Daptomycin is an intravenous cyclic lipopeptide antibiotic derived from fermentation of Streptomyces roseosporus. Lipopeptides have a spectrum of activity similar to vancomycin; daptomycin is the first antibiotic from this class to be studied clinically. In vitro, daptomycin has been shown to be effective against a broad spectrum of gram-positive organisms. Daptomycin also demonstrates greater in vitro activity than dalfopristin-quinupristin, linezolid, or vancomycin against some gram-positive bacteria. Daptomycin is FDA-approved for complicated skin and skin structure infections caused by gram-positive organisms, including both methicillin-susceptible and resistant strains of S. aureus as well as for methicillin-susceptible and resistant S. aureus bloodstream infections, including patients with right-sided infective endocarditis. Because daptomycin is inactivated by pulmonary surfactant, it is ineffective for treating pneumonia. Phase 3 clinical trials in community-acquired pneumonia showed reduced efficacy of daptomycin. Daptomycin is FDA-approved for adults and pediatric patients 1 year of age and older.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-There are multiple formulations of daptomycin that have differences concerning storage and reconstitution. Generic products may also have different storage recommendations. Carefully follow the reconstitution and storage instructions in product labeling.
-Use a 21 gauge or smaller needle for all transfers.
-Because only limited data are available regarding compatibility with other IV substances, do not add additives or other medications to daptomycin vials or infusion bags.
-Do not use daptomycin in conjunction with ReadyMED elastomeric infusion pumps. Stability studies of daptomycin solutions stored in ReadyMED elastomeric infusion pumps identified an impurity, 2-mercaptobenzothiazole (MBT), leaching from this pump system into the daptomycin solution. MBT is used to manufacture rubber and has been reported to leach from rubber stoppers and syringe components into medicinal products. Cutaneous exposure to MBT has been associated with dermal sensitization, and chronic administration of MBT to laboratory rodents has been associated with an increased risk of certain tumors.
Intravenous Administration
Cubicin RF powder vials for injection (including generics)
Reconstitution
-Reconstitute a 500 mg vial with 10 mL of Sterile Water for Injection or Bacteriostatic Water for Injection. The vial solution concentration will be 50 mg/mL.
-Do not reconstitute with saline products as this will result in a hyperosmotic solution that may result in infusion site reactions if the reconstituted product is administered by IV injection over 2 minutes.
-Transfer the 10 mL of Sterile Water for Injection or Bacteriostatic Water for Injection through the center of the rubber stopper. Point the transfer needle against the inside wall of the vial.
-Prior to use, rotate or swirl the vial for a few minutes to obtain complete reconstitution.
-Vials are not preserved and are for single-use only.
-For IV push injection administration, slowly remove the reconstituted 50 mg/mL solution from the vial using a polypropylene syringe with an elastomeric plunger stopper.
-For intermittent IV infusion administration, further dilution is required.
-Storage (vials): Follow storage recommendations in the manufacturer's instructions. Vials reconstituted with Sterile Water for Injection are stable for 1 day at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Vials reconstituted with Bacteriostatic Water for Injection are stable for 2 days at room temperature and 3 days under refrigeration.
-Storage (syringes): Follow storage recommendations in the manufacturer's instructions. Solutions reconstituted with Sterile Water for Injection are stable in polypropylene syringes with an elastomeric plunger stopper for 1 day at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Solutions reconstituted with Bacteriostatic Water for Injection are stable in this syringe type for 2 days at room temperature and 5 days under refrigeration.
Dilution (for intermittent IV infusion)
-Adults, Adolescents, and Children 7 to 17 years: Further dilute in 50 mL of 0.9% Sodium Chloride Injection.
-Children 1 to 6 years: Further dilute in 25 mL of 0.9% Sodium Chloride Injection.
-Storage: Follow storage recommendations in the manufacturer's instructions. Solutions reconstituted with Sterile Water for Injection that are immediately diluted with 0.9% Sodium Chloride Injection are stable for 19 hours at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Solutions reconstituted with Bacteriostatic Water for Injection that are immediately diluted with 0.9% Sodium Chloride Injection are stable for 2 days at room temperature and 5 days under refrigeration.
Intermittent IV Infusion
-Adults, Adolescents, and Children 7 to 17 years: Infuse IV over 30 minutes.
-Children 1 to 6 years: Infuse IV over 60 minutes.
-Do not infuse other medications simultaneously through the same IV line. If the same IV line is used for sequential infusion of different drugs, flush the line with a compatible IV solution before and after daptomycin administration.
Intermittent IV Push
NOTE: Daptomycin should not be administered as an IV push in pediatric patients.
-Use only the reconstituted 50 mg/mL solution.
-Administer via slow IV push over 2 minutes.
Cubicin powder vials for injection (including generics)
Reconstitution
-To minimize foaming, avoid vigorous agitation or shaking of the vial during or after reconstitution.
-Reconstitute the daptomycin vial with 0.9% Sodium Chloride Injection according to the manufacturer's instructions to a final concentration of 50 mg/mL.
-Transfer the appropriate volume of 0.9% Sodium Chloride Injection through the center of the rubber stopper. Point the transfer needle against the inside wall of the vial.
-Ensure that all the powder is wetted by gently rotating the vial. Allow the wetted product to stand undisturbed for 10 minutes. Gently rotate or swirl the vial contents for a few minutes, as needed, to obtain a completely reconstituted solution.
-Vials are not preserved and are for single-use only.
-For IV push injection administration, slowly remove the reconstituted 50 mg/mL solution from the vial using a syringe.
-For intermittent IV infusion administration, further dilution is required.
-Storage: Follow storage recommendations in the manufacturer's instructions. The reconstituted solution is stable in the vial for 12 hours at room temperature and up to 48 hours if stored under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Some products require protection from light.
Dilution (for intermittent IV infusion)
-Adults, Adolescents, and Children 7 to 17 years: Further dilute in 50 mL of 0.9% Sodium Chloride Injection or other compatible solution according to the manufacturer's instructions.
-Children 1 to 6 years: Further dilute in 25 mL of 0.9% Sodium Chloride Injection or other compatible solution according to the manufacturer's instructions.
-Storage: Follow storage recommendations in the manufacturer's instructions. Diluted solutions are stable for 12 hours at room temperature or 48 hours under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). The combined storage time (reconstituted solution in the vial and the diluted solution in the infusion bag) should not exceed 12 hours at room temperature or 48 hours under refrigeration. Extended storage times may be allowed according to the manufacturer's instructions.
Intermittent IV Infusion
-Adults, Adolescents, and Children 7 to 17 years: Infuse IV over 30 minutes.
-Children 1 to 6 years: Infuse IV over 60 minutes.
-Do not infuse other medications simultaneously through the same IV line. If the same IV line is used for sequential infusion of different drugs, flush the line with a compatible IV solution before and after daptomycin administration.
Intermittent IV Push
NOTE: Daptomycin should not be administered as an IV push in pediatric patients.
-Use only the reconstituted 50 mg/mL solution.
-Administer via slow IV push over 2 minutes.
