Mechanism of Action of Daptomycin
Daptomycin is a cyclic lipopeptide natural product that is active against Gram positive bacteria only.
The mechanism of action involves binding (in the presence of calcium ions) to bacterial membranes of both growing and stationary phase cells causing depolarisation and leading to a rapid inhibition of protein, DNA, and RNA synthesis. This results in bacterial cell death with negligible cell lysis.
Drug Label Information | Brands:
BRANDS OF DAPTOMYCIN IN KENYA
NB: No brands registered yet.
Daptomycin is indicated for the treatment of the following infections:.
– Adult and paediatric (1 to 17 years of age) patients with complicated skin and soft-tissue infections (cSSTI).
– Adult patients with right-sided infective endocarditis (RIE) due to Staphylococcus aureus. It is recommended that the decision to use daptomycin should take into account the antibacterial susceptibility of the organism and should be based on expert advice.
– Adult and paediatric (1 to 17 years of age) patients with Staphylococcus aureus bacteraemia (SAB). In adults, use in bacteraemia should be associated with RIE or with cSSTI, while in paediatric patients, use in bacteraemia should be associated with cSSTI.
Daptomycin is active against Gram positive bacteria only . In mixed infections where Gram negative and/or certain types of anaerobic bacteria are suspected, Daptomycin should be co-administered with appropriate antibacterial agent(s).
DOSAGE AND ADMINISTRATION:
– cSSTI without concurrent SAB: Daptomycin 4 mg/kg is administered once every 24 hours for 7-14 days or until the infection is resolved
– cSSTI with concurrent SAB: Daptomycin 6 mg/kg is administered once every 24 hours. The duration of therapy may need to be longer than 14 days in accordance with the perceived risk of complications in the individual patient.
– Known or suspected RIE due to Staphylococcus aureus: Daptomycin 6 mg/kg is administered once every 24 hours. The duration of therapy should be in accordance with available official recommendations.
Daptomycin is administered intravenously in 0.9% sodium chloride . Daptomycin should not be used more frequently than once a day.
Daptomycin is contraindicated in patients with known hypersensitivity to it.
ADVERSE DRUG REACTIONS:
Infections and infestations
Common: Fungal infections, urinary tract infection, candida infection
Not known:Clostridium difficile-associated diarrhoea
Blood and lymphatic system disorders
Uncommon: Thrombocythaemia, eosinophilia, international normalised ratio (INR) increased, leukocytosis
Rare: Prothrombin time (PT) prolonged
Not known: Thrombocytopaenia
Immune system disorders
Not known: Hypersensitivity, manifested by isolated spontaneous reports including, but not limited to angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), pulmonary eosinophilia, vesicobullous rash with mucous membrane involvement and sensation of oropharyngeal swelling, anaphylaxis, infusion reactions including the following symptoms: tachycardia, wheezing, pyrexia, rigors, systemic flushing, vertigo, syncope and metallic taste
Metabolism and nutrition disorders
Uncommon: Decreased appetite, hyperglycaemia, electrolyte imbalance
Common: Anxiety, insomnia
Nervous system disorders
Common: Dizziness, headache
Uncommon: Paraesthesia, taste disorder, tremor, eye irritation
Not known: Peripheral neuropathy
Ear and labyrinth disorders
Uncommon: Supraventricular tachycardia, extrasystole
Common: Hypertension, hypotension
Respiratory, thoracic and mediastinal disorders
Not known: Eosinophilic pneumonia1, cough
Common: Gastrointestinal and abdominal pain, nausea, vomiting, constipation, diarrhoea, flatulence, bloating and distension
Uncommon: Dyspepsia, glossitis
Common: Liver function tests abnormal2 (increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP))
Skin and subcutaneous tissue disorders
Not known*: Acute generalised exanthematous pustulosis
Musculoskeletal and connective tissue disorders
Common: Limb pain, serum creatine phosphokinase (CPK)2 increased
Uncommon: Myositis, increased myoglobin, muscular weakness, muscle pain, arthralgia, serum lactate dehydrogenase (LDH) increased, muscle cramps
Not known: Rhabdomyolysis
Renal and urinary disorders
Uncommon: Renal impairment, including renal failure and renal insufficiency, serum creatinine increased
Reproductive system and breast disorders
General disorders and administration site conditions
Common: Infusion site reactions, pyrexia, asthenia
Uncommon: Fatigue, pain
Daptomycin undergoes little to no Cytochrome P450 (CYP450)-mediated metabolism. It is unlikely that daptomycin will inhibit or induce the metabolism of medicinal products metabolised by the P450 system.
Inhibitors of HMG-CoA reductase may cause myopathy, which is manifested as muscle pain or weakness associated with elevated levels of creatine phosphokinase (CPK).
Caution is warranted when Daptomycin is co-administered with tobramycin.