Daptomycin

Trade Names:Cubicin- Powder for injection, lyophilized 500 mg

Pharmacology

Binds to bacterial membranes and causes a rapid depolarization of membrane potential, which inhibits protein, DNA, and RNA synthesis, resulting in bacterial cell death.

Pharmacokinetics

Absorption

At a dose of 4 mg/kg, steady-state concentrations are achieved by the third daily dose. The mean steady-state trough concentration (days 4 to 8) is 5.9 mcg/mL.

Distribution

Vd at steady state is approximately 0.1 L/kg. The mean serum protein binding is approximately 92% following a dose of 4 mg/kg.

Elimination

Primarily excreted by the kidney (78%).

Special Populations

Dosage adjustment is needed in patients with severe renal function impairment (Ccr less than 30 mL/min).

Indications and Usage

Treatment of complicated skin and skin structure infections caused by susceptible strains of gram-positive microorganisms; treatment of Staphylococcus aureus bloodstream infections, including those with right-sided infective endocarditis caused by methicillin-susceptible and methicillin-resistant isolates.

Contraindications

Standard considerations.

Dosage and Administration

IV 4 mg/kg/day administered over a 30-min infusion every 24 h for 7 to 14 days.

IV 6 mg/kg over a 30-min infusion every 24 h for 2 to 6 wk.

IV For patients with Ccr less than 30 mL/min, including those on hemodialysis or continuous ambulatory peritoneal dialysis, administer 4 mg/kg for complicated skin and skin structure infections or 6 mg/kg for S. aureus bloodstream infections once every 48 h.

General Advice

• Reconstitute powder using 10 mL of sodium chloride 0.9% injection.
• Reconstituted solution must be further diluted in sodium chloride 0.9% injection before infusing.
• Reconstituted solution may have a pale yellow to light brown color.
• If other drugs are being administered through same IV line, flush IV line before and after infusion of daptomycin with sodium chloride 0.9% injection or Ringer's lactate injection.
• Do not mix with dextrose-containing diluents.

Storage/Stability

Store vials in refrigerator (36° to 46°F). Reconstituted solution is stable for 12 h at room temperature (68° to 77°F) or up to 48 h if stored under refrigeration. The diluted solution is stable for 12 h at room temperature or up to 48 h if stored under refrigeration. The combined time (reconstituted vial and infusion bag) at room temperature should not exceed 12 h; the combined time (reconstituted vial and infusion bag) under refrigeration should not exceed 48 h.

Drug Interactions

If possible, consider temporarily discontinuing HMG-CoA reductase inhibitors, which have been known to cause rhabdomyolysis, until therapy has been completed.

C _max and AUC of daptomycin increased 12.7% and 8.7%, respectively, when administered with tobramycin.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (6%); hypotension (5%); cardiac failure (1% to 2%).

CNS

Insomnia (9%); headache (7%); dizziness (6%); anxiety, asthenia (5%); confusion (1% to 2%).

Dermatologic

Rash (7%); pruritus (6%); erythema, increased sweating (5%).

EENT

Pharyngolaryngeal pain (8%); sore throat (1% to 2%).

GI

Diarrhea, vomiting (12%); constipation (11%); nausea (10%); abdominal pain (6%); dyspepsia, loose stools (4%); GI hemorrhage (2%).

Genitourinary

Decreased renal function (11%); UTI (7%); acute renal failure, renal failure (3%); vaginal candidiasis (2%).

Hematologic

Anemia (13%); eosinophilia (2%).

Hepatic

Abnormal LFTs (3%).

Lab Tests

Elevated CPK (9%); increased blood phosphorus (3%); increased INR ratio (2%).

Local

Injection-site erythema (3%).

Metabolic-Nutritional

Hypokalemia (9%); edema (7%); hyperkalemia (5%); hyperglycemia, hypoglycemia (1% to 2%).

Musculoskeletal

Pain in extremity (9%); back pain (7%); osteomyelitis (6%); arthralgia (3%); limb pain (2%); rhabdomyolysis (postmarketing).

Respiratory

Pleural effusion (6%); cough, dyspnea, pneumonia (3%).

Miscellaneous

Chest pain, peripheral edema, pyrexia (7%); injection-site reactions (6%); bacteremia, sepsis (5%); fungal infections (3%); back pain, Candida infections, cellulitis, decreased appetite (1% to 2%); anaphylaxis, hypersensitivity reactions (including difficulty swallowing, hives, pruritus, shortness of breath, truncal erythema) (postmarketing).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Dosage adjustment is needed in patients with severe renal function impairment (Ccr less than 30 mL/min).

Superinfection

May result in bacterial or fungal overgrowth of nonsusceptible microorganisms.

Elevated CPK

Discontinue daptomycin in patients with unexplained signs and symptoms of myopathy in conjunction with CPK elevation of more than 1,000 units/L (approximately 5 × ULN), or in patients without reported symptoms who have marked elevations in CPK of more than 2,000 units/L (at least 10 × ULN).

Persisting or relapsing S. aureus infection

Perform repeat blood cultures. If culture is positive for S. aureus , perform minimum inhibitory concentration susceptibility testing of the isolate, as well as diagnostic evaluation. Consider appropriate surgical intervention and changes in the antibiotic regimen.

Pseudomembranous colitis

Consider the possibility in patients who develop diarrhea.

Patient Information

• Advise patient, family, or caregiver that medication will be prepared and administered by a health care provider in a health care setting.
• Advise patient to report injection-site pain or redness; muscle weakness, pain, or tenderness; or abnormal sensations in the legs or arms (eg, pain, numbness) to health care provider.
• Advise patient to report the following signs of superinfection to health care provider: black, furry tongue; foul-smelling stools; vaginal itching or discharge; white patches in mouth.
• Warn patient that diarrhea containing blood or pus may be a sign of a serious disorder and to seek medical care if noted and not treat at home.

Copyright © 2009 Wolters Kluwer Health.