Dapzura RT powder vials for injection
Reconstitution
-Reconstitute a 500 mg vial with 10 mL of Sterile Water for Injection or Bacteriostatic Water for Injection. The vial solution concentration will be 50 mg/mL.
-Do not reconstitute with saline products as this will result in a hyperosmotic solution that may result in infusion site reactions if the reconstituted product is administered by IV injection over 2 minutes.
-Transfer the 10 mL of Sterile Water for Injection or Bacteriostatic Water for Injection through the center of the rubber stopper. Point the transfer needle against the inside wall of the vial.
-Prior to use, rotate or swirl the vial for a few minutes to obtain complete reconstitution.
-Vials are not preserved and are for single-use only.
-For IV push injection administration, slowly remove the reconstituted 50 mg/mL solution from the vial using a polypropylene syringe with an elastomeric plunger stopper.
-For intermittent IV infusion administration, further dilution is required.
-Storage (vials): Follow storage recommendations in the manufacturer's instructions. Vials reconstituted with Sterile Water for Injection are stable for 18 hours at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Vials reconstituted with Bacteriostatic Water for Injection are stable for 2 days at room temperature and 5 days under refrigeration.
-Storage (syringes): Follow storage recommendations in the manufacturer's instructions. Solutions reconstituted with Sterile Water for Injection are stable in polypropylene syringes with an elastomeric plunger stopper for 18 hours at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Solutions reconstituted with Bacteriostatic Water for Injection are stable in this syringe type for 2 days at room temperature and 5 days under refrigeration.
Dilution (for intermittent IV infusion)
-Adults, Adolescents, and Children 7 to 17 years: Further dilute in 50 mL of 0.9% Sodium Chloride Injection.
-Children 1 to 6 years: Further dilute in 25 mL of 0.9% Sodium Chloride Injection.
-Storage: Follow storage recommendations in the manufacturer's instructions. Solutions reconstituted with Sterile Water for Injection that are immediately diluted with 0.9% Sodium Chloride Injection are stable for 1 day at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Solutions reconstituted with Bacteriostatic Water for Injection that are immediately diluted with 0.9% Sodium Chloride Injection are stable for 2 days at room temperature and 5 days under refrigeration.
Intermittent IV Infusion
-Adults, Adolescents, and Children 7 to 17 years: Infuse IV over 30 minutes.
-Children 1 to 6 years: Infuse IV over 60 minutes.
-Do not infuse other medications simultaneously through the same IV line. If the same IV line is used for sequential infusion of different drugs, flush the line with a compatible IV solution before and after daptomycin administration.
Intermittent IV Push
NOTE: Daptomycin should not be administered as an IV push in pediatric patients.
-Use only the reconstituted 50 mg/mL solution.
-Administer via slow IV push over 2 minutes.
Frozen Pre-mixed Bags
-Consider an alternative formulation if a dose is required that does not equal 350, 500, 700, or 1,000 mg.
-Thaw and equilibrate container to room temperature; thaw frozen container at room temperature [20 to 25 degrees C (68 to 77 degrees F)] or under refrigeration [2 to 8 degrees C (36 to 46 degrees F)]. Do not thaw product by immersion in water baths or by microwave irradiation. Do not force thaw.
-Agitate after the solution has reached room temperature
-No further dilution is necessary.
-Storage: The thawed solution is stable for 30 days under refrigeration (5 degrees C or 41 degrees F) or for 48 hours at room temperature (25 degrees C or 77 degrees F). Do not refreeze thawed solution.
Intermittent IV Infusion
-Adults and Adolescents and Children 7 to 17 years: Infuse IV over 30 minutes.
-Children 1 to 6 years: Infuse IV over 60 minutes.
-Do not infuse other medications simultaneously through the same IV line. If the same IV line is used for sequential infusion of different drugs, flush the line with a compatible IV solution before and after daptomycin administration.
General adverse reactions associated with daptomycin in adult clinical trials included fatigue (< 1%), flushing (< 1%), hypersensitivity reactions (< 1%), rigors (< 1%), and weakness (< 1%). Pyrexia (fever) was reported in 3.9% of pediatric patients in clinical trials and was also noted in postmarketing reports.
Gastrointestinal (GI) adverse reactions were the most commonly reported side effects to daptomycin therapy in clinical trials. Among these, the most frequently reported included diarrhea (adults, 5.2%; pediatrics, 7%), abdominal pain (adults, 6%; pediatrics, 2%), and vomiting (pediatrics, 2.7% to 11%). Other GI adverse reactions reported in less than 1% of adult patients in clinical trials include abdominal distension, increased serum lactate dehydrogenase, jaundice, dysgeusia, and stomatitis. Dry mouth (xerostomia), epigastric discomfort, gingival pain, oral hypoesthesia, and decreased appetite (anorexia) were also reported. Nausea and vomiting were noted in postmarketing surveillance.
Increased CPK was reported in approximately 3% to 7% of adult patients and 6% to 7% of pediatric patients during daptomycin clinical trials. In adult clinical trials, patients reported myopathy, defined as muscle pain or weakness, and had CPK elevations to more than 10 times the upper limit of normal (ULN). Symptoms resolved within 3 days, and CPK returned to normal within 7 to 10 days after stopping daptomycin. Rhabdomyolysis, with or without acute renal failure, has been reported. In phase I and II studies, CPK elevations appeared to be more frequent when daptomycin was dosed more than once daily. Musculoskeletal adverse reactions reported in less than 1% of adult patients in clinical trials include arthralgia, muscle cramps, muscle weakness, and myalgia. Postmarketing reports have included increased myoglobin and rhabdomyolysis; some rhabdomyolysis reports involved patients treated concurrently with HMG-CoA reductase inhibitors. Discontinue daptomycin in patients with unexplained signs and symptoms of myopathy in conjunction with CPK elevations to concentrations more than 1,000 units/L (approximately 5 times the ULN) and in patients without reported symptoms who have marked elevations in CPK, with concentrations more than 2,000 units/L (10 times the ULN or more). Rhabdomyolysis may be complicated by renal insufficiency. Proteinuria and renal impairment were also noted in clinical trials and may be associated with daptomycin therapy.
Dizziness (2.2%), headache (adults, 5.4%; pediatrics, 2.7%), and insomnia (9%) were the most commonly reported central nervous system adverse reactions in clinical trials with daptomycin. Other CNS adverse reactions that have been reported with daptomycin in < 1% of adult patients in clinical trials include mental status change, paresthesias, and vertigo. Dyskinesia and hallucinations have also been reported as possible drug-related adverse reactions. Peripheral neuropathy has been noted in postmarketing reports.
Dyspnea (2.1%) and pharyngolaryngeal pain (8%) were the most frequently reported respiratory adverse reactions with daptomycin therapy in adult clinical trials. Cough was reported postmarketing.
Cardiovascular adverse reactions reported during adult clinical trials of daptomycin include chest pain (unspecified) (7%), edema (7%), hypertension (6%), hypotension (2.4%), and supraventricular arrhythmia (< 1%). Atrial fibrillation, atrial flutter, and cardiac arrest have also been reported as possible drug-related adverse reactions.
