Daptomycin

What is Daptomycin?

• Daptomycin (CUBICIN) is a lipopeptide antibacterial used to treat certain bacterial skin and bloodstream infections in adults.

Daptomycin

Daptomycin (3D Stick)

Daptomycin Ball et al

What are the uses of this medicine?

CUBICIN is a lipopeptide antibacterial indicated for the treatment of:

• Complicated skin and skin structure infections (cSSSI) in adult and pediatric patients (1 to 17 years of age) and,
• Staphylococcus aureus bloodstream infections (bacteremia), in adult patients including those with right-sided infective endocarditis,
• Staphylococcus aureus bloodstream infections (bacteremia) in pediatric patients (1 to 17 years of age).

Limitations of use:

• CUBICIN is not indicated for the treatment of pneumonia.
• CUBICIN is not indicated for the treatment of left-sided infective endocarditis due to S. aureus.
• CUBICIN is not recommended in pediatric patients younger than one year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs.

How does this medicine work?

• Daptomycin (dap" toe mye' sin) is a cyclic lipopeptide antibiotic that is poorly absorbed orally and must be given intravenously.
• Daptomycin appears to act by binding to bacterial membranes causing their depolarization and disruption and cell death.
• Daptomycin binds to bacterial cell membranes and causes a rapid depolarization of membrane potential.
• This loss of membrane potential causes inhibition of DNA, RNA, and protein synthesis, which results in bacterial cell death.

Who Should Not Use this medicine ?

This medicine cannot be used in patients:

• with known hypersensitivity to daptomycin

What drug interactions can this medicine cause?

• Experience with the coadministration of HMG-CoA reductase inhibitors and CUBICIN in patients is limited; therefore, consideration should be given to suspending use of HMG-CoA reductase inhibitors temporarily in patients receiving CUBICIN.
• Clinically relevant plasma concentrations of daptomycin have been observed to cause a significant concentration-dependent false prolongation of prothrombin time (PT) and elevation of International Normalized Ratio (INR) when certain recombinant thromboplastin reagents are utilized for the assay.

Is this medicine FDA approved?

• Daptomycin was approved for use in 2006 and current indications include complicated skin and skin structure infections and severe bacteremia and endocarditis caused by susceptible organisms.

How should this medicine be used?

Recommended dosage:

The typical dose is 4 to 6 mg/kg once daily for 7 to 28 days, depending upon the type of infection and organism as fallows:

Dosage in Adults for cSSSI:

• Administer CUBICIN 4 mg/kg to adult patients intravenously in 0.9% sodium chloride injection once every 24 hours for 7 to 14 days.

Dosage in Pediatric Patients (1 to 17 Years of Age) for cSSSI:

• The recommended dosage regimens based on age for pediatric patients with cSSSI are shown in table below:

Recommended Dosage of CUBICIN in Pediatric Patients (1 to 17 Years of Age) with cSSSI, Based on Age

Age Range	Dosage Regimen	Duration of therapy
12 to 17 years	5 mg/kg once every 24 hours infused over 30 minutes	Up to 14 days
7 to 11 years	7 mg/kg once every 24 hours infused over 30 minutes	Up to 14 days
2 to 6 years	9 mg/kg once every 24 hours infused over 60 minutes	Up to 14 days
1 to less than 2 years	10 mg/kg once every 24 hours infused over 60 minutes	Up to 14 days

Dosage in Adult Patients with Staphylococcus aureus Bloodstream Infections (Bacteremia), Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin-Susceptible and Methicillin-Resistant Isolates:

• Administer CUBICIN 6 mg/kg to adult patients intravenously in 0.9% sodium chloride injection once every 24 hours for 2 to 6 weeks.
• There are limited safety data for the use of CUBICIN for more than 28 days of therapy.
• In the Phase 3 trial, there were a total of 14 adult patients who were treated with CUBICIN for more than 28 days.

Dosage in Pediatric Patients (1 to 17 Years of Age) with Staphylococcus aureus Bloodstream Infections (Bacteremia):

• The recommended dosage regimens based on age for pediatric patients with S. aureus bloodstream infections (bacteremia) are shown in table below:

Recommended Dosage of CUBICIN in Pediatric Patients (1 to 17 Years of Age) with S. aureus Bacteremia, Based on Age

Age group	Dosage	Duration of therapy
12 to 17 years	7 mg/kg once every 24 hours infused over 30 minutes	Up to 42 days
7 to 11 years	9 mg/kg once every 24 hours infused over 30 minutes	Up to 42 days
1 to 6 years	12 mg/kg once every 24 hours infused over 60 minutes	Up to 42 days

Administration:

• Administer to adult patients intravenously in 0.9% sodium chloride, either by injection over a 2-minute period or by infusion over a 30-minute period.
• Unlike in adults, do NOT administer by injection over a two (2) minute period to pediatric patients.
• Administer CUBICIN intravenously in 0.9% sodium chloride injection once every 24 hours for up to 14 days for cSSSI.
• Administer CUBICIN intravenously in 0.9% sodium chloride injection once every 24 hours for up to 42 days for Staphylococcus aureus bloodstream infections (bacteremia).

