Ceftazidime; avibactam is a combination product consisting of a third-generation cephalosporin and a beta-lactamase inhibitor. The drug is indicated for the treatment of complicated intra-abdominal infections (when used in combination with metronidazole), complicated urinary tract infections, and hospital-acquired and ventilator-associated pneumonia (HAP/VAP) in adult and pediatric patients, including neonates. Approval was based on the results of several randomized phase 2 and phase 3 studies and on previous findings regarding safety and efficacy of ceftazidime. Decreased efficacy was seen in adult patients with complicated intra-abdominal infections and baseline CrCl 30 to 50 mL/minute during clinical trials; monitor renal function daily in all patients with changing renal function with dose adjustment as needed.
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 whenever solution and container permit. The diluted solution ranges from clear to light yellow.
-Each vial contains 2.5 g ceftazidime; avibactam (2 g ceftazidime and 0.5 g avibactam).
Intravenous Administration
Reconstitution
-Using aseptic technique, reconstitute the dry powder with 10 mL of 1 of the following solutions: Sterile Water for Injection, Lactated Ringer's Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or any combination of dextrose and sodium chloride that contains up to 2.5% Dextrose Injection and 0.45% Sodium Chloride Injection.
-Ensure the dry powder is dissolved completely by gently mixing.
-The constituted solution will have an approximate ceftazidime concentration of 167 mg/mL and an approximate avibactam concentration of 42 mg/mL with an approximate final volume of 12 mL.
-The constituted solution is NOT for direct injection and MUST be diluted before intravenous infusion.
-Storage: The solution should be further diluted within 30 minutes of reconstitution.
Dilution
-Prepare the required dose for infusion by withdrawing the appropriate volume from the reconstituted vial.-Adults and Pediatric patients weighing 40 kg or more
--For a 2.5 g dose (2 g ceftazidime and 0.5 g avibactam), withdraw 12 mL (entire contents) of the reconstituted solution for further dilution.
-For a 1.25 g dose (1 g ceftazidime and 0.25 g avibactam), withdraw 6 mL of the reconstituted solution for further dilution.
-For a 0.94 g dose (0.75 g ceftazidime and 0.19 g avibactam), withdraw 4.5 mL of the reconstituted solution for further dilution.
-Pediatric patients weighing less than 40 kg
--Withdraw appropriate dose of the reconstituted solution based on a final concentration of 209 mg/mL (167 mg/mL ceftazidime and 42 mg/mL avibactam).
-Adults and Pediatric patients weighing 40 kg or more: Using the same solution that was selected for reconstitution, dilute to a total volume of 50 to 250 mL (8 to 40 mg/mL ceftazidime and 2 to 10 mg/mL avibactam). Dilution to 250 mL should only be used for the 2.5 g dose. If Sterile Water for Injection was used for reconstitution, use any other appropriate diluent for dilution.
-Pediatric patients weighing less than 40 kg: Using the same solution that was selected for reconstitution, dilute to a total volume of 8 to 40 mg/mL ceftazidime and 2 to 10 mg/mL avibactam. If Sterile Water for Injection was used for reconstitution, use any other appropriate diluent for dilution.
-Gently mix.
-Storage: Administer diluted solution within 12 hours if stored at room temperature of 25 degrees C (77 degrees F). Diluted solution may be stored for up to 24 hours under refrigeration at 2 to 8 degrees C (36 to 46 degrees F), with subsequent storage for up to 12 hours at room temperature.
Intermittent IV infusion:
-Administer via intravenous infusion over 2 hours.
Intermittent Extended IV Infusion*:
NOTE: Administration by extended infusion is not FDA-approved.
-Administering as an extended infusion (3-hour infusion) may increase the likelihood of pharmacodynamic target achievement in difficult to treat infections.
This monograph describes adverse reactions associated with use of ceftazidime; avibactam. For additional information regarding potential adverse events related to ceftazidime, see the ceftazidime monograph.
Gastrointestinal reactions were among the most frequently reported adverse events associated with ceftazidime; avibactam during adult clinical trials and include diarrhea (3% to 8%), nausea (3% to 7%), vomiting (5%), constipation (2%), and abdominal pain (1%). Vomiting and diarrhea were reported in more than 3% of pediatric patients during clinical trials.