Ophthalmic adverse reactions to daptomycin were infrequent in clinical trials. Ocular irritation was reported in < 1% of adult patients during clinical trials. Blurred vision may also be a drug-related side effect. Visual disturbances were noted in postmarketing reports.
Leukocytosis, thrombocytopenia, thrombocytosis, eosinophilia, and increased INR were reported in less than 1% of adult patients during daptomycin clinical trials. Additionally, lymphadenopathy, thrombocythemia, and prolonged bleeding time may also be drug-related side effects. Anemia was reported in postmarketing experience.
The most frequently reported dermatologic reactions in clinical trials with daptomycin were increased sweating (hyperhidrosis) (5%), pruritus (adults, 6%; pediatrics, 3.1%), and rash (4.3%). Vesicular rash and eczema (less than 1%) were also reported. Serious skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), vesiculobullous rash/bullous rash (with or without mucous membrane involvement), including Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), have been reported in postmarketing experience with daptomycin. Evaluate patients who develop skin rash, fever, peripheral eosinophilia, and systemic organ (e.g., hepatic, renal, pulmonary) impairment while receiving daptomycin. If DRESS is suspected, discontinue daptomycin promptly and institute appropriate treatment.
Hypersensitivity or anaphylactoid reactions, including angioedema, pruritus, hives, shortness of breath, dysphagia, truncal erythema, and pulmonary eosinophilia, have been reported with the daptomycin and may be life-threatening. If an allergic reaction to daptomycin occurs, discontinue the drug and institute appropriate therapy.
Eosinophilic pneumonia has been reported with daptomycin in postmarketing experience. In general, patients developed eosinophilic pneumonia 2 to 4 weeks after starting daptomycin. Patients experienced fever, dyspnea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates or organizing pneumonia. Instruct patients to immediately contact a health care professional if they experience these signs or symptoms. Prompt evaluation, daptomycin discontinuation, and systemic steroid therapy are recommended. The condition has recurred upon daptomycin rechallenge.
Infection, including urinary tract infection (2.4%), sepsis (5%), and bacteremia (5%), was reported in adult patients during daptomycin clinical trials. Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with daptomycin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Other adverse events include candidiasis, vaginal candidiasis or vaginitis, fungemia, oral candidiasis, and fungal urinary tract infection.
Tinnitus was reported in adult patients during daptomycin clinical trials and may be drug-related.
Abnormal liver function tests were reported in 3% of adult patients during daptomycin clinical trials; elevated hepatic enzymes (alanine aminotransferase and aspartate aminotransferase increased) were reported. Hypomagnesemia, increased serum bicarbonate, and other electrolyte disturbances occurred in < 1% of adult patients in clinical trials. Additionally hyperphosphatemia and increased blood alkaline phosphatase have been reported as possible drug-related adverse reactions.
Acute kidney injury, renal insufficiency, renal failure (unspecified), and tubulo-interstitial nephritis (TIN) have been reported in postmarketing experience with daptomycin. Patients who develop new or worsening renal impairment while receiving daptomycin should undergo medical evaluation. If TIN is suspected, discontinue daptomycin promptly and institute appropriate treatment.
Do not use daptomycin with ReadyMED elastomeric infusion pumps due to an impurity, 2-mercaptobenzothiazole (MBT), leaching from the system into the daptomycin solution.
Daptomycin is contraindicated in patients with a history of daptomycin hypersensitivity.
Daptomycin is inactivated by pulmonary surfactant and should not be used in treating infections of the lung (e.g., pneumonia). Phase 3 clinical trials of daptomycin in adults with community-acquired pneumonia showed reduced efficacy and increased rates of serious cardiorespiratory adverse events in patients who received daptomycin.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including daptomycin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
There are limited data to determine clinical efficacy of daptomycin in patients with renal impairment or renal failure. In skin and skin structure infection trials, only 6% of patients had a CrCl less than 50 mL/minute in the intent-to-treat (ITT) population. Patients with a CrCl of 30 to 50 mL/minute had a clinical success rate of 47% with daptomycin (n = 15) vs. 57% with the comparator (n = 35). In a subgroup analysis of the ITT population in the S. aureus bacteremia trial, patients with a CrCl of 30 to 50 mL/minute had a lower clinical success rate vs. the comparator (14%, n = 14 vs. 41%, n = 17). Monitor renal function and creatine phosphokinase (CPK) more frequently than once weekly in patients with renal impairment. Daptomycin is not recommended in pediatric patients with renal impairment because dosage adjustments have not been established in these patients.
Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values to more than 10 times the upper limit of normal (ULN), has been reported with daptomycin. Rhabdomyolysis, with or without acute renal failure, has also been reported. Monitor patients for muscle pain or weakness, particularly of the distal extremities. Monitor CPK concentrations weekly, and more frequently in patients who received recent prior or concomitant therapy with an HMG-CoA reductase inhibitor, who experience CPK elevations during daptomycin treatment, and adults with renal impairment. Discontinue daptomycin in patients with unexplained signs and symptoms of myopathy in conjunction with CPK elevations to concentrations more than 1,000 units/L (approximately 5 times the ULN) and in patients without reported symptoms who have marked elevations in CPK, with concentrations more than 2,000 units/L (10 times the ULN or more). Consider temporary discontinuation of agents associated with rhabdomyolysis, such as HMG-CoA reductase inhibitors, in patients who are receiving daptomycin.
Cases of peripheral neuropathy have been reported with daptomycin in postmarketing experience. Monitor for signs and symptoms of neuropathy in patients receiving daptomycin and consider discontinuation.
Serious rash, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, vesiculobullous rash (with or without mucous membrane involvement), and acute generalized exanthematous pustulosis (AGEP), have been reported in postmarketing experience with daptomycin. Patients who develop skin rash, fever, peripheral eosinophilia, and systemic organ (e.g., hepatic, renal, pulmonary) impairment while receiving daptomycin should undergo medical evaluation. If DRESS is suspected, discontinue daptomycin promptly and institute appropriate treatment.
Daptomycin may cause laboratory test interference. Clinically relevant plasma concentrations 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. This may be minimized by obtaining specimens for PT or INR measurements near the time of trough plasma concentrations of daptomycin. However, sufficient daptomycin concentrations may still be present at trough to cause an interaction; consider utilizing an alternative assay method if PT/INR values are elevated above what is expected.
Avoid daptomycin use in neonates and infants due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (both peripheral and central). Animal toxicity studies have found neonatal dogs to have a higher susceptibility for daptomycin-related adverse nervous system and/or muscular reactions compared with either juvenile or adult dogs.
During clinical studies of daptomycin for various complicated or serious infections, lower clinical success rates were observed in geriatric adults 65 years of age and older compared to younger adults. Treatment-emergent adverse reactions were also more common in older adult patients.