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection: 500 mg lyophilized powder for reconstitution in a single-dose vial

This medicine is available in fallowing brand namesː

• CUBICIN

What side effects can this medication cause?

The most common side effects of this medicine include: In Adult cSSSI Patients:

• diarrhea, headache, dizziness, rash, abnormal liver function tests, elevated creatine phosphokinase (CPK), urinary tract infections, hypotension, and dyspnea.

In Pediatric cSSSI Patients:

• diarrhea, vomiting, abdominal pain, pruritus, pyrexia, elevated CPK, and headache.

In Adult S. aureus bacteremia/endocarditis Patients:

• sepsis, bacteremia, abdominal pain, chest pain, edema, pharyngolaryngeal pain, pruritus, increased sweating, insomnia, elevated CPK, and hypertension.

In Pediatric S. aureus bacteremia Patients:

• vomiting and elevated CPK

What special precautions should I follow?

• Anaphylaxis/hypersensitivity reactions have been reported with the use of antibacterial agents, including CUBICIN, and may be life-threatening. If an allergic reaction to CUBICIN occurs, discontinue the drug and institute appropriate therapy.
• Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values to greater than 10 times the upper limit of normal (ULN), has been reported with the use of CUBICIN. Monitor CPK levels and follow muscle pain or weakness; if elevated CPK or myopathy occurs, consider discontinuation of CUBICIN.
• Eosinophilic pneumonia has been reported in patients receiving CUBICIN. Discontinue CUBICIN and consider treatment with systemic steroids.
• DRESS has been reported in post-marketing experience with CUBICIN. Discontinue CUBICIN and institute appropriate treatment.
• Tubulointerstitial Nephritis (TIN) has been reported in post-marketing experience with CUBICIN. Discontinue CUBICIN and institute appropriate treatment.
• Cases of peripheral neuropathy have been reported during the CUBICIN postmarketing experience. Monitor for neuropathy and consider discontinuation.
• Avoid use of CUBICIN in pediatric patients younger than 12 months due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems. Avoid use of CUBICIN in this age group.
• Clostridioides difficile–associated diarrhea (CDAD) has been reported with the use of nearly all systemic antibacterial agents, including CUBICIN. Evaluate patients if diarrhea occurs.
• Patients with persisting or relapsing S. aureus bacteremia/endocarditis or poor clinical response should have repeat blood cultures. Failure of treatment due to persisting or relapsing S. aureus bacteremia/endocarditis may be due to reduced daptomycin susceptibility.
• Decreased efficacy was observed in adult patients with moderate baseline renal impairment.

What to do in case of emergency/overdose?

Management of overdosage:

• In the event of overdosage, supportive care is advised with maintenance of glomerular filtration.
• Daptomycin is cleared slowly from the body by hemodialysis and by peritoneal dialysis.
• The use of high-flux dialysis membranes during 4 hours of hemodialysis may increase the percentage of dose removed compared with that removed by low-flux membranes.

Can this medicine be used in pregnancy?

• Limited published data on use of CUBICIN in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.

Can this medicine be used in children?

• The safety and effectiveness of CUBICIN in the treatment of cSSSI and S. aureus bloodstream infections (bacteremia) have been established in the age groups 1 to 17 years of age.
• Safety and effectiveness in pediatric patients below the age of one year have not been established.
• CUBICIN is not indicated in pediatric patients with renal impairment because dosage has not been established in these patients.
• CUBICIN has not been studied in pediatric patients with other bacterial infections.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• Daptomycin

Inactive ingredients:

• Sodium Hydroxide

Who manufactures and distributes this medicine?

Distributed by: Merck Sharp & Dohme Corp., a subsidiary of MERCK & CO.,INC., Whitehouse Station, NJ , USA

What should I know about storage and disposal of this medication?

• Store original packages at refrigerated temperatures, 2°C to 8°C (36°F to 46°F); avoid excessive heat.
• Storage conditions for the reconstituted and diluted solutions are described in another section of the prescribing information.

• Dailymed label info on Daptomycin
• FDA Daptomycin

Daptomycin Resources
Latest articles Most recent articles Ongoing trials	Wikipedia

• Dailymed label info on Daptomycin
• FDA Daptomycin

Daptomycin Resources
Latest articles Most recent articles Ongoing trials	Wikipedia