Neurological or psychiatric adverse events reported with ceftazidime; avibactam during adult clinical trials include headache (3%), dizziness (2%), anxiety (less than 1%), and dysgeusia (less than 1%). Seizures, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported in ceftazidime-treated patients, particularly in the setting of renal impairment. Seizures are rare, but a serious complication of cephalosporin therapy. The epileptogenic properties of cephalosporins are thought to be related to their beta-lactam ring. High doses and renal impairment are associated with an increased risk of seizures.
Laboratory abnormalities observed in less than 1% of patients treated with ceftazidime; avibactam during adult clinical trials include elevated hepatic enzymes (AST, ALT, GGT), thrombocytopenia, thrombocytosis, leukopenia, and hypokalemia. Elevated hepatic enzymes were reported in more than 3% of pediatric patients younger than 3 months during clinical trials (n = 46). Positive direct Coombs test occurred in 3% to 21% of adult patients receiving ceftazidime; avibactam in clinical trials compared with 1% to 7% of patients receiving a carbapenem comparator. No adverse reactions representing hemolytic anemia were reported in any treatment group. Hepatic dysfunction (including cholestasis), bleeding, pancytopenia, aplastic anemia, prolonged bleeding time, and false-positive test for urinary glucose have been reported in postmarketing surveillance with ceftazidime or other cephalosporin class antibiotics.
Ceftazidime; avibactam has been associated with the development of rash, maculopapular rash, and urticaria in less than 1% of adult patients during clinical trials. Pruritus was reported in 2% of patients. Rash was reported in more than 3% of pediatric patients during clinical trials.
During clinical trials, acute kidney injury (renal failure (unspecified)), renal impairment, and nephrolithiasis developed in less than 1% of patients receiving treatment with ceftazidime; avibactam. Toxic nephropathy has been reported in postmarketing surveillance with ceftazidime or other cephalosporin class antibiotics. Monitor creatinine clearance prior to and during treatment. If renal dysfunction occurs during therapy, increase CrCl monitoring to at least once daily and adjust the dosage accordingly. In a Phase 3 trial in adult patients with complicated intraabdominal infections, death occurred more frequently in drug recipients with a baseline CrCl of 30 to 50 mL/minute (19.5%) than in those patients with a CrCl more than 50 mL/minute (1%). It should be noted that the daily dose received by these patients was 33% lower than the recommended dose.
Microbial overgrowth and superinfection can occur with antibiotic use. Candidiasis (less than 1%) and C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis have been reported with ceftazidime; avibactam. 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.
Injection site phlebitis was reported in less 1% of adult patients and more than 3% of pediatric patients during ceftazidime; avibactam clinical trials.
Ceftazidime, avibactam is contraindicated for use in patients with a cephalosporin hypersensitivity or cephamycin hypersensitivity. Prior to initiating treatment, question patients regarding penicillin hypersensitivity and/or carbapenem hypersensitivity. The structural similarity between ceftazidime and other beta-lactam antibiotics means that cross-reactivity can occur. Beta-lactams can cause a variety of hypersensitivity reactions ranging from mild rash to fatal anaphylaxis. Patients who have previously experienced a severe beta-lactam hypersensitivity, such as a serious rash, should not receive ceftazidime; avibactam. If an allergic reaction develops during treatment, discontinue use of ceftazidime; avibactam.
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 ceftazidime; avibactam, 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.
Use caution when administering ceftazidime; avibactam to patients with renal impairment or renal failure since both drug components are eliminated via renal mechanisms. In a clinical study in adult patients with complicated intraabdominal infections, cure rates were lower in patients with an estimated creatinine clearance (CrCl) of 30 to 50 mL/minute when compared to those with normal renal function; however, it should be noted that doses used in this study were 33% lower than currently recommended. In order to ensure accurate dosing, monitor CrCl at least daily in all adult and pediatric patients with changing renal function, particularly early during treatment. For patients with a CrCl less than 50 mL/minute, dosage and dose frequency must be adjusted. Administration of an unadjusted dose in patients with impaired renal function may result in elevated ceftazidime serum concentrations. Elevated concentrations of ceftazidime have resulted in neurotoxicity, including seizures, encephalopathy, asterixis, coma, neuromuscular excitability, and myoclonia.
