Aztreonam is a parenteral synthetic beta-lactam antibiotic and the first monobactam to be marketed. The spectrum of aztreonam is limited to aerobic gram-negative bacteria; it has no gram-positive or anaerobic activity. Aztreonam may be used place of an aminoglycoside since it is less nephrotoxic. Clinical uses of aztreonam include bacteremias, skin and soft-tissue infections, urinary tract infections, respiratory tract infections, intra-abdominal infections, and gynecologic infections caused by susceptible organisms. Aztreonam may also be used for postoperative infections including abscesses infections complicating viscous perforations, cutaneous infections, and infections of serous surfaces. It is effective against most commonly seen gram-negative aerobic pathogens seen in general surgery. Aztreonam is not indicated for meningitis. Aztreonam inhalation therapy was designated an orphan drug for the control of gram-negative bacteria in the respiratory tract in cystic fibrosis patients in March 2002 and for the improvement of respiratory symptoms in patients with bronchiectasis and gram-negative bacteria in the airways in May 2009. The FDA first approved aztreonam injection in December 1986. In February 2010, aztreonam for inhalation received FDA approval for improvement of respiratory symptoms in cystic fibrosis patients >= 7 years old with Pseudomonas aeruginosa.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Intravenous (IV) Infusion
Powder Vials for Injection
Reconstitution
-Reconstitute with at least 3 mL of Sterile Water for Injection per g of aztreonam.
-FURTHER DILUTION IS NECESSARY FOR IV INFUSION.
-Shake immediately and vigorously.
-Storage: Use within 48 hours if kept at room temperature (15 to 30 degrees C or 59 to 98 degrees F) or within 7 days if kept under refrigeration (2 to 8 degrees C or 38 to 48 degrees F).
Dilution
-Further dilute the appropriate dose in a compatible IV solution.
-Compatible IV solutions include 0.9% Sodium Chloride Injection, Ringer's Injection, Lactated Ringer's Injection, 5% Dextrose Injection, 10% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and 0.2% Sodium Chloride Injection, Sodium Lactate (M/6) Injection, Inosol B and 5% Dextrose Injection, Isolyte E Injection, Isolyte E with 5% Dextrose Injection, Isolyte M with 5% Dextrose Injection, Normosol-R Injection, Normosol-R and 5% Dextrose Injection, Normosol-M and 5% Dextrose Injection, 5% Mannitol Injection, 10% Mannitol Injection, Lactated Ringers and 5% Dextrose Injection, and Plasma-Lyte M and 5% Dextrose Injection.
-If using a volume control administration set, the final dilution of aztreonam should not exceed a concentration of 20 mg/mL.
-Shake immediately and vigorously.
-Storage: For solutions at concentrations not exceeding 20 mg/mL (2% w/v) and for solutions at concentrations exceeding 20 mg/mL (2% w/v) using Sterile Water for Injection or 0.9% Sodium Chloride Injection, use within 48 hours if kept at room temperature (15 to 30 degrees C or 59 to 98 degrees F) or within 7 days if kept under refrigeration (2 to 8 degrees C or 38 to 48 degrees F). For other solutions at concentrations exceeding 20 mg/mL (2% w/v), use promptly after preparation.
Frozen Pre-mixed Bags
-Thaw frozen Galaxy containers at room temperature (25 degrees C or 77 degrees F) or under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Do not force thaw by immersion in water baths or by microwave irradiation. Check for leaks by squeezing bag firmly. Do not add supplementary medication.
-Contents of the solution may precipitate in the frozen state and should dissolve with little or no agitation once the solution has reached room temperature.
-Storage: The thawed solution is stable for 48 hours at room temperature or 14 days under refrigeration.
Intermittent IV Infusion:
-Infuse appropriate dose IV over 20 to 60 minutes.
-For neonates, an infusion time of 15 minutes has been recommended.
-For premixed-bags, do not use plastic containers in series connections as this could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.
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.
Intravenous (IV) Push
Powder Vials for Injection
Reconstitution
-Reconstitute each vial with 6 to 10 mL of Sterile Water for Injection.
-Shake immediately and vigorously.
-Storage: Use within 48 hours if kept at room temperature (15 to 30 degrees C or 59 to 98 degrees F) or within 7 days if kept under refrigeration (2 to 8 degrees C or 38 to 48 degrees F).
Intermittent IV Push
-Slowly inject directly into a vein or the tubing of a suitable administration set over 3 to 5 minutes.
