Daptomycin Monograph for Professionals - Drugs.com (2024)

Brand names: Cubicin, Cubicin RF
Drug class: Cyclic Lipopeptides
VA class: AM900
Chemical name: N-Decanoyl-l-tryptophyl-l-asparaginyl-l-aspartyl-l-threonylglycyl-l-ornithyl-l-aspartyl-d-alanyl-l-aspartylglycyl-d-seryl-threo-3-methyl-l-glutamyl-3-anthraniloyl-l-alanine ε1-lactone
Molecular formula: C₇₂H₁₀₁N₁₇O₂₆
CAS number: 103060-53-3

Medically reviewed by Drugs.com on Mar 11, 2024. Written by ASHP.

Introduction

Antibacterial; cyclic lipopeptide antibiotic.

Uses for Daptomycin

Skin and Skin Structure Infections

Treatment of complicated skin and skin structure infections caused by susceptible Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]), Streptococcus pyogenes (group A β-hemolytic streptococci, GAS), S. agalactiae (group B streptococci, GBS), S. dysgalactiae subsp. equisimilis, and Enterococcus faecalis (vancomycin-susceptible strains only).

For information on management of skin and skin structure infections, consult current clinical practice guidelines from the Infectious Diseases Society of America (IDSA) available at [Web].

Bacteremia and Endocarditis

Treatment of bacteremia (blood stream infection) caused by susceptible S. aureus (including MRSA).

Also used for treatment of S. aureus bacteremia in patients with right-sided infective endocarditis. Efficacy not established in patients with left-sided infective endocarditis caused by S. aureus; limited data suggest a poor outcome in such patients despite daptomycin treatment.

Not studied in patients with prosthetic valve endocarditis.

For information on diagnosis and management of infective endocarditis and its complications, including anti-infective treatment of staphylococcal bacteremia and endocarditis, consult current AHA guidelines available at [Web].

Daptomycin Dosage and Administration

Administration

Administer by IV injection or infusion.

Do not add additives or other drugs to daptomycin solutions; do not infuse simultaneously through same IV line with daptomycin. If same IV line is used for sequential infusion of different drugs, flush line with a compatible infusion solution (see Compatibility under Stability) before and after infusion of daptomycin.

Do not use in conjunction with ReadyMed elastomeric infusion pumps; stability studies identified an impurity (i.e., 2-mercaptobenzothiazole) leaching from this pump system into the daptomycin solution.

Use strict aseptic technique when preparing daptomycin solutions since the drug contains no preservatives.

Commercially available for IV use as 2 different formulations: a lyophilized powder for solution that does not contain sucrose (Cubicin or generics) and a lyophilized powder for solution that contains 713 mg of sucrose per vial (Cubicin RF). Instructions for storage, reconstitution, and dilution differ for the 2 daptomycin formulations; follow recommendations for the specific formulation used.

IV Injection

Reconstitution

Daptomycin (Cubicin or generics): Reconstitute single-dose vial containing 500 mg of daptomycin with 10 mL of 0.9% sodium chloride injection to provide solution containing 50 mg/mL. Add the diluent using beveled sterile transfer needle (≤21 gauge) or needleless device; direct diluent toward vial wall. Gently rotate vial to ensure that entire lyophilized powder is wetted. Allow vial to remain undisturbed for 10 minutes, then rotate or swirl for a few minutes (as needed) to obtain a completely reconstituted solution. To minimize foaming, avoid agitating or vigorously shaking vial during or after reconstitution. For IV injection, remove appropriate volume of reconstituted solution from vial using beveled sterile needle (≤21 gauge) and administer without further dilution. Discard any unused portion of reconstituted solution.

Daptomycin (Cubicin RF): Do not reconstitute with sodium chloride solution since this would result in hyperosmotic solution. Reconstitute single-dose vials containing 500 mg of daptomycin with 10 mL of sterile water for injection or bacteriostatic water for injection to provide a solution containing 50 mg/mL. Add the diluent using beveled sterile transfer needle (≤21 gauge); direct diluent toward vial wall. Rotate or swirl vial for a few minutes (as needed) to obtain completely reconstituted solution. For IV injection, remove appropriate volume of reconstituted solution from vial using beveled sterile needle (≤21 gauge) and administer without further dilution. Discard any unused portion of reconstituted solution.