All cephalosporins may rarely cause hypothrombinemia and increase the risk of bleeding; however, those cephalosporins containing the MTT side chain (e.g., cefoperazone, cefamandole, cefotetan) have the greatest association with bleeding. Cephalosporins should be used cautiously in patients with a preexisting coagulopathy (e.g., vitamin K deficiency) since these individuals are at a higher risk for developing bleeding complications. Treatment with ceftazidime; avibactam may result in a false-positive direct Coombs' tests; in clinical studies, no cases of hemolytic anemia were reported.
No adequate or well-controlled studies with ceftazidime; avibactam have been conducted in pregnant women. Data from animal studies revealed no teratogenic effects in the off-spring of rats and rabbits given doses up to 40-times the recommended human dose. Because animal studies are not always predictive of human response, ceftazidime; avibactam should be used during pregnancy only if clearly needed.
Use caution if administering ceftazidime; avibactam to breast-feeding mothers, as small quantities of ceftazidime are excreted in human breast milk; the presence of avibactam in human milk is unknown. Although considered unlikely, exposure of infants to ceftazidime through breast-feeding may alter gut flora and result in diarrhea or related complications (e.g., dehydration). Because the risk of serious reactions is relatively rare, the use of many cephalosporins is considered compatible with breast feeding. Previous American Academy of Pediatrics recommendations considered ceftazidime as generally compatible with breast-feeding.
Administration of ceftazidime; avibactam may result in laboratory test interference. Specifically, a false-positive reaction for glucose in the urine has been observed in patients receiving cephalosporins, such as ceftazidime; avibactam, and using Benedict's solution, Fehling's solution, or Clinitest tablets for urine glucose testing. However, this reaction has not been observed with glucose oxidase tests (e.g., Tes-tape, Clinistix, Diastix). Patients with diabetes mellitus who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on ceftazidime; avibactam treatment. Additionally, a positive direct Coombs test may develop in some patients. In hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs test of newborns whose mothers received ceftazidime; avibactam before delivery, clinicians should keep in mind that a positive Coombs test may be due to the drug.
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: Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Serratia marcescens
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 complicated urinary tract infection (UTI), including pyelonephritis and catheter-associated urinary tract infection, as well as cystitis* and pyelonephritis due to infections with difficult-to-treat resistance:
-for the treatment of uncomplicated cystitis due to infections with difficult-to-treat resistance using extended-infusion dosing*:
Intravenous dosage:
Adults: 2.5 g (2 g ceftazidime and 0.5 g avibactam) administered over 3 hours IV every 8 hours for 3 to 7 days.
-for the treatment of complicated UTI, including pyelonephritis, using conventional dosing:
Intravenous dosage:
Adults: 2.5 g (2 g ceftazidime and 0.5 g avibactam) IV every 8 hours for 7 to 14 days with or without an aminoglycoside.
Infants, Children, and Adolescents 6 months to 17 years: 62.5 mg/kg/dose (50 mg/kg/dose ceftazidime and 12.5 mg/kg/dose avibactam) (Max: 2.5 g [2 g ceftazidime and 0.5 g avibactam]/dose) IV every 8 hours for 7 to 14 days.
Infants 3 to 5 months: 50 mg/kg/dose (40 mg/kg/dose ceftazidime and 10 mg/kg/dose avibactam) IV every 8 hours for 7 to 14 days.
Infants 1 to 2 months: 37.5 mg/kg/dose (30 mg/kg/dose ceftazidime and 7.5 mg/kg/dose avibactam) IV every 8 hours for 7 to 14 days.
Neonates 31 weeks gestation and older: 25 mg/kg/dose (20 mg/kg/dose ceftazidime and 5 mg/kg/dose avibactam) IV every 8 hours for 7 to 14 days.
-for the treatment of complicated UTI, including pyelonephritis, due to infections with difficult-to-treat resistance using extended-infusion dosing*:
Intravenous dosage:
Adults: 2.5 g (2 g ceftazidime and 0.5 g avibactam) administered over 3 hours IV every 8 hours for 7 to 14 days.
-for the treatment of catheter-associated UTI, using conventional dosing:
Intravenous dosage:
Adults: 2.5 g (2 g ceftazidime and 0.5 g avibactam) IV every 8 hours for 7 to 14 days.
