Daptomycin Hospira

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Daptomycin Hospira 350 mg powder for solution for injection/infusion
Daptomycin Hospira 500 mg powder for solution for injection/infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Daptomycin Hospira 350 mg powder for solution for injection/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.

Daptomycin Hospira 500 mg powder for solution for injection/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 

Daptomycin Hospira 350 mg powder for solution for injection/infusion
Powder for solution for injection/infusion.

A light yellow to light brown lyophilised cake or powder. 

Daptomycin Hospira 500 mg powder for solution for injection/infusion
Powder for solution for injection/infusion.

A light yellow to light brown lyophilised cake or powder.

4. CLINICAL PARTICULARS 

4.1 Therapeutic indications 

Daptomycin 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.



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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, daptomycin 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 sections 4.8 and 5.2).

Posology 

Adults
- cSSTI without concurrent SAB: daptomycin 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: daptomycin 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: daptomycin 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. 

Daptomycin is administered intravenously in 0.9% sodium chloride (see section 6.6). Daptomycin 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) daptomycin 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 sections 4.4 and 5.2). The dosage regimen for daptomycin in paediatric patients with 
renal impairment has not been established.



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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; RIE = right-sided 
infective endocarditis
(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 (PK) studies and modelling results 
(see sections 4.4 and 5.2). 
(2) The same dose adjustments, which are based on PK data in volunteers including PK modelling 
results, are recommended for adult patients on haemodialysis (HD) or continuous ambulatory 
peritoneal dialysis (CAPD). Whenever possible, Daptomycin Hospira should be administered 
following the completion of dialysis on dialysis days (see section 5.2). 

Hepatic impairment
No dose adjustment is necessary when administering daptomycin 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 Daptomycin Hospira 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). 



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Paediatric patients (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 Daptomycin Hospira for paediatric SAB should be in accordance with the 

perceived risk of complications in the individual patient. The duration of Daptomycin Hospira 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 Daptomycin Hospira was 12 days, with a range of 

1 to 44 days. The duration of therapy should be in accordance with available official recommendations.

Daptomycin Hospira is administered intravenously in 0.9 % sodium chloride (see section 6.6). 
Daptomycin Hospira 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 daptomycin 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, daptomycin 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, Daptomycin Hospira is given by intravenous infusion over a 
30-minute period (see section 6.6). In paediatric patients aged 1 to 6 years, Daptomycin Hospira is given 
by intravenous infusion over a 60-minute period (see section 6.6).

Reconstituted solutions of Daptomycin Hospira range in colour from yellow to light brown.

4.3 Contraindications 

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



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4.4 Special warnings and precautions for use 

General 
If a focus of infection other than cSSTI or RIE is identified after initiation of daptomycin 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 daptomycin. If an allergic reaction to 
daptomycin occurs, discontinue use and institute appropriate therapy. 

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

RIE due to Staphylococcus aureus 
Clinical data on the use of daptomycin to treat RIE due to Staphylococcus aureus are limited to 19 adult 
patients (see “Information from clinical trials” in section 5.1). The safety and efficacy of daptomycin in 
children and adolescents aged below 18 years with RIE due to Staphylococcus aureus have not been 
established.

The efficacy of daptomycin 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 
daptomycin 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.

Clostridium difficile-associated diarrhoea 
Clostridium difficile-associated diarrhoea (CDAD) has been reported with daptomycin (see section 4.8). If 
CDAD is suspected or confirmed, daptomycin 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) have 
been observed when certain recombinant thromboplastin reagents are utilised for the assay (see section 
4.5). 



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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 daptomycin (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 
daptomycin -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. 

- Daptomycin Hospira 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. Daptomycin Hospira 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 
daptomycin 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 daptomycin 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 daptomycin (see section 4.8). In most 
reported cases associated with daptomycin, 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 daptomycin and improved when daptomycin 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 daptomycin should undergo 
prompt medical evaluation, including, if appropriate, bronchoalveolar lavage, to exclude other causes (e.g. 
bacterial infection, fungal infection, parasites, other medicinal products). Daptomycin should be 
discontinued immediately and treatment with systemic steroids should be initiated when appropriate. 