Data on the use of daptomycin in human pregnancy are insufficient to inform a drug-associated risk for major birth defects and miscarriage. Daptomycin was not teratogenic in rats and rabbits at exposures significantly higher (75 mg/kg/day) than the expected human exposure; maternal toxicity, including decreased body weight gain and food consumption, was observed at the highest dose. Due to a high molecular weight, placental crossing of daptomycin is expected to be limited. However, vancomycin, which is similar in molecular weight to daptomycin, crosses the placenta in the second trimester resulting in detectable concentrations in amniotic fluid and cord blood.
Daptomycin is excreted in human milk. There are no data on the effects of daptomycin on the breast-fed infant or milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for daptomycin and any potential adverse effects on the breast-fed infant from daptomycin or the underlying maternal condition. In 1 patient treated for a pelvic infection with daptomycin (6.7 mg/kg IV) and ertapenem for 28 days, daptomycin breast-milk concentrations were obtained on day 27 of therapy. Concentrations were highest at 8 hours after the dose with a concentration of 44.7 mcg/L. At 20 hours after the dose, a concentration of 29.2 mcg/L was obtained, and the final sample had no detectable drug (less than 25 mcg/L). Estimated milk:plasma ratio was 0.0012. Vancomycin, clindamycin, and sulfamethoxazole; trimethoprim may be potential alternatives to consider during breast-feeding. However, assess site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility before choosing an alternative agent. Vancomycin is excreted in breast milk; however, absorption from the GI tract of any ingested vancomycin would be minimal. Alternative antimicrobials that previous American Academy of Pediatrics recommendations considered as usually compatible with breast-feeding include clindamycin and sulfamethoxazole; trimethoprim.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Corynebacterium jeikeium, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus (MRSA), Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Staphylococcus haemolyticus, Streptococcus agalactiae (group B streptococci), Streptococcus dysgalactiae, Streptococcus pyogenes (group A beta-hemolytic streptococci)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of Staphylococcus aureus bacteremia:
Intravenous dosage:
Adults: 6 mg/kg/dose IV every 24 hours for 2 to 6 weeks is the FDA-approved dosage. Doses of 8 to 10 mg/kg/dose IV every 24 hours may be warranted for MRSA. In patients with persistent MRSA bacteremia and vancomycin treatment failures, the clinical practice guidelines recommend 10 mg/kg/dose IV every 24 hours in combination with another agent (gentamicin, rifampin, linezolid, sulfamethoxazole/trimethoprim, or a beta-lactam). Treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia. Studies have demonstrated the safety of doses of at least 8 mg/kg/dose IV every 24 hours. Limited safety data are available for use beyond 28 days.
Children and Adolescents 12 to 17 years: 7 mg/kg/dose IV every 24 hours for up to 6 weeks.
Children 7 to 11 years: 9 mg/kg/dose IV every 24 hours for up to 6 weeks.
Children 1 to 6 years: 12 mg/kg/dose IV every 24 hours for up to 6 weeks.
Infants*: Safety and efficacy have not been established; limited data are available. Based on pharmacokinetic data, doses of 8 to 10 mg/kg/dose IV every 24 hours have been recommended in this age group. 6 to 10 mg/kg/dose IV every 24 hours is suggested by the Infectious Diseases Society of America (IDSA) for bacteremia. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 9 with bacteremia; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. Treat for 2 to 6 weeks for bacteremia. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.
Neonates*: Safety and efficacy have not been established; very limited data are available. Doses of 6 to 15 mg/kg/dose IV every 12 to 24 hours have been successfully used in case reports of neonates and premature neonates (n = 7) with MRSA and vancomycin-resistant enterococcal bacteremia. 6 mg/kg/dose IV every 12 hours is the most commonly reported dose; however, differences in peak concentrations have been observed with this dose between various studies. Doses higher than 6 mg/kg/dose may be necessary in neonates to achieve adequate drug exposure. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 9 with bacteremia; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. Treat 2 to 6 weeks for bacteremia. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.
For the treatment of skin and skin structure infections, including cellulitis, erysipelas, necrotizing infections, diabetic foot ulcer, and surgical incision site infections:
-for the treatment of unspecified complicated skin and skin structure infections:
Intravenous dosage:
Adults: 4 mg/kg/dose IV every 24 hours for 7 to 14 days.
Children and Adolescents 12 to 17 years: 5 mg/kg/dose IV every 24 hours for up to 14 days.
Children 7 to 11 years: 7 mg/kg/dose IV every 24 hours for up to 14 days.
Children 2 to 6 years: 9 mg/kg/dose IV every 24 hours for up to 14 days.
Children 1 year: 10 mg/kg/dose IV every 24 hours for up to 14 days.
Infants*: Safety and efficacy have not been established; limited data are available describing the use of daptomycin in pediatric patients. Based on pharmacokinetic data, doses of 8 to 10 mg/kg/dose IV every 24 hours have been recommended in this age group. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 3 with complicated skin and soft tissue infections; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.
Neonates*: Safety and efficacy have not been established; very limited data are available. Doses of 6 to 15 mg/kg/dose IV every 12 to 24 hours have been successfully used in case reports of neonates and premature neonates (n = 7) with methicillin-resistant S. aureus and vancomycin-resistant enterococcal bacteremia. 6 mg/kg/dose IV every 12 hours is the most commonly reported dose; however, differences in peak concentrations have been observed with this dose between various studies. Doses higher than 6 mg/kg/dose may be necessary in neonates to achieve adequate drug exposure. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 3 with complicated skin and soft tissue infections; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.
-for the treatment of cellulitis and erysipelas:
Intravenous dosage:
Adults: 4 mg/kg/dose IV every 24 hours for 5 to 14 days.
Children and Adolescents 12 to 17 years: 5 mg/kg/dose IV every 24 hours for 5 to 14 days.
Children 7 to 11 years: 7 mg/kg/dose IV every 24 hours for 5 to 14 days.
Children 2 to 6 years: 9 mg/kg/dose IV every 24 hours for 5 to 14 days.
Children 1 year: 10 mg/kg/dose IV every 24 hours for 5 to 14 days.
-for the treatment of necrotizing infections of the skin, fascia, and muscle:
Intravenous dosage:
Adults: 4 mg/kg/dose IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for Streptococcus and S. aureus infections in patients with severe penicillin hypersensitivity.
Children and Adolescents 12 to 17 years: 5 mg/kg/dose IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for Streptococcus and S. aureus infections in patients with severe penicillin hypersensitivity.
Children 7 to 11 years: 7 mg/kg/dose IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for Streptococcus and S. aureus infections in patients with severe penicillin hypersensitivity.
Children 2 to 6 years: 9 mg/kg/dose IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for Streptococcus and S. aureus infections in patients with severe penicillin hypersensitivity.
Children 1 year: 10 mg/kg/dose IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for Streptococcus and S. aureus infections in patients with severe penicillin hypersensitivity.
-for the treatment of diabetic foot ulcer:
Intravenous dosage:
Adults: 4 mg/kg/dose IV every 24 hours for 7 to 14 days for infections due to methicillin-resistant S. aureus or in combination with other agents if a polymicrobial infection is suspected. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.
-for the treatment of surgical incision site infections:
Intravenous dosage:
Adults: 4 mg/kg/dose IV every 24 hours in patients with risk factors for methicillin-resistant S. aureus.