Rate of Administration

Daptomycin (Cubicin or generics; Cubicin RF): Administer by IV injection over 2 minutes.

IV Infusion

Reconstitution and Dilution

Daptomycin (Cubicin or generics): Reconstitute single-dose vial containing 500 mg of daptomycin with 10 mL of 0.9% sodium chloride injection to provide solution containing 50 mg/mL. Add the diluent using beveled sterile transfer needle (≤21 gauge) or needleless device; direct diluent toward vial wall. Gently rotate vial to ensure that entire lyophilized powder is wetted. Allow vial to remain undisturbed for 10 minutes, then rotate or swirl for a few minutes (as needed) to obtain a completely reconstituted solution. To minimize foaming, avoid agitating or vigorously shaking vial during or after reconstitution. For IV infusion, slowly remove appropriate volume of reconstituted solution from vial using beveled sterile needle (≤21 gauge) and add to 50 mL of 0.9% sodium chloride injection in IV infusion bag. Do not exceed final concentration of 20 mg/mL. Discard any unused portion of reconstituted solution.

Daptomycin (Cubicin RF): Do not reconstitute with sodium chloride solution since this would result in hyperosmotic solution. Reconstitute single-dose vials containing 500 mg of daptomycin with 10 mL of sterile water for injection or bacteriostatic water for injection to provide a solution containing 50 mg/mL. Add the diluent using beveled sterile transfer needle (≤21 gauge); direct diluent toward vial wall. Rotate or swirl vial for a few minutes (as needed) to obtain completely reconstituted solution. For IV infusion, remove appropriate volume of reconstituted daptomycin solution from vial using a beveled sterile needle (≤21 gauge) and add to 50 mL of 0.9% sodium chloride injection in an IV infusion bag. Discard any unused portion of reconstituted solution.

Rate of Administration

Daptomycin (Cubicin or generics; Cubicin RF): Administer by IV infusion over 30 minutes.

Dosage

Adults

Skin and Skin Structure Infections

Complicated Infections

IV

4 mg/kg once every 24 hours for 7–14 days.

Bacteremia and Endocarditis

IV

6 mg/kg once every 24 hours for at least 2–6 weeks for treatment of S. aureus bacteremia and right-sided infective endocarditis. Limited safety data regarding use beyond 28 days.

Prescribing Limits

Adults

IV

Do not administer more frequently than once daily. (See Musculoskeletal Effects under Cautions.)

Special Populations

Hepatic Impairment

Dosage adjustment not necessary in adults with mild to moderate hepatic impairment; pharmaco*kinetics not evaluated in adults with severe hepatic impairment.

Renal Impairment

Reduce dosage in adults with Cl_cr <30 mL/minute and in those undergoing hemodialysis or CAPD.

Treatment of complicated skin and skin structure infections in adults with Cl_cr <30 mL/minute: 4 mg/kg IV once every 48 hours.

Treatment of bacteremia and right-sided endocarditis in adults with Cl_cr <30 mL/minute: 6 mg/kg IV once every 48 hours.

Hemodialysis patients: Give dose on hemodialysis days following the procedure, if possible.

Geriatric Patients

No dosage adjustments except those related to renal impairment. (See Renal Impairment under Dosage and Administration.)

Obese Patients

Dosage adjustment not warranted.

Cautions for Daptomycin

Contraindications

• Known hypersensitivity to daptomycin.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity, including anaphylaxis and other life-threatening reactions, reported in patients receiving daptomycin.

Postmarketing reports of angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), pruritus, urticaria, shortness of breath, difficulty swallowing, truncal erythema, and pulmonary eosinophilia (see Eosinophilic Pneumonia under Cautions).

If hypersensitivity reaction occurs, discontinue daptomycin and initiate appropriate therapy.

Musculoskeletal Effects

Myopathy, defined as muscle aching or muscle weakness, in conjunction with increased serum CK concentrations up to 10 times ULN reported in patients receiving daptomycin. Rhabdomyolysis, with or without renal failure, also reported.