Intramuscular Administration
Powder Vials for Injection
Reconstitution
-Reconstitute vials with at least 3 mL of an appropriate diluent per g of aztreonam.
-Appropriate diluents include Sterile Water for Injection, Sterile Bacteriostatic Water for Injection (with benzyl alcohol or with methyl- and polyparabens), 0.9% Sodium Chloride Injection, and Bacteriostatic Sodium Chloride (with benzyl alcohol) Injection.
-Shake immediately and vigorously.
-Storage: For solutions at concentrations not exceeding 20 mg/mL (2% w/v) and for solutions at concentrations exceeding 20 mg/mL (2% w/v) using Sterile Water for Injection or 0.9% Sodium Chloride Injection, use within 48 hours if kept at room temperature (15 to 30 degrees C or 59 to 98 degrees F) or within 7 days if kept under refrigeration (2 to 8 degrees C or 38 to 48 degrees F). For other solutions at concentrations exceeding 20 mg/mL (2% w/v), use promptly after preparation.
Intramuscular Injection
-In adults, inject doses of 1 g or less deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh).
-According to the FDA-approved product labeling, there are insufficient data regarding intramuscular administration of aztreonam in pediatric patients; however, aztreonam has been administered IM to pediatric patients in clinical practice when acceptable IV access was not available. Inject deeply into a large muscle mass (e.g., anterolateral thigh). When multiple IM injections are necessary, rotate administration sites.
--In general, IM administration of antibiotics in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
-Aztreonam is well tolerated; do not admix with any local anesthetic agent.
Inhalation Administration
Oral Inhalation Administration
Nebulized Solution
Reconstitution
-Do not reconstitute aztreonam for inhalation until ready to administer a dose.
-Gently tap the aztreonam vial so that the powder settles to the bottom of the vial.
-Using the blue cap tab, slowly flip up the blue cap. Pull the blue cap down to a horizontal position, where the bottom of the blue cap faces up.
-Slowly pull the blue cap in a counterclockwise direction until the metal seal opens and is completely removed. Do not twist the blue cap.
-Carefully remove the rubber stopper.
-Twist the tip off of the provided 1 mL sterile diluent (0.17% Sodium Chloride) ampule and squeeze contents into the aztreonam vial.
-Gently swirl the vial until the contents have completely dissolved.
Administration
-Have patient use a bronchodilator before administration of the aztreonam nebulized solution. A short-acting bronchodilator can be administered 15 minutes to 4 hours before aztreonam. Alternatively, a long-acting bronchodilator can be administered 30 minutes to 12 hours before aztreonam. For patients taking multiple inhaled therapies, the recommended order of administration is bronchodilator, mucolytic, and then aztreonam.
-Administer aztreonam immediately after reconstitution using an Altera Nebulizer System only. Do not administer via any other nebulizer.
-Do not mix any with any other drugs.
-Administration typically takes 2 to 3 minutes via the nebulizer mouthpiece.
Elevated hepatic enzymes due to systemic aztreonam occurs more commonly in pediatric patients versus adults. The increased incidence of these adverse effects may be due to either the increased severity of illness or the higher doses of aztreonam administered to pediatric patients. Elevated hepatic enzymes (AST, ALT, alkaline phosphatase) have been reported in less than 1% of adult patients receiving aztreonam, and most enzyme elevations returned to pretreatment levels upon discontinuation of the drug. During pediatric studies of aztreonam, 3.8% of patients had elevated AST and 6.5% had elevated ALT. However, 15% to 20% of children less than 2 years of age who received aztreonam 50 mg/kg every 6 hours experienced elevated AST and ALT to more than 3 times the upper limit of normal. In adults receiving systemic aztreonam, fewer than 1% had signs or symptoms of hepatobiliary dysfunction, hepatitis, or jaundice.
Aztreonam has been associated with gastrointestinal side effects. Nausea has been reported at rates of 1% to 1.3% in adult patients with systemic administration. Vomiting was reported in 6% of patients receiving nebulized aztreonam and in 1% to 1.3 % of patients during systemic clinical trials. Diarrhea was noted in 1% to 1.3% of adults and 1.4% of pediatric patients during systemic clinical trials. Abdominal pain was noted in 7% of patients receiving nebulized aztreonam. Abdominal cramps, GI bleeding, oral ulceration, altered taste (dysgeusia), numb tongue, and halitosis have also been reported in less than 1% of patients receiving systemic aztreonam.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis (less than 1%) has been reported with systemic aztreonam. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Other infections due to overgrowth of unsusceptible organisms may be seen during systemic aztreonam treatment including vaginal candidiasis (less than 1%).