For the treatment of endocarditis:
Intravenous dosage:
Adults: 6 mg/kg/dose IV every 24 hours for 2 to 6 weeks is the FDA-approved dosage for right-sided S. aureus endocarditis. Guidelines suggest doses of 8 to 10 mg/kg/dose IV every 24 hours for MRSA endocarditis and 10 to 12 mg/kg/dose IV every 24 hours for multi-drug resistant enterococcal endocarditis as part of combination therapy. Daptomycin is also an alternative option in patients with MSSA left-sided endocarditis. Treat native-valve S. aureus endocarditis for 6 weeks and multi-drug resistant enterococcal endocarditis for more than 6 weeks. Studies have demonstrated the safety of doses of at least 8 mg/kg/dose IV every 24 hours. Limited safety data are available for use beyond 28 days.
Children and Adolescents 7 to 17 years*: 6 mg/kg/dose IV every 24 hours for 6 weeks is recommended by guidelines.
Children 1 to 6 years*: 10 mg/kg/dose IV every 24 hours for 6 weeks is recommended by guidelines.
Infants*: Safety and efficacy have not been established; limited data are available. Based on pharmacokinetic data, doses of 8 to 10 mg/kg/dose IV every 24 hours have been recommended in this age group. 6 to 10 mg/kg/dose IV every 24 hours is suggested by the Infectious Diseases Society of America (IDSA) for infective endocarditis. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 9 with bacteremia; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. Guidelines recommend treatment for 6 weeks for endocarditis. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.
Neonates*: Safety and efficacy have not been established; very limited data are available. Doses of 6 to 15 mg/kg/dose IV every 12 to 24 hours have been successfully used in case reports of neonates and premature neonates (n = 7) with MRSA and vancomycin-resistant enterococcal bacteremia. 6 mg/kg/dose IV every 12 hours is the most commonly reported dose; however, differences in peak concentrations have been observed with this dose between various studies. Doses higher than 6 mg/kg/dose may be necessary in neonates to achieve adequate drug exposure. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 9 with bacteremia; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. Guidelines recommend treatment for 6 weeks for endocarditis. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.
For the treatment of infections due to vancomycin-resistant enterococci (VRE)*:
Intravenous dosage:
Adults: Doses of 8 to 12 mg/kg/dose IV every 24 hours have been used safely and effectively in patients with vancomycin-resistant enterococci (VRE) infections, including bloodstream infections. 10 to 12 mg/kg/dose IV every 24 hours is recommended by guidelines for multi-drug resistant enterococcal endocarditis as part of combination therapy.
Children and Adolescents 7 to 17 years: Safety and efficacy have not been established; limited data are available describing the use of daptomycin in pediatric patients. 8 to 10 mg/kg/dose IV every 24 hours has been recommended for VRE bacteremia. 8 mg/kg/dose IV every 24 hours was successfully used in a case report of a 10-year old girl with severe sepsis due to vancomycin- and linezolid-resistant Enterococcus faecium (VAN-B VRE).
Children 1 to 6 years: Safety and efficacy have not been established; limited data are available describing the use of daptomycin in pediatric patients. Based on pharmacokinetic data, doses of 8 to 10 mg/kg/dose IV every 24 hours have been recommended in this age group. One case report describes the use of daptomycin 4 mg/kg/dose IV every 12 hours in combination with linezolid in a 21-month-old child with vancomycin-resistant enterococcal bacteremia; blood cultures were sterilized 14 days after daptomycin initiation.
Infants: Safety and efficacy have not been established; limited data are available describing the use of daptomycin in pediatric patients. Based on pharmacokinetic data, doses of 8 to 10 mg/kg/dose IV every 24 hours have been recommended in this age group. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.
Neonates: Safety and efficacy have not been established; very limited data are available. Doses of 6 to 15 mg/kg/dose IV every 12 to 24 hours have been successfully used in case reports of neonates and premature neonates (n = 7) with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcal bacteremia. 6 mg/kg/dose IV every 12 hours is the most commonly reported dose; however, differences in peak concentrations have been observed with this dose between various studies. Doses higher than 6 mg/kg/dose may be necessary in neonates to achieve adequate drug exposure. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in neonates in order to ensure safe and effective therapy.
For the treatment of bone and joint infections*, including osteomyelitis*, infectious arthritis*, infectious bursitis*, and orthopedic device-related infection*:
-for the treatment of unspecified osteomyelitis* due to methicillin-resistant S. aureus:
Intravenous dosage:
Adults: 6 mg/kg/dose IV every 24 hours for at least 8 weeks, which may be followed by long-term suppressive therapy. May consider the addition of rifampin; for patients with concurrent bacteremia, add rifampin after bacteremia clearance.
Children and Adolescents 12 to 17 years: 7 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Children 7 to 11 years: 9 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Children 1 to 6 years: 12 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
-for the treatment of native vertebral osteomyelitis* due to Staphylococcus sp.:
Intravenous dosage:
Adults: 6 to 8 mg/kg/dose IV every 24 hours for 6 weeks.
-for the treatment of native vertebral osteomyelitis* due to Enterococcus sp.:
Intravenous dosage:
Adults: 6 mg/kg/dose IV every 24 hours for 6 weeks. Add an aminoglycoside for 4 to 6 weeks in patients with endocarditis or bacteremia; may consider shorter aminoglycoside duration in patients with bacteremia.
-for the treatment of infectious arthritis* due to methicillin-resistant S. aureus:
Intravenous dosage:
Adults: 6 mg/kg/dose IV every 24 hours. Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks.
Children and Adolescents 12 to 17 years: 7 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Children 7 to 11 years: 9 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Children 1 to 6 years: 12 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
-for the treatment of infectious bursitis* due to methicillin-resistant S. aureus:
Intravenous dosage:
Adults: 6 mg/kg/dose IV every 24 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
Children and Adolescents 12 to 17 years: 7 mg/kg/dose IV every 24 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
Children 7 to 11 years: 9 mg/kg/dose IV every 24 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
Children 1 to 6 years: 12 mg/kg/dose IV every 24 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
-for the treatment of prosthetic joint infections* due to S. aureus:
Intravenous dosage:
Adults: 6 mg/kg/dose IV every 24 hours in combination with rifampin for 2 to 6 weeks, followed by oral step-down therapy, which may be followed by long-term suppressive therapy.
-for the treatment of prosthetic joint infections* due to Enterococcus sp.:
Intravenous dosage:
Adults: 6 mg/kg/dose IV every 24 hours for 4 to 6 weeks with or without an aminoglycoside, which may be followed by long-term suppressive therapy.
-for the treatment of spinal implant infections* due to methicillin-resistant S. aureus:
Intravenous dosage:
Adults: 6 mg/kg/dose IV every 24 hours plus rifampin followed by long-term oral therapy.
For the empiric treatment of febrile neutropenia*:
Intravenous dosage:
Adults: 6 mg/kg/dose IV every 24 hours is recommended by clinical practice guidelines for patients with suspected MRSA, vancomycin-resistant pathogens (VRE), or when vancomycin is not an option. Daptomycin as part of combination therapy with an antibiotic that has gram negative coverage has been successfully used in patients with febrile neutropenia in small studies.
