daptomycin

Action and Spectrum

Mechanism of action 

The mechanism of action of daptomycin involves binding to the bacterial cell membrane and causing the release of intracellular potassium ions, leading to depolarization of the membrane. This depolarization disrupts the ability of the bacterium to synthesize proteins, DNA, and other essential molecules, leading to cell death. 

Spectrum 

The spectrum of activity of daptomycin includes: 

• Staphylococcus aureus (including MRSA) 
• Streptococcus species (including Streptococcus pneumoniae and Streptococcus pyogenes) 
• Enterococcus species (including Enterococcus faecalis and Enterococcus faecium) 

Drug Interaction

Adverse Reaction

Frequency defined:  

1-10% 

Pharyngolaryngeal pain 

Elevated blood creatinine phosphokinase 

Abdominal pain 

Pruritis 

Diarrhea 

Bacteremia 

Rash  

UTI 

Dizziness 

Insomnia 

Chest pain 

Edema 

Hypertension 

Headache 

Sweating  

Sepsis 

Abnormal LFT 

Hypotension 

Dyspnea 

Post-marketing reports 

Eosinophilic pneumonia 

Visual disturbances 

Anemia 

Pyrexia 

Peripheral neuropathy 

Rhabdomyolysis 

Pyrexia 

Renal insufficiency 

Toxic epidermal necrolysis 

Black Box Warning

Contraindication / Caution

Contraindications 

• Hypersensitivity: It is contraindicated in patients with a known hypersensitivity to daptomycin or its components. 
• Neuromuscular disorders: It should be used cautiously in patients with neuromuscular disorders, such as myasthenia gravis, because it may exacerbate these conditions. 
• Renal impairment: It is eliminated through the kidneys, so it should be used cautiously in patients with severe renal impairment. 
• Pregnancy: There is limited data on the use of daptomycin in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 
• Breastfeeding: It is not known whether daptomycin is excreted in human milk. It should be used with caution by nursing mothers. 

Cautions 

• Neuromuscular disorders: It should be used cautiously in patients with neuromuscular disorders, such as myasthenia gravis, because it may exacerbate these conditions. 
• Renal impairment: It is eliminated through the kidneys, so it should be used with caution in patients with renal impairment. The dosage may need to be adjusted in patients with severe renal impairment. 
• Electrolyte disturbances may cause electrolyte disturbances, such as hypokalemia and hypocalcemia. It is recommended to monitor electrolytes periodically during treatment. 
• Myopathy: It may cause myopathy, including myositis and rhabdomyolysis. It is recommended to monitor for signs and symptoms of myopathy, such as muscle weakness, pain, or tenderness. 
• Drug interactions: It may interact with other medications, such as anticoagulants and statins. It is important to inform a healthcare provider of all medications being taken, including prescription and over-the-counter drugs, as well as herbal supplements. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is known 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology 

Daptomycin is a cyclic lipopeptide antibiotic that works by binding to the bacterial cell membrane and disrupting the normal function of the membrane. This leads to a rapid depolarization of the membrane potential, which can cause inhibition of protein, DNA, and RNA synthesis, leading to bacterial cell death. 

Pharmacodynamics 

The pharmacodynamics of daptomycin involves its interaction with the bacterial cell membrane and the inhibition of cell wall synthesis. Daptomycin binds to the lipid membranes of bacteria, disrupting the membrane potential and releasing enzymes that lyse the cell. It also inhibits the cell wall synthesis, which is essential for the structural integrity and survival of the bacteria. 

Pharmacokinetics 

Absorption 

The peak plasma concentration for a 4 mg/kg dose is 58 mcg/mL and occurs at a peak plasma time of 0.5-0.8 hr. For a 6 mg/kg dose, the peak plasma concentration is 94 mcg/mL. 

The AUC for a 4 mg/kg dose of daptomycin is 494 mcg•hr/mL, and the AUC for a 6 mg/kg dose is 632 mcg•hr/mL. 

Distribution 

It has a high protein binding percentage of 92%, which means that a significant portion of the drug is bound to proteins in the bloodstream. 

The Vd is 0.1 L/kg, which is relatively low and indicates that the drug is highly concentrated in the plasma and not widely distributed throughout the body. 

Metabolism 

It is metabolized in the liver and is primarily excreted in the urine.  

Elimination/excretion 

The half-life of daptomycin is 8 hr, which means that it is eliminated from the body relatively quickly. 

Daptomycin is dialyzable, with 11-15% of the dose being removed by continuous ambulatory peritoneal dialysis or hemodialysis. 

The renal clearance of daptomycin is 3.7-4.8 mL/hr/kg. The total body clearance of daptomycin is 8-9 mL/hr/kg. The main route of excretion for daptomycin is through the urine, with 78% of the drug being eliminated through this route. The remainder of the drug is eliminated through other routes, including feces and bile. 

Adminstartion

Administration 

It is typically administered intravenously (IV) as a solution. It is given as a daily dose and should be administered over 30-60 minutes to minimize the risk of infusion-related reactions. 

IV incompatibilities 

It should not be mixed with dextrose-containing diluents in the same IV bag or administered through the same IV line as other drugs.  

This is because dextrose can interact with the drug and potentially decrease its stability and effectiveness. 

Daptomycin should not be mixed with other medications in the same IV bag or administered through the same IV line. This minimizes the risk of drug-drug interactions and ensures that the drug’s total dosage is delivered to the patient. 

IV compatibilities 

It is compatible with 0.9% NaCl (sodium chloride) and LR (lactated Ringer’s) solutions. This means that it can be mixed with these solutions in the same IV bag or administered through the same IV line without the risk of chemical reactions or drug degradation 

Patient Information Leaflet

Patient information leaflet 

Generic Name: daptomycin 

Pronounced: [ DAP-to-my-sin ] 

Why do we use daptomycin? 

A cyclic lipopeptide antibiotic called daptomycin is used to treat bacteremia brought on by Staphylococcus aureus and complex skin and skin structure infections caused by sensitive Gram-positive bacteria