daptomycin

REMS

Complicated skin and skin structure infections caused by gram-positive bacteria.
Staphylococcus aureus
bacteremia, including right-sided infective endocarditis caused by methicillin-susceptible and methicillin-resistant strains (in adults).
Staphylococcus aureus
bacteremia (in pediatric patients).

Action ⬆ ⬇

Causes rapid depolarization of membrane potential following binding to bacterial membrane; this results in inhibition of protein, DNA, and RNA synthesis.

Therapeutic effects:

Death of bacteria with resolution of infection.

Spectrum:

Active against Staphylococcus aureus (including methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, some Streptococcus dysgalactiae, and Enterococcus faecalis (vancomycin-susceptible strains).

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Protein Binding: 92%.

Metabolism/Excretion: Metabolism not known; mostly excreted by kidneys.

Half-Life: 8.1 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity.

Use Cautiously in:

CCr <30 mL/min (dose ↓ required);
Moderate-to-severe renal impairment (may have ↓ clinical response);
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Children 1 yr ( risk of muscular, neuromuscular, and CNS effects; avoid use);
Geri: Older adults may have clinical response with risk of adverse reactions.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, hypotension

Derm: DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), pruritus, rash

GI: ↑liver enzymes, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), constipation, diarrhea, nausea, vomiting

GU: renal impairment

Hemat: anemia

Local: injection site reactions

MS: ↑creatine kinase

Neuro: dizziness

Resp: dyspnea, EOSINOPHILIC PNEUMONIA

Misc: ANGIOEDEMA, fever

Interactions ⬆ ⬇

Drug-drug:

Tobramycin↑ blood levels.
Concurrent HMG-CoA reductase inhibitors may ↑ the risk of myopathy.

Route/Dosage ⬆ ⬇

Complicated Skin/Skin Structure Infections

IV (Adults ): 4 mg/kg every 24 hr for 7–14 days.
IV (Children 12–17 yr): 5 mg/kg every 24 hr for up to 14 days.
IV (Children 7–11 yr): 7 mg/kg every 24 hr for up to 14 days.
IV (Children 2–6 yr): 9 mg/kg every 24 hr for up to 14 days.
IV (Children 1–<2 yr): 10 mg/kg every 24 hr for up to 14 days.

Renal Impairment

IV (Adults ): CCr <30 mL/min: 4 mg/kg every 48 hr for 7–14 days; Hemodialysis and CAPD: 4 mg/kg every 48 hr for 7–14 days with dose administered after hemodialysis on hemodialysis days.

Staphylococcus aureus Bacteremia/Right-Sided Infective Endocarditis

IV (Adults ): 6 mg/kg every 24 hr for 2–6 wk.

Renal Impairment

IV (Adults ): CCr <30 mL/min: 6 mg/kg every 48 hr for 2–6 wk; Hemodialysis and CAPD: 6 mg/kg every 48 hr for 2–6 wk with dose administered after hemodialysis on hemodialysis days.

Staphylococcus aureus Bacteremia

IV (Children 12–17 yr): 7 mg/kg every 24 hr for up to 42 days.
IV (Children 7–11 yr): 9 mg/kg every 24 hr for up to 42 days.
IV (Children 1–6 yr): 12 mg/kg every 24 hr for up to 42 days.

Availability ⬆ ⬇

(Generic available)

Lyophilized powder for injection: 350 mg/vial; 500 mg/vial

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several wk following cessation of therapy.
Monitor for signs and symptoms of eosinophilic pneumonia (new onset or worsening fever, dyspnea, difficulty breathing, new infiltrates on chest imaging studies). Discontinue daptomycin if symptoms occur.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling), associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
Monitor for development of muscle pain or weakness, particularly of distal extremities. Discontinue daptomycin in patients with unexplained signs and symptoms of myopathy in conjunction with CK elevation >1000 units/L, or in patients without reported symptoms who have marked elevations in CK >2000 units/L. Consider temporarily suspending agents associated with rhabdomyolysis (HMG-CoA reductase inhibitors) in patients receiving daptomycin.

Lab Test Considerations:

Monitor CK weekly, more frequently in patients with unexplained ↑. Discontinue daptomycin if CK >1000 units/L and signs and symptoms of myopathy occur. In patients with renal insufficiency, monitor both renal function and CK more frequently.
- May cause false prolongation of PT and ↑ INR.
- Monitor renal function prior to and periodically during therapy. If new or worsening renal impairment occurs, evaluate renal function. If tubulointerstitial nephritis is suspected, discontinue daptomycin and begin treatment.

Implementation ⬆ ⬇

Do not confuse daptomycin with dactinomycin.

IV Administration:

Rate: Administer over 2 min (for adults only).
Intermittent Infusion: Adults:Diluent: Dilute further in 50 mL of 0.9% NaCl for adults, adolescents and children 7 yrs. Solution is stable for 12 hr at room temperature or 48 hr if refrigerated. Do not administer solutions that are cloudy or contain a precipitate.
Rate: Infuse over 30 min.
Intermittent Infusion: Children 1–6 yrs:Diluent: Dilute further into a 25 mL IV infusion bag of 0.9% NaCl.
Rate: Infuse over 60 min at a rate of 0.42 mL/min.
Intermittent Infusion: Children 7–17 yrs:Diluent: Dilute further into a 50 mL IV infusion bag of 0.9% NaCl.
Rate: Infuse over 30 min at a rate of 1.67 mL/min.

Patient/Family Teaching ⬆ ⬇

Inform patient of purpose of daptomycin.
Instruct patient to notify health care professional if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care professional immediately if weakness, numbness, or tingling in forearms and lower legs, or signs and symptoms of eosinophilic pneumonia or DRESS occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Monitor infants exposed to daptomycin through breast milk for GI disturbances.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