For the treatment of intraabdominal infections*, including peritonitis*, appendicitis*, intraabdominal abscess*, spontaneous bacterial peritonitis*, and peritoneal dialysis-related peritonitis*:
-for the treatment of complicated healthcare-acquired or hospital-acquired intraabdominal infections* with adequate source control:
Intravenous dosage:
Adults: 4 to 6 mg/kg/dose IV every 24 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
-for the treatment of spontaneous bacterial peritonitis*:
Intravenous dosage:
Adults: 4 to 6 mg/kg/dose IV every 24 hours as part of combination therapy for at least 5 to 7 days as an alternative.
-for the treatment of peritoneal dialysis-related peritonitis*:
Continuous Intraperitoneal dosage*:
Adults: 100 mg/L intraperitoneal loading dose, followed by 20 mg/L in each dialysate exchange. Treat for 21 days.
Therapeutic Drug Monitoring:
Pediatric patients
-Although not widely utilized in clinical practice, consider monitoring of serum peak and trough concentrations when daptomycin is used in neonates and young infants to ensure safe and effective therapy. Daptomycin dosing data is very limited and variable concentrations have been reported when the same dose has been utilized in neonates and young infants in various studies.
-If daptomycin concentrations are obtained, measure peak at the end of an infusion and trough immediately before the subsequent infusion.
-Therapeutic concentrations have not been determined. Trough concentrations are not predictive of efficacy/toxicity. Daptomycin displays concentration-dependent activity, where the AUC:MIC ratio is the pharmacodynamic parameter correlated with efficacy. However, this parameter has not been evaluated in clinical studies.
-Peak concentrations observed in case reports of neonates have been highly variable. Peak concentrations in the range of 10 to 40 mcg/mL have been reported with doses of 6 mg/kg/dose; peak concentrations of approximately 35 mcg/mL have been reported with doses of 15 mg/kg/dose. This compares with peak concentrations of 58, 99, and 133 mcg/mL observed with doses of 4, 6, and 8 mg/kg/dose, respectively, in adults. Although lower peak concentrations have been observed in neonates, effective therapy has been noted in reported cases. Daptomycin displays a post-antibiotic effect, which may explain its efficacy despite the lower peak concentrations.
-Trough concentrations of approximately 7 to 12 mcg/mL have been observed with doses of 6 to 15 mg/kg/dose every 12 hours in neonates, which is comparable to trough concentrations seen in adults receiving 6 mg/kg/dose every 24 hours.
Maximum Dosage Limits:
-Adults
6 mg/kg/dose IV every 24 hours is FDA-approved maximum dosage; however, doses up to 12 mg/kg/dose IV every 24 hours have been used off-label.
-Geriatric
6 mg/kg/dose IV every 24 hours is FDA-approved maximum dosage; however, doses up to 12 mg/kg/dose IV every 24 hours have been used off-label.
-Adolescents
7 mg/kg/dose IV every 24 hours is FDA-approved maximum dosage; however, doses up to 10 mg/kg/dose IV every 24 hours have been used off-label.
-Children
12 years: 7 mg/kg/dose IV every 24 hours is FDA-approved maximum dosage; however, doses up to 10 mg/kg/dose IV every 24 hours have been used off-label.
7 to 11 years: 9 mg/kg/dose IV every 24 hours is FDA-approved maximum dosage; however, doses up to 10 mg/kg/dose IV every 24 hours have been used off-label.
1 to 6 years: 12 mg/kg/dose IV every 24 hours.
-Infants
Safety and efficacy have not been established; doses up to 10 mg/kg/dose IV every 24 hours have been used off-label.
-Neonates
Safety and efficacy have not been established; doses up to 15 mg/kg/dose IV every 12 hours have been used off-label.
Patients with Hepatic Impairment Dosing
No dosage adjustment is required in patients with mild to moderate hepatic impairment; however, the pharmacokinetics in patients with severe hepatic impairment (Child-Pugh class C) have not been evaluated.
Patients with Renal Impairment Dosing
Adults
CrCl 30 mL/minute or more: No dosage adjustment required.
CrCl less than 30 mL/minute: Extend the dosing interval to every 48 hours.
Pediatric patients*
The following dose adjustments, based on a dose of 6 mg/kg/dose IV every 24 hours, have been recommended.
CrCl 30 mL/minute/1.73 m2 or more: No dosage adjustment required.
CrCl 10 to 29 mL/minute/1.73 m2: 4 mg/kg/dose IV every 24 hours.
CrCl less than 10 mL/minute/1.73 m2: 4 mg/kg/dose IV every 48 hours.
Neonates*
A dose of 6 mg/kg/dose IV every 24 hours was successfully used in a full-term neonate with renal impairment (serum creatinine 0.6 mg/dL) and vancomycin-resistant enterococcal bacteremia. The patient received an 8-week course of daptomycin, including 6 weeks after the last positive blood culture.
Intermittent hemodialysis
Adults
Extend the dosing interval to every 48 hours. When possible, the daptomycin dose should be given after hemodialysis on hemodialysis days.
Pediatric patients*
4 mg/kg/dose IV every 48 hours after dialysis.
Continuous renal replacement therapy (CRRT)*
NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.
Adults
4 to 8 mg/kg IV every 24 hours or 8 mg/kg IV every 48 hours. General recommendations for patients receiving CVVH, CVVHD, and CVVHDF suggest 4 or 6 mg/kg/dose IV every 48 hours. However, some experts state that dose may result in underdosing and suggest 4 to 6 mg/kg IV every 24 hours or 8 mg/kg IV every 48 hours. More specific recommendations for CVVH, CVVHD, and CVVHDF based on ultrafiltrate rate (UFR) suggest 6 to 8 mg/kg IV every 24 hours for patients receiving an UFR of 1 to 2 L/hour and 8 mg/kg IV every 24 hours for patients receiving an UFR of at least 3 L/hour. Doses more than 8 mg/kg IV every 24 hours increase the risk of CPK elevations and myopathy. Use clinical judgment and frequent monitoring if pursuing doses of 10 to 12 mg/kg IV every 24 hours in patients receiving an UFR of at least 3 L/hour.
Pediatric patients*
8 mg/kg/dose IV every 48 hours.
Hybrid hemodialysis*
NOTE: Hybrid treatments include prolonged intermittent renal replacement therapy (PIRRT), sustained low-efficiency dialysis (SLED), slow extended daily dialysis/diafiltration (SLEDD-f), and extended daily dialysis (EDD). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), the type of infection, the duration of renal replacement therapy, the ultrafiltration rate, the dialysis flow rate, and how often dialysis sessions occur.
Adults
In a single-dose pharmacokinetic study in 10 critically ill patients receiving an 8-hour EDD session, daptomycin 6 mg/kg IV was administered 8 hours prior to dialysis. Daptomycin half-life in these critically ill patients was comparable to healthy controls. The mean fraction of drug removal by a single dialysis treatment was 23.3%. The authors recommended 6 mg/kg IV every 24 hours if administered within 8 hours of EDD initiation to decrease the risk of treatment failure.
