms of severe skin reactions, and be 
closely monitored. If signs and symptoms suggestive of these reactions appear, Cubicin should be 
discontinued immediately and an alternative treatment should be considered. If the patient has 
developed a severe cutaneous adverse reaction with the use of daptomycin, treatment with daptomycin 
must not be restarted in this patient at any time.

Tubulointerstitial nephritis
Tubulointerstitial nephritis (TIN) has been reported in post-marketing experience with daptomycin. 
Patients who develop fever, rash, eosinophilia and/or new or worsening renal impairment while 
receiving Cubicin should undergo medical evaluation. If TIN is suspected, Cubicin should be 
discontinued promptly and appropriate therapy and/or measures should be taken.

Renal impairment
Renal impairment has been reported during treatment with Cubicin. Severe renal impairment may in 
itself also pre-dispose to elevations in daptomycin levels which may increase the risk of development 
of myopathy (see above).

An adjustment of Cubicin dose interval is needed for adult patients whose creatinine clearance is 
< 30 ml/min (see sections 4.2 and 5.2). The safety and efficacy of the dose interval adjustment have 
not been evaluated in controlled clinical trials and the recommendation is mainly based on 
pharmacokinetic modelling data. Cubicin should only be used in such patients when it is considered 
that the expected clinical benefit outweighs the potential risk.

Caution is advised when administering Cubicin to patients who already have some degree of renal 
impairment (creatinine clearance < 80 ml/min) before commencing therapy with Cubicin. Regular 
monitoring of renal function is advised (see also section 5.2).

In addition, regular monitoring of renal function is advised during concomitant administration of 
potentially nephrotoxic agents, regardless of the patient’s pre-existing renal function (see also 
section 4.5).

The dosage regimen for Cubicin in paediatric patients with renal impairment has not been established.

Obesity
In obese subjects with Body Mass Index (BMI) > 40 kg/m2 but with creatinine clearance > 70 ml/min, 
the AUC0-∞ daptomycin was significantly increased (mean 42 % higher) compared with non-obese 
matched controls. There is limited information on the safety and efficacy of daptomycin in the very 
obese and so caution is recommended. However, there is currently no evidence that a dose reduction 
is required (see section 5.2).

Sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

Daptomycin undergoes little to no Cytochrome P450 (CYP450)-mediated metabolism. It is unlikely 
that daptomycin will inhibit or induce the metabolism of medicinal products metabolised by the P450 
system.

Interaction studies for Cubicin were performed with aztreonam, tobramycin, warfarin and probenecid. 

 



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Daptomycin had no effect on the pharmacokinetics of warfarin or probenecid, nor did these medicinal 
products alter the pharmacokinetics of daptomycin. The pharmacokinetics of daptomycin were not 
significantly altered by aztreonam.

Although small changes in the pharmacokinetics of daptomycin and tobramycin were observed during 
co-administration by intravenous infusion over a 30-minute period using a Cubicin dose of 2 mg/kg, 
the changes were not statistically significant. The interaction between daptomycin and tobramycin 
with an approved dose of Cubicin is unknown. Caution is warranted when Cubicin is co-administered 
with tobramycin.

Experience with the concomitant administration of Cubicin and warfarin is limited. Studies of 
Cubicin with anticoagulants other than warfarin have not been conducted. Anticoagulant activity in 
patients receiving Cubicin and warfarin should be monitored for the first several days after therapy 
with Cubicin is initiated.

There is limited experience regarding concomitant administration of daptomycin with other medicinal 
products that may trigger myopathy (e.g. HMG-CoA reductase inhibitors). However, some cases of 
marked rises in CPK levels and cases of rhabdomyolysis occurred in adult patients taking one of these 
medicinal products at the same time as Cubicin. It is recommended that other medicinal products 
associated with myopathy should if possible be temporarily discontinued during treatment with 
Cubicin unless the benefits of concomitant administration outweigh the risk. If co-administration 
cannot be avoided, CPK levels should be measured more frequently than once weekly and patients 
should be closely monitored for any signs or symptoms that might represent myopathy. See
sections 4.4, 4.8 and 5.3.

Daptomycin is primarily cleared by renal filtration and so plasma levels may be increased during 
co-administration with medicinal products that reduce renal filtration (e.g. NSAIDs and COX-2 
inhibitors). In addition, there is a potential for a pharmacodynamic interaction to occur during 
co-administration due to additive renal effects. Therefore, caution is advised when daptomycin is 
co-administered with any other medicinal product known to reduce renal filtration.

During post–marketing surveillance, cases of interference between daptomycin and particular reagents 
used in some assays of prothrombin time/international normalised ratio (PT/INR) have been reported. 
This interference led to a false prolongation of PT and elevation of INR. If unexplained abnormalities 
of PT/INR are observed in patients taking daptomycin, consideration should be given to a possible in 
vitro interaction with the laboratory test. The possibility of erroneous results may be minimised by 
drawing samples for PT or INR testing near the time of trough plasma concentrations of daptomycin
(see section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy
No clinical data on pregnancies are available for daptomycin. Animal studies do not indicate direct or
indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or 
postnatal development (see section 5.3).

Cubicin should not be used during pregnancy unless clearly necessary i.e., only if the expected benefit 
outweighs the possible risk.

Breast-feeding
In a single human case study, Cubicin was intravenously administered daily for 28 days to a nursing 
mother at a dose of 500 mg/day, and samples of the patient’s breast milk were collected over a 
24-hour period on day 27. The highest measured concentration of daptomycin in the breast milk was 
0.045 µg/ml, which is a low concentration. Therefore, until more experience is gained, breast-feeding 
should be discontinued when Cubicin is administered to nursing women.

 



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Fertility
No clinical data on fertility are available for daptomycin. Animal studies do not indicate direct or 
indirect harmful effects with respect to fertility (see section 5.3).

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.

On the basis of reported adverse drug reactions, Cubicin is presumed to be unlikely to produce an 
effect on the ability to drive or use machinery.

4.8 Undesirable effects

Summary of the safety profile
In clinical studies, 2,011 adult subjects received Cubicin. Within these trials, 1,221 subjects received 
a daily dose of 4 mg/kg, of whom 1,108 were patients and 113 were healthy volunteers; 460 subjects 
received a daily dose of 6 mg/kg, of whom 304 were patients and 156 were healthy volunteers. In 
paediatric studies, 372 patients received Cubicin, of whom 61 received a single dose and 311 received 
a therapeutic regimen for cSSTI or SAB (daily doses ranged from 4 mg/kg to 12 mg/kg). Adverse 
reactions (i.e. considered by the investigator to be possibly, probably, or definitely related to the 
medicinal product) were reported at similar frequencies for Cubicin and comparator regimens.

The most frequently reported adverse reactions (frequency common (≥ 1/100 to < 1/10)) are:
Fungal infections, urinary tract infection, candida infection, anaemia, anxiety, insomnia, dizziness, 
headache, hypertension, hypotension, gastrointestinal and abdominal pain, nausea, vomiting, 
constipation, diarrhoea, flatulence, bloating and distension, liver function tests abnormal (increased 
alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP)), 
rash, pruritus, limb pain, serum creatine phosphokinase (CPK) increased, infusion site reactions, 
pyrexia, asthenia.

Less frequently reported, but more serious, adverse reactions include hypersensitivity reactions,
eosinophilic pneumonia (occasionally presenting as organising pneumonia), drug reaction with 
eosinophilia and systemic symptoms (DRESS), angioedema and rhabdomyolysis.

Tabulated list of adverse reactions
The following adverse reactions were reported during therapy and during follow-up with frequencies 
corresponding to very common ( 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to 
< 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from 
the available data):

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Table 1 Adverse reactions from clinical studies and post-marketing reports

System organ class Frequency Adverse reactions
Infections and infestations Common: Fungal infections, urinary tract infection, candida 

infection

Uncommon: Fungaemia

Not known*: Clostridioides difficile-associated diarrhoea**

Blood and lymphatic system 
disorders

Common: Anaemia

Uncommon: Thrombocythaemia, eosinophilia, international 
normalised ratio (INR) increased, leukocytosis

Rare:

Not known*:

Prothrombin time (PT) prolonged

Thrombocytopaenia

 



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System organ class Frequency Adverse reactions

Immune system disorders Not known*: Hypersensitivity**, manifested by isolated 
spontaneous reports including, but not limited to 
angioedema, pulmonary eosinophilia, sensation of 
oropharyngeal swelling, anaphylaxis**, infusion 
reactions including the following symptoms: 
tachycardia, wheezing, pyrexia, rigors, systemic 
flushing, vertigo, syncope and metallic taste

Metabolism and nutrition 
disorders

Uncommon: Decreased appetite, hyperglycaemia, electrolyte 
imbalance

Psychiatric disorders Common: Anxiety, insomnia
Nervous system disorders Common: Dizziness, headache

Uncommon: Paraesthesia, taste disorder, tremor, eye irritation
Not known*: Peripheral neuropathy**

Ear and labyrinth disorders Uncommon: Vertigo
Cardiac disorders Uncommon: Supraventricular tachycardia, extrasystole
Vascular disorders Common: Hypertension, hypotension

Uncommon: Flushes
Respiratory, thoracic and 
mediastinal disorders

Not known*: Eosinophilic pneumonia1**, cough

Gastrointestinal disorders Common: Gastrointestinal and abdominal pain, nausea, 
vomiting, constipation, diarrhoea, flatulence, 
bloating and distension

Uncommon: Dyspepsia, glossitis
Hepatobiliary disorders Common: Liver function tests abnormal2 (increased alanine 

aminotransferase (ALT), aspartate aminotransferase
(AST) or alkaline phosphatase (ALP))

Rare: Jaundice
Skin and subcutaneous tissue
disorders

Common: Rash, pruritus
Uncommon: Urticaria
Not known*: Acute generalised exanthematous pustulosis

(AGEP), drug reaction with eosinophilia and
systemic symptoms (DRESS)**, vesiculobullous 
rash with or without mucous membrane involvement
(SJS or TEN)**

Musculoskeletal and
connective tissue disorders

Common: Limb pain, serum creatine phosphokinase (CPK)2

increased
Uncommon: Myositis, increased myoglobin, muscular weakness,

muscle pain, arthralgia, serum lactate dehydrogenase 
(LDH) increased, muscle cramps

Not known*: Rhabdomyolysis3 **
Renal and urinary disorders Uncommon: Renal impairment, including renal failure and renal 

insufficiency, serum creatinine increased
Not known*: Tubulointerstitial nephritis (TIN)**

Reproductive system and 
breast disorders

Uncommon: Vaginitis

General disorders and 
administration site conditions

Common: Infusion site reactions, pyrexia, asthenia
Uncommon: Fatigue, pain

* Based on post-marketing reports. Since these reactions are reported voluntarily from a 
population of uncertain size, it is not possible to reliably estimate their frequency which is 
therefore categorised as not known.