Monitor for development of muscle pain or weakness, particularly of distal extremities. Determine serum CK concentrations weekly during daptomycin treatment; monitor more frequently than once weekly in those who develop increases in serum CK concentrations and in those previously or concomitantly treated with an HMG-CoA reductase inhibitor (statin). Also monitor serum CK concentrations and renal function more frequently than once weekly in patients with renal impairment.

Discontinue daptomycin in patients with unexplained signs or symptoms of myopathy in conjunction with increases in CK >1000 U/L (i.e., approximately 5 times ULN) or in patients without reported symptoms who have substantial increases in serum CK concentrations (i.e., >2000 U/L [≥10 times ULN]).

Elevated serum CK concentrations reported more frequently if daptomycin given more frequently than once daily in clinical trials; do not administer more frequently than once daily.

Consider temporarily discontinuing drugs associated with rhabdomyolysis (e.g., HMG-CoA reductase inhibitors) during daptomycin treatment. (See Specific Drugs under Drug Interactions.)

Eosinophilic Pneumonia

Eosinophilic pneumonia reported in some patients receiving daptomycin. Patients generally developed fever, dyspnea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates 2–4 weeks after the drug was initiated. Improvement or resolution of symptoms generally occurred when daptomycin was discontinued; most patients received treatment with systemic corticosteroids. Reinitiation of daptomycin has resulted in recurrence of eosinophilic pneumonia.

FDA determined that there appears to be a temporal association between daptomycin and development of eosinophilic pneumonia; some were receiving the drug for non-FDA-labeled uses. Consider that eosinophilic pneumonia can progress to respiratory failure and is potentially fatal if not quickly recognized and appropriately managed.

Closely monitor for signs and symptoms of eosinophilic pneumonia (e.g., new onset or worsening fever, dyspnea, difficulty breathing, new pulmonary infiltrates).

Immediately discontinue daptomycin if there are any signs or symptoms of eosinophilic pneumonia. Initiate prompt medical evaluation; treatment with systemic corticosteroids is recommended.

Nervous System Effects

Postmarketing reports of peripheral neuropathy in patients receiving daptomycin; be alert to possible manifestations of neuropathy.

Persisting or Relapsing Staphylococcus aureus Bacteremia/Endocarditis

Treatment failure due to persisting or relapsing S. aureus infection has occurred in patients receiving daptomycin; fatalities reported. S. aureus with reduced susceptibility or resistance to daptomycin have been reported and have emerged during treatment with the drug.

In a clinical study in patients with bacteremia, 16% of daptomycin-treated patients and 10% of patients receiving a comparator anti-infective (vancomycin or a penicillinase-resistant penicillin) had persisting or relapsing S. aureus infections. In vitro studies indicated reduced susceptibility to daptomycin developed during or following treatment. Most patients with persisting or relapsing infections had deep-seated infections and did not receive necessary surgical intervention.

Perform repeat blood cultures in patients with persisting or relapsing infection or with poor clinical response. If cultures are positive for S. aureus, perform in vitro susceptibility testing using standardized MIC procedures. Also perform diagnostic evaluation to rule out sequestered foci of infection. Surgical intervention (e.g., debridement, removal of prosthetic devices, valve replacement surgery) and/or a change in anti-infective regimen may be required.

Reduced Efficacy in Patients with Moderate Renal Impairment

In a subgroup analysis of a phase 3 clinical study in patients with S. aureus bacteremia/endocarditis, clinical success rate in daptomycin-treated patients with baseline Cl_cr 30 to <50 mL/minute was only 14% and was lower than that observed in those with baseline Cl_cr 50–80 or >80 mL/minute (46 or 60%, respectively). Decreased clinical success rates to this extent not observed in patients receiving comparator anti-infectives.

Although only limited data available from phase 3 clinical studies in patients with complicated skin and skin structure infections, clinical success rate in daptomycin-treated patients with Cl_cr 30 to <50 mL/minute was 47% compared with clinical success rate of 66% in those with Cl_cr 50–70 mL/minute.

Consider these efficacy data when selecting anti-infective treatment for patients with baseline moderate to severe renal impairment.

Tests Used to Monitor Coagulation

Daptomycin causes concentration-dependent false prolongation of the PT and elevated INR if certain recombinant thromboplastin reagents are used for these tests.