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Renal impairment 
Renal impairment has been reported during treatment with daptomycin. 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 daptomycin 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. Daptomycin 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 daptomycin to patients who already have some degree of renal 
impairment (creatinine clearance <80 ml/min) before commencing therapy with Daptomycin Hospira. 
Regular monitoring of renal function is advised (see 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 section 4.5). 

The dosage regimen for daptomycin 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). 

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 daptomycin were performed with aztreonam, tobramycin, warfarin and probenecid. 
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 
coadministration by intravenous infusion over a 30-minute period using a daptomycin dose of 2 mg/kg, 
the changes were not statistically significant. The interaction between daptomycin and tobramycin with an 
approved dose of daptomycin is unknown. Caution is warranted when daptomycin is co-administered with 
tobramycin.

Experience with the concomitant administration of daptomycin and warfarin is limited. Studies of 
daptomycin with anticoagulants other than warfarin have not been conducted. Anticoagulant activity in 
patients receiving daptomycin and warfarin should be monitored for the first several days after therapy 
with Daptomycin Hospira 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 daptomycin. It is recommended that other medicinal products 



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associated with myopathy should if possible be temporarily discontinued during treatment with 
daptomycin 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). 

Daptomycin Hospira 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, daptomycin 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 mcg/ml, which is a low concentration. Therefore, until more experience is gained, breast-feeding 
should be discontinued when daptomycin is administered to nursing women. 

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, daptomycin 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 daptomycin. 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 



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received a daily dose of 6 mg/kg, of whom 304 were patients and 156 were healthy volunteers. In 
paediatric studies, 372 patients received daptomycin, 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 daptomycin 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 rash 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*: Clostridium difficile-associated diarrhoea**

Blood and lymphatic system 
disorders

Common: Anaemia

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

Rare: Prothrombin time (PT) prolonged

Not known*: Thrombocytopaenia

Immune system disorders Not known*: Hypersensitivity**, manifested by isolated 
spontaneous reports including, but not limited to 
angioedema, drug rash with eosinophilia and 
systemic symptoms (DRESS), pulmonary 
eosinophilia, vesicobullous rash with mucous 
membrane involvement and 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



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System organ class Frequency Adverse reactions
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

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
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). 
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, 



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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. 

Pharmacokinetic/pharmacodynamic 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. 

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 



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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 
daptomycin 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 
daptomycin. 

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 daptomycin 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 daptomycin, 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 daptomycin 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 
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 



14

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 Paedatric 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 Paedatric 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.

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;



15

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 Paedatric 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 Paedatric 
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 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. 



16

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/h/kg 
and its renal clearance is 4 to 7 ml/h/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 daptomycin 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 daptomycin, 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 daptomycin, total clearance of daptomycin in 
children 7-11 years of age with Gram-positive infection was higher than in adolescents, whereas 
elimination half-life was shorter. After a single 4, 8, or 10 mg/kg dose of daptomycin, 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 daptomycin, 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 



17

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 summarized 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 



18

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 receiving12 mg/kg once daily would be 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 daptomycin 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. 



19

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. 

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 (for pH adjustment) 
Citric acid (solubiliser/stabiliser)

6.2 Incompatibilities 

Daptomycin Hospira 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 

2 years



20

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.

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 hours 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 

Do not store above 30°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 

Single use 10 ml type I clear glass vials with gray rubber closure and aluminium cap.

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 Hospira 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.

Daptomycin Hospira 350 mg powder for solution for injection/infusion

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

The fully reconstituted product will appear clear and may have a few small bubbles or foam around the 
edge of the vial.

To prepare Daptomycin Hospira for intravenous infusion, please adhere to the following instructions: 
Aseptic technique should be used throughout to reconstitute lyophilised Daptomycin Hospira. 
To minimise foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.

1. The polypropylene flip off cap should be removed to expose the central portion of the rubber 
stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and 



21

allow to dry (perform the same for the sodium chloride solution vial, if applicable). 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 directly over the product plug in the vial.

2. Release the syringe plunger and allow the syringe plunger to equalise the pressure before removing 
the syringe from the vial.

