Daptomycin

FDA Drug Information • Also known as: Daptomycin, Dapzura Rt

Brand Names: Daptomycin, Dapzura Rt
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION Daptomycin for injection contains daptomycin, a cyclic lipopeptide antibacterial agent derived from the fermentation of Streptomyces roseosporus . The chemical name is N -decanoyl-L-tryptophyl-D‑asparaginyl-L-aspartyl-L-threonylglycyl-L-ornithyl-L-aspartyl-D-alanyl-L-aspartylglycyl-D-seryl- threo -3‑methyl-L-glutamyl-3-anthraniloyl-L-alanine ε 1 -lactone. The chemical structure is: The empirical formula is C 72 H 101 N 17 O 26 ; the molecular weight is 1620.67. Daptomycin for injection is supplied in a single-dose vial as a sterile, preservative-free, pale yellow to light brown, lyophilized cake containing approximately 500 mg of daptomycin for intravenous (IV) use following reconstitution with 0.9% sodium chloride injection [see Dosage and Administration ( 2.7 )] . The only inactive ingredient is sodium hydroxide, which is used for pH adjustment. Freshly reconstituted solutions of daptomycin for injection range in color from pale yellow to light brown. chemical-structure

What Is Daptomycin Used For?

1 INDICATIONS AND USAGE Daptomycin for injection 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) ( 1.1 ) and, Staphylococcus aureus bloodstream infections (bacteremia), in adult patients including those with right-sided infective endocarditis. ( 1.2 ) Staphylococcus aureus bloodstream infections (bacteremia) in pediatric patients (1 to 17 years of age). ( 1.3 ) Limitations of use: Daptomycin for injection is not indicated for the treatment of pneumonia. ( 1.4 ) Daptomycin for injection is not indicated for the treatment of left-sided infective endocarditis due to S. aureus . ( 1.4 ) Daptomycin for injection 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. ( 1.4 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of daptomycin for injection and other antibacterial drugs, daptomycin for injection should be used to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.5 ) 1.1 Complicated Skin and Skin Structure Infections (cSSSI) Daptomycin for injection is indicated for the treatment of adult and pediatric patients (1 to 17 years of age) with complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive bacteria: Staphylococcus aureus (including methicillin-resistant isolates), Streptococcus pyogenes , Streptococcus agalactiae , Streptococcus dysgalactiae subsp. equisimilis , and Enterococcus faecalis (vancomycin-susceptible isolates only). 1.2 Staphylococcus aureus Bloodstream Infections (Bacteremia) in Adult Patients, Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin-Susceptible and Methicillin-Resistant Isolates Daptomycin for injection is indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia), including adult patients with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates. 1.3 Staphylococcus aureus Bloodstream Infections (Bacteremia) in Pediatric Patients (1 to 17 Years of Age) Daptomycin for injection is indicated for the treatment of pediatric patients (1 to 17 years of age) with Staphylococcus aureus bloodstream infections (bacteremia). 1.4 Limitations of Use Daptomycin for injection is not indicated for the treatment of pneumonia. Daptomycin for injection is not indicated for the treatment of left-sided infective endocarditis due to S. aureus . The clinical trial of daptomycin for injection in adult patients with S. aureus bloodstream infections included limited data from patients with left-sided infective endocarditis; outcomes in these patients were poor [see Clinical Studies ( 14.2...