Minimize interference with PT/INR testing by drawing blood specimens for coagulation tests near time of trough plasma daptomycin concentrations; consider that trough plasma concentrations still may be high enough to interfere with such testing.

If abnormally elevated PT/INR tests occur in a patient receiving daptomycin, repeat coagulation testing using blood specimens drawn just prior to next daptomycin dose (i.e., at trough concentrations). If these results remain substantially elevated over what would otherwise be expected, consider alternative methods of measuring PT/INR. Also evaluate patient for other causes of abnormally elevated PT/INR.

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible bacteria or fungi. Monitor carefully; institute appropriate therapy if superinfection occurs.

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile. C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including daptomycin, and may range in severity from mild diarrhea to fatal colitis. C. difficile produces toxins A and B which contribute to development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

Consider CDAD if diarrhea develops during or after therapy and manage accordingly. Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.

If CDAD is suspected or confirmed, anti-infectives not directed against C. difficile should be discontinued. Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of daptomycin and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Do not use for treatment of pneumonia.

Safety and efficacy not studied in patients with prosthetic valve endocarditis.

Specific Populations

Pregnancy

Category B.

Use during pregnancy only if potential benefits outweigh possible risks to fetus.

Lactation

Distributed into human milk. (See Distribution under Pharmaco*kinetics.)

Use with caution in nursing women.

Pediatric Use

Safety and efficacy in pediatric patients not established.

Avoid use in children <12 months of age because of potential risk of adverse muscular, neuromuscular, peripheral nervous system, and CNS effects; such effects observed in neonatal dogs receiving IV daptomycin.

Geriatric Use

In clinical studies, success rates were lower and incidence of treatment-emergent adverse effects were higher in patients ≥65 years of age compared with younger adults.

Daptomycin exposures are higher in healthy geriatric adults than in healthy young adults; however, daptomycin dosage adjustments not needed in geriatric patients based solely on age.

Consider age-related decreases in renal function when selecting dosage and adjust dosage if necessary. (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Pharmaco*kinetics not altered in patients with moderate hepatic impairment (Child-Pugh class B); not studied in patients with severe hepatic impairment.

Renal Impairment

Decreased clearance and increased AUC and half-life in patients with renal impairment.

Monitor renal function and serum CK concentrations more frequently than once weekly in patients with renal insufficiency.

Dosage adjustments recommended in patients with Cl_cr <30 mL/minute. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Complicated skin and skin structure infections: Diarrhea, nervous system effects (headache, dizziness), rash, abnormal liver function test results, CK elevations, urinary tract infections, hypotension, dyspnea.

Bacteremia and endocarditis: Abdominal pain, insomnia, pharyngolaryngeal pain, infections (sepsis, bacteremia), chest pain, edema, pruritus, increased sweating, CK elevations, hypotension.

Drug Interactions

Does not inhibit or induce CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A4; pharmaco*kinetic interactions with drugs metabolized by these CYP isoenzymes unlikely.

Specific Drugs and Laboratory Tests

Daptomycin Pharmaco*kinetics

Absorption

Bioavailability

Generally exhibits linear and time-independent pharmaco*kinetics at a dosage of 4–12 mg/kg once every 24 hours administered by IV infusion over 30 minutes.

Steady-state trough serum concentrations are achieved by the third daily dose.

Distribution

Extent

Distributed into human milk. In a nursing woman receiving daptomycin (6.7 mg/kg IV once daily for 28 days), highest concentration of the drug in breast milk was 45 ng/mL; calculated maximum daily daptomycin dose for a nursing infant (assuming mean milk consumption of 150 mL/kg daily) was 0.1% of maternal dose.

Plasma Protein Binding

90–93% bound to plasma proteins, principally albumin.

Elimination

Metabolism

In vitro studies indicate daptomycin is not metabolized by CYP isoenzymes. Inactive metabolites have been detected in urine; site and extent of metabolism have not been identified.

Elimination Route

Eliminated principally by renal excretion; approximately 78 and 6% of a dose recovered in urine and feces, respectively.

Half-life

Mean elimination half-life at steady state is 7.7–8.3 hours in adults.