** See section 4.4.
1 While the exact incidence of eosinophilic pneumonia associated with daptomycin is unknown, 

to date the reporting rate of spontaneous reports is very low (< 1/10,000).

 



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2 In some cases of myopathy involving raised CPK and muscle symptoms, the patients also 
presented with elevated transaminases. These transaminase increases were likely to be related 
to the skeletal muscle effects. The majority of transaminase elevations were of Grade 1-3 
toxicity and resolved upon discontinuation of treatment.

3 When clinical information on the patients was available to make a judgement, approximately 
50 % of the cases occurred in patients with pre-existing renal impairment, or in those receiving 
concomitant medicinal products known to cause rhabdomyolysis.

The safety data for the administration of daptomycin via 2-minute intravenous injection are derived 
from two pharmacokinetic studies in healthy adult volunteers. Based on these study results, both 
methods of daptomycin administration, the 2-minute intravenous injection and the 30-minute 
intravenous infusion, had a similar safety and tolerability profile. There was no relevant difference in 
local tolerability or in the nature and frequency of adverse reactions.

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

In the event of overdose, supportive care is advised. Daptomycin is slowly cleared from the body by 
haemodialysis (approximately 15 % of the administered dose is removed over 4 hours) or by 
peritoneal dialysis (approximately 11 % of the administered dose is removed over 48 hours).

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antibacterials for systemic use, Other antibacterials, ATC code: 
J01XX09

Mechanism of action
Daptomycin is a cyclic lipopeptide natural product that is active against Gram positive bacteria only.

The mechanism of action involves binding (in the presence of calcium ions) to bacterial membranes 
of both growing and stationary phase cells causing depolarisation and leading to a rapid inhibition of 
protein, DNA, and RNA synthesis. This results in bacterial cell death with negligible cell lysis.

PK/PD relationship
Daptomycin exhibits rapid, concentration dependent bactericidal activity against Gram positive 
organisms in vitro and in in vivo animal models. In animal models AUC/MIC and Cmax/MIC correlate 
with efficacy and predicted bacterial kill in vivo at single doses equivalent to human adult doses of 
4 mg/kg and 6 mg/kg once daily.

Mechanisms of resistance
Strains with decreased susceptibility to daptomycin have been reported especially during the 
treatment of patients with difficult-to-treat infections and/or following administration for prolonged 
periods. In particular, there have been reports of treatment failures in patients infected with 
Staphylococcus aureus, Enterococcus faecalis or Enterococcus faecium, including bacteraemic 
patients, that have been associated with the selection of organisms with reduced susceptibility or frank 
resistance to daptomycin during therapy.

The mechanism(s) of daptomycin resistance is (are) not fully understood.

 

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Breakpoints
Minimum inhibitory concentration (MIC) breakpoint established by the European Committee on 
Antimicrobial Susceptibility Testing (EUCAST) for Staphylococci and Streptococci (except S. 
pneumoniae) are Susceptible ≤ 1 mg/l and Resistant > 1 mg/l.

Susceptibility
The prevalence of resistance may vary geographically and over time for selected species and local 
information on resistance is desirable, particularly when treating severe infections. As necessary, 
expert advice should be sought when the local prevalence of resistance is such that the utility of the 
agent in at least some types of infections is questionable.

Commonly Susceptible Species
Staphylococcus aureus *
Staphylococcus haemolyticus
Coagulase negative staphylococci 
Streptococcus agalactiae*
Streptococcus dysgalactiae subsp equisimilis*
Streptococcus pyogenes*
Group G streptococci
Clostridium perfringens
Peptostreptococcus spp
Inherently resistant organisms
Gram negative organisms
* denotes species against which it is considered that activity has been satisfactorily demonstrated in 
clinical studies.

Clinical efficacy in adults
In two adult clinical trials in complicated skin and soft tissues infections, 36 % of patients treated with
Cubicin met the criteria for systemic inflammatory response syndrome (SIRS). The most common 
type of infection treated was wound infection (38 % of patients), while 21 % had major abscesses. 
These limitations of the patients population treated should be taken into account when deciding to use 
Cubicin.

In a randomised controlled open-label study in 235 adult patients with Staphylococcus aureus
bacteraemia (i.e. at least one positive blood culture of Staphylococcus aureus prior to receiving the 
first dose) 19 of 120 patients treated with Cubicin met the criteria for RIE. Of these 19 patients 11
were infected with methicillin-susceptible and 8 with methicillin-resistant Staphylococcus aureus. 
The success rates in RIE patients are shown in the table below.

Population Daptomycin Comparator
Differences in 

Success
n/N (%) n/N (%) Rates (95 % CI)

ITT (intention to treat) Population

RIE 8/19 (42.1 %) 7/16 (43.8 %) -1.6 % (-34.6, 31.3)

PP (per protocol) Population

RIE 6/12 (50.0 %) 4/8 (50.0 %) 0.0 % (-44.7, 44.7)

Failure of treatment due to persisting or relapsing Staphylococcus aureus infections was observed in 
19/120 (15.8 %) patients treated with Cubicin, 9/53 (16.7 %) patients treated with vancomycin and 
2/62 (3.2 %) patients treated with an anti-staphylococcal semi-synthetic penicillin. Among these 
failures six patients treated with Cubicin and one patient treated with vancomycin were infected with 
Staphylococcus aureus that developed increasing MICs of daptomycin on or following therapy (see 
“Mechanisms of resistance” above). Most patients who failed due to persisting or relapsing 

 



13

Staphylococcus aureus infection had deep-seated infection and did not receive necessary surgical 
intervention.

Clinical efficacy in paediatric patients
The safety and efficacy of daptomycin was evaluated in paediatric patients aged 1 to 17 years (Study 
DAP-PEDS-07-03) with cSSTI caused by Gram positive pathogens. Patients were enrolled in a 
stepwise approach into well-defined age groups and given age-dependent doses once daily for up to 
14 days, as follows:
• Age group 1 (n=113): 12 to 17 years treated with daptomycin dosed at 5 mg/kg or standard-of-

care comparator (SOC);
• Age group 2 (n=113): 7 to 11 years treated with daptomycin dosed at 7 mg/kg or SOC;
• Age group 3 (n=125): 2 to 6 years treated with daptomycin dosed at 9 mg/kg or SOC;
• Age group 4 (n=45): 1 to < 2 years treated with daptomycin dosed at 10 mg/kg or SOC.

The primary objective of Study DAP-PEDS-07-03 was to assess the safety of treatment. Secondary 
objectives included an assessment of efficacy of age-dependent doses of intravenous daptomycin in 
comparison with standard-of-care therapy. The key efficacy endpoint was the sponsor-defined clinical 
outcome at test-of-cure (TOC), which was defined by a blinded medical director. A total of 
389 subjects were treated in the study, including 256 subjects who received daptomycin and 
133 subjects who received standard-of-care. In all populations the clinical success rates were 
comparable between the daptomycin and SOC treatment arms, supporting the primary efficacy 
analysis in the ITT population.

Summary of sponsor-defined clinical outcome at TOC:

Clinical Success in Paediatric cSSTI
Daptomycin

n/N (%)
Comparator

n/N (%) % difference

Intent-to-treat 227/257 (88.3 %) 114/132 (86.4 %) 2.0

Modified intent-to-treat 186/210 (88.6 %) 92/105 (87.6 %) 0.9

Clinically evaluable 204/207 (98.6 %) 99/99 (100 %) -1.5

Microbiologically evaluable (ME) 164/167 (98.2 %) 78/78 (100 %) -1.8

The overall therapeutic response rate also was similar for the daptomycin and SOC treatment arms for 
infections caused by MRSA, MSSA and Streptococcus pyogenes (see table below; ME population); 
response rates were > 94 % for both treatment arms across these common pathogens.

Summary of overall therapeutic response by type of baseline pathogen (ME population):

Pathogen
Overall Successa rate in Paediatric cSSTI

n/N (%)
Daptomycin Comparator

Methicillin-susceptible Staphylococcus aureus 
(MSSA)

68/69 (99 %) 28/29 (97 %)

Methicillin-resistant Staphylococcus aureus (MRSA) 63/66 (96 %) 34/34 (100 %)
Streptococcus pyogenes 17/18 (94 %) 5/5 (100 %)
a Subjects achieving clinical success (Clinical Response of “Cure” or “Improved”) and 
microbiological success (pathogen–level response of “Eradicated” or “Presumed Eradicated”) are
classified as overall therapeutic success.

 



14

The safety and efficacy of daptomycin was evaluated in paediatric patients aged 1 to 17 years (Study 
DAP-PEDBAC-11-02) with bacteraemia caused by Staphylococcus aureus. Patients were randomised 
in a 2:1 ratio into the following age groups and given age-dependent doses once daily for up to 
42 days, as follows:

• Age group 1 (n=21): 12 to 17 years treated with daptomycin dosed at 7 mg/kg or SOC
comparator;

• Age group 2 (n=28): 7 to 11 years treated with daptomycin dosed at 9 mg/kg or SOC;
• Age group 3 (n=32): 1 to 6 years treated with daptomycin dosed at 12 mg/kg or SOC;

The primary objective of Study DAP-PEDBAC-11-02 was to assess the safety of intravenous 
daptomycin versus SOC antibiotics. Secondary objectives included: Clinical outcome based on the 
blinded Evaluator’s assessment of clinical response (success [cure, improved], failure, or non-
evaluable) at the TOC Visit; and Microbiological response (success, failure, or non-evaluable) based 
on evaluation of Baseline infecting pathogen at TOC.

A total of 81 subjects were treated in the study, including 55 subjects who received daptomycin and 
26 subjects who received standard-of-care. No patients 1 to <2 years of age were enrolled in the study. 
In all populations the clinical success rates were comparable in the daptomycin versus the SOC 
treatment arm.

Summary of Blinded Evaluator defined clinical outcome at TOC:

Clinical Success in Paediatric SAB
Daptomycin

n/N (%)
Comparator

n/N (%) % difference

Modified intent-to-treat (MITT) 46/52 (88.5 %) 19/24 (79.2 %) 9.3 %

Microbiologically modified 
intent-to-treat (mMITT) 45/51 (88.2 %) 17/22 (77.3 %) 11.0 %

Clinically evaluable (CE) 36/40 (90.0 %) 9/12 (75.0 %) 15.0 %

The microbiological outcome at TOC for the daptomycin and SOC treatment arms for infections 
caused by MRSA and MSSA are presented in the table below (mMITT population).