Infants, Children, and Adolescents 6 months to 17 years: 62.5 mg/kg/dose (50 mg/kg/dose ceftazidime and 12.5 mg/kg/dose avibactam) (Max: 2.5 g [2 g ceftazidime and 0.5 g avibactam]/dose) IV every 8 hours for 7 to 14 days.
Infants 3 to 5 months: 50 mg/kg/dose (40 mg/kg/dose ceftazidime and 10 mg/kg/dose avibactam) IV every 8 hours for 7 to 14 days.
Infants 1 to 2 months: 37.5 mg/kg/dose (30 mg/kg/dose ceftazidime and 7.5 mg/kg/dose avibactam) IV every 8 hours for 7 to 14 days.
Neonates 31 weeks gestation and older: 25 mg/kg/dose (20 mg/kg/dose ceftazidime and 5 mg/kg/dose avibactam) IV every 8 hours for 7 to 14 days.
For the treatment of complicated intraabdominal infections, including peritonitis, appendicitis, and intraabdominal abscess:
-for the treatment of complicated intraabdominal infections using conventional dosing:
Intravenous dosage:
Adults: 2.5 g (2 g ceftazidime and 0.5 g avibactam) IV every 8 hours as part of combination therapy for 5 to 14 days.
Children and Adolescents 2 to 17 years: 62.5 mg/kg/dose (50 mg/kg/dose ceftazidime and 12.5 mg/kg/dose avibactam) IV every 8 hours (Max: 2.5 g [2 g ceftazidime and 0.5 g avibactam]) as part of combination therapy for 5 to 14 days.
Infants and Children 6 months to 1 year: 62.5 mg/kg/dose (50 mg/kg/dose ceftazidime and 12.5 mg/kg/dose avibactam) IV every 8 hours as part of combination therapy for 5 to 14 days.
Infants 3 to 5 months: 50 mg/kg/dose (40 mg/kg/dose ceftazidime and 10 mg/kg/dose avibactam) IV every 8 hours as part of combination therapy for 5 to 14 days.
Infants 1 to 2 months: 37.5 mg/kg/dose (30 mg/kg/dose ceftazidime and 7.5 mg/kg/dose avibactam) IV every 8 hours as part of combination therapy for 5 to 14 days.
Neonates 31 weeks gestation and older: 25 mg/kg/dose (20 mg/kg/dose ceftazidime and 5 mg/kg/dose avibactam) IV every 8 hours as part of combination therapy for 5 to 14 days.
-for the treatment of complicated healthcare-acquired or hospital-acquired intraabdominal infections with adequate source control due to resistant gram-negative organisms using extended-infusion dosing*:
Intravenous dosage:
Adults: 2.5 g (2 g ceftazidime and 0.5 g avibactam) administered over 3 hours IV every 8 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
For the treatment of nosocomial pneumonia, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP):
-for the treatment of nosocomial pneumonia, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), using conventional dosing:
Intravenous dosage:
Adults: 2.5 g (2 g ceftazidime and 0.5 g avibactam) IV every 8 hours for 7 days. The FDA-approved duration is 7 to 14 days.
Infants, Children, and Adolescents 6 months to 17 years: 62.5 mg/kg/dose (50 mg/kg/dose ceftazidime and 12.5 mg/kg/dose avibactam) (Max: 2.5 g [2 g ceftazidime and 0.5 g avibactam]/dose) IV every 8 hours for 7 to 14 days.
Infants 3 to 5 months: 50 mg/kg/dose (40 mg/kg/dose ceftazidime and 10 mg/kg/dose avibactam) IV every 8 hours for 7 to 14 days.
Infants 1 to 2 months: 37.5 mg/kg/dose (30 mg/kg/dose ceftazidime and 7.5 mg/kg/dose avibactam) IV every 8 hours for 7 to 14 days.
Neonates 31 weeks gestation and older: 25 mg/kg/dose (20 mg/kg/dose ceftazidime and 5 mg/kg/dose avibactam) IV every 8 hours for 7 to 14 days.
-for the treatment of nosocomial pneumonia, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), due to resistant gram-negative organisms using extended-infusion dosing*:
Intravenous dosage:
Adults: 2.5 g (2 g ceftazidime and 0.5 g avibactam) administered over 3 hours IV every 8 hours with or without aztreonam for 7 days.