3. Hold the vial by the vial neck, tilt the vial and swirl vial contents until the product is completely 
reconstituted.

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 
Daptomycin Hospira range in colour from 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 infusion. 
8. Expel air, large bubbles, and any excess solution in order to obtain the required dose. 
9. Transfer the reconstituted solution into a sodium chloride 9 mg/ml (0.9%) infusion bag (typical 

volume 50 ml).
10. 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 Daptomycin Hospira containing infusion 
solutions: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin 
and lidocaine.

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

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

The fully reconstituted product will appear clear and may have a few small bubbles or foam around the 
edge of the vial.

To prepare Daptomycin Hospira for intravenous injection, please adhere to the following instructions: 
Aseptic technique should be used throughout to reconstitute lyophilised Daptomycin Hospira. 
To minimise foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.

1. The polypropylene flip off cap should be removed to expose the central portion of the rubber 
stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and 
allow to dry (perform the same for the sodium chloride solution vial, if applicable). 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 directly over the product plug in the vial.

2. Release the syringe plunger and allow the syringe plunger to equalise the pressure before removing 
the syringe from the vial.



22

3. Hold the vial by the vial neck, tilt the vial and swirl vial contents until the product is completely 
reconstituted.

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 
Daptomycin Hospira range in colour from 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.

Daptomycin Hospira 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.

Daptomycin Hospira 500 mg powder for solution for injection/infusion

Daptomycin Hospira given as 30 or 60-minute intravenous infusion 
A 50 mg/ml concentration of Daptomycin Hospira for infusion is obtained by reconstituting the 
lyophilised product with 10 ml of sodium chloride 9 mg/ml (0.9%) solution for injection.

The fully reconstituted product will appear clear and may have a few small bubbles or foam around the 
edge of the vial.

To prepare Daptomycin Hospira for intravenous infusion, please adhere to the following instructions: 
Aseptic technique should be used throughout to reconstitute lyophilised Daptomycin Hospira. 
To minimise foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.

1. The polypropylene flip off cap should be removed to expose the central portion of the rubber 
stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and 
allow to dry (perform the same for the sodium chloride solution vial, if applicable). 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 directly over the product plug in the vial.

2. Release the syringe plunger and allow the syringe plunger to equalise the pressure before removing 
the syringe from the vial.

3. Hold the vial by the vial neck, tilt the vial and swirl vial contents until the product is completely 
reconstituted.

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 Daptomycin 
Hospira range in colour from yellow to light brown. 



23

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 infusion. 
8. Expel air, large bubbles, and any excess solution in order to obtain the required dose. 
9. Transfer the reconstituted solution into a sodium chloride 9 mg/ml (0.9%) infusion bag (typical 

volume 50 ml).
10. 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 Daptomycin Hospira containing infusion 
solutions: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin 
and lidocaine.

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

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

The fully reconstituted product will appear clear and may have a few small bubbles or foam around the 
edge of the vial.

To prepare Daptomycin Hospira for intravenous injection, please adhere to the following instructions: 
Aseptic technique should be used throughout to reconstitute lyophilised Daptomycin Hospira. 
To minimise foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.

1. The polypropylene flip off cap should be removed to expose the central portion of the rubber 
stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and 
allow to dry (perform the same for the sodium chloride solution vial, if applicable). 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 directly over the plug in the vial.

2. Release the syringe plunger and allow the syringe plunger to equalise the pressure before removing 
the syringe from the vial.

3. Hold the vial by the vial neck, tilt the vial and swirl vial contents until the product is completely 
reconstituted.

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 Daptomycin 
Hospira range in colour from 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. 



24

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.

Daptomycin Hospira 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 

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

8. MARKETING AUTHORISATION NUMBER(S) 
EU/1/17/1175/001
EU/1/17/1175/002
EU/1/17/1175/003
EU/1/17/1175/004

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

<Date of first authorisation: 22-March-2017>
<Date of latest renewal: {DD month YYYY}>

10. DATE OF REVISION OF THE TEXT 

<{MM/YYYY}>
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.



25

ANNEX II

A. MANUFACTURERS 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



26

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release

Hospira UK Limited
Horizon
Honey Lane
Maidenhead
Hurley
SL6 6RJ
United Kingdom

Pfizer Service Company BVBA
Hoge Wei 10
1930 Zaventem
Belgium

The printed package leaflet of the medicinal product must state the name and address of the manufacturer 
responsible for the release of the concerned batch.