Peritoneal dialysis
Adults
Extend the dosing interval to every 48 hours.
Pediatric patients*
4 mg/kg/dose IV every 48 hours.
*non-FDA-approved indication
Amlodipine; Atorvastatin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Atorvastatin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ezetimibe; Simvastatin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Fluvastatin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
HMG-CoA reductase inhibitors: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Lovastatin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Pitavastatin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Pravastatin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Red Yeast Rice: (Moderate) Certain red yeast rice products (i.e., pre-2005 Cholestin formulations) contain lovastatin. HMG-CoA reductase inhibitors such as lovastatin are known to cause myopathy. Elevated CPK has been reported in clinical trials of daptomycin, a lipopeptide antibiotic. In a placebo-controlled phase I trial of daptomycin that included 10 healthy subjects stabilized on simvastatin therapy, there was no increase in the incidence of adverse reactions nor was myopathy reported. However, data regarding coadministration of daptomycin with HMG-CoA reductase inhibitors are limited; temporary suspension of HMG-CoA reductase inhibitor therapy should be considered in patients receiving daptomycin.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Rosuvastatin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Rosuvastatin; Ezetimibe: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Simvastatin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Tobramycin: (Moderate) The pharmacokinetics of daptomycin and tobramycin may be altered when the two antibiotics are coadministered. The serum concentration of daptomycin may be increased and the serum concentration of tobramycin may be decreased. The manufacturer recommends caution when daptomycin is coadministered with tobramycin.
Warfarin: (Moderate) Monitor patients for signs and symptoms of bleeding during coadministration. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary. The concomitant use of warfarin with antibiotics may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. In 16 healthy adults, a 5-day daptomycin course coadministered with a single oral dose of warfarin (25 mg) on the fifth day had no significant effect on the pharmacokinetics of either drug and did not significantly alter the INR; however, there are no data describing concurrent use beyond a single warfarin dose.
Lipopeptide antibiotics, like daptomycin, interfere with the integrity of cell wall structure in gram-positive bacteria via a unique mechanism of action. Specifically, lipopeptides bind to bacterial membranes and cause a rapid depolarization of membrane potential; they do not penetrate the bacterial cytoplasm. This loss of membrane potential leads to inhibition of protein, DNA, and RNA synthesis and, eventually, bacterial cell death. Lipopeptides appear to be bactericidal against gram-positive bacteria.
Ironically, the unique mechanism of action of daptomycin causes it to be inactivated by pulmonary surfactant. Pulmonary surfactant is primarily dipalmitoylphosphatidylcholine with significant amounts of phosphatidylglycerol, which is also a prominent component of gram-positive bacterial membranes. These phospholipids interact with daptomycin and sequester the antibiotic, thereby preventing it from exerting its antibacterial effects. Phase 3 clinical trials in adults with community-acquired pneumonia showed reduced efficacy of daptomycin.
Daptomycin displays rapid, concentration-dependent bactericidal activity against gram-positive bacteria and a post-antibiotic effect (PAE). Concentration-dependent killing describes the principle that bactericidal effects increase as the concentration increases. PAE is where suppression of bacterial growth continues after the antibiotic concentration falls below the bacterial MIC. Based on animal models, the pharmacokinetic/pharmacodynamic (PK/PD) activity of daptomycin appears to correlate best with the area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio for certain pathogens, including S. aureus. The principal PK/PD parameter associated with clinical success has not been determined by trials.
The susceptibility interpretive criteria for daptomycin are delineated by pathogen. The MICs are defined for beta-hemolytic streptococci, Streptococcus sp. viridans group, and Staphylococcus sp. as susceptible at 1 mcg/mL or less. The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for Enterococcus sp. The MICs are defined by the FDA for Enterococcus faecalis (including vancomycin-resistant isolates) as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL. The MICs are defined by CLSI for Enterococcus faecium as susceptible-dose dependent (SDD) at 4 mcg/mL or less and resistant at 8 mcg/mL or more (based on a dosage of 8 to 12 mg/kg IV every 24 hours). The MICs are defined by CLSI for other Enterococcus sp. as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. Susceptibility test interpretive criteria (STIC) are based on a dosage of 6 mg/kg IV once every 24 hours for patients with a CrCl more than 30 mL/minute for all isolates except E. faecium MICs as defined by CLSI. MICs are not intended to be used for respiratory isolates.
Nonsusceptible isolates have emerged during daptomycin therapy. Mechanisms of resistance are not clearly defined; however, single-point mutations in mprF, the lysylphosphatidyglycerol synthetase gene, have been present in resistant strains. Additionally, prior exposure to vancomycin and elevated vancomycin MICs have been associated with increases in daptomycin MICs, which may suggest possible cross-resistance.
Daptomycin is administered intravenously. Protein binding is approximately 90% to 93%, primarily to albumin, and is reversible; it is not altered by daptomycin concentration, dose, or number of doses received. In patients with significant renal impairment, protein binding is decreased. Daptomycin is distributed into lung tissue; however, it is inhibited by pulmonary surfactant. The steady-state volume of distribution in healthy adults is approximately 0.1 L/kg. The metabolism of daptomycin has not been determined; however, inactive metabolites have been identified in the urine. Daptomycin is primarily (78%) excreted by the kidneys; 5.7% of a dose is excreted in the feces. The clearance and elimination half-life of daptomycin in adults is approximately 7 to 9 mL/hour/kg and 8 to 9 hours, respectively.
Affected cytochrome P450 isoenzymes: none
In vitro studies have shown that daptomycin is not metabolized by human liver microsomes. In vitro studies have also shown that daptomycin does not induce or inhibit the following CYP450 enzymes: 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A4.
-Route-Specific Pharmacokinetics
Intravenous Route
After a 30 minute intravenous infusion of daptomycin, the maximum serum concentrations (Cmax) occur in about 30 to 60 minutes (Tmax). The Cmax is approximately 57.8 mcg/mL for a dose of 4 mg/kg, 93.9 mcg/mL for a dose of 6 mg/kg, 123.3 mcg/mL for a dose of 8 mg/kg, 141.1 mcg/mL for a dose of 10 mg/kg, and 183.7 mcg/mL for a dose of 12 mg/kg. The AUC is 494 mcg x hour/mL for a dose of 4 mg/kg, 632 mcg x hour/mL for a dose of 6 mg/kg, 858 mcg x hour/mL for a dose of 8 mg/kg, 1,039 mcg x hour/mL for a dose of 10 mg/kg, and 1,277 mcg x hour/mL for a dose of 12 mg/kg. The Cmax in inflammatory fluid has a Tmax of about 4 hours. Steady state serum concentrations are obtained in about 3 days. After administration of daptomycin over a 2 minute period, the steady-state AUC value is approximately 475 mcg x hour/mL for a 4 mg/kg dose and 701 mcg x hour/mL for a 6 mg/kg dose. The Cmax for these doses was simulated to be 77.7 mcg/mL for the 4 mg/kg dose and 116.6 mcg/mL for the 6 mg/kg dose.