For the treatment of sepsis*, including infections due to difficult-to-treat resistance:
-for the treatment of sepsis* using conventional dosing:
Intravenous dosage:
Adults: 2.5 g (2 g ceftazidime and 0.5 g avibactam) IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Infants, Children, and Adolescents 6 months to 17 years: 62.5 mg/kg/dose (50 mg/kg/dose ceftazidime and 12.5 mg/kg/dose avibactam) IV every 8 hours (Max: 2.5 g [2 g ceftazidime and 0.5 g avibactam]). Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Infants 3 to 5 months: 50 mg/kg/dose (40 mg/kg/dose ceftazidime and 10 mg/kg/dose avibactam) IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
-for the treatment of sepsis using extended-infusion dosing due infections with difficult-to-treat resistance*:
Intravenous dosage:
Adults: 2.5 g (2 g ceftazidime and 0.5 g avibactam) administered over 3 hours IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Maximum Dosage Limits:
-Adults
7.5 g/day (6 g/day ceftazidime and 1.5 g/day avibactam) IV.
-Geriatric
7.5 g/day (6 g/day ceftazidime and 1.5 g/day avibactam) IV.
-Adolescents
187.5 mg/kg/day (150 mg/kg/day ceftazidime and 37.5 mg/kg/day avibactam; Max: 7.5 g/day [6 g/day ceftazidime and 1.5 g/day avibactam]) IV.
-Children
187.5 mg/kg/day (150 mg/kg/day ceftazidime and 37.5 mg/kg/day avibactam; Max: 7.5 g/day [6 g/day ceftazidime and 1.5 g/day avibactam]) IV.
-Infants
6 to 11 months: 187.5 mg/kg/day (150 mg/kg/day ceftazidime and 37.5 mg/kg/day avibactam) IV.
3 to 5 months: 150 mg/kg/day (120 mg/kg/day ceftazidime and 30 mg/kg/day avibactam) IV.
1 to 2 months: 112.5 mg/kg/day (90 mg/kg/day ceftazidime and 22.5 mg/kg/day avibactam) IV.
-Neonates
31 weeks gestation and older: 75 mg/kg/day (60 mg/kg/day ceftazidime and 15 mg/kg/day avibactam) IV.
younger than 31 weeks gestation: Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed.
Patients with Renal Impairment Dosing
Adults
CrCl more than 50 mL/minute: no dosage adjustment needed.
CrCl 31 to 50 mL/minute: 1.25 g (1 g ceftazidime and 0.25 g avibactam) IV every 8 hours.
CrCl 16 to 30 mL/minute: 0.94 g (0.75 g ceftazidime and 0.19 g avibactam) IV every 12 hours.
CrCl 6 to 15 mL/minute: 0.94 g (0.75 g ceftazidime and 0.19 g avibactam) IV every 24 hours.
CrCl 5 mL/minute or less: 0.94 g (0.75 g ceftazidime and 0.19 g avibactam) IV every 48 hours.
Pediatric patients 2 to 17 years
eGFR more than 50 mL/minute/1.73 m2: no dosage adjustment needed.
eGFR 31 to 50 mL/minute/1.73 m2: 31.25 mg/kg/dose (25 mg/kg/dose ceftazidime and 6.25 mg/kg/dose avibactam) IV every 8 hours (Max: 1.25 g [1 g ceftazidime and 0.25 g avibactam]).
eGFR 16 to 30 mL/minute/1.73 m2: 23.75 mg/kg/dose (19 mg/kg/dose ceftazidime and 4.75 mg/kg/dose avibactam) IV every 12 hours (Max: 0.94 g [0.75 g ceftazidime and 0.19 g avibactam]).
eGFR 6 to 15 mL/minute/1.73 m2: 23.75 mg/kg/dose (19 mg/kg/dose ceftazidime and 4.75 mg/kg/dose avibactam) IV every 24 hours (Max: 0.94 g [0.75 g ceftazidime and 0.19 g avibactam]).
eGFR 5 mL/minute/1.73 m2 or less: 23.75 mg/kg/dose (19 mg/kg/dose ceftazidime and 4.75 mg/kg/dose avibactam) IV every 48 hours (Max: 0.94 g [0.75 g ceftazidime and 0.19 g avibactam]).
Pediatric patients younger than 2 years
There are insufficient data to recommend a dosage regimen for pediatric patients younger than 2 years with renal impairment.
