DAPTOMYCIN
Clinical safety rating: safe
Animal studies have demonstrated safety
Calcium-dependent binding to bacterial membranes, causing depolarization and inhibition of protein, DNA, and RNA synthesis.
| Metabolism | Minimally metabolized; renally excreted primarily as unchanged drug. |
| Excretion | Renal excretion of unchanged drug: approximately 78% (range 76-80%). Minimal biliary/fecal elimination (<5%). |
| Half-life | Terminal half-life: approximately 8-9 hours in patients with normal renal function. Prolonged in renal impairment; requires dose adjustment for CrCl <30 mL/min. |
| Protein binding | 90-95% bound, primarily to albumin. Binding is reversible and concentration-dependent. |
| Volume of Distribution | Steady-state Vd: approximately 0.1 L/kg. Low Vd indicates limited extravascular distribution; primarily distributes into extracellular fluid. |
| Bioavailability | Not available orally; intravenous administration only (100% bioavailability via IV route). |
| Onset of Action | Intravenous: Bactericidal activity begins within 1-2 hours post-infusion, with time-dependent killing. |
| Duration of Action | Duration: 12-24 hours. Once-daily dosing achieves sustained bactericidal concentrations. Post-antibiotic effect: approximately 2-6 hours against susceptible gram-positive organisms. |
4-6 mg/kg intravenously once daily.
| Dosage form | POWDER |
| Renal impairment | CrCl >= 30 mL/min: no adjustment; CrCl < 30 mL/min: 4-6 mg/kg every 48 hours. |
| Liver impairment | No dose adjustment required for Child-Pugh class A, B, or C. |
| Pediatric use | 1-6 years: 10 mg/kg IV once daily; 7-11 years: 9 mg/kg IV once daily; 12-17 years: 7 mg/kg IV once daily. |
| Geriatric use | No specific dose adjustment; monitor renal function and use same dosing as adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
HMG-CoA reductase inhibitors may increase risk of myopathy May cause myopathy and rhabdomyolysis monitor CPK levels.
| Breastfeeding | Not recommended. Unknown if excreted in human milk; M/P ratio not available. Discontinue nursing or drug. |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies show no fetal harm, but no adequate human studies. Use only if clearly needed. |
| Fetal Monitoring | Monitor for maternal adverse effects: CPK levels weekly, renal function, signs of myopathy. No specific fetal monitoring required. |
■ FDA Black Box Warning
None.
| Common Effects | Myopathy |
| Serious Effects |
["Hypersensitivity to daptomycin"]
| Precautions | ["Myopathy and rhabdomyolysis (monitor CPK levels)","Eosinophilic pneumonia","Peripheral neuropathy","Clostridioides difficile-associated diarrhea","Decreased efficacy in patients with moderate to severe renal impairment"] |
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| Fertility Effects | No known effects on fertility in animal studies. |