-Special Populations
Hepatic Impairment
The pharmacokinetics of daptomycin are not altered in patients with Child-Pugh class B hepatic insufficiency. Therefore, no dosage adjustment is recommended in patients with mild to moderate hepatic insufficiency; daptomycin has not been studied in patients with severe hepatic dysfunction.
Renal Impairment
Dosage adjustments are required in patients with severe renal impairment because daptomycin is mainly excreted by the kidneys. As compared to patients with normal renal function, the total clearance is 9% lower in patients with mild renal impairment (CrCl 50 to 80 mL/minute), 22% lower in patients with moderate renal impairment (CrCl 30 to 49 mL/minute), and 46% lower in patients with severe renal impairment (CrCl less than 30 mL/minute). Patients with CrCl 30 to 80 mL/minute have mean AUC values similar to patients with normal renal function. However, patients with CrCl less than 30 mL/minute exhibit mean AUC values twice those of patients with normal renal function; patients on hemodialysis or CAPD had mean AUC values 3 times those with normal renal function. Daptomycin is removed by hemodialysis; about 15% of an administered dose is eliminated in a 4-hour hemodialysis session and about 11% after 48 hours of CAPD. Timing of dosage regimens should allow for a normally scheduled dose to be administered after a hemodialysis session. The half-life in patients undergoing hemodialysis is 30.51 hours and is 27.56 hours in patients undergoing CAPD. Serum protein binding is also somewhat decreased in patients with CrCl less than 30 mL/minute, including patients receiving hemodialysis or CAPD.
Pediatrics
Children and Adolescents 12 years and older
The clearance of daptomycin is slightly higher in children and adolescents 12 years and older compared to adults. In 2 pharmacokinetic studies in patients 12 to 17 years, values for clearance and elimination half-life were 11.8 mL/hour/kg and 7.1 hours, respectively, after multiple doses of 5 mg/kg/dose IV every 24 hours (n = 6) and 12.4 mL/hour/kg and 7.5 hours, respectively, after multiple doses of 7 mg/kg/dose IV every 24 hours (n = 13).
Children 7 to 11 years
The clearance of daptomycin is significantly higher in children younger than 12 years compared to older children, adolescents, and adults. In 2 pharmacokinetic studies in patients 7 to 11 years, values for clearance and elimination half-life were 13.2 mL/hour/kg and 6.8 hours, respectively, after multiple doses of 7 mg/kg/dose IV every 24 hours (n = 2) and 15.9 mL/hour/kg and 6 hours, respectively, after multiple doses of 9 mg/kg/dose IV every 24 hours (n = 19).
Children 2 to 6 years
The clearance of daptomycin is significantly higher in children younger than 12 years compared to older children, adolescents, and adults. In a pharmacokinetic study, values for clearance and elimination half-life for patients 2 to 6 years (n = 12) were 19 mL/hour/kg and 5.4 to 5.7 hours, respectively, after administration of single IV doses of 8 and 10 mg/kg. The AUC values for the 8 and 10 mg/kg/dose were approximately 429 and 550 mcg x hour/mL, respectively. The authors concluded that a dose of 8 to 10 mg/kg/dose in children 2 to 6 years would provide similar systemic exposure to adults receiving 4 to 6 mg/kg/dose. In 2 other pharmacokinetic studies in patients 2 to 6 years receiving multiple doses of 9 mg/kg/dose IV every 24 hours (n = 7) or 12 mg/kg/dose IV every 24 hours (n = 19), similar pharmacokinetic parameters were noted (clearance, 19.9 to 20.8 mL/hour/kg; elimination half-life, 4.6 to 5.1 hours).
Children younger than 2 years
The clearance of daptomycin is significantly higher in children younger than 2 years compared to older children, adolescents, and adults and is similar to what has been observed in children 2 to 6 years of age. In a pharmacokinetic study in children 13 to 24 months (n = 5), mean values for AUC, clearance, and elimination half-life were 282 mcg x hour/mL, 21.8 mL/hour/kg, and 4.41 hours, respectively, after a single 6 mg/kg IV dose. Mean Vd was 0.122 L/kg. In another pharmacokinetic study in children younger than 2 years (n = 27), mean AUC, clearance, and elimination half-life was 462 mcg x hour/mL, 23.1 mL/hour/kg, and 4.8 hours, respectively, after multiple doses of 10 mg/kg/dose IV every 24 hours. These data suggest that children younger than 2 years need higher weight-based doses of daptomycin compared with adults to achieve similar systemic exposure.
Neonates and Infants
The clearance of daptomycin is significantly higher in neonates and infants compared to older children, adolescents, and adults and is similar to what has been observed in children 2 to 6 years of age. In a pharmacokinetic study in 20 neonates and young infants (median gestational age 32 weeks [range 23 to 40 weeks]; median postnatal age 3 days [range 1 to 85 days]), the median AUC, Vd, total clearance, and elimination half-life after a single IV dose of 6 mg/kg was 262.4 mcg x hour/mL (range 166.7 to 340.2 mcg x hour/mL), 0.21 L/kg (range 0.11 to 0.34 L/kg), 21 mL/hour/kg (range 16 to 34 mL/hour/kg), and 6.2 hours (range 3.7 to 9 hours), respectively. The median AUC for infants in this study was approximately 50% lower than that observed in adults receiving 4 mg/kg/dose every 24 hours (494 mcg x hour/mL) and approximately 65% lower than that observed in adults receiving 6 mg/kg/dose every 24 hours (747 mcg x hour/mL). In another pharmacokinetic study in pediatric patients 3 to 24 months of age, similar results were observed. The mean AUC for infants 3 to 6 months (n = 7) and infants 7 to 12 months (n = 7) after a single IV dose of 4 mg/kg was 215 mcg x hour/mL and 219 mcg x hour/mL, respectively. Clearance (approximately 20 mL/hour/kg), Vd (0.128 to 0.135 L/kg), and elimination half-life values (5.1 to 5.45 hours) were similar for the 2 groups. These data suggest that neonates and infants may need higher weight-based doses of daptomycin compared with adults to achieve similar systemic exposure.
Geriatric
In elderly patients (75 years of age and older), the total clearance of a single 4 mg/kg dose of daptomycin was approximately 35% lower with a mean AUC that was 58% higher as compared to younger subjects. There was no difference in Cmax.
Gender Differences
In adults, daptomycin pharmacokinetics are not significantly influenced by gender.
Obesity
In a pharmacokinetic evaluation of moderately obese patients (n = 6) with a BMI of 25 to 39.9 kg/m2 and extremely obese patients (n = 6) with a BMI of more than 40 kg/m2, total plasma clearance of daptomycin (normalized to total body weight) was approximately 15% lower in the moderately obese patients and 23% lower in the extremely obese patients as compared to controls. This resulted in an AUC that was 30% higher in the moderately obese patients and 31% higher in the extremely obese patients versus controls. These differences may be due to differences in renal clearance of daptomycin. However, no dosage adjustments are recommended.