Pathogen

Microbiological Success rate in 
Paediatric SAB

n/N (%)
Daptomycin Comparator

Methicillin-susceptible Staphylococcus aureus 
(MSSA)

43/44 (97.7 %) 19/19 (100.0 %)

Methicillin-resistant Staphylococcus aureus (MRSA) 6/7 (85.7 %) 3/3 (100.0 %)

5.2 Pharmacokinetic properties

Daptomycin pharmacokinetics are generally linear and time-independent at doses of 4 to 12 mg/kg 
administered as a single daily dose by 30-minute intravenous infusion for up to 14 days in healthy 
adult volunteers. Steady-state concentrations are achieved by the third daily dose.

Daptomycin administered as a 2-minute intravenous injection also exhibited dose proportional 
pharmacokinetics in the approved therapeutic dose range of 4 to 6 mg/kg. Comparable exposure 
(AUC and Cmax) was demonstrated in healthy adult subjects following administration of daptomycin 
as a 30-minute intravenous infusion or as a 2-minute intravenous injection.

Animal studies showed that daptomycin is not absorbed to any significant extent after oral 

 



15

administration.

Distribution
The volume of distribution at steady state of daptomycin in healthy adult subjects was approximately 
0.1 l/kg and was independent of dose. Tissue distribution studies in rats showed that daptomycin 
appears to only minimally penetrate the blood-brain barrier and the placental barrier following single 
and multiple doses.

Daptomycin is reversibly bound to human plasma proteins in a concentration independent manner. In
healthy adult volunteers and adult patients treated with daptomycin, protein binding averaged about 
90 % including subjects with renal impairment.

Biotransformation
In in vitro studies, daptomycin was not metabolised by human liver microsomes. In vitro studies with 
human hepatocytes indicate that daptomycin does not inhibit or induce the activities of the following 
human cytochrome P450 isoforms: 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A4. It is unlikely that 
daptomycin will inhibit or induce the metabolism of medicinal products metabolised by the P450 
system.

After infusion of 14C-daptomycin in healthy adults, the plasma radioactivity was similar to the 
concentration determined by microbiological assay. Inactive metabolites were detected in urine, as 
determined by the difference in total radioactive concentrations and microbiologically active 
concentrations. In a separate study, no metabolites were observed in plasma, and minor amounts of 
three oxidative metabolites and one unidentified compound were detected in urine. The site of 
metabolism has not been identified.

Elimination
Daptomycin is excreted primarily by the kidneys. Concomitant administration of probenecid and 
daptomycin has no effect on daptomycin pharmacokinetics in humans suggesting minimal to no active 
tubular secretion of daptomycin.

Following intravenous administration, plasma clearance of daptomycin is approximately 7 to 
9 ml/hr/kg and its renal clearance is 4 to 7 ml/hr/kg.

In a mass balance study using radiolabelled material, 78 % of the administered dose was recovered 
from the urine based on total radioactivity, whilst urinary recovery of unchanged daptomycin was 
approximately 50 % of the dose. About 5 % of the administered radiolabel was excreted in the faeces.

Special populations

Elderly
Following administration of a single 4 mg/kg intravenous dose of Cubicin over a 30-minute period, 
the mean total clearance of daptomycin was approximately 35 % lower and the mean AUC0-∞ was
approximately 58 % higher in elderly subjects (≥ 75 years of age) compared with those in healthy 
young subjects (18 to 30 years of age). There were no differences in Cmax. The differences noted are 
most likely due to the normal reduction in renal function observed in the geriatric population.

No dose adjustment is necessary based on age alone. However, renal function should be assessed and 
the dose should be reduced if there is evidence of severe renal impairment.

Children and adolescents (1 to 17 years of age)
The pharmacokinetics of daptomycin in paediatric subjects was evaluated in 3 single-dose 
pharmacokinetic studies. After a single 4 mg/kg dose of Cubicin, total clearance normalised by weight 
and elimination half-life of daptomycin in adolescents (12-17 years of age) with Gram-positive 
infection were similar to adults. After a single 4 mg/kg dose of Cubicin, total clearance of daptomycin 
in children 7-11 years of age with Gram-positive infection was higher than in adolescents, whereas 

 



16

elimination half-life was shorter. After a single 4, 8, or 10 mg/kg dose of Cubicin, total clearance and 
elimination half-life of daptomycin in children 2-6 years of age were similar at different doses; total 
clearance was higher and elimination half-life was shorter than in adolescents. After a single 6 mg/kg 
dose of Cubicin, the clearance and elimination half-life of daptomycin in children 13-24 months of 
age were similar to children 2-6 years of age who received a single 4-10 mg/kg dose. The results of
these studies show that exposures (AUC) in paediatric patients across all doses are generally lower 
than those in adults at comparable doses.

Paediatric patients with cSSTI
A Phase 4 study (DAP-PEDS-07-03) was conducted to assess safety, efficacy, and pharmacokinetics 
of daptomycin in paediatric patients (1 to 17 years old, inclusive) with cSSTI caused by Gram-
positive pathogens. Daptomycin pharmacokinetics in patients in this study are summarised in Table 2.
Following administration of multiple doses, daptomycin exposure was similar across different age 
groups after dose adjustment based on body weight and age. Plasma exposures achieved with these 
doses were consistent with those achieved in the adult cSSTI study (following 4 mg/kg once daily in 
adults).

Table 2 Mean (Standard Deviation) of Daptomycin Pharmacokinetics in Paediatric cSSTI 
Patients (1 to 17 Years of Age) in Study DAP-PEDS-07-03

Age Range 12-17 years (N=6) 7-11 years (N=2)a 2-6 years (N=7)
1 to <2 years 

(N=30)b

Dose
Infusion Time

5 mg/kg
30 minutes

7 mg/kg
30 minutes

9 mg/kg
60 minutes

10 mg/kg
60 minutes

AUC0-24hr 
(g×hr/ml)

387 (81) 438 439 (102) 466

Cmax (g/ml) 62.4 (10.4) 64.9, 74.4 81.9 (21.6) 79.2
Apparent t1/2 (hr) 5.3 (1.6) 4.6 3.8 (0.3) 5.04
CL/wt (ml/hr/kg) 13.3 (2.9) 16.0 21.4 (5.0) 21.5

Pharmacokinetic parameter values estimated by noncompartmental analysis
aIndividual values reported as only two patients in this age group provided pharmacokinetic samples to enable 
pharmacokinetic analysis; AUC, apparent t1/2 and CL/wt could be determined for only one of the two patients
bPharmacokinetic analysis conducted on the pooled pharmacokinetic profile with mean concentrations across subjects at each 
time point

Paediatric patients with SAB
A Phase 4 study (DAP-PEDBAC-11-02) was conducted to assess safety, efficacy, and 
pharmacokinetics of daptomycin in paediatric patients (1 to 17 years old, inclusive) with SAB. 
Daptomycin pharmacokinetics inpatients in this study are summarised in Table 3. Following 
administration of multiple doses, daptomycin exposure was similar across different age groups after 
dose adjustment based on body weight and age. Plasma exposures achieved with these doses were 
consistent with those achieved in the adult SAB study (following 6 mg/kg once daily in adults).

Table 3 Mean (Standard Deviation) of Daptomycin Pharmacokinetics in Paediatric SAB 
Patients (1 to 17 Years of Age) in Study DAP-PEDBAC-11-02

Age Range 12-17 years (N=13) 7-11 years (N=19) 1 to 6 years (N=19)*
Dose

Infusion Time
7 mg/kg

30 minutes
9 mg/kg

30 minutes
12 mg/kg

60 minutes
AUC0-24hr 
(g×hr/ml)

656 (334) 579 (116) 620 (109)

Cmax (g/ml) 104 (35.5) 104 (14.5) 106 (12.8)
Apparent t1/2 (hr) 7.5 (2.3) 6.0 (0.8) 5.1 (0.6)
CL/wt (ml/hr/kg) 12.4 (3.9) 15.9 (2.8) 19.9 (3.4)

Pharmacokinetic parameter values estimated using a model-based approach with sparsely collected pharmacokinetic samples 
from individual patients in the study.
*Mean (Standard Deviation) calculated for patients 2 to 6 years of age, since no patients 1 to <2 years of age were enrolled in
the study. Simulation using a population pharmacokinetic model demonstrated that the AUCss (area under the concentration-
time curve at steady state) of daptomycin in paediatric patients 1 to <2 years of age receiving 12 mg/kg once daily would be 

 



17

comparable to that in adult patients receiving 6 mg/kg once daily.

Obesity
Relative to non-obese subjects daptomycin systemic exposure measured by AUC was about 28 % 
higher in moderately obese subjects (Body Mass Index of 25-40 kg/m2) and 42 % higher in extremely
obese subjects (Body Mass Index of > 40 kg/m2). However, no dose adjustment is considered to be 
necessary based on obesity alone.

Gender
No clinically significant gender-related differences in daptomycin pharmacokinetics have been 
observed.

Renal impairment
Following administration of a single 4 mg/kg or 6 mg/kg intravenous dose of daptomycin over a 
30-minute period to adult subjects with various degrees of renal impairment, total daptomycin 
clearance (CL) decreased and systemic exposure (AUC) increased as renal function (creatinine 
clearance) decreased.

Based on pharmacokinetic data and modelling, the daptomycin AUC during the first day after 
administration of a 6 mg/kg dose to adult patients on HD or CAPD was 2-fold higher than that 
observed in adult patients with normal renal function who received the same dose. On the second day 
after administration of a 6 mg/kg dose to HD and CAPD adult patients the daptomycin AUC was 
approximately 1.3-fold higher than that observed after a second 6 mg/kg dose in adult patients with 
normal renal function. On this basis, it is recommended that adult patients on HD or CAPD receive 
daptomycin once every 48 hours at the dose recommended for the type of infection being treated (see 
section 4.2).

The dosage regimen for Cubicin in paediatric patients with renal impairment has not been established.

Hepatic impairment
The pharmacokinetics of daptomycin is not altered in subjects with moderate hepatic impairment
(Child-Pugh B classification of hepatic impairment) compared with healthy volunteers matched for 
gender, age and weight following a single 4 mg/kg dose. No dosage adjustment is necessary when 
administering daptomycin in patients with moderate hepatic impairment. The pharmacokinetics of 
daptomycin in patients with severe hepatic impairment (Child-Pugh C classification) have not been 
evaluated.

