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).

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity.

Use Cautiously in:

Severe renal impairment (↓ dose);
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: ↑CK

Neuro: dizziness

Resp: dyspnea, EOSINOPHILIC PNEUMONIA

Misc: ANGIOEDEMA, fever

Interactions ⬆ ⬇

Drug-drug:

Tobramycin may ↑ levels and risk of toxicity.
HMG-CoA reductase inhibitors may ↑ risk of myopathy; consider discontinuing statin before starting daptomycin; if used with statin, closely monitor CK levels.

Availability ⬆ ⬇

(Generic available)

Lyophilized powder for injection: 350 mg/vial; 500 mg/vial
Premixed infusion: 350 mg/50 mL 0.9% NaCl; 500 mg/50 mL 0.9% NaCl; 700 mg/100 mL 0.9% NaCl; 1000 mg/100 mL 0.9% NaCl

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.

US Brand Names ⬆ ⬇

~~Cubicin,~~ ~~Cubicin RF~~

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).

Classifications ⬆ ⬇

Therapeutic Classification: anti-infectives

Pharmacologic Classification: cyclic lipopeptide antibacterial agents

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

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of daptomycin. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes.
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. Instruct patient to avoid using HMG-CoA reductase inhibitors (cholesterol-lowering agents such as atorvastatin, fluvastatin, lovastatin, pitavastatin, simvastatin) unless approved by health care professional, as concurrent use with daptomycin may ↑ risk of myopathy.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Monitor breastfed infants exposed to daptomycin for GI disturbances.

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Indications ⬇