Special Populations

In geriatric adults ≥75 years of age, clearance is reduced approximately 35% and AUC is increased approximately 58% compared with younger adults (18–30 years of age).

Pharmaco*kinetics not altered in adults with moderate hepatic impairment (Child-Pugh class B); pharmaco*kinetics not studied in adults with severe hepatic impairment.

Clearance is decreased and AUC and half-life increased in adults with renal impairment compared with adults with normal renal function. Mean half-life is 10.75 hours in those with mild renal impairment (Cl_cr 50–80 mL/minute), 14.7 hours in those with moderate renal impairment (Cl_cr 30 to <50 mL/minute), or 27.83 hours in those with severe renal impairment (Cl_cr <30 mL/minute).

Removed by hemodialysis (approximately 15% of a dose removed over 4 hours) and peritoneal dialysis (approximately 11% of a dose removed over 48 hours).

In obese adults, plasma clearance of daptomycin normalized to total body weight is approximately 15% lower in those who are moderately obese and 23% lower in those who are extremely obese compared with non-obese adults. This difference is most likely the result of differences in renal clearance of daptomycin.

Stability

Storage

Parenteral

Powder for IV Use

Daptomycin (Cubicin or generics): 2–8°C; avoid excessive heat. Following reconstitution, stable in original vial for up to 12 hours at room temperature or up to 48 hours at 2–8°C. After further dilution, stable in infusion bag for 12 hours at room temperature or 48 hours when refrigerated. Combined storage time (vial and infusion bag) should be ≤12 hours at room temperature or ≤48 hours when refrigerated.

Daptomycin (Cubicin RF): 20–25°C (may be exposed to 15–30°C). Stability of reconstituted solutions and reconstituted and further diluted solutions varies based on diluent and container used. (See Table 1.)

Polypropylene syringe with elastomeric plunger stopper.

Compatibility

Parenteral

Solution Compatibility1 23 24 25 HID

Solution compatibility depends on specific daptomycin formulation (Cubicin or generics, Cubicin RF). All daptomycin formulations are incompatible with dextrose-containing solutions.

Drug CompatibilityHID

Actions and Spectrum

• Lipopeptide antibiotic.

• Usually bactericidal in action.

• Binds to cell membranes in susceptible bacteria and causes rapid membrane depolarization leading to inhibition of protein, DNA, and RNA synthesis and cell death.

• Spectrum of activity includes many gram-positive bacteria; inactive against gram-negative bacteria.

• Gram-positive aerobes: Active in vitro and in clinical infections against Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]), Streptococcus pyogenes (group A β-hemolytic streptococci, GAS), S. agalactiae (group B streptococci, GBS), S. dysgalactiae subsp. equisimilis, and Enterococcus faecalis (vancomycin-susceptible strains only). Also active in vitro against some strains of Corynebacterium jeikeium, E. faecalis (vancomycin-resistant strains), E. faecium (including vancomycin-resistant strains), S. epidermidis (including oxacillin-resistant strains), and S. haemolyticus.

• Reduced susceptibility to daptomycin has been produced in vitro by serial passage of S. aureus in the presence of increasing concentrations of the drug. In addition, daptomycin-resistant S. aureus have emerged in patients treated with the drug. Mechanism of resistance or transferable elements that might confer resistance to daptomycin not identified to date.

• Although further study needed, there is evidence that cross-resistance can occur between daptomycin and vancomycin. Some strains of MRSA that develop resistance to daptomycin also may develop resistance or reduced susceptibility to vancomycin and daptomycin-resistant MRSA may emerge during daptomycin therapy in some patients with prior exposure to vancomycin.

Advice to Patients

• Advise patients that antibacterials (including daptomycin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).

• Importance of completing full course of therapy, even if feeling better after a few days.

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with daptomycin or other antibacterials in the future.

• Advise patients that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment. Importance of informing clinician of any previous allergic reactions to daptomycin.

• Importance of patients immediately informing clinicians if they develop new or worsening fever, cough, shortness of breath, or difficulty breathing.

• Importance of contacting a clinician if muscle pain, weakness, tingling, or numbness occurs, particularly in forearms or lower legs.

• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued. Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as ≥2 months after the last dose.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

AHFS DI Essentials™. © Copyright 2024, Selected Revisions March 20, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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