5.3 Preclinical safety data

Daptomycin administration was associated with minimal to mild degenerative/regenerative changes in 
skeletal muscle in the rat and dog. Microscopic changes in skeletal muscle were minimal 
(approximately 0.05 % of myofibres affected) and at the higher doses were accompanied by 
elevations in CPK. No fibrosis or rhabdomyolysis was observed. Depending on the study duration, all 
muscle effects, including microscopic changes, were fully reversible within 1-3 months following 
cessation of dosing. No functional or pathological changes in smooth or cardiac muscle were 
observed.

The lowest observable effect level (LOEL) for myopathy in rats and dogs occurred at exposure levels 
of 0.8 to 2.3-fold the human therapeutic levels at 6 mg/kg (30-minute intravenous infusion) for 
patients with normal renal function. As the pharmacokinetics (see section 5.2) is comparable, the 
safety margins for both methods of administration are very similar.

A study in dogs demonstrated that skeletal myopathy was reduced upon once daily administration as 
compared to fractionated dosing at same total daily dose, suggesting that myopathic effects in animals 
were primarily related to time between doses.

 



18

Effects on peripheral nerves were observed at higher doses than those associated with skeletal muscle 
effects in adult rats and dogs, and were primarily related to plasma Cmax. Peripheral nerve changes 
were characterised by minimal to slight axonal degeneration and were frequently accompanied by 
functional changes. Reversal of both the microscopic and functional effects was complete within 
6 months post-dose. Safety margins for peripheral nerve effects in rats and dogs are 8- and 6-fold, 
respectively, based on comparison of Cmax values at the No Observed Effect Level (NOEL) with the 
Cmax achieved on dosing with 30-minute intravenous infusion of 6 mg/kg once daily in patients with 
normal renal function.

The findings of in vitro and some in vivo studies designed to investigate the mechanism of 
daptomycin myotoxicity indicate that the plasma membrane of differentiated spontaneously 
contracting muscle cells is the target of toxicity. The specific cell surface component directly targeted 
has not been identified. Mitochondrial loss/damage was also observed; however the role and 
significance of this finding in the overall pathology are unknown. This finding was not associated 
with an effect on muscle contraction.

In contrast to adult dogs, juvenile dogs appeared to be more sensitive to peripheral nerve lesions as 
compared to skeletal myopathy. Juvenile dogs developed peripheral and spinal nerve lesions at doses 
lower than those associated with skeletal muscle toxicity.

In neonatal dogs, daptomycin caused marked clinical signs of twitching, muscle rigidity in the limbs, 
and impaired use of limbs, which resulted in decreases in body weight and overall body condition at 
doses ≥ 50 mg/kg/day and necessitated early discontinuation of treatment in these dose groups. At 
lower dose levels (25 mg/kg/day), mild and reversible clinical signs of twitching and one incidence of 
muscle rigidity were observed without any effects on body weight. There was no histopathological 
correlation in the peripheral and central nervous system tissue, or in the skeletal muscle, at any dose 
level, and the mechanism and clinical relevance for the adverse clinical signs are therefore unknown.

Reproductive toxicity testing showed no evidence of effects on fertility, embryofoetal, or postnatal 
development. However, daptomycin can cross the placenta in pregnant rats (see section 5.2). 
Excretion of daptomycin into milk of lactating animals has not been studied.

Long-term carcinogenicity studies in rodents were not conducted. Daptomycin was not mutagenic or 
clastogenic in a battery of in vivo and in vitro genotoxicity tests.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium hydroxide

6.2 Incompatibilities

Cubicin is not physically or chemically compatible with glucose-containing solutions. This medicinal 
product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3 Shelf life

3 years

After reconstitution: Chemical and physical in-use stability of the reconstituted solution in the vial has 
been demonstrated for 12 hours at 25 °C and up to 48 hours at 2 °C – 8 °C. Chemical and physical 
stability of the diluted solution in infusion bags is established as 12 hours at 25 °C or 24 hours at 2 °C
– 8 °C.

 



19

For the 30-minute intravenous infusion, the combined storage time (reconstituted solution in vial and 
diluted solution in infusion bag; see section 6.6) at 25 °C must not exceed 12 hours (or 24 at 2 °C –
8 °C).

For the 2-minute intravenous injection, the storage time of the reconstituted solution in the vial (see 
section 6.6) at 25 °C must not exceed 12 hours (or 48 at 2 °C – 8 °C).

However, from a microbiological point of view the product should be used immediately. No 
preservative or bacteriostatic agent is present in this product. If not used immediately, in-use storage 
times are the responsibility of the user and would not normally be longer than 24 hours at 2 °C – 8 °C, 
unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

6.4 Special precautions for storage

Store in a refrigerator (2 °C – 8 °C).
For storage conditions after reconstitution and after reconstitution and dilution of the medicinal 
product see section 6.3.

6.5 Nature and contents of container

Cubicin 350 mg powder for solution for injection or infusion 
Single use 10 ml type I clear glass vials with type I rubber stoppers and aluminium closures with 
yellow plastic flip off caps.

Cubicin 500 mg powder for solution for injection or infusion 
Single use 10 ml type I clear glass vials with type I rubber stoppers and aluminium closures with blue 
plastic flip off caps.

Available in packs containing 1 vial or 5 vials. Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

In adults, daptomycin may be administered intravenously as an infusion over 30 minutes or as an 
injection over 2 minutes. Daptomycin should not be administered as a 2-minute injection to paediatric 
patients. Paediatric patients 7 to 17 years old should receive daptomycin infused over 30 minutes. In 
paediatric patients under 7 years old receiving a 9-12 mg/kg dose, daptomycin should be administered 
over 60 minutes (see sections 4.2 and 5.2). Preparation of the solution for infusion requires an 
additional dilution step as detailed below.

Cubicin given as 30 or 60-minute intravenous infusion
A 50 mg/ml concentration of Cubicin 350 mg powder for infusion is obtained by reconstituting the 
lyophilised product with 7 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection.

A 50 mg/ml concentration of Cubicin 500 mg powder for infusion is obtained by reconstituting the 
lyophilised product with 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection.

The lyophilised product takes approximately 15 minutes to dissolve. The fully reconstituted product 
will appear clear and may have a few small bubbles or foam around the edge of the vial.

Cubicin 350 mg powder for solution for injection or infusion 
To prepare Cubicin for intravenous infusion, please adhere to the following instructions:
Aseptic technique should be used throughout to reconstitute or dilute lyophilised Cubicin.
For Reconstitution:
1. The polypropylene flip off cap should be removed to expose the central portions of the rubber 

stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution 
and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other 

 



20

surface. Draw 7 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection into a syringe
using a sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device, 
then slowly inject through the centre of the rubber stopper into the vial pointing the needle 
towards the wall of the vial.

2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to 
stand for 10 minutes.

3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear 
reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the 
product.

4. The reconstituted solution should be checked carefully to ensure that the product is in solution 
and visually inspected for the absence of particulates prior to use. Reconstituted solutions of 
Cubicin range in colour from pale yellow to light brown.

5. The reconstituted solution should then be diluted with sodium chloride 9 mg/ml (0.9 %)
(typical volume 50 ml).

For Dilution:
1. Slowly remove the appropriate reconstituted liquid (50 mg daptomycin/ml) from the vial using 

a new sterile needle that is 21 gauge or smaller in diameter by inverting the vial in order to 
allow the solution to drain towards the stopper. Using a syringe, insert the needle into the 
inverted vial. Keeping the vial inverted, position the needle tip at the very bottom of the 
solution in the vial when drawing the solution into the syringe. Before removing the needle 
from the vial, pull the plunger all the way back to the end of the syringe barrel in order to 
remove the required solution from the inverted vial.

2. Expel air, large bubbles, and any excess solution in order to obtain the required dose.
3. Transfer the required reconstituted dose into 50 ml sodium chloride 9 mg/ml (0.9 %).
4. The reconstituted and diluted solution should then be infused intravenously over 30 or 

60 minutes as directed in section 4.2.

Cubicin 500 mg powder for solution for injection or infusion
To prepare Cubicin for intravenous infusion, please adhere to the following instructions:
Aseptic technique should be used throughout to reconstitute or dilute lyophilised Cubicin.
For Reconstitution:
1. The polypropylene flip off cap should be removed to expose the central portions of the rubber 

stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution 
and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other 
surface. Draw 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection into a syringe
using a sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device, 
then slowly inject through the centre of the rubber stopper into the vial pointing the needle 
towards the wall of the vial.

2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to 
stand for 10 minutes.

3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear 
reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the 
product.

4. The reconstituted solution should be checked carefully to ensure that the product is in solution 
and visually inspected for the absence of particulates prior to use. Reconstituted solutions of 
Cubicin range in colour from pale yellow to light brown.

5. The reconstituted solution should then be diluted with sodium chloride 9 mg/ml (0.9 %)
(typical volume 50 ml).

For Dilution:
1. Slowly remove the appropriate reconstituted liquid (50 mg daptomycin/ml) from the vial using 

a new sterile needle that is 21 gauge or smaller in diameter by inverting the vial in order to 
allow the solution to drain towards the stopper. Using a syringe, insert the needle into the 
inverted vial. Keeping the vial inverted, position the needle tip at the very bottom of the 
solution in the vial when drawing the solution into the syringe. Before removing the needle 
from the vial, pull the plunger all the way back to the end of the syringe barrel in order to 
remove the required solution from the inverted vial.

 



21

2. Expel air, large bubbles, and any excess solution in order to obtain the required dose.
3. Transfer the required reconstituted dose into 50 ml sodium chloride 9 mg/ml (0.9 %).
4. The reconstituted and diluted solution should then be infused intravenously over 30 or 

60 minutes as directed in section 4.2.

The following have been shown to be compatible when added to Cubicin containing infusion 
solutions: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, 
heparin and lidocaine.

Cubicin given as 2-minute intravenous injection (adult patients only)
Water should not be used for reconstitution of Cubicin for intravenous injection. Cubicin should only 
be reconstituted with sodium chloride 9 mg/ml (0.9 %).

A 50 mg/ml concentration of Cubicin 350 mg powder for injection is obtained by reconstituting the 
lyophilised product with 7 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection.

A 50 mg/ml concentration of Cubicin 500 mg powder for injection is obtained by reconstituting the
lyophilised product with 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection.

The lyophilised product takes approximately 15 minutes to dissolve. The fully reconstituted product 
will appear clear and may have a few small bubbles or foam around the edge of the vial.

Cubicin 350 mg powder for solution for injection or infusion
To prepare Cubicin for intravenous injection, please adhere to the following instructions:
Aseptic technique should be used throughout to reconstitute lyophilised Cubicin.
1. The polypropylene flip off cap should be removed to expose the central portions of the rubber 

stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution 
and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other 
surface. Draw 7 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection into a syringe
using a sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device, 
then slowly inject through the centre of the rubber stopper into the vial pointing the needle 
towards the wall of the vial.