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 

- Periodic Safety Update Reports 
The requirements for submission of periodic safety update reports for this medicinal product are set out 

in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT

Risk Management Plan (RMP)
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any 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.



27

The Marketing Authorisation Holder shall ensure that all physicians who are expected to prescribe/use 

Daptomycin Hospira are provided with:

- Summary of Product Characteristics
- Dosage card

The dosage card should contain the following key messages:

- That there is a risk of severe skeletal muscle toxicity and so measuring the CPK at treatment 
initiation and at regular intervals is important. Patients at higher risk of developing myopathy 
should have more frequent CPK measurements.

- That Daptomycin Hospira can interfere with coagulation tests (PT/INR) and this might lead to false 
results. To minimise this risk, physicians should be advised that for coagulation levels testing it is 
recommended to draw blood samples near the time of Daptomycin Hospira trough plasma 
concentration.

- The dosage card should contain the appropriate algorithms for calculating the Daptomycin Hospira 
dose for reconstitution, to help minimise the risk of medication errors (high osmolarity, overdose).

The Marketing Authorisation Holder shall ensure that all laboratories expected to perform Daptomycin 

Hospira susceptibility testing are provided with:

- Summary of Product Characteristics
- Laboratory susceptibility testing leaflet

The laboratory susceptibility testing leaflet should contain the following key messages:

- That susceptibility testing minimises the risk of treatment failure by identifying strains with 
potential resistance to daptomycin.

- That daptomycin susceptibility testing needs Ca in the testing medium and testing methods with 
mediums providing consistent Ca concentrations are recommended.



28

ANNEX III

LABELLING AND PACKAGE LEAFLET



29

A. LABELLING



30

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON FOR 1 VIAL 
CARTON FOR 5 VIALS

1. NAME OF THE MEDICINAL PRODUCT

Daptomycin Hospira 350 mg powder for solution for injection/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

Sodium hydroxide
Citric acid

4. PHARMACEUTICAL FORM AND CONTENTS

Powder for solution for injection/infusion
1 vial
5 vials

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Intravenous use. 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 
THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



31

9. SPECIAL STORAGE CONDITIONS

Do not store above 30°C.

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

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/17/1175/001
EU/1/17/1175/002

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted.

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.



32

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

Daptomycin Hospira 350 mg powder for solution for injection/infusion
daptomycin 
IV

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

350 mg

6. OTHER



34

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON FOR 1 VIAL 
CARTON FOR 5 VIALS

1. NAME OF THE MEDICINAL PRODUCT

Daptomycin Hospira 500 mg powder for solution for injection/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

Sodium hydroxide
Citric acid

4. PHARMACEUTICAL FORM AND CONTENTS

Powder for solution for injection/infusion
1 vial 
5 vials

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Intravenous use. 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 
THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



35

9. SPECIAL STORAGE CONDITIONS

Do not store above 30°C.

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

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/17/1175/003
EU/1/17/1175/004

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.



36

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



37

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL

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

Daptomycin Hospira 500 mg powder for solution for injection/infusion
daptomycin 
IV

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

500 mg

6. OTHER



38

B. PACKAGE LEAFLET



39

Package leaflet: Information for the patient

Daptomycin Hospira 350 mg powder for solution for injection/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 Daptomycin Hospira is and what it is used for 
2. What you need to know before you are given Daptomycin Hospira 
3. How Daptomycin Hospira is given 
4. Possible side effects 
5. How to store Daptomycin Hospira 
6. Contents of the pack and other information

1. What Daptomycin Hospira is and what it is used for 

The active substance in Daptomycin Hospira powder for solution for injection/infusion is daptomycin. 
Daptomycin is an antibacterial that can stop the growth of certain bacteria. Daptomycin Hospira 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. 

Daptomycin Hospira 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 Daptomycin Hospira. 

2. What you need to know before you are given Daptomycin Hospira 

You should not be given Daptomycin Hospira
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.



40

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

Daptomycin Hospira (see section 3 of this leaflet). 
- Occasionally, patients receiving Daptomycin Hospira 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 
Daptomycin Hospira. The symptoms generally go away within a few days of stopping Daptomycin 
Hospira. 

- If you are very overweight. There is a possibility that your blood levels of Daptomycin Hospira 
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 Daptomycin Hospira. 

