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| Primary information |
|---|
| ID | 10409 |
| Therapeutic ID | Th1067 |
| Protein Name | Daptomycin |
| Sequence | NA
|
| Molecular Weight | 1620.693 |
| Chemical Formula | C72H101N17O26 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Normal range: 7.5-9 hours 27.83 ± 14.85 hours in patients with creatinine clearance <30 mL/min |
| Description | Daptomycin is a lipopeptide antibiotic that kills susceptible gram positive bacteria by disrupting their membrane potential. It is a naturally-occurring compound found in the soil bacterium <i>Streptomyces roseosporus</i>. Antibiotics are used in the treatment of infections caused by bacteria. They work by killing bacteria or preventing their growth. Daptomycin will not work for colds, flu, or other virus infections. It was approved in September 2003 for the treatment of complicated skin and soft tissue infections. It has a safety profile similar to other agents commonly administered to treat gram-positive infections. |
| Indication/Disease | For the treatment of complicated skin and skin structure infections caused by susceptible strains of Gram-positive microorganisms. |
| Pharmacodynamics | Daptomycin is a 13 member amino acid cyclic lipopeptide antibiotic active against Gram-positive bacteria only. It has proven in vitro activity against enterococci (including glycopeptide-resistant Enterococci (GRE)), staphylococci (including methicillin-resistant <i>Staphylococcus aureus</i>), streptococci and corynebacteria. Daptomycin is derived from the fermentation product of Streptomyces roseosporus.
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| Mechanism of Action | Daptomycin appears to bind or insert into the outer membrane of gram positive bacteria. The binding and integration of daptomycin into the cell membrane is calcium dependent. Calcium ions cause a conformational change in daptomycin, augmenting its amphipathicity (hydrophilic head group and hydrophobic tail group), leading to incorporation into the cell membrane.
This binding causes rapid depolarisation, resulting in a loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis, which results in bacterial cell death. The bactericidal activity of daptomycin is concentration-dependent. There is in vitro evidence of synergy with β-lactam antibiotics. |
| Toxicity | NA |
| Metabolism | Minor amounts of three oxidative metabolites and one unidentified compound have been detected in urine. The site of metabolism has not been identified. |
| Absorption | NA |
| 0.1 L/Kg [healthy adult subjects] |
| Clearance | As daptomycin is primarily renally excreted, patients with mild, moderate, and severe renal impairment had reduced total plasma clearance 9, 22, and 46 percent lower than healthy controls, respectively. Daptomycin clearance was also lower in obese (15-23%) and geriatric (aged 75 and older, by 35%) patients, whereas it tended to be higher in pediatric patients, even when normalized for body weight |
| Categories | Agents Causing Muscle Toxicity, Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Antibacterials for Systemic Use, Antiinfectives for Systemic Use, Cyclic Lipopeptides, Drugs that are Mainly Renally Excreted, Lipids, Lipopeptide Antibacterial, Lipopeptides, P-glycoprotein substrates, Peptides, Peptides, Cyclic |
| Patents Number | US6468967 |
| Date of Issue | 22-Oct-2002 |
| Date of Expiry | 24-Sep-2019 |
| Drug Interaction | NA |
| Target | Cytoplasmic membrane |
| Brand Name | CUBICIN |
| Company | Cubist Pharmaceuticals, Inc |
| Brand Description | Cubist Pharmaceuticals, Inc |
| Prescribed For | Complicated skin and skin structure infections (cSSSI), Staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates |
| Chemical Name | N-decanoyl-L-tryptophyl-Dasparaginyl-L-aspartyl-L-threonylglycyl-L-ornithyl-L-aspartyl-D-alanyl-L-aspartylglycyl-Dseryl-threo-3-methyl-L-glutamyl-3-anthraniloyl-L-alanine ε1-lactone |
| Formulation | CUBICIN contains 500 mg of daptomycin and reconstituted with 0.9% sodium chloride injection. The only inactive ingredient is sodium hydroxide, which is used in minimal quantities for pH adjustment. |
| Physical Appearance | CUBICIN is a Sterile, preservative-free, pale yellow to light brown, lyophilized cake containing approx 500 mg of daptomycin |
| Route of Administration | Intravenous (Intravenous) Injection |
| Recommended Dosage | CUBICIN 4 mg/kg should be administered intravenously in 0.9% sodium chloride injection once every 24 hours for 7 to 14 days. Staphylococcus aureus Bloodstream Infections (Bacteremia) - CUBICIN 6 mg/kg should be administered intravenously in 0.9% sodium chloride injection once every 24 hours for 2 to 6 weeks. |
| Contraindication | CUBICIN is contraindicated in patients with known hypersensitivity to daptomycin |
| Side Effects | fatigue, weakness, rigors, flushing, hypersensitivity, leukocytosis, thrombocytopenia, thrombocytosis, eosinophilia, increased International Normalized Ratio (INR), supraventricular arrhythmia, eczema, abdominal distension, stomatitis, jaundice, increased serum lactate dehydrogenase, hypomagnesemia, increased serum bicarbonate, electrolyte disturbance, myalgia, muscle cramps, muscle weakness, arthralgia, vertigo, mental status change, paresthesia, taste disturbance, eye irritation |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |