Daptomycin - Prescribing Guidance

Publication: 01/09/2008  
Next review: 12/01/2025  
Clinical Guideline
CURRENT 
ID: 1402 
Approved By: Drug and Therapeutics Committee 
Copyright© Leeds Teaching Hospitals NHS Trust 2022  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

INTRAVENOUS DAPTOMYCIN ANTIMICROBIAL PRESCRIBING GUIDELINES

RESTRICTIONS TO PRESCRIBING
Daptomycinis classed as a protected antimicrobial and is fully restricted therefore needs approval and an antimicrobial code from an infection specialist.

Please refer to the British National Formulary (BNF) or the Summary of Product Characteristics (SPC) for information on:

  • Dosage and routes of administration
  • Pharmacokinetics
  • Interactions
  • Side effects
  • Allergy information

DRUG INFORMATION

Class of antimicrobial: Cyclic lipopeptide antibiotic.

Contraindications: Hypersensitivity to daptomycin or to any excipients including sodium hydroxide.

Cautions: obesity (limited information on safety and efficacy).

Mechanism of action: The mechanism of action has been described as being novel and it involves the insertion into and disruption of the functional integrity of the Gram positive plasma membrane. This results in rapid loss of membrane potential, cessation of macromolecular synthesis and cell death.

Antimicrobial spectrum: Daptomycin is active against a range of aerobic and anaerobic Gram positive bacteria but has no significant anti Gram negative activity.

Daptomycin has in vitro activity against:
Staphylococcus aureus [methicillin resistant and methicillin susceptible strains]
Coagulase negative staphylococci
Streptococci [including β-haemolytic streptococci and Streptococcus pneumoniae]*
Enterococci

*NB. Activity against oral streptococci is variable, so confirmation of susceptibility should ideally be sought before use in patients infected with these bacteria.

Daptomycin does not have in vitro activity against:
Gram negative bacteria

Clinical indications
Daptomycin should be prescribed for conditions set out in Trust guideline or on the advice of an infection specialist. In deep seated infections, daptomycin should normally be given with another active agent because of the risk of resistance developing on therapy. May be considered to faciliate discharge via OPAT.
Routes of administration
Daptomycin must be given by intravenous infusion over 30 minutes for patients 7 years and older and over 60 minutes for patients under 7 years old. There is no oral preparation available.

Weight based calculation of dosing
Daptomycin should be dosed based on actual body weight. No dosage adjustment is recommended for obese patients.

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ADULT PATIENTS:

Table 1- Adult dosing recommendations based on INDICATION
*Doses should be rounded to the nearest 50mg*

Indication

Dosing

Duration

Skin and soft-tissue infections caused by Gram positive organisms

4mg/kg ONCE every 24 hours

7-14 days

Infective endocarditis due to Staphylococcus aureus or susceptible streptococci, Staphylococcus aureus bacteraemia, deep seated staphylococcalinfection

6-8mg/kg ONCE every 24 hours

Duration to be discuss with an Infection specialist

Deep seated enterococcal infection, including endocarditis

8-10mg/kg ONCE every 24 hours

Duration to be discuss with an Infection specialist

Diabetic foot infection (including osteomyelitis), peri-prosthetic infection, prosthetic vascular graft infection (where not suitable alternatives can be used)

Needs discussion with infection specialist

Duration to be discuss with an infection specialist

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PAEDIATRIC PATIENTS:

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).

Table 2: paediatric dose recommendations for skin and soft-tissue infection (SSTI) without Staphylococcus aureus bacteraemia.

Table 2- Paediatric doses: SSTI without Staphylococcus aureus bacteraemia

Age group

Dosage

Duration of therapy

1 to < 2 years

 10 mg/kg once every 24 hours

Up to 14 days

2 to 6 years

 9 mg/kg once every 24 hours

7 to 11 years

 7 mg/kg once every 24 hours

12 to 17 years

 5 mg/kg once every 24 hours

Table 3: paediatric dose recommendations for skin and soft-tissue infection (SSTI) associated with Staphylococcus aureus bacteraemia.

Table 3- Paediatric doses: SSTI with Staphylococcus aureus bacteraemia

Age group

Dosage

Duration of therapy

1 to < 2 years

 12 mg/kg once every 24 hours

Duration of treatment in accordance with risk of complications in individual patients.

2 to 6 years

7 to 11 years

 9 mg/kg once every 24 hours

12 to 17 years

 7 mg/kg once every 24 hours

Table 4: paediatric dose recommendations for endocarditis and other deep-seated infection

Table 4- Paediatric doses: Endocarditis and other deep-seated infection

Age group

Dosage

Duration of therapy

1 to < 2 years

 12 mg/kg once every 24 hours

Duration of treatment in accordance with risk of complications in individual patients.

