Cubicin RF (daptomycin) Injection

Cubicin RF is available in generic form. Common side effects of Cubicin RF include:

• diarrhea,
• headache,
• dizziness,
• rash,
• abnormal liver function tests,
• elevated creatinine phosphokinase (CPK),
• urinary tract infections,
• low blood pressure (hypotension),
• shortness of breath,
• vomiting,
• abdominal pain,
• itching,
• fever,
• sepsis,
• bacteremia,
• chest pain,
• swelling,
• sore throat,
• increased sweating,
• insomnia, and
• high blood pressure (hypertension).

Important Administration Duration Instructions

Adults

Administer the appropriate volume of the reconstituted Cubicin RF (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 sections below].

Pediatric Patients (1 to 17 Years of Age)

Unlike in adults, do NOT administer Cubicin RF by injection over a two (2) minute period to pediatric patients.

• Pediatric Patients 7 to 17 years of Age: Administer Cubicin RF intravenously by infusion over a 30-minute period [see sections below].
• Pediatric Patients 1 to 6 years of Age: Administer Cubicin RF intravenously by infusion over a 60-minute period [see sections below].

Dosage In Adults For cSSSI

Administer Cubicin RF 4 mg/kg to adult patients intravenously 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 1. Administer Cubicin RF intravenously once every 24 hours for up to 14 days.

Table 1: Recommended Dosage of Cubicin RF in Pediatric Patients (1 to 17 Years of Age) with cSSSI, Based on Age

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 RF 6 mg/kg to adult patients intravenously 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 2. Administer Cubicin RF intravenously in 0.9% sodium chloride injection once every 24 hours for up to 42 days.

Table 2: Recommended Dosage of Cubicin RF in Pediatric Patients (1 to 17 Years of Age) with S. aureus Bacteremia, Based on Age

Dosage In Patients With Renal Impairment

Adult Patients

No dosage adjustment is required in adult patients with creatinine clearance (CLCR) greater than or equal to 30 mL/min. The recommended dosage regimen for Cubicin RF in adult patients with CLCR less than 30 mL/min, including adult patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), is 4 mg/kg (cSSSI) or 6 mg/kg (S. aureus bloodstream infections) once every 48 hours (Table 3). When possible, Cubicin RF should be administered following the completion of hemodialysis on hemodialysis days.

Table 3: Recommended Dosage of Cubicin RF in Adult Patients

Pediatric Patients

The dosage regimen for Cubicin RF in pediatric patients with renal impairment has not been established.

HMG-CoA Reductase Inhibitors

• In healthy adult subjects, concomitant administration of Cubicin and simvastatin had no effect on plasma trough concentrations of simvastatin, and there were no reports of skeletal myopathy.
• 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.
• 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 RF.

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 Cubicin RF, it is recommended that clinicians:
• Repeat the assessment of PT/INR, requesting that the specimen be drawn just prior to the next Cubicin RF 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.

• Limited published data on use of Cubicin RF in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.
• Limited published data report that daptomycin is present in human milk at infant doses of 0.1% of the maternal dose.
• There is no information on the effects of daptomycin on the breastfed infant or the effects of daptomycin on milk production.
• The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Cubicin and any potential adverse effects on the breastfed infant from Cubicin RF or from the underlying maternal condition.