2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to 
stand for 10 minutes.

3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear 
reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the 
product.

4. The reconstituted solution should be checked carefully to ensure that the product is in solution
and visually inspected for the absence of particulates prior to use. Reconstituted solutions of 
Cubicin range in colour from pale yellow to light brown.

5. Slowly remove the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile 
needle that is 21 gauge or smaller in diameter.

6. Invert the vial in order to allow the solution to drain towards the stopper. Using a new syringe, 
insert the needle into the inverted vial. Keeping the vial inverted, position the needle tip at the 
very bottom of the solution in the vial when drawing the solution into the syringe. Before 
removing the needle from the vial, pull the plunger all the way back to the end of the syringe 
barrel in order to remove all of the solution from the inverted vial.

7. Replace needle with a new needle for the intravenous injection.
8. Expel air, large bubbles, and any excess solution in order to obtain the required dose.
9. The reconstituted solution should then be injected intravenously slowly over 2 minutes as 

directed in section 4.2.

Cubicin 500 mg powder for solution for injection or infusion
To prepare Cubicin for intravenous injection, please adhere to the following instructions:
Aseptic technique should be used throughout to reconstitute lyophilised Cubicin.
1. The polypropylene flip off cap should be removed to expose the central portions of the rubber 

 



22

stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution 
and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other 
surface. Draw 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection into a syringe
using a sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device, 
then slowly inject through the centre of the rubber stopper into the vial pointing the needle 
towards the wall of the vial.

2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to 
stand for 10 minutes.

3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear 
reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the 
product.

4. The reconstituted solution should be checked carefully to ensure that the product is in solution 
and visually inspected for the absence of particulates prior to use. Reconstituted solutions of 
Cubicin range in colour from pale yellow to light brown.

5. Slowly remove the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile 
needle that is 21 gauge or smaller in diameter.

6. Invert the vial in order to allow the solution to drain towards the stopper. Using a new syringe, 
insert the needle into the inverted vial. Keeping the vial inverted, position the needle tip at the 
very bottom of the solution in the vial when drawing the solution into the syringe. Before 
removing the needle from the vial, pull the plunger all the way back to the end of the syringe 
barrel in order to remove all of the solution from the inverted vial.

7. Replace needle with a new needle for the intravenous injection.
8. Expel air, large bubbles, and any excess solution in order to obtain the required dose.
9. The reconstituted solution should then be injected intravenously slowly over 2 minutes as 

directed in section 4.2.

Cubicin vials are for single-use only.

From a microbiological point of view, the product should be used immediately after reconstitution 
(see section 6.3).

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

8. MARKETING AUTHORISATION NUMBER(S)

Cubicin 350 mg powder for solution for injection or infusion
EU/1/05/328/001
EU/1/05/328/003

Cubicin 500 mg powder for solution for injection or infusion 
EU/1/05/328/002
EU/1/05/328/004

 



23

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 19 January 2006
Date of latest renewal: 29 November 2010

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu

 



24

ANNEX II

A. MANUFACTURER 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

 



25

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release

Laboratoires Merck Sharp & Dohme Chibret 
Route de Marsat
Riom 
63963, Clermont Ferrand Cedex 9
France

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)
The requirements for submission of PSURs 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 marketing authorisation holder (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 agreed 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.

 



26

ANNEX III

LABELLING AND PACKAGE LEAFLET

 



27

A. LABELLING

 



28

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR 1 VIAL
CARTON FOR 5 VIALS

1. NAME OF THE MEDICINAL PRODUCT

Cubicin 350 mg powder for solution for injection or infusion
daptomycin

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each vial contains 350 mg daptomycin.
One ml provides 50 mg of daptomycin after reconstitution with 7 ml of sodium chloride 9 mg/ml 
(0.9 %) solution.

3. LIST OF EXCIPIENTS

Excipient: Sodium hydroxide

4. PHARMACEUTICAL FORM AND CONTENTS

1 vial
5 vials

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Intravenous use.
Read the package leaflet before use for directions on reconstitution.
When administration is by injection reconstitute with 0.9 % sodium chloride only.

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
Read the leaflet for the shelf life of the reconstituted product

 



29

9. SPECIAL STORAGE CONDITIONS

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

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

Dispose of in accordance with local requirements

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/05/328/001 1 vial
EU/1/05/328/003 5 vials

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 

 



30

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Cubicin 350 mg powder for solution for injection or infusion
daptomycin
IV

2. METHOD OF ADMINISTRATION

When used by injection, reconstitute with 0.9 % sodium chloride only.

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

350 mg

6. OTHER

 



31

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR 1 VIAL
CARTON FOR 5 VIALS

1. NAME OF THE MEDICINAL PRODUCT

Cubicin 500 mg powder for solution for injection or infusion
daptomycin

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each vial contains 500 mg daptomycin.
One ml provides 50 mg of daptomycin after reconstitution with 10 ml of sodium chloride 9 mg/ml 
(0.9 %) solution.

3. LIST OF EXCIPIENTS

Excipient: Sodium hydroxide

4. PHARMACEUTICAL FORM AND CONTENTS

1 vial
5 vials

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Intravenous use.
Read the package leaflet before use for directions on reconstitution.
When administration is by injection reconstitute with 0.9 % sodium chloride only.

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
Read the leaflet for the shelf life of the reconstituted product

 



32

9. SPECIAL STORAGE CONDITIONS

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

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

Dispose of in accordance with local requirements

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/05/328/002 1 vial
EU/1/05/328/004 5 vials

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

 



33

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Cubicin 500 mg powder for solution for injection or infusion
daptomycin
IV

2. METHOD OF ADMINISTRATION

When used by injection, reconstitute with 0.9 % sodium chloride only.

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

500 mg

6. OTHER

 



34

B. PACKAGE LEAFLET

 



35

Package leaflet: Information for the patient

Cubicin 350 mg powder for solution for injection or infusion
daptomycin

Read all of this leaflet carefully before you start using 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 or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4.

What is in this leaflet
1. What Cubicin is and what it is used for
2. What you need to know before you are given Cubicin
3. How Cubicin is given
4. Possible side effects
5. How to store Cubicin
6. Contents of the pack and other information

1. What Cubicin is and what it is used for

The active substance in Cubicin powder for solution for injection or infusion is daptomycin. 
Daptomycin is an antibacterial that can stop the growth of certain bacteria. Cubicin is used in adults
and in children and adolescents (age from 1 to 17 years) to treat infections of the skin and the tissues 
below the skin. It is also used to treat infections in the blood when associated with skin infection.

Cubicin is also used in adults to treat infections in the tissues that line the inside of the heart 
(including heart valves) which are caused by a type of bacteria called Staphylococcus aureus. It is also
used to treat infections in the blood caused by the same type of bacteria when associated with heart 
infection.

Depending on the type of infection(s) that you have, your doctor may also prescribe other 
antibacterials while you are receiving treatment with Cubicin.

2. What you need to know before you are given Cubicin

You should not be given Cubicin
If you are allergic to daptomycin or to sodium hydroxide or to any of the other ingredients of this 
medicine (listed in section 6).
If this applies to you, tell your doctor or nurse. If you think you may be allergic, ask your doctor or 
nurse for advice.

Warnings and precautions
Talk to your doctor or nurse before you are given Cubicin:
- If you have, or have previously had kidney problems. Your doctor may need to change the dose 

of Cubicin (see section 3 of this leaflet).
- Occasionally, patients receiving Cubicin may develop tender or aching muscles or muscle 

weakness (see section 4 of this leaflet for more information). If this happens tell your doctor. 
Your doctor will make sure you have a blood test and will advise whether or not to continue 
with Cubicin. The symptoms generally go away within a few days of stopping Cubicin.

 



36

- If you have ever developed a severe skin rash or skin peeling, blistering and/or mouth sores, or 
serious kidney problems after taking daptomycin.

- If you are very overweight. There is a possibility that your blood levels of Cubicin could be 
higher than those found in persons of average weight and you may need careful monitoring in 
case of side effects.

If any of these applies to you, tell your doctor or nurse before you are given Cubicin.

Tell your doctor or nurse straight away if you develop any of the following symptoms:
- Serious, acute allergic reactions have been observed in patients treated with nearly all 

antibacterial agents, including Cubicin. The symptoms can include wheezing, difficulty 
breathing, swelling of the face, neck and throat, rashes and hives, or fever.

- Serious skin disorders have been reported with the use of Cubicin. The symptoms that occur
with these skin disorders can include:
- a new or worsening fever,
- red raised or fluid-filled skin spots which may start in your armpits or on your chest or 

groin areas and which can spread over a large area of your body,
- blisters or sores in your mouth or on your genitals.

- A serious kidney problem has been reported with the use of Cubicin. The symptoms can include 
fever and rash.

- Any unusual tingling or numbness of the hands or feet, loss of feeling or difficulties with 
movements. If this happens, tell your doctor who will decide whether you should continue the 
treatment.

- Diarrhoea, especially if you notice blood or mucus, or if diarrhoea becomes severe or 
persistent.

- New or worsening fever, cough or difficulty breathing. These may be signs of a rare but serious 
lung disorder called eosinophilic pneumonia. Your doctor will check the condition of your 
lungs and decide whether or not you should continue Cubicin treatment.

Cubicin may interfere with laboratory tests that measure how well your blood is clotting. The results 
can suggest poor blood clotting when, in fact, there is no problem. Therefore, it is important that your 
doctor takes into account that you are receiving Cubicin. Please inform your doctor that you are on 
treatment with Cubicin.

Your doctor will perform blood tests to monitor the health of your muscles both before you start 
treatment and frequently during treatment with Cubicin.

Children and adolescents
Cubicin should not be administered to children below one year of age as studies in animals have 
indicated that this age group may experience severe side effects.

Use in elderly
People over the age of 65 can be given the same dose as other adults, provided their kidneys are 
working well.

Other medicines and Cubicin
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines.
It is particularly important that you mention the following:

- Medicines called statins or fibrates (to lower cholesterol) or ciclosporin (a medicinal product 
used in transplantation to prevent organ rejection or for other conditions, e.g. rheumatoid 
arthritis or atopic dermatitis). It is possible that the risk of side effects affecting the muscles 
may be higher when any of these medicines (and some others that can affect muscles) is taken 
during treatment with Cubicin. Your doctor may decide not to give you Cubicin or to stop the 
other medicine for a while.

- Pain killing medicines called non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 
inhibitors (e.g. celecoxib). These could interfere with the effects of Cubicin in the kidney.