Tell your doctor 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 Daptomycin Hospira. Tell a doctor or a nurse straight away if you experience 
symptoms suggestive of allergic reaction, such as wheezing, difficulty breathing, swelling of the 
face, neck and throat, rashes and hives, fever (see section 4 of this leaflet for more information). 

- 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 Daptomycin Hospira treatment. 

Daptomycin Hospira 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 Daptomycin Hospira. Please inform your doctor that 
you are on treatment with Daptomycin Hospira. 

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

Children and adolescents 
Daptomycin Hospira 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 Daptomycin Hospira
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 
Daptomycin Hospira. Your doctor may decide not to give you Daptomycin Hospira or to stop the 
other medicine for a while. 



41

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

- 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 
Daptomycin Hospira 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 Daptomycin Hospira, because it may pass into your breast milk 
and could affect the baby. 

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

3. How Daptomycin Hospira is given 

Daptomycin Hospira 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 Daptomycin Hospira less often, e.g. once every other 
day. If you are receiving dialysis, and your next dose of Daptomycin Hospira is due on a dialysis day, you 
will be usually given Daptomycin Hospira 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: 

Very rare serious side effects (may affect up to 1 in 10,000 people) 
A hypersensitivity reaction (serious allergic reaction including anaphylaxis, angioedema, drug rash with 
eosinophilia and systemic symptoms (DRESS)) has been reported, in some cases during administration of 



42

daptomycin. 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, 
- Rash with blistering, sometimes affecting the mouth and genitals, 
- 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. In 
very rare cases (reported in less than 1 in every 10,000 patients), muscle problems can be serious, 
including muscle breakdown (rhabdomyolysis), which can result in kidney damage. 

Serious side effects with frequency not known (frequency cannot be estimated from the available data) 
A rare but potentially serious lung disorder called eosinophilic pneumonia has been reported in patients 
given daptomycin, mostly after more than 2 weeks of treatment. The symptoms can include difficulty 
breathing, new or worsening cough, or new or worsening fever. If you experience these symptoms, tell 
your doctor or nurse straight away. 

If you experience raised or fluid-filled skin spots over a large area of your body, tell your doctor or nurse 
straight away.

The most frequently reported side effects are described below: 

Common: 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 daptomycin treatment are described below: 

Uncommon: 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, 



43

- Trembling, 
- Changes in heart rhythm, flushes, 
- 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: 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 Daptomycin Hospira

- 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. 
- Do not store above 30°C. 

6. Contents of the pack and other information 

What Daptomycin Hospira contains 
- The active substance is daptomycin. One vial of powder contains 350 mg daptomycin. 
- The other ingredients are sodium hydroxide and citric acid.

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

Daptomycin Hospira is available in packs containing 1 vial or 5 vials.



44

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Hospira UK Limited
Horizon
Honey Lane
Maidenhead
Hurley
SL6 6RJ
United Kingdom

Manufacturer
Pfizer Service Company BVBA
Hoge Wei 10 
1930 Zaventem 
Belgium

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

BE
Pfizer SA/NV
Tél/Tel: + 32 2 554 62 11

LU
Pfizer SA/NV
Tél/Tel: + 32 2 554 62 11

BG
Пфайзер Люксембург САРЛ, Клон България
Тел.: +359 2 970 4333

LT
Pfizer Luxembourg SARL filialas Lietuvoje
Tel: + 370 52 51 4000

CZ
Pfizer, spol. s r.o.
Tel: +420-283-004-111

HU
Pfizer Kft.
Tel: + 36 1 488 37 00

DK
Pfizer ApS
Tlf: + 45 44 20 11 00

MT
Drugsales Ltd
Tel: + 356 21 419 070/1/2

DE
Pfizer Pharma PFE GmbH
Tel:+ 49 (0)800 8535555

NL
Pfizer bv
Tel: +31 (0)10 406 43 01

EE
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

NO
Pfizer AS
Tlf: +47 67 52 61 00

EL
Pfizer ΕΛΛΑΣ A.E.
Τηλ.: +30 210 6785 800

AT
Pfizer Corporation Austria Ges.m.b.H.
Tel:+43 (0)1 521 15-0



45

ES
Pfizer, S.L.  
Tel: +34 91 490 99 00

PL
Pfizer Polska Sp. z o.o.
Tel: +48 22 335 61 00

FR
Pfizer 
Tél: + 33 (0)1 58 07 34 40

PT
Laboratórios Pfizer, Lda.
Tel: +351 21 423 55 00

HR
Pfizer Croatia d.o.o.
Tel: +385 1 3908 777

RO
Pfizer România S.R.L.
Tel: +40 (0)21 207 28 00

IE
Pfizer Healthcare Ireland
Tel: 1800 633 363 (toll free)
        +44 (0) 1304 616161

