Daptomycin

Standard licensed dose: 4-6 mg/kg OD IV

Doses up to 12mg/kg OD may be recommended by a Micro/ID consultant or registrar

In obese patients (BMI 30 or more) doses of 8-12mg/kg should be based on Adjusted Bodyweight (AdjBW). The DynaMedex adjusted bodyweight calculator can be used.

Doses of daptomycin should not typically exceed 1g.

Renal impairment

*dose ranges use creatinine clearance, rather than eGFR

Hepatic impairment

No dose adjustment is necessary in patients with mild or moderate hepatic impairment. Use with caution in severe hepatic impairment as no data available.

Baseline and then minimum weekly monitoring of U&Es, LFTs, FBC, Creatine Kinase (CK). More frequent monitoring may be indicated for higher doses, impaired renal function (CrCl less than 80ml/min), pre-existing raised LFTs or CK, or taking other medicines that increase CK.

Myopathy, myositis, myoglobinaemia and rhabdomyolysis – daptomycin is associated with raised CK levels and with muscular pain and weakness. Patients should be advised to report any new muscle symptoms and reviewed regularly during treatment. Asymptomatic rises in CK should be carefully reviewed, especially if over 5x upper limit of normal, discussion with Micro/ID may be required. Patients with low serum albumin (less than 25g/L) may be at higher risk of these adverse effects.

Eosinophilic pneumonitis – daptomycin is associated with eosinophilic pneumonia and pulmonary eosinophilia, in severe cases, hypoxic respiratory insufficiency requiring mechanical ventilation may occur. Patients should be monitored for new onset respiratory symptoms. If a reaction is suspected daptomycin should be stopped immediately. See MHRA drug safety update - Daptomycin: risk of eosinophilic pneumonia. Patients with low serum albumin (less than 25g/L) may be at higher risk of this adverse effect.

Peripheral neuropathy -Patients who develop signs or symptoms that might represent a peripheral neuropathy during therapy with daptomycin should be investigated.

Severe cutaneous adverse reactions including drug reaction with eosinophilia and systemic symptoms (DRESS) and vesiculobullous rash with or without mucous membrane involvement (Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN) have been reported with daptomycin. Daptomycin use should be immediately reviewed if skin and/or mucosal reactions occur.

Tubulointerstitial nephritis has been reported in post-marketing experience with daptomycin. Patients who develop fever, rash, eosinophilia and/or new or worsening renal impairment while receiving daptomycin should have treatment reviewed. If suspected stop daptomycin and manage appropriately.

Statins, fibrates and ciclosporin: additive risk of rhabdomyolysis or raised CK. Where possible these drugs should be withheld during daptomycin therapy. If not possible then:

• CK should be monitored more frequently than once weekly (e.g. every 2-3 days at least during the first two weeks of treatment then more frequently than once weekly)

      AND

• patients should be closely monitored for any signs or symptoms that might represent myopathy. 

Vitamin K antagonists: Appropriate monitoring should be undertaken. It would be prudent to monitor coagulation status within 3 days of starting or stopping daptomycin.

This is not a complete list. Please see the BNF, Summary of Product Characteristics or speak to a pharmacist.

Pregnancy

Animal data and limited human data suggest safe. Use if expected benefit outweighs the possible risk.

Breastfeeding

Limited data suggest safe - present in milk in small amounts, but absorption from gastrointestinal tract negligible 

• Cipla EU Ltd. Daptomycin 500 mg powder for solution for injection or infusion summary of product characteristics. Electronic Medicines Compendium [Internet]. 2024 [cited 2024 Mar 13]. Available from: https://www.medicines.org.uk/emc/product/14666/smpc Last update: 22/1/2024
• Scottish Antimicrobial Prescribing Group. Daptomycin: adult outpatient parenteral antimicrobial therapy (OPAT) good practice prescribing guide [Internet]. 2023 [cited 2024 Mar 13]. Available from: https://rightdecisions.scot.nhs.uk/m/npepdqo1/202302-sapg-opatgoodprescribing-daptomycin.pdf
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• Medicines and Healthcare products Regulatory Agency. Drug Safety Update: Daptomycin: risk of eosinophilic pneumonia [Internet]. 2014 [cited 2024 Mar 13]. Available from: https://www.gov.uk/drug-safety-update/daptomycin-risk-of-eosinophilic-pneumonia
• Garreau R, Pham TT, Bourguignon L, Millet A, Parant F, Bussy D, et al. Daptomycin exposure as a risk factor for daptomycin-induced eosinophilic pneumonia and muscular toxicity. Clinical Infectious Diseases. 2023;77(10):1372-80.
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• Finfer S, Bellomo R, McEvoy S, et al. Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the Saline versus Albumin Fluid Evaluation (SAFE) study. BMJ 2006; 333(7577): 1044