 



37

- Oral anti-coagulants (e.g. warfarin), which are medicines that prevent blood from clotting. It 
may be necessary for your doctor to monitor your blood clotting times.

Pregnancy and breast-feeding
Cubicin is not usually given to pregnant women. If you are pregnant or breast-feeding, think you may 
be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before you are 
given this medicine.

Do not breast-feed if you are receiving Cubicin, because it may pass into your breast milk and could 
affect the baby.

Driving and using machines
Cubicin has no known effects on the ability to drive or use machines.

Cubicin contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially
‘sodium-free’.

3. How Cubicin is given

Cubicin will usually be given to you by a doctor or a nurse.

Adults (18 years of age and above)
The dose will depend on how much you weigh and the type of infection being treated. The usual dose 
for adults is 4 mg for every kilogram (kg) of body weight once daily for skin infections or 6 mg for 
every kg of body weight once daily for a heart infection or a blood infection associated with skin or
heart infection. In adult patients, this dose is given directly into your blood stream (into a vein), either 
as an infusion lasting about 30 minutes or as an injection lasting about 2 minutes. The same dose is 
recommended in people aged over 65 years provided their kidneys are working well.
If your kidneys do not work well, you may receive Cubicin less often, e.g. once every other day. If 
you are receiving dialysis, and your next dose of Cubicin is due on a dialysis day, you will be usually 
given Cubicin after the dialysis session.

Children and adolescents (1 to 17 years of age)
The dose for children and adolescents (1 to 17 years of age) will depend on the age of patient and the 
type of infection being treated. This dose is given directly into the blood stream (into a vein), as an 
infusion lasting about 30-60 minutes.

A course of treatment usually lasts for 1 to 2 weeks for skin infections. For blood or heart infections 
and skin infections your doctor will decide how long you should be treated.

Detailed instructions for use and handling are given at the end of the leaflet.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The most serious side effects are described below:

Serious side effects with frequency not known (frequency cannot be estimated from the available 
data)
- A hypersensitivity reaction (serious allergic reaction including anaphylaxis and angioedema)

has been reported, in some cases during administration of Cubicin. This serious allergic 
reaction needs immediate medical attention. Tell your doctor or nurse straight away if you 

 



38

experience any of the following symptoms:
- Chest pain or tightness,
- Rash or hives,
- Swelling around throat,
- Rapid or weak pulse,
- Wheezing,
- Fever,
- Shivering or trembling,
- Hot flushes,
- Dizziness,
- Fainting,
- Metallic taste.

- Tell your doctor straight away if you experience unexplained muscle pain, tenderness, or 
weakness. Muscle problems can be serious, including muscle breakdown (rhabdomyolysis), 
which can result in kidney damage.

Other serious side effects that have been reported with the use of Cubicin are:
- A rare but potentially serious lung disorder called eosinophilic pneumonia, mostly after more 

than 2 weeks of treatment. The symptoms can include difficulty breathing, new or worsening 
cough, or new or worsening fever.

- Serious skin disorders. The symptoms can include:
- a new or worsening fever,
- red raised or fluid-filled skin spots which may start in your armpits or on your chest or 

groin areas and which can spread over a large area of your body,
- blisters or sores in your mouth or on your genitals.

- A serious kidney problem. The symptoms can include fever and rash.
If you experience these symptoms, tell your doctor or nurse straight away. Your doctor will perform 
additional tests to make a diagnosis.

The most frequently reported side effects are described below:

Common side effects (may affect up to 1 in 10 people)
- Fungal infections such as thrush,
- Urinary tract infection,
- Decreased number of red blood cells (anaemia),
- Dizziness, anxiety, difficulty in sleeping,
- Headache,
- Fever, weakness (asthenia),
- High or low blood pressure,
- Constipation, abdominal pain,
- Diarrhoea, feeling sick (nausea) or being sick (vomiting),
- Flatulence,
- Abdominal swelling or bloating,
- Skin rash or itching,
- Pain, itchiness or redness at the site of infusion,
- Pain in arms or legs,
- Blood testing showing higher levels of liver enzymes or creatine phosphokinase (CPK).

Other side effects which may occur following Cubicin treatment are described below:

Uncommon side effects (may affect up to 1 in 100 people)
- Blood disorders (e.g. increased number of small blood particles called platelets, which may 

increase the tendency for blood clotting, or higher levels of certain types of white blood cells),
- Decreased appetite,
- Tingling or numbness of the hands or feet, taste disturbance,
- Trembling,
- Changes in heart rhythm, flushes,

 



39

- Indigestion (dyspepsia), inflammation of the tongue,
- Itchy rash of skin,
- Muscle pain, cramping, or weakness, inflammation of the muscles (myositis), joint pain,
- Kidney problems,
- Inflammation and irritation of the vagina,
- General pain or weakness, tiredness (fatigue),
- Blood test showing increased levels of blood sugar, serum creatinine, myoglobin, or lactate

dehydrogenase (LDH), prolonged blood clotting time or imbalance of salts,
- Itchy eyes.

Rare side effects (may affect up to 1 in 1,000 people)
- Yellowing of the skin and eyes,
- Prothrombin time prolonged.

Frequency not known (frequency cannot be estimated from the available data)
Antibacterial-associated colitis, including pseudomembranous colitis (severe or persistent diarrhoea 
containing blood and/or mucus, associated with abdominal pain or fever), easy bruising, bleeding 
gums, or nosebleeds.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. 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 Cubicin

- 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 label after EXP. 

The expiry date refers to the last day of the month.
- Store in a refrigerator (2 °C – 8 °C).

6. Contents of the pack and other information

What Cubicin contains
- The active substance is daptomycin. One vial of powder contains 350 mg daptomycin.
- The other ingredient is sodium hydroxide.

What Cubicin looks like and contents of the pack
Cubicin powder for solution for injection or infusion is supplied as a pale yellow to light brown cake 
or powder in a glass vial. It is mixed with a solvent to form a liquid before it is administered.

Cubicin is available in packs containing 1 vial or 5 vials.

Marketing Authorisation Holder
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


40

Manufacturer
Laboratoires Merck Sharp & Dohme Chibret
Route de Marsat
Riom 
63963, Clermont Ferrand Cedex 9
France

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.

Belgique/België/Belgien
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel.: +370 5 278 02 47
msd_lietuva@merck.com

България 
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel.: +420 233 010 111
dpoc_czechslovak@merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +361 888 53 00
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: +45 4482 4000
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com

Deutschland
MSD SHARP & DOHME GMBH
Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)
e-mail@msd.de

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@ msd.no

Ελλάδα
MSD Α.Φ.Β.Ε.Ε.
Τηλ: +30 210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
msd_info@merck.com

Polska
MSD Polska Sp.z o.o.
Tel.: +48 22 549 51 00
msdpolska@merck.com

France
MSD France
Tél: + 33 (0) 1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

 



41

Hrvatska
Merck Sharp & Dohme d.o.o. 
Tel: + 385 1 6611 333
croatia_info@merck.com

România
Merck Sharp & Dohme Romania S.R.L.
Tel: +40 21 529 29 00
msdromania@merck.com

Ireland
Merck Sharp & Dohme Ireland (Human Health) 
Limited
Tel: +353 (0)1 299 8700
medinfo_ireland@merck.com

Slovenija
Merck Sharp & Dohme, inovativna zdravila d.o.o.
Tel: + 386 1 5204 201
msd_slovenia@merck.com

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel.: +421 2 58282010
dpoc_czechslovak@merck.com

Ιtalia
MSD Italia S.r.l.
Tel: +39 06 361911
medicalinformation.it@merck.com

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0) 9 804650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 800 00 673 (+357 22866700)
cyprus_info@merck.com 

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364224
msd_lv@merck.com.

United Kingdom
Merck Sharp & Dohme Limited
Tel: +44 (0) 1992 467272
medicalinformationuk@merck.com

This leaflet was last revised in <{MM/YYYY}><{month YYYY}>.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu

 



42

The following information is intended for healthcare professionals only

Important: Please refer to the Summary of Product Characteristics before prescribing.

Instructions for use and handling

350 mg presentation:

In adults, daptomycin may be administered intravenously as an infusion over 30 minutes or as an 
injection over 2 minutes. Unlike in adults, daptomycin should not be administered by injection over a 
2-minute period in paediatric patients. Paediatric patients 7 to 17 years old should receive daptomycin 
infused over 30 minutes. In paediatric patients under 7 years old receiving a 9-12 mg/kg dose, 
daptomycin should be administered over 60 minutes. Preparation of the solution for infusion requires 
an additional dilution step as detailed below.

Cubicin given as an intravenous infusion over 30 or 60 minutes

A 50 mg/ml concentration of Cubicin for infusion can be achieved by reconstituting the lyophilised 
product with 7 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection.

The lyophilised product takes approximately 15 minutes to dissolve. The fully reconstituted product 
will appear clear and may have a few small bubbles or foam around the edge of the vial.

To prepare Cubicin for intravenous infusion, please adhere to the following instructions:
Aseptic technique should be used throughout to reconstitute or dilute lyophilised Cubicin.
For Reconstitution:
1. The polypropylene flip off cap should be removed to expose the central portions of the rubber 

stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution 
and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other 
surface. Draw 7 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection into a syringe
using a sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device,
then slowly inject through the centre of the rubber stopper into the vial pointing the needle 
towards the wall of the vial.

2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to 
stand for 10 minutes.

3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear 
reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the 
product.

4. The reconstituted solution should be checked carefully to ensure that the product is in solution 
and visually inspected for the absence of particulates prior to use. Reconstituted solutions of 
Cubicin range in colour from pale yellow to light brown.

5. The reconstituted solution should then be diluted with sodium chloride 9 mg/ml (0.9 %) 
(typical volume 50 ml).

For Dilution:
1. Slowly remove the appropriate reconstituted liquid (50 mg daptomycin/ml) from the vial using 

a new sterile needle that is 21 gauge or smaller in diameter by inverting the vial in order to 
allow the solution to drain towards the stopper. Using a syringe, insert the needle into the 
inverted vial. Keeping the vial inverted, position the needle tip at the very bottom of the 
solution in the vial when drawing the solution into the syringe. Before removing the needle 
from the vial, pull the plunger all the way back to the end of the syringe barrel in order to 
remove the required solution from the inverted vial.

2. Expel air, large bubbles, and any excess solution in order to obtain the required dose.
3. Transfer the required reconstituted dose into 50 ml sodium chloride 9 mg/ml (0.9 %).
4. The reconstituted and diluted solution should then be infused intravenously over 30 or

60 minutes.

 



43

Cubicin is not physically or chemically compatible with glucose-containing solutions. The following 
have been shown to be compatible when added to Cubicin containing infusion solutions: aztreonam, 
ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin and lidocaine.