SI
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja 
farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

IS
Icepharma hf.
Sími: +354 540 8000

SK
Pfizer Luxembourg SARL, organizačná zložka
Tel: +421–2–3355 5500

IT
Pfizer S.r.l.
Tel: +39 06 33 18 21

FI
Pfizer PFE Finland Oy
Puh/Tel: +358 (0)9 430 040

CY
Pharmaceutical Trading Co Ltd 
Τηλ: 24656165

SE
Pfizer AB
Tel: +46 (0)8 550 520 00

LV
Pfizer Luxembourg SARL filiāle Latvijā
Tel: + 371 670 35 775

UK
Hospira UK Limited 
Tel: + 44 (0) 1628 515500

This leaflet was last revised in MM/YYYY

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



46

------------------------------------------------------------------------------------------------------------------------

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. 

Daptomycin Hospira given as 30 or 60-minute intravenous infusion 

A 50 mg/ml concentration of Daptomycin Hospira 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 fully reconstituted product will appear clear and may have a few small bubbles or foam around the 
edge of the vial. 

To prepare Daptomycin Hospira for intravenous infusion, please adhere to the following instructions: 
Aseptic technique should be used throughout to reconstitute lyophilised Daptomycin Hospira. 
To minimise foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.

1. The polypropylene flip off cap should be removed to expose the central portion of the rubber stopper. 
Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry
(perform the same for the sodium chloride solution vial, if applicable). 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 
directly over the product plug in the vial.

2. Release the syringe plunger and allow the syringe plunger to equalise the pressure before removing the 
syringe from the vial.

3. Hold the vial by the vial neck, tilt the vial and swirl vial contents until the product is completely 
reconstituted.

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 Daptomycin 
Hospira range in colour from 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 infusion. 
8. Expel air, large bubbles, and any excess solution in order to obtain the required dose. 



47

9. Transfer the reconstituted solution into a sodium chloride 9 mg/ml (0.9%) infusion bag (typical 
volume 50 ml).

10. The reconstituted and diluted solution should then be infused intravenously over 30 or 60 minutes. 

Daptomycin Hospira is not physically or chemically compatible with glucose-containing solutions. The 
following have been shown to be compatible when added to Daptomycin Hospira 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. 

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

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

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

The fully reconstituted product will appear clear and may have a few small bubbles or foam around the 
edge of the vial. 

To prepare Daptomycin Hospira for intravenous injection, please adhere to the following instructions: 
Aseptic technique should be used throughout to reconstitute lyophilised Daptomycin Hospira.
To minimise foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.

1. The polypropylene flip off cap should be removed to expose the central portion of the rubber stopper. 
Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry
(perform the same for the sodium chloride solution vial, if applicable). 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
directly over the product plug in the vial.

2. Release the syringe plunger and allow the syringe plunger to equalise the pressure before removing 
the syringe from the vial.

3. Hold the vial by the vial neck, tilt the vial and swirl vial contents until the product is completely 
reconstituted.

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 Daptomycin 
Hospira range in colour from 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. 



48

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 aseptic 
conditions. 

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

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



49

Package leaflet: Information for the patient

Daptomycin Hospira 500 mg powder for solution for injection/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 Daptomycin Hospira is and what it is used for 
2. What you need to know before you are given Daptomycin Hospira
3. How Daptomycin Hospira is given 
4. Possible side effects 
5. How to store Daptomycin Hospira
6. Contents of the pack and other information

1. What Daptomycin Hospira is and what it is used for 

The active substance in Daptomycin Hospira powder for solution for injection/infusion is daptomycin. 
Daptomycin is an antibacterial that can stop the growth of certain bacteria. Daptomycin Hospira 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. 

