Daptomycin

Daptomycin Chemical Structure: Daptomycin in Kenya

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.

INDICATIONS

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.

CONTRAINDICATIONS:

Daptomycin is contraindicated in patients with known hypersensitivity to it.

ADVERSE DRUG REACTIONS:

Infections and infestations

Common: Fungal infections, urinary tract infection, candida infection
Uncommon: Fungaemia
Not known:Clostridium difficile-associated diarrhoea

Blood and lymphatic system disorders

Common: Anaemia
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

Psychiatric disorders

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: Vertigo

Cardiac disorders

Uncommon: Supraventricular tachycardia, extrasystole

Vascular disorders

Common: Hypertension, hypotension
Uncommon: Flushes

Respiratory, thoracic and mediastinal disorders

Not known: Eosinophilic pneumonia1, cough

Gastrointestinal disorders

Common: Gastrointestinal and abdominal pain, nausea, vomiting, constipation, diarrhoea, flatulence, bloating and distension
Uncommon: Dyspepsia, glossitis

Hepatobiliary disorders

Common: Liver function tests abnormal2 (increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP))
Rare: Jaundice

Skin and subcutaneous tissue disorders

Common:Rash, pruritus
Uncommon: Urticaria
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

Uncommon: Vaginitis

General disorders and administration site conditions

Common: Infusion site reactions, pyrexia, asthenia
Uncommon: Fatigue, pain

DRUG INTERACTIONS:

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.