The combined storage time (reconstituted solution in vial and diluted solution in infusion bag) at 
25 °C must not exceed 12 hours (24 hours if refrigerated).

Stability of the diluted solution in infusion bags is established as 12 hours at 25 °C or 24 hours if 
stored under refrigeration at 2 °C – 8 °C.

Cubicin given as 2-minute intravenous injection (adult patients only)

Water should not be used for reconstitution of Cubicin for intravenous injection. Cubicin should only 
be reconstituted with sodium chloride 9 mg/ml (0.9 %).

A 50 mg/ml concentration of Cubicin for injection is obtained by reconstituting the lyophilised 
product with 7 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection.

The lyophilised product takes approximately 15 minutes to dissolve. The fully reconstituted product 
will appear clear and may have a few small bubbles or foam around the edge of the vial.

To prepare Cubicin for intravenous injection, please adhere to the following instructions:
Aseptic technique should be used throughout to reconstitute lyophilised Cubicin.
1. The polypropylene flip off cap should be removed to expose the central portions of the rubber 

stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution 
and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other 
surface. Draw 7 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection into a syringe
using a sterile transfer needle that is 21 gauge or smaller diameter, or a needleless device, then 
slowly inject through the centre of the rubber stopper into the vial pointing the needle towards 
the wall of the vial.

2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to 
stand for 10 minutes.

3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear 
reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the 
product.

4. The reconstituted solution should be checked carefully to ensure that the product is in solution 
and visually inspected for the absence of particulates prior to use. Reconstituted solutions of 
Cubicin range in colour from pale yellow to light brown.

5. Slowly remove the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile
needle that is 21 gauge or smaller in diameter.

6. Invert the vial in order to allow the solution to drain towards the stopper. Using a new syringe, 
insert the needle into the inverted vial. Keeping the vial inverted, position the needle tip at the 
very bottom of the solution in the vial when drawing the solution into the syringe. Before 
removing the needle from the vial, pull the plunger all the way back to the end of the syringe 
barrel in order to remove all of the solution from the inverted vial.

7. Replace needle with a new needle for the intravenous injection.
8. Expel air, large bubbles, and any excess solution in order to obtain the required dose.
9. The reconstituted solution should then be injected intravenously slowly over 2 minutes.

Chemical and physical in-use stability on the reconstituted solution in the vial has been demonstrated 
for 12 hours at 25 °C and up to 48 hours if stored under refrigeration (2 °C – 8 °C).

However, from a microbiological point of view the product should be used immediately. If not used 
immediately, in-use storage times are the responsibility of the user and would normally not be longer 
than 24 hours at 2 °C – 8 °C unless reconstitution /dilution has taken place in controlled and validated 

 



44

aseptic conditions.

This medicinal product must not be mixed with other medicinal products except those mentioned
above.

Cubicin vials are for single-use only. Any unused portion remaining in the vial should be discarded.

 



45

Package leaflet: Information for the patient

Cubicin 500 mg powder for solution for injection or infusion
daptomycin

Read all of this leaflet carefully before you start using 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 or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm 

them, even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4.

What is in this leaflet
1. What Cubicin is and what it is used for
2. What you need to know before you are given Cubicin
3. How Cubicin is given
4. Possible side effects
5. How to store Cubicin
6. Contents of the pack and other information

1. What Cubicin is and what it is used for

The active substance in Cubicin powder for solution for injection or infusion is daptomycin. 
Daptomycin is an antibacterial that can stop the growth of certain bacteria. Cubicin is used in adults
and in children and adolescents (age from 1 to 17 years) to treat infections of the skin and the tissues 
below the skin. It is also used to treat infections in the blood when associated with skin infection.

Cubicin is also used in adults to treat infections in the tissues that line the inside of the heart 
(including heart valves) which are caused by a type of bacteria called Staphylococcus aureus. It is also
used to treat infections in the blood caused by the same type of bacteria when associated with heart 
infection.
Depending on the type of infection(s) that you have, your doctor may also prescribe other 
antibacterials while you are receiving treatment with Cubicin.

2. What you need to know before you are given Cubicin

You should not be given Cubicin
If you are allergic to daptomycin or to sodium hydroxide or to any of the other ingredients of this 
medicine (listed in section 6).
If this applies to you, tell your doctor or nurse. If you think you may be allergic, ask your doctor or 
nurse for advice.

Warnings and precautions
Talk to your doctor or nurse before you are given Cubicin:

- If you have, or have previously had kidney problems. Your doctor may need to change the 
dose of Cubicin (see section 3 of this leaflet).

- Occasionally, patients receiving Cubicin may develop tender or aching muscles or muscle 
weakness (see section 4 of this leaflet for more information). If this happens tell your doctor. 
Your doctor will make sure you have a blood test and will advise whether or not to continue 
with Cubicin. The symptoms generally go away within a few days of stopping Cubicin.

 



46

- If you have ever developed a severe skin rash or skin peeling, blistering and/or mouth sores, or
serious kidney problems after taking daptomycin.

- If you are very overweight. There is a possibility that your blood levels of Cubicin could be 
higher than those found in persons of average weight and you may need careful monitoring in 
case of side effects.

If any of these applies to you, tell your doctor or nurse before you are given Cubicin.

Tell your doctor or nurse straight away if you develop any of the following symptoms:
- Serious, acute allergic reactions have been observed in patients treated with nearly all 

antibacterial agents, including Cubicin. The symptoms can include wheezing, difficulty 
breathing, swelling of the face, neck and throat, rashes and hives, or fever.

- Serious skin disorders have been reported with the use of Cubicin. The symptoms that occur
with these skin disorders can include:
- a new or worsening fever,
- red raised or fluid-filled skin spots which may start in your armpits or on your chest or 

groin areas and which can spread over a large area of your body,
- blisters or sores in your mouth or on your genitals.

- A serious kidney problem has been reported with the use of Cubicin. The symptoms can include 
fever and rash.

- Any unusual tingling or numbness of the hands or feet, loss of feeling or difficulties with 
movements. If this happens, tell your doctor who will decide whether you should continue the 
treatment.

- Diarrhoea, especially if you notice blood or mucus, or if diarrhoea becomes severe or 
persistent.

- New or worsening fever, cough or difficulty breathing. These may be signs of a rare but serious 
lung disorder called eosinophilic pneumonia. Your doctor will check the condition of your 
lungs and decide whether or not you should continue Cubicin treatment.

Cubicin may interfere with laboratory tests that measure how well your blood is clotting. The results 
can suggest poor blood clotting when, in fact, there is no problem. Therefore, it is important that your
doctor takes into account that you are receiving Cubicin. Please inform your doctor that you are on 
treatment with Cubicin.

Your doctor will perform blood tests to monitor the health of your muscles both before you start 
treatment and frequently during treatment with Cubicin.

Children and adolescents
Cubicin should not be administered to children below one year of age as studies in animals have 
indicated that this age group may experience severe side effects.

Use in elderly
People over the age of 65 can be given the same dose as other adults, provided their kidneys are 
working well.

Other medicines and Cubicin
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines.
It is particularly important that you mention the following:

- Medicines called statins or fibrates (to lower cholesterol) or ciclosporin (a medicinal product 
used in transplantation to prevent organ rejection or for other conditions, e.g. rheumatoid
arthritis or atopic dermatitis). It is possible that the risk of side effects affecting the muscles 
may be higher when any of these medicines (and some others that can affect muscles) is taken 
during treatment with Cubicin. Your doctor may decide not to give you Cubicin or to stop the 
other medicine for a while.

- Pain killing medicines called non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 
inhibitors (e.g. celecoxib). These could interfere with the effects of Cubicin in the kidney.

- Oral anti-coagulants (e.g. warfarin), which are medicines that prevent blood from clotting. It

 



47

may be necessary for your doctor to monitor your blood clotting times.

Pregnancy and breast-feeding
Cubicin is not usually given to pregnant women. If you are pregnant or breast-feeding, think you may 
be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before you are 
given this medicine.

Do not breast-feed if you are receiving Cubicin, because it may pass into your breast milk and could 
affect the baby.

Driving and using machines
Cubicin has no known effects on the ability to drive or use machines.

Cubicin contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’.

3. How Cubicin is given

Cubicin will usually be given to you by a doctor or a nurse.

Adults (18 years of age and above)
The dose will depend on how much you weigh and the type of infection being treated. The usual dose 
for adults is 4 mg for every kilogram (kg) of body weight once daily for skin infections or 6 mg for 
every kg of body weight once daily for a heart infection or a blood infection associated with skin or 
heart infection. In adult patients, this dose is given directly into your blood stream (into a vein), either 
as an infusion lasting about 30 minutes or as an injection lasting about 2 minutes. The same dose is 
recommended in people aged over 65 years provided their kidneys are working well.
If your kidneys do not work well, you may receive Cubicin less often, e.g. once every other day. If 
you are receiving dialysis, and your next dose of Cubicin is due on a dialysis day, you will be usually 
given Cubicin after the dialysis session.

Children and adolescents (1 to 17 years of age)
The dose for children and adolescents (1 to 17 years of age) will depend on the age of patient and the 
type of infection being treated. This dose is given directly into the blood stream (into a vein), as an 
infusion lasting about 30-60 minutes.
A course of treatment usually lasts for 1 to 2 weeks for skin infections. For blood or heart infections 
and skin infections your doctor will decide how long you should be treated.

Detailed instructions for use and handling are given at the end of the leaflet.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The most serious side effects are described below:

Serious side effects with frequency not known (frequency cannot be estimated from the available 
data)
- A hypersensitivity reaction (serious allergic reaction including anaphylaxis and angioedema)

has been reported, in some cases during administration of Cubicin. This serious allergic 
reaction needs immediate medical attention. Tell your doctor or nurse straight away if you 
experience any of the following symptoms:
- Chest pain or tightness,

 



48

- Rash or hives,
- Swelling around throat,
- Rapid or weak pulse,
- Wheezing,
- Fever,
- Shivering or trembling,
- Hot flushes,
- Dizziness,
- Fainting,
- Metallic taste.

- Tell your doctor straight away if you experience unexplained muscle pain, tenderness, or 
weakness. Muscle problems can be serious, including muscle breakdown (rhabdomyolysis), 
which can result in kidney damage.

Other serious side effects that have been reported with the use of Cubicin are:
- A rare but potentially serious lung disorder called eosinophilic pneumonia, mostly after more 

than 2 weeks of treatment. The symptoms can include difficulty breathing, new or worsening 
cough, or new or worsening fever.