Intermittent hemodialysis
Administer the dose and frequency based on patients estimated creatinine clearance, as shown above. Both ceftazidime and avibactam are removed by hemodialysis; therefore, administer the dose after hemodialysis on hemodialysis days.
*non-FDA-approved indication
Amikacin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Aminoglycosides: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Bumetanide: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
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.
Ethacrynic Acid: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
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.
Furosemide: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Gentamicin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
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.
Loop diuretics: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
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.
Paromomycin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Plazomicin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Probenecid: (Major) Avoid concurrent administration of ceftazidime; avibactam with probenicid. Use of these medications together may decrease the renal clearance of avibactam; thereby resulting in prolonged drug exposures. Avibactam is a substrate of the renal organic anion transporters (OAT)1 and OAT3; probenecid is a potent inhibitor of these transporters. An in vitro study found probencid blocked 56% to 70% of avibactam uptake by these transporters.
Probenecid; Colchicine: (Major) Avoid concurrent administration of ceftazidime; avibactam with probenicid. Use of these medications together may decrease the renal clearance of avibactam; thereby resulting in prolonged drug exposures. Avibactam is a substrate of the renal organic anion transporters (OAT)1 and OAT3; probenecid is a potent inhibitor of these transporters. An in vitro study found probencid blocked 56% to 70% of avibactam uptake by these transporters.
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.
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.
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.
Streptomycin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Tobramycin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Torsemide: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including cephalosporins, may increase the 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. Additionally, certain cephalosporins (cefotetan, cefoperazone, cefamandole) are associated with prolongation of the prothrombin time due to the methylthiotetrazole (MTT) side chain at the R2 position, which disturbs the synthesis of vitamin K-dependent clotting factors in the liver. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
Ceftazidime, a beta-lactam antibiotic, is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. PBPs are responsible for several steps in cell wall synthesis and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. Thus, the intrinsic activity of ceftazidime and other beta-lactams against a particular organism depends on their ability to gain access to and bind with the necessary PBP. In particular, ceftazidime preferentially binds to PBP-3 of gram-negative rods. Since PBP-3 is responsible for formation of the septum during cell division, ceftazidime's inhibition of these proteins causes elongation of the bacteria, inhibition of bacterial cell division, and breakage of the cell wall resulting in cell lysis and death. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.
Beta-lactams, including ceftazidime, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T above the MIC). This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Cephalosporins require free drug concentrations to be above the MIC for 35% to 40% of the dosing interval for bacteriostatic activity and 60% to 70% of the dosing interval for bactericidal activity.
Due to the presence of an aminothiazolyl side chain, third-generation cephalosporins display enhanced activity against gram-negative bacteria, particularly the Enterobacterales. Also, because ceftazidime contains a 2-carboxy-2-oxypropane imino group, it shows increased activity against P. aeruginosa, which gives it an important advantage over other cephalosporins. However, the presence of the 2-carboxy-2-oxypropane imino group limits ceftazidime's activity against most gram-positive bacteria. In addition, ceftazidime is inactive against the anaerobes B. fragilis and Clostridium sp.
Avibactam (like tazobactam, sulbactam, and clavulanic acid) is an inhibitor of bacterial beta-lactamases. Avibactam protects ceftazidime against the following beta-lactamases: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPC), AmpC, and certain oxacillinases (OXA). Avibactam will not protect ceftazidime against metallo-beta-lactamase producing bacteria, or bacteria that overexpress efflux pumps or have porin mutations.
The susceptibility interpretive criteria for ceftazidime; avibactam are delineated by pathogen. The MICs are defined for P. aeurginosa and Enterobacterales as susceptible at 8/4 mcg/mL or less and resistant at 16/4 mcg/mL or more based on a dosage of 2.5 g (2 g ceftazidime and 0.5 g avibactam) IV every 8 hours.
Resistance to cephalosporins occurs as a result of decreased permeability, alterations of PBPs, and hydrolysis by beta-lactamases.
Ceftazidime; avibactam is administered intravenously.