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Adult Patients 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. ( 2.1 , 2.7 ) Recommended dosage regimen for adult patients ( 2.2 , 2.4 , 2.6 ): Creatinine Clearance (CL CR ) Dosage Regimen cSSSI For 7 to 14 days S. aureus Bacteremia For 2 to 6 weeks ≥30 mL/min 4 mg/kg once every 24 hours 6 mg/kg once every 24 hours <30 mL/min, including hemodialysis and CAPD 4 mg/kg once every 48 hours* 6 mg/kg once every 48 hours* *Administered following hemodialysis on hemodialysis days. Pediatric Patients Unlike in adults, do NOT administer by injection over a two (2) minute period to pediatric patients. ( 2.1 , 2.7 ) Administer to pediatric patients intravenously in 0.9% sodium chloride, by infusion over a 30- or 60-minute period, based on age. ( 2.1 , 2.7 ) Recommended dosage regimen for pediatric patients (1 to 17 years of age) with cSSSI, based on age ( 2.3 ): Age group Dosage* 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 2 to 6 years 9 mg/kg once every 24 hours infused over 60 minutes 1 to less than 2 years 10 mg/kg once every 24 hours infused over 60 minutes * Recommended dosage is for pediatric patients (1 to 17 years of age) with normal renal function. Dosage adjustment for pediatric patients with renal impairment has not been established. Recommended dosage regimen for pediatric patients (1 to 17 years of age) with S. aureus bacteremia, based on age ( 2.5 ): 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 1 to 6 years 12 mg/kg once every 24 hours infused over 60 minutes * Recommended dosage is for pediatric patients (1 to 17 years of age) with normal renal function. Dosage adjustment for pediatric patients with renal impairment has not been established. There are two formulations of daptomycin that have differences concerning storage and reconstitution. Carefully follow the reconstitution and storage procedures in labeling. ( 2.7 ) Do not use in conjunction with ReadyMED ® elastomeric infusion pumps in adult and pediatric patients. ( 2.9 ) 2.1 Important Administration Duration Instructions Adults Administer the appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) to adult patients intravenously either by injection over a two (2) minute period or by intravenous infusion over a thirty (30) minute period [see Dosage and Administration ( 2.2 , 2.4 , 2.7 )]. Pediatric Patients (1 to 17 Years of Age) Unlike in adults, do NOT administer daptomycin for injection by injection over a two (2) minute period to pediatric patients. Pediatric Patients 7 to 17 Years of Age : Administer daptomycin for injection intravenously by infusion over a...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are described, or described in greater detail, in other sections: Anaphylaxis/Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Myopathy and Rhabdomyolysis [see Warnings and Precautions ( 5.2 )] Eosinophilic Pneumonia [see Warnings and Precautions ( 5.3 )] Drug Reaction with Eosinophilia and Systemic Symptoms [see Warnings and Precautions ( 5.4 )] Tubulointerstitial Nephritis [see Warnings and Precautions ( 5.5 )] Peripheral Neuropathy [see Warnings and Precautions ( 5.6 )] Increased International Normalized Ratio (INR)/Prolonged Prothrombin Time [see Warnings and Precautions ( 5.11 ) and Drug Interactions ( 7.2 )] Adult cSSSI Patients: The most common adverse reactions that occurred in ≥2% of adult cSSSI patients receiving daptomycin for injection 4 mg/kg were diarrhea, headache, dizziness, rash, abnormal liver function tests, elevated creatine phosphokinase (CPK), urinary tract infections, hypotension, and dyspnea. ( 6.1 ) Pediatric cSSSI Patients: The most common adverse reactions that occurred in ≥2% of pediatric patients receiving daptomycin for injection were diarrhea, vomiting, abdominal pain, pruritus, pyrexia, elevated CPK, and headache. ( 6.1 ) Adult S. aureus bacteremia/endocarditis Patients: The most common adverse reactions that occurred in ≥5% of S. aureus bacteremia/endocarditis patients receiving daptomycin for injection 6 mg/kg were sepsis, bacteremia, abdominal pain, chest pain, edema, pharyngolaryngeal pain, pruritus, increased sweating, insomnia, elevated CPK, and hypertension. ( 6.1 ) Pediatric S. aureus bacteremia Patients: The most common adverse reactions that occurred in ≥5% of pediatric patients receiving daptomycin for injection were vomiting and elevated CPK. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hainan Poly Pharm. Co., Ltd. at 1-800-571-8369 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trial Experience in Adult Patients Clinical trials enrolled 1,864 adult patients treated with daptomycin for injection and 1,416 treated with comparator. Complicated Skin and Skin Structure Infection Trials in Adults In Phase 3 complicated skin and skin structure infection (cSSSI) trials in adult patients, daptomycin for injection was discontinued in 15/534 (2.8%) patients due to an adverse reaction, while comparator was discontinued in 17/558 (3.0%) patients. The rates of the most common adverse reactions, organized by body system, observed in adult patients with cSSSI (receiving 4 mg/kg daptomycin for injection) are displayed in Table 6. Table 6: Incidence of Adverse Reactions that Occurred in ≥2% of Adult Patients in the Daptomycin for Injection Treatment Group and ≥ the Comparator Treatment Group in Phase 3 cSSSI Trials Adverse Reaction Adult Patients (%) Daptomycin for Injection 4 mg/kg (N=534) Comparator Comparator: vancomycin (1 g IV q12h) or an anti-staphylococcal semi-synthetic penicillin (i.e., nafcillin, oxacillin, cloxacillin, or flucloxacillin; 4 to 12 g/day IV in divided doses). (N=558) Gastrointestinal disorders Diarrhea 5.2 4.3 Nervous system disorders Headache 5.4 5.4 Dizziness 2.2 2.0 Skin/subcutaneous disorders Rash 4.3 3.8 Diagnostic investigations Abnormal liver function tests 3.0 1.6 Elevated CPK 2.8 1.8 Infections Urinary tract infections 2.4 0.5 Vascular disorders Hypotension 2.4 1.4 Respiratory disorders Dyspnea 2.1 1.6 Drug-related adverse reactions (possibly or probably drug-related) that occurred in <1% of adult patients receiving daptomycin for injection in the cSSSI trials are as follows: Body as a Whole: fatigue, weakness, rigors, flushing, hypersensitivity Blood/Lymphatic System: leukocytosis,...