- Serious skin disorders. The symptoms can include:
- a new or worsening fever,
- red raised or fluid-filled skin spots which may start in your armpits or on your chest or 

groin areas and which can spread over a large area of your body,
- blisters or sores in your mouth or on your genitals.

- A serious kidney problem. The symptoms can include fever and rash.
If you experience these symptoms, tell your doctor or nurse straight away. Your doctor will perform 
additional tests to make a diagnosis.

The most frequently reported side effects are described below:

Common side effects (may affect up to 1 in 10 people)
- Fungal infections such as thrush,
- Urinary tract infection,
- Decreased number of red blood cells (anaemia),
- Dizziness, anxiety, difficulty in sleeping,
- Headache,
- Fever, weakness (asthenia),
- High or low blood pressure,
- Constipation, abdominal pain,
- Diarrhoea, feeling sick (nausea) or being sick (vomiting),
- Flatulence,
- Abdominal swelling or bloating,
- Skin rash or itching,
- Pain, itchiness or redness at the site of infusion,
- Pain in arms or legs,
- Blood testing showing higher levels of liver enzymes or creatine phosphokinase (CPK).

Other side effects which may occur following Cubicin treatment are described below:

Uncommon side effects (may affect up to 1 in 100 people)
- Blood disorders (e.g. increased number of small blood particles called platelets, which may 

increase the tendency for blood clotting, or higher levels of certain types of white blood cells),
- Decreased appetite,
- Tingling or numbness of the hands or feet, taste disturbance,
- Trembling,
- Changes in heart rhythm, flushes,
- Indigestion (dyspepsia), inflammation of the tongue,
- Itchy rash of skin,

 



49

- Muscle pain, cramping, or weakness, inflammation of the muscles (myositis), joint pain,
- Kidney problems,
- Inflammation and irritation of the vagina,
- General pain or weakness, tiredness (fatigue),
- Blood test showing increased levels of blood sugar, serum creatinine, myoglobin, or lactate 

dehydrogenase (LDH), prolonged blood clotting time or imbalance of salts,
- Itchy eyes.

Rare side effects (may affect up to 1 in 1,000 people)
- Yellowing of the skin and eyes,
- Prothrombin time prolonged.

Frequency not known (frequency cannot be estimated from the available data)
Antibacterial-associated colitis, including pseudomembranous colitis (severe or persistent diarrhoea 
containing blood and/or mucus, associated with abdominal pain or fever), easy bruising, bleeding 
gums, or nosebleeds.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. 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 Cubicin

- 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 label after EXP. 

The expiry date refers to the last day of the month.
- Store in a refrigerator (2 °C – 8 °C).

6. Contents of the pack and other information

What Cubicin contains
- The active substance is daptomycin. One vial of powder contains 500 mg daptomycin.
- The other ingredient is sodium hydroxide.

What Cubicin looks like and contents of the pack
Cubicin powder for solution for injection or infusion is supplied as a pale yellow to light brown cake 
or powder in a glass vial. It is mixed with a solvent to form a liquid before it is administered.

Cubicin is available in packs containing 1 vial or 5 vials.

Marketing Authorisation Holder
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

Manufacturer
Laboratoires Merck Sharp & Dohme Chibret
Route de Marsat
Riom 
63963, Clermont Ferrand Cedex 9
France

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


50

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.

Belgique/België/Belgien
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel.: +370 5 278 02 47
msd_lietuva@merck.com

България 
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel.: +420 233 010 111
dpoc_czechslovak@merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +361 888 53 00
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: +45 4482 4000
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com

Deutschland
MSD SHARP & DOHME GMBH
Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)
e-mail@msd.de

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@ msd.no

Ελλάδα
MSD Α.Φ.Β.Ε.Ε.
Τηλ: +30 210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
msd_info@merck.com

Polska
MSD Polska Sp.z o.o.
Tel.: +48 22 549 51 00
msdpolska@merck.com

France
MSD France
Tél: + 33 (0) 1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o. 
Tel: + 385 1 6611 333
croatia_info@merck.com

România
Merck Sharp & Dohme Romania S.R.L.
Tel: +40 21 529 29 00
msdromania@merck.com

 



51

Ireland
Merck Sharp & Dohme Ireland (Human Health) 
Limited
Tel: +353 (0)1 299 8700
medinfo_ireland@merck.com

Slovenija
Merck Sharp & Dohme, inovativna zdravila d.o.o.
Tel: + 386 1 5204 201
msd_slovenia@merck.com

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel.: +421 2 58282010
dpoc_czechslovak@merck.com

Ιtalia
MSD Italia S.r.l.
Tel: +39 06 361911
medicalinformation.it@merck.com

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0) 9 804650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 800 00 673 (+357 22866700)
cyprus_info@merck.com 

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364224
msd_lv@merck.com.

United Kingdom
Merck Sharp & Dohme Limited
Tel: +44 (0) 1992 467272
medicalinformationuk@merck.com

This leaflet was last revised in <{MM/YYYY}><{month YYYY}>.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu

 



52

The following information is intended for healthcare professionals only

Important: Please refer to the Summary of Product Characteristics before prescribing.

Instructions for use and handling

500 mg presentation:

In adults, daptomycin may be administered intravenously as an infusion over 30 minutes or as an 
injection over 2 minutes. Unlike in adults, daptomycin should not be administered by injection over a 
2-minute period in paediatric patients. Paediatric patients 7 to 17 years old should receive daptomycin 
infused over 30 minutes. In paediatric patients under 7 years old receiving a 9-12 mg/kg dose, 
daptomycin should be administered over 60 minutes. Preparation of the solution for infusion requires 
an additional dilution step as detailed below.

Cubicin given as an intravenous infusion over 30 or 60 minutes

A 50 mg/ml concentration of Cubicin for infusion can be achieved by reconstituting the lyophilised 
product with 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection.

The lyophilised product takes approximately 15 minutes to dissolve. The fully reconstituted product 
will appear clear and may have a few small bubbles or foam around the edge of the vial.

To prepare Cubicin for intravenous infusion, please adhere to the following instructions:
Aseptic technique should be used throughout to reconstitute or dilute lyophilised Cubicin.

For Reconstitution:
1. The polypropylene flip off cap should be removed to expose the central portions of the rubber 

stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution 
and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other 
surface. Draw 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection into a syringe
using a sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device, 
then slowly inject through the centre of the rubber stopper into the vial pointing the needle 
towards the wall of the vial.

2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to 
stand for 10 minutes.

3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear 
reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the 
product.

4. The reconstituted solution should be checked carefully to ensure that the product is in solution 
and visually inspected for the absence of particulates prior to use. Reconstituted solutions of 
Cubicin range in colour from pale yellow to light brown.

5. The reconstituted solution should then be diluted with sodium chloride 9 mg/ml (0.9 %) 
(typical volume 50 ml).

For Dilution:
1. Slowly remove the appropriate reconstituted liquid (50 mg daptomycin/ml) from the vial using 

a new sterile needle that is 21 gauge or smaller in diameter by inverting the vial in order to 
allow the solution to drain towards the stopper. Using a syringe, insert the needle into the 
inverted vial. Keeping the vial inverted, position the needle tip at the very bottom of the 
solution in the vial when drawing the solution into the syringe. Before removing the needle 
from the vial, pull the plunger all the way back to the end of the syringe barrel in order to 
remove the required solution from the inverted vial.

2. Expel air, large bubbles, and any excess solution in order to obtain the required dose.
3. Transfer the required reconstituted dose into 50 ml sodium chloride 9 mg/ml (0.9 %).
4. The reconstituted and diluted solution should then be infused intravenously over 30 or 

 



53

60 minutes.

Cubicin is not physically or chemically compatible with glucose-containing solutions. The following 
have been shown to be compatible when added to Cubicin containing infusion solutions: aztreonam, 
ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin and lidocaine.

The combined storage time (reconstituted solution in vial and diluted solution in infusion bag) at 
25 °C must not exceed 12 hours (24 hours if refrigerated).

Stability of the diluted solution in infusion bags is established as 12 hours at 25 °C or 24 hours if 
stored under refrigeration at 2 °C – 8 °C.

Cubicin given as 2 -minute intravenous injection (adult patients only)

Water should not be used for reconstitution of Cubicin for intravenous injection. Cubicin should only 
be reconstituted with sodium chloride 9 mg/ml (0.9 %).

A 50 mg/ml concentration of Cubicin for injection is obtained by reconstituting the lyophilised 
product with 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection.

The lyophilised product takes approximately 15 minutes to dissolve. The fully reconstituted product
will appear clear and may have a few small bubbles or foam around the edge of the vial.

To prepare Cubicin for intravenous injection, please adhere to the following instructions:
Aseptic technique should be used throughout to reconstitute lyophilised Cubicin.
1. The polypropylene flip off cap should be removed to expose the central portions of the rubber 

stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution 
and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other 
surface. Draw 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection into a syringe
using a sterile transfer needle that is 21 gauge or smaller diameter, or a needleless device, then 
slowly inject through the centre of the rubber stopper into the vial pointing the needle towards 
the wall of the vial.

2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to 
stand for 10 minutes.

3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear 
reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the 
product.

4. The reconstituted solution should be checked carefully to ensure that the product is in solution 
and visually inspected for the absence of particulates prior to use. Reconstituted solutions of 
Cubicin range in colour from pale yellow to light brown.

5. Slowly remove the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile 
needle that is 21 gauge or smaller in diameter.

6. Invert the vial in order to allow the solution to drain towards the stopper. Using a new syringe, 
insert the needle into the inverted vial. Keeping the vial inverted, position the needle tip at the 
very bottom of the solution in the vial when drawing the solution into the syringe. Before 
removing the needle from the vial, pull the plunger all the way back to the end of the syringe 
barrel in order to remove all of the solution from the inverted vial.

7. Replace needle with a new needle for the intravenous injection.
8. Expel air, large bubbles, and any excess solution in order to obtain the required dose.
9. The reconstituted solution should then be injected intravenously slowly over 2 minutes.

Chemical and physical in-use stability on the reconstituted solution in the vial has been demonstrated 
for 12 hours at 25 °C and up to 48 hours if stored under refrigeration (2 °C – 8 °C).

However, from a microbiological point of view the product should be used immediately. If not used 
immediately, in-use storage times are the responsibility of the user and would normally not be longer 

 



54

than 24 hours at 2 °C – 8 °C unless reconstitution /dilution has taken place in controlled and validated 
aseptic conditions.

This medicinal product must not be mixed with other medicinal products except those mentioned 
above.

Cubicin vials are for single-use only. Any unused portion remaining in the vial should be discarded.

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER 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
	A. LABELLING
	B. PACKAGE LEAFLET