-Ceftazidime: Approximately 10% of the circulating drug is protein-bound. Ceftazidime is distributed into most body tissues and fluids. Average tissue or fluid ceftazidime concentrations after a 2 g IV dose include bile (36.4 mcg/mL), synovial fluid (25.6 mcg/mL), peritoneal fluid (48.6 mcg/mL), sputum (9 mcg/mL), CSF (9.8 mcg/mL), CSF with inflamed meninges (9.4 mcg/mL), aqueous humor (11 mcg/mL), blister fluid (19.7 mcg/mL), lymphatic fluid (23.4 mcg/mL), bone (31.1 mcg/mL), heart muscle (12.7 mcg/mL), skin (6.6 mcg/mL), skeletal muscle (9.4 mcg/mL), and myometrium (18.7 mcg/mL). Up to 90% of an administered dose is excreted unchanged into the urine over a 24-hour period, primarily via glomerular filtration; urine concentrations average 2,100 mcg/mL after a 500 mg IM dose and 12,000 mcg/mL after a 2 g IV dose. Mean renal clearance is about 100 mL/minute. In patients with normal renal function, the elimination half-life of ceftazidime is 1.5 to 2 hours, but half-life increases as renal function declines.
-Avibactam: At steady state, avibactam has a volume of distribution of 22 L, with 5% to 8% of the circulating drug being bound to human plasma protein. The drug does not appear to undergo hepatic metabolism; however, it is a substrate for renal organic anion transporters (OAT)1 and OAT3. These transporters may contribute to the elimination of the drug by actively removing it from the blood compartment. Excretion occurs primarily in the kidneys, with 85% of a dose recovered as unchanged drug within 96 hours. Renal clearance is 158 mL/minute, suggesting active tubular secretion contributes to the excretion of avibactam. In patients with normal renal function, the elimination half-life is 2 hours.
Affected cytochrome P450 isoenzymes and drug transporters: OAT1 and OAT3
Avibactam is a substrate of OAT1 and OAT3. Inhibitors of these transporters may decrease the renal clearance of avibactam, resulting in prolonged drug exposure.
-Route-Specific Pharmacokinetics
Intravenous Route
-Ceftazidime: The maximum serum concentration (Cmax) and drug exposure (AUC) of ceftazidime increase in a dose proportional manner. Drug accumulation has not been observed after repeated IV infusions every 8 hours for up to 11 days.
-Avibactam: Over a dose range of 50 to 2,000 mg, avibactam demonstrates approximately linear pharmacokinetics. Drug accumulation has not been observed after repeated IV infusions every 8 hours for up to 11 days.
-Special Populations
Hepatic Impairment
Ceftazidime and avibactam are not metabolized by the liver; thus, hepatic dysfunction does not appear to affect the pharmacokinetics of these drugs.
Renal Impairment
-Ceftazidime: Ceftazidime is eliminated almost entirely by the kidneys. Elimination half-life is expected to increase as renal function declines; dosing regimens must be adjusted accordingly. Approximately 55% of a 1 g ceftazidime dose is removed from circulation by a 4-hour hemodialysis session.
-Avibactam: Clearance of avibactam is significantly decreased in patients with mild (CrCL 50 to 80 mL/minute), moderate (CrCL 30 to 50 mL/minute), and severe renal dysfunction (CrCL 30 mL/minute or less). Compared to individuals with normal renal function, drug exposures in patients with mild, moderate, and severe renal disease (non-dialysis) are increased by 2.6-fold, 3.8-fold, and 7-fold, respectively. Approximately 55% of a 100 mg avibactam dose is removed from circulation by a 4-hour hemodialysis session; the extraction coefficient is 0.77.
Pediatrics
Population pharmacokinetic analyses and target attainment simulations in pediatric patients demonstrated that the recommended pediatric dosing regimens for patients from 2 to 17 years with eGFR of 50 mL/minute/1.73 m2 or higher and for patients from birth (31 weeks gestation and older) to younger than 2 years without renal impairment result in systemic exposure similar to that in adult patients receiving ceftazidime; avibactam 2.5 g.
Geriatric
A single 0.5 g avibactam dose administered to elderly patients (older than 65 years, n = 16) resulted in a mean drug exposure (AUC) that was 17% higher than the AUC observed in younger adults (18 to 45 years, n = 17). This difference was not determined to be clinically significant; no dose adjustments are recommended based on age.
Gender Differences
A single 0.5 g avibactam dose administered to healthy males (n = 17) resulted in maximum serum concentrations (Cmax) that were 18% lower than the values observed in healthy women (n = 16). This difference was not determined to be clinically significant; no dose adjustments are recommended based on gender.