Intravenous Complicated skin and skin structure infections
Adult: 4 mg/kg once daily for 7-14 days given via infusion over 30 minutes or by injection over 2 minutes. Child: 1-<2 years 10 mg/kg once daily via infusion over 60 minutes. 2-6 years 9 mg/kg once daily via infusion over 60 minutes. 7-11 years 7 mg/kg once daily via infusion over 30 minutes. 12-17 years 5 mg/kg once daily via infusion over 30 minutes. All doses are given for 14 days.
Intravenous Staphylococcus aureus bacteraemia
Adult: 6 mg/kg once daily for 2-6 weeks given via infusion over 30 minutes. Child: 1-6 years 12 mg/kg once daily via infusion over 60 minutes. 7-11 years 9 mg/kg once daily via infusion over 30 minutes. 12-17 years 7 mg/kg once daily via infusion over 30 minutes. Treatment duration may vary according to clinical response for up to 42-44 days.
Reconstitute vial labelled as 500 mg or 350 mg with 10 mL and 7 mL of 0.9% NaCl injection respectively. Gently rotate the vial to wet the powder and allow to stand for 10 minutes. Then, gently swirl or rotate the vial for a few minutes to obtain a clear reconstituted solution. Do not shake/agitate vial vigorously. For IV infusion, further dilute the reconstituted solution with 50 mL 0.9% NaCl injection.
Incompatibility
Dextrose-containing solutions.
Contraindications
Hypersensitivity.
Special Precautions
Patient with persisting or relapsing Staphylococcus aureus bacteraemia or endocarditis. Renal impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Eosinophillic pneumonia, drug reaction with eosinophilia and systemic symptoms (DRESS), hypersensitivity reactions, anaphylaxis, myopathy/rhabdomyolysis, peripheral neuropathy; fungal or bacterial superinfection, including C. difficile-associated diarrhoea (prolonged use); tubulointerstitial nephritis. Blood and lymphatic system disorders: Anaemia. Cardiac disorders: Supraventricular tachycardia, extrasystole. Ear and labyrinth disorders: Vertigo. Gastrointestinal disorders: Abdominal pain, nausea, vomiting, constipation, diarrhoea, flatulence, bloating, distention, dyspepsia, glossitis. General disorders and administration site conditions: Infusion site reactions, pyrexia, asthenia. Infections and infestations: Fungal infection, urinary tract infection, candida infection, fungaemia. Investigations: Increased INR, ALT, AST, alkaline phosphatase, creatinine phosphokinase. Metabolism and nutrition disorders: Decreased appetite, hyperglycaemia, electrolyte imbalance. Musculoskeletal and connective tissue disorders: Limb pain. Nervous system disorders: Dizziness, headache. Psychiatric disorders: Anxiety, insomnia. Skin and subcutaneous tissue disorders: Rash, pruritus. Vascular disorders: Hypertension, hypotension. Potentially Fatal: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), pseudomembranous colitis.
Monitor CPK at least weekly during therapy. Monitor for signs and symptoms of eosinophilic pneumonia, muscle pain or weakness (especially in distal extremities), new onset or worsening peripheral neuropathy.
Drug Interactions
Enhanced adverse/toxic effects (e.g. myopathy) with HMG-CoA reductase inhibitors (e.g. simvastatin). Increased plasma concentration with NSAIDs. Synergistic antibacterial effects against staphylococci and enterococci with aminoglycosides, rifampicin, and β-lactam anti-infectives.
Lab Interference
False prolongation of prothrombin time (PT) and elevation of INR.
Action
Description: Mechanism of Action: Daptomycin is a cyclic lipopeptide antibacterial. It binds to bacterial cell membranes and causes rapid depolarisation thereby leading to inhibition of DNA, RNA and protein synthesis thus resulting in bacterial cell death. Pharmacokinetics: Absorption: Time to peak plasma concentration: 0.5-0.8 hours. Distribution: Primarily distributed into extracellular space. Crosses the blood-brain barrier and placenta. Volume of distribution: 0.1 L/kg. Plasma protein binding: 90-93%, mainly to serum albumin. Metabolism: Little or no metabolism is known, although minor amounts of oxidative metabolites have been detected. Excretion: Via urine (78%, primarily as unchanged drug); faeces (approx 6%). Elimination half-life: 8-9 hours.
Chemical Structure
Daptomycin Source: National Center for Biotechnology Information. "PubChem Compound Summary for CID 16134395, Daptomycin" PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Daptomycin. Accessed 27 October, 2021.
Storage
Store between 2-8°C. Avoid excessive heat. Reconstituted solution: Store at 25°C, stable for 12 hours; or between 2-8°C, stable for 24 hours.
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