A local injection site reaction (1.9% adults), including phlebitis/thrombophlebitis and discomfort/swelling, can occur following IV administration of aztreonam. In children, local injection reactions consisting of pain (1.5% to 12%), erythema (0.5% to 2.9%), induration (0.5% to 0.9%), and phlebitis (0.5% to 2.1%) occur more frequently than in adult patients.
In clinical trials of nebulized aztreonam in patients with cystic fibrosis, respiratory adverse events were the most commonly reported events, but some events have also been noted in patients receiving systemic therapy. Cough occurred in 54% of nebulized aztreonam-treated patients. Nasal congestion and wheezing were reported in 16% of nebulized aztreonam-treated patients and in less than 1% of patients receiving systemic therapy. Pharyngolaryngeal pain occurred in 12% of nebulized aztreonam-treated patients and chest discomfort occurred in 8% of nebulized aztreonam-treated patients. Bronchospasm immediately after administration was reported in 3% of patients receiving nebulized aztreonam;cases of dyspnea have been noted during postmarketing use of nebulized aztreonam. Bronchospasm has also been reported in less than 1% of patients receiving systemic aztreonam therapy and may be related to hypersensitivity reactions. Dyspnea, chest pain (unspecified), and sneezing have also been reported in less than 1% of patients receiving systemic therapy.
Rare cases of toxic epidermal necrolysis have been reported (less than 1%) in association with systemic aztreonam in patients undergoing bone marrow transplantation with multiple other risk factors and concomitantly receiving other drugs associated with toxic epidermal necrolysis. Rash has been reported in 1% to 1.3% of adult patients and 4.3% of pediatric patients receiving systemic aztreonam, but has also been reported in 2% of patients receiving the inhalation product. Other dermatologic adverse events reported with systemic aztreonam in less than 1% of patients include purpura, erythema multiforme, exfoliative dermatitis, urticaria, petechiae, pruritus, and diaphoresis.
Fever (pyrexia) was noted in 13% of patients receiving nebulized aztreonam in clinical trials as compared to 6% of patients receiving placebo. In patients receiving systemic therapy, fever was more commonly reported in pediatric patients (1%) than in adult patients (less than 1%). Other adverse effects noted in less than 1% of adult patients receiving systemic therapy include weakness, headache, malaise, and muscular aches. Increased serum creatinine was reported in 5.8% of pediatric patients.
Neutropenia due to systemic aztreonam occurs more commonly in pediatric patients versus adults. The increased incidence of these adverse effects may be due to either the increased severity of illness or the higher doses administered to pediatric patients. In pediatric trials, neutropenia (neutrophil count less than 1000/mm3) was noted 3.2% of patients and in 11.3% of children less than 2 years of age receiving aztreonam 30 mg/kg every 6 hours. In adults, neutropenia was noted in less than 1% of patients. Other hematologic adverse events reported in less than 1% of adult patients during systemic trials include pancytopenia, thrombocytopenia, anemia, and leukocytosis. Eosinophilia was reported in less than 1% of adults and in 6.3% of pediatric patients during systemic trials. Thrombocytosis was reported in less than 1% of adults and in 3.6% of pediatric patients.
Hypersensitivity reactions have been reported with both systemic and nebulized aztreonam therapy. Anaphylaxis/anaphylactoid reactions and angioedema have been reported in less than 1% of patients receiving systemic therapy. Allergic reactions including facial rash, facial swelling, and throat tightness have been reported in patients with nebulized administration.
Cardiovascular adverse events reported in less than 1% of patients receiving systemic aztreonam therapy include hypotension, flushing, and transient ECG changes including ventricular bigeminy and premature ventricular contractions (PVCs).
Nervous system adverse events reported in less than 1% of patients receiving systemic aztreonam therapy include seizures, confusion, encephalopathy, vertigo, paresthesias, insomnia, and dizziness.
Adverse events of the special senses that occurred in less than 1% of patients receiving systemic aztreonam in clinical trials include tinnitus and diplopia.
Vaginitis and breast tenderness were reported in less than 1% of patients receiving systemic aztreonam in clinical trials.