Daptomycin Hospira 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 Daptomycin Hospira. 

2. What you need to know before you are given Daptomycin Hospira 

You should not be given Daptomycin Hospira
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.



50

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

Daptomycin Hospira (see section 3 of this leaflet). 
- Occasionally, patients receiving Daptomycin Hospira 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 
Daptomycin Hospira. The symptoms generally go away within a few days of stopping Daptomycin 
Hospira. 

- If you are very overweight. There is a possibility that your blood levels of Daptomycin Hospira
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 Daptomycin Hospira. 

Tell your doctor 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 Daptomycin Hospira. Tell a doctor or a nurse straight away if you experience 
symptoms suggestive of allergic reaction, such as wheezing, difficulty breathing, swelling of the 
face, neck and throat, rashes and hives, fever (see section 4 of this leaflet for more information). 

- 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 Daptomycin Hospira treatment. 

Daptomycin Hospira 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 Daptomycin Hospira. Please inform your doctor that 
you are on treatment with Daptomycin Hospira. 

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

Children and adolescents 
Daptomycin Hospira 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 Daptomycin Hospira
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 
Daptomycin Hospira. Your doctor may decide not to give you Daptomycin Hospira or to stop the 
other medicine for a while. 



51

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

- 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 
Daptomycin Hospira 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 Daptomycin Hospira, because it may pass into your breast milk 
and could affect the baby. 

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

3. How Daptomycin Hospira is given 

Daptomycin Hospira 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 Daptomycin Hospira less often, e.g. once every other 
day. If you are receiving dialysis, and your next dose of Daptomycin Hospira is due on a dialysis day, you 
will be usually given Daptomycin Hospira 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: 

Very rare serious side effects (may affect up to 1 in 10,000 people) 
A hypersensitivity reaction (serious allergic reaction including anaphylaxis, angioedema, drug rash with 
eosinophilia and systemic symptoms (DRESS)) has been reported, in some cases during administration of 



52

daptomycin. 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, 
- Rash with blistering, sometimes affecting the mouth and genitals, 
- 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. In 
very rare cases (reported in less than 1 in every 10,000 patients), muscle problems can be serious, 
including muscle breakdown (rhabdomyolysis), which can result in kidney damage. 

Serious side effects with frequency not known (frequency cannot be estimated from the available data) 
A rare but potentially serious lung disorder called eosinophilic pneumonia has been reported in patients 
given daptomycin, mostly after more than 2 weeks of treatment. The symptoms can include difficulty 
breathing, new or worsening cough, or new or worsening fever. If you experience these symptoms, tell 
your doctor or nurse straight away. 

If you experience raised or fluid-filled skin spots over a large area of your body, tell your doctor or nurse 
straight away.

The most frequently reported side effects are described below: 

Common: 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 daptomycin treatment are described below: 

Uncommon: 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, 



53

- Trembling, 
- Changes in heart rhythm, flushes, 
- 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: 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 Daptomycin Hospira

- 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. 
- Do not store above 30°C.

6. Contents of the pack and other information 

What Daptomycin Hospira contains 
- The active substance is daptomycin. One vial of powder contains 500 mg daptomycin.
- The other ingredients are sodium hydroxide and citric acid.

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

Daptomycin Hospira is available in packs containing 1 vial or 5 vials.



54

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Hospira UK Limited
Horizon
Honey Lane
Maidenhead
Hurley
SL6 6RJ
United Kingdom

