Daptomycin

As well as standard dosing, higher dosing (off-label) may be used in certain situations, table below of suggestions. 

Dosing should be rounded to whole vials were possible (see below) and be adjusted in special population (e.g. obesity – see below).

For difficult-to-treat, infections (including bacteraemia) caused by E. faecium, infection specialists may recommend increasing to 12mg/kg once daily.

*Use actual body weight, or if body mass index (BMI) is ≥ 30 kg/m² then use adjusted body weight (see Dosing in Obesity section below).

Rounding of dose:

• Where possible use whole vials (350mg and 500mg vial strengths available)
• Round up to the nearest 50mg dose.
• Dose rounding may result in a higher mg/kg dose than recommended above. Doses > 12 mg/kg are not recommended.  Discuss with pharmacy if the dose is unclear.

Dosing in obesity

Dosing should be adjusted for patients with BMI ≥ 30 kg/m². Please ensure up to date measurements are obtained.

If the patients BMI ≥ 30 kg/m² use adjusted body weight equation to calculate weight (kg) for daptomycin dosing:

Adjusted body weight = (0.4 x (actual body weight – ideal body weight) + ideal body weight

Ideal body weight can be obtained from Ideal Body Weight Chart.

Dosing in renal impairment

The following dosing is suggested:

Creatinine clearance (CrCl) between 30-50 ml/min, dose as in normal renal function.

Information on optimal dosing and efficacy in creatinine clearance (CrCl) <30 ml/min is limited.

CrCl <30 ml/min, suggest dose every 48 hours. More frequent monitoring is required (see below for monitoring requirements).

For patients on renal replacement therapy please seek specialist pharmacy for advice.

Creatinine clearance can be calculated from Creatinine Clearance & Weight Charts.

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Renal function and plasma creatinine phosphokinase (CK) should be monitored at baseline and at least weekly thereafter. More frequent monitoring (twice weekly) may be required in renal impairment or those at risk of developing myopathy (e.g. patients on statins). 

CK is a surrogate marker for toxicity (e.g. myopathy, rhabdomyolysis). Daptomycin should be discontinued if:

• Symptomatic (e.g. myopathy, rhabdomyolysis) rise in CK observed (especially if CK > 5 times upper normal limit)
• Asymptomatic rise in CK observed (CK > 10 times upper limit normal)

Routine daptomycin therapeutic drug monitoring is not recommended because there is no clear evidence that links daptomycin concentration monitoring with clinical outcome.  However, daptomycin trough concentrations may be useful in patients requiring renal replacement therapy (e.g. three weekly haemodialysis) to predict toxicity (in this instance, please seek specialist pharmacy advice).

Daptomycin levels are a ‘send away’ test; please refer to laboratory medicine web pages Test Directory | Edinburgh and Lothians Laboratory Medicine (edinburghlabmed.co.uk)

Contraindications

Known hypersensitivity to Daptomycin.

Daptomycin is not effective in lung tissue and should be avoided in patients with significant pulmonary disease (pneumonia or lung abscess) but can be used in patients with endocarditis with septic pulmonary emboli.

Cautions and adverse effects

Daptomycin is usually well tolerated. Common adverse effects include gastrointestinal disturbance, and abnormal liver function tests. Uncommon side effects are myopathy and rhabdomyolysis and of unknown frequency peripheral neuropathy and severe cutaneous adverse reaction.

Where possible concomitant administration of daptomycin with other drugs which may cause myopathies e.g. statins, sodium fusidate, should be avoided. If a statin is continued, twice weekly CK monitoring is recommended.

A rare but serious side effect is eosinophilic pneumonitis, if this reaction is suspected stop daptomycin and discuss with an infection specialist immediately. This is not an exhaustive list, refer to BNF or SPC.