INTRAVENOUS DAPTOMYCIN ANTIMICROBIAL PRESCRIBING GUIDELINES

• Drug information
• Adult patients
• Paediatric patients
• Renal impairment
• Special dosing considerations
• Monitoring
• Other useful information

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:

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

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

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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:

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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.