Drug Interactions

7 DRUG INTERACTIONS 7.1 HMG-CoA Reductase Inhibitors In healthy adult subjects, concomitant administration of daptomycin for injection and simvastatin had no effect on plasma trough concentrations of simvastatin, and there were no reports of skeletal myopathy [see Clinical Pharmacology ( 12.3 )]. However, inhibitors of HMG-CoA reductase may cause myopathy, which is manifested as muscle pain or weakness associated with elevated levels of creatine phosphokinase (CPK). In the adult Phase 3 S. aureus bacteremia/endocarditis trial, some patients who received prior or concomitant treatment with an HMG-CoA reductase inhibitor developed elevated CPK [see Adverse Reactions ( 6.1 )] . Experience with the coadministration of HMG-CoA reductase inhibitors and daptomycin for injection in patients is limited; therefore, consideration should be given to suspending use of HMG-CoA reductase inhibitors temporarily in patients receiving daptomycin for injection. 7.2 Drug-Laboratory Test Interactions 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. The possibility of an erroneously elevated PT/INR result due to interaction with a recombinant thromboplastin reagent may be minimized by drawing specimens for PT or INR testing near the time of trough plasma concentrations of daptomycin. However, sufficient daptomycin concentrations may be present at trough to cause interaction. If confronted with an abnormally high PT/INR result in a patient being treated with daptomycin for injection, it is recommended that clinicians: Repeat the assessment of PT/INR, requesting that the specimen be drawn just prior to the next daptomycin for injection dose (i.e., at trough concentration). If the PT/INR value obtained at trough remains substantially elevated above what would otherwise be expected, consider evaluating PT/INR utilizing an alternative method. Evaluate for other causes of abnormally elevated PT/INR results.

Contraindications

4 CONTRAINDICATIONS Daptomycin for injection is contraindicated in patients with known hypersensitivity to daptomycin [see Warnings and Precautions ( 5.1 )] . Known hypersensitivity to daptomycin ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Limited published data on use of daptomycin for injection in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies performed in rats and rabbits daptomycin was administered intravenously during organogenesis at doses 2 and 4-times, respectively, the recommended 6 mg/kg human dose (on a body surface area basis). No evidence of adverse developmental outcomes was observed. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In pregnant rats, daptomycin was administered intravenously at doses of 5, 20, or 75 mg/kg/day during the gestation days 6 to 18. Maternal body weight gain was decreased at 75 mg/kg/day. No embryo/fetal effects were noted at the highest dose of 75 mg/kg/day, a dose approximately 2-fold higher than in humans at the recommended maximum dose of 6 mg/kg (based on body surface area). In pregnant rabbits, daptomycin was administered intravenously at doses of 5, 20, or 75 mg/kg/day during the gestation days 6 to 15. Maternal body weight gain and food consumption were decreased at 75 mg/kg/day. No embryo/fetal effects were noted at the highest dose of 75 mg/kg/day, a dose approximately 4-fold higher than in humans at the maximum recommended dose of 6 mg/kg (based on body surface area). In a combined fertility and pre/postnatal development study, daptomycin was administered intravenously to female rats at doses of 2, 25, 75 mg/kg/day from 14-days pre-mating through lactation/postpartum day 20). No effects on pre/postnatal development were observed up to the highest dose of 75 mg/kg/day, a dose approximately 2-fold higher than the...

Overdosage

10 OVERDOSAGE In the event of overdosage, supportive care is advised with maintenance of glomerular filtration. Daptomycin is cleared slowly from the body by hemodialysis (approximately 15% of the administered dose is removed over 4 hours) and by peritoneal dialysis (approximately 11% of the administered dose is removed over 48 hours). 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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Daptomycin for injection is supplied as a sterile pale yellow to light brown lyophilized cake in a single-dose vial containing 500 mg of daptomycin: Package of 1 (NDC 14335-120-01). 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 [see Dosage and Administration ( 2.7 )].

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.