Manufacturer
Pfizer Service Company BVBA
Hoge Wei 10 
1930 Zaventem 
Belgium

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

BE
Pfizer SA/NV
Tél/Tel: + 32 2 554 62 11

LU
Pfizer SA/NV
Tél/Tel: + 32 2 554 62 11

BG
Пфайзер Люксембург САРЛ, Клон България
Тел.: +359 2 970 4333

LT
Pfizer Luxembourg SARL filialas Lietuvoje
Tel: + 370 52 51 4000

CZ
Pfizer, spol. s r.o.
Tel: +420-283-004-111

HU
Pfizer Kft.
Tel: + 36 1 488 37 00

DK
Pfizer ApS
Tlf: + 45 44 20 11 00

MT
Drugsales Ltd
Tel: + 356 21 419 070/1/2

DE
Pfizer Pharma PFE GmbH
Tel:+ 49 (0)800 8535555

NL
Pfizer bv
Tel: +31 (0)10 406 43 01

EE
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

NO
Pfizer AS
Tlf: +47 67 52 61 00

EL
Pfizer ΕΛΛΑΣ A.E.
Τηλ.: +30 210 6785 800

AT
Pfizer Corporation Austria Ges.m.b.H.
Tel:+43 (0)1 521 15-0



55

ES
Pfizer, S.L.  
Tel: +34 91 490 99 00

PL
Pfizer Polska Sp. z o.o.
Tel: +48 22 335 61 00

FR
Pfizer 
Tél: + 33 (0)1 58 07 34 40

PT
Laboratórios Pfizer, Lda.
Tel: +351 21 423 55 00

HR
Pfizer Croatia d.o.o.
Tel: +385 1 3908 777

RO
Pfizer România S.R.L.
Tel: +40 (0)21 207 28 00

IE
Pfizer Healthcare Ireland
Tel: 1800 633 363 (toll free)
        +44 (0) 1304 616161

SI
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja 
farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

IS
Icepharma hf.
Sími: +354 540 8000

SK
Pfizer Luxembourg SARL, organizačná zložka
Tel: +421–2–3355 5500

IT
Pfizer S.r.l.
Tel: +39 06 33 18 21

FI
Pfizer PFE Finland Oy
Puh/Tel: +358 (0)9 430 040

CY
Pharmaceutical Trading Co Ltd 
Τηλ: 24656165

SE
Pfizer AB
Tel: +46 (0)8 550 520 00

LV
Pfizer Luxembourg SARL filiāle Latvijā
Tel: + 371 670 35 775

UK
Hospira UK Limited 
Tel: + 44 (0) 1628 515500

This leaflet was last revised in MM/YYYY

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



56

------------------------------------------------------------------------------------------------------------------------

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. 

Daptomycin Hospira given as 30 or 60-minute intravenous infusion 

A 50 mg/ml concentration of Daptomycin Hospira 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 fully reconstituted product will appear clear and may have a few small bubbles or foam around the 
edge of the vial. 

To prepare Daptomycin Hospira for intravenous infusion, please adhere to the following instructions: 
Aseptic technique should be used throughout to reconstitute lyophilised Daptomycin Hospira. 
To minimise foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.

1. The polypropylene flip off cap should be removed to expose the central portion of the rubber stopper. 
Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry
(perform the same for the sodium chloride solution vial, if applicable). 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 
directly over the product plug in the vial.

2. Release the syringe plunger and allow the syringe plunger to equalise the pressure before removing the 
syringe from the vial.

3. Hold the vial by the vial neck, tilt the vial and swirl vial contents until the product is completely 
reconstituted.

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 Daptomycin 
Hospira range in colour from 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 infusion. 
8. Expel air, large bubbles, and any excess solution in order to obtain the required dose. 



57

9. Transfer the reconstituted solution into a sodium chloride 9 mg/ml (0.9%) infusion bag (typical 
volume 50 ml).

10. The reconstituted and diluted solution should then be infused intravenously over 30 or 60 minutes. 

Daptomycin Hospira is not physically or chemically compatible with glucose-containing solutions. The 
following have been shown to be compatible when added to Daptomycin Hospira 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. 

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

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

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

The fully reconstituted product will appear clear and may have a few small bubbles or foam around the 
edge of the vial. 

To prepare Daptomycin Hospira for intravenous injection, please adhere to the following instructions: 
Aseptic technique should be used throughout to reconstitute lyophilised Daptomycin Hospira. 
To minimise foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.

1. The polypropylene flip off cap should be removed to expose the central portion of the rubber stopper. 
Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry
(perform the same for the sodium chloride solution vial, if applicable). 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 
directly over the product plug in the vial.

2. Release the syringe plunger and allow the syringe plunger to equalise the pressure before removing 
the syringe from the vial.

3. Hold the vial by the vial neck, tilt the vial and swirl vial contents until the product is completely 
reconstituted.

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 Daptomycin 
Hospira range in colour from 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. 



58

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 aseptic 
conditions. 

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

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


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