2 to 6 years

7 to 11 years

 9 mg/kg once every 24 hours

12 to 17 years

 7 mg/kg once every 24 hours

>6- 17 years

 6 mg/kg once every 24 hours

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RENAL IMPAIRMENT

Adult patients: Use https://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation
Dosage adjustments are required in patients with a creatinine clearance of <30ml/min, including those receiving haemodialysis or CAPD. The recommended dosing interval for patients with a creatinine clearance of <30ml/min is every 48 hours. Haemodialysis patients should receive their dose after the dialysis session. The mg/kg dosing regimen should reflect the clinical indication e.g. 6-8mg/kg 48 hourly for staphylococcal endocarditis.
Dosage adjustments based on age are not recommended for elderly patients with normal renal function.

Paediatric patients:

For Children >1 year:

 

eGFR

Recommended dose

≥ 30ml/minute

Use normal dose

< 30ml/minute

Use normal dose every 48 hours

Intermittent haemodialysis/ Peritoneal dialysis/CVVHD

Discuss with specialist pharmacist in conjunction with microbiologist

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SPECIAL DOSING CONSIDERATIONS

Hepatic impairment
No dose adjustments needed.
Pregnancy
Daptomycin should not be used during pregnancy unless clearly necessary i.e. only if the expected benefit outweighs the possible risk
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.
Breast feeding
Considered safe to prescribe while breastfeeding. There is very limited published evidence regarding safety. Only a small amount is present in breast milk, with minimal absorption from the infant’s gastrointestinal tract.  

Interactions
A full list of daptomycin interactions can be found on the BNF. Note daptomycin interacts with statin therapy, there is a potential to elevate CK therefore statin should be withheld.

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MONITORING

Therapeutic drug monitoring not required. Check creatinine phosphokinase (CK) at baseline and weekly intervals during therapy (only required if treatment expected to be greater than 1 week). Discontinue if symptoms/signs of myopathy present and discuss with pharmacist if CK exceeds 10 times the upper limit of normal or is rapidly rising.

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ANY OTHER USEFUL INFORMATION

Discharge information:if being discharged with OPAT/CIVAS team please refer to the OPAT monographs for the requirements on discharge.

Provenance

Record: 1402
Objective:
Clinical condition:
Target patient group:
Target professional group(s): Secondary Care Doctors
Pharmacists
Adapted from:

Evidence base

EVIDENCE BASE

  • Benvenuto, M., Benziger, D., Yankelev, S. and Vigliani, G. 2006. Pharmacokinetics and Tolerability of Daptomycin at Doses up to 12 Milligrams per Kilogram of Body Weight Once Daily in Healthy Volunteers. Antimicrobial Agents and Chemotherapy. 50(10),pp.3245-3249.
  • BNF Link
  • Britt, N., Potter, E., Patel, N. and Steed, M. 2016. Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients. Clinical Infectious Diseases.,p.ciw815.
  • Cottagnoud P et al. Daptomycin Is Highly Efficacious against Penicillin-Resistant and Penicillin- and Quinolone-Resistant Pneumococci in Experimental Meningitis. Antimicrobial Agent and Chemotherapy 2004: 3928-3933
  • Critchley IA, Draghi DC, Sahm DF et al. Activity of daptomycin against susceptible and multidrug-resistant Gram-positive pathogens collected in the SECURE study [Europe] during 2000–2001. J Antimicrob Chemother 2003; 51: 639–49.
  • Dvorchik B, Arbeit RD, Chung J et al. Population pharmacokinetics of daptomycin. Antimicrob Agents Chemother. 2004; 48:2799-807.
  • Dvorchik B. Moderate liver impairment has no influence on daptomycin pharmacokinetics. J Clin Pharmacol. 2004;44:715-22.
  • Dvorchik B, Damphousse D. Singledose pharmacokinetics of daptomycin in young and geriatric volunteers. J Clin Pharmacol. 2004; 44:612-20.
  • Kullar, R., Casapao, A., Davis, S., Levine, D., Zhao, J., Crank, C., Segreti, J., Sakoulas, G., Cosgrove, S. and Rybak, M. 2013. A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis. Journal of Antimicrobial Chemotherapy. 68(12),pp.2921-2926.
  • Schriever C et al. Daptomycin: A novel cyclic lipopeptide antimicrobial American Journal of Health-System Pharmacy 2005: Vol. 62, Issue 11, 1145-1158
  • Seaton, R., Menichetti, F., Dalekos, G., Beiras-Fernandez, A., Nacinovich, F., Pathan, R. and Hamed, K. 2015. Evaluation of Effectiveness and Safety of High-Dose Daptomycin: Results from Patients Included in the European Cubicin® Outcomes Registry and Experience. Advances in Therapy. 32(12),pp.1192-1205.
  • Silverman JA, Perlmutter NG, Shapiro HM. Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus. Antimicrob Agents Chemother 2003; 47: 2538–44.
  • Specialist Pharmacy Service. 2018. Daptomycin [Online]. Available from: Daptomycin – Medicines – SPS - Specialist Pharmacy Service – The first stop for professional medicines advice. Accessed: 18/08/21.
  • Summary of Product Characteristics. Cubicin® powder for concentrate for solution for infusion. Date of revision of text 08 August 2018. Merck Sharp & Dohme https://www.medicines.org.uk/emc/medicine/17341 Assessed 14th February 2019.

Approved By

Drug and Therapeutics Committee

Document history

LHP version 3.0

Related information

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