Cases of arthralgia and joint swelling have been noted during postmarketing use of nebulized aztreonam. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
A false-positive reaction for glucose in the urine has been observed in patients receiving aztreonam and using Benedict's solution, Fehling's solution, and Clinitest tablets. This reaction, however, has not been observed with Tes-tape (glucose Enzymatic Test Strip, USP, Lilly).
Aztreonam does not treat viral infection (e.g., common cold). Prescribing aztreonam in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Patients should complete the full course of treatment.
Aztreonam is a monocyclic beta-lactam. The incidence of allergic drug reactions to aztreonam is estimated at roughly 2% from reported clinical trial literature, and some reactions are consistent with IgE-mediated responses. Use would usually be contraindicated in any patient with direct aztreonam hypersensitivity. The manufacturer states that aztreonam should be used cautiously in patients with sensitivity to any beta-lactam related antibiotic (e.g., penicillin hypersensitivity, cephalosporin hypersensitivity, carbacephem hypersensitivity, carbapenem hypersensitivity) due to the minor chemical structural similarities in the agents. However, in actuality, such cross-sensitive reactions to aztreonam are thought quite rare, and there is clinical evidence to support aztreonam's low potential for such events. Patients with known and established penicillin allergy who receive skin testing to determine if they will cross-react to aztreonam rarely have positive skin tests, and many such patients have received full therapeutic dosing with aztreonam without incident. Clinicians should be aware that it is certainly possible to have cross-hypersensitivity, but such reactions do not appear common.
Aztreonam is renally excreted. Therefore, in patients with renal disease resulting in renal impairment with a glomerular filtration rate of less than 30 mL/min or renal failure requiring dialysis, systemic dosage adjustment is necessary. Since aztreonam is known to be substantially excreted by the kidney, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Given the low systemic exposure after nebulization, clinically relevant accumulation is unlikely to occur. Nebulized aztreonam may be administered to patients with all degrees of renal impairment.
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 aztreonam, 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.
Like with other inhaled therapies, acute bronchospasm has been associated with aztreonam solution for inhalation. Reduction of FEV1 by 15% or more immediately after administration with nebulized aztreonam was observed in 3% of patients in clinical trials despite the use of a bronchodilator prior to the administration of aztreonam. In clinical trials, patients with increased FEV1 during the 28 day treatment period were sometimes treated for pulmonary exacerbations when FEV1 declined after the 28 day treatment period. Healthcare providers should consider the patient's baseline FEV1 prior to aztreonam therapy and the presence of other symptoms when evaluating post-treatment changes in FEV1.
Aztreonam solution for inhalation is approved for use in children >= 7 years old and adolescents. Safety and efficacy of nebulized aztreonam in neonates, infants and children less than 7 years old has not been established. Systemic aztreonam is approved for use in infants >= 9 months, children, and adolescents. However, systemic aztreonam is not approved in pediatric patients with septicemia and skin and skin-structure infections where the skin infection is believed or known to be due to H. influenzae type b. Safety and efficacy of systemic aztreonam in neonates and infants less than 9 months has not been established.
Use aztreonam during pregnancy only if clearly needed. Data on aztreonam use during pregnancy are insufficient to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There have been no adequate, well-controlled studies of aztreonam in pregnant women. Aztreonam crosses the placenta and enters fetal circulation. In animal studies with aztreonam for injection, there was no evidence of developmental toxicity or drug-induced changes in maternal, fetal, or neonatal parameters. Systemic absorption of aztreonam after inhaled administration is expected to be minimal. There are risks to the mother associated with cystic fibrosis in pregnancy; cystic fibrosis may increase the risk for preterm delivery.
Previous American Academy of Pediatrics (AAP) recommendations considered aztreonam as usually compatible with breast-feeding. Aztreonam is excreted in breast milk at very low concentrations after systemic administration. After a single 1 g IM dose in 6 women, average peak milk concentration, occurring 6 hours after the dose, was 0.3 mg/L. After a single 1 g IV dose in 6 other women, average peak milk concentration, occurring 2.4 hours after the dose was 0.2 mg/L. Aztreonam was detectable in milk between 2 and 8 hours after an IM dose and 1.5 and 8 hours after an IV dose. In another report, a single 1 g IV dose produced milk concentrations ranging from 0.4 to 1 mg/L at 1 to 5 hours after the dose with little variation in milk concentrations during this time in each woman. On average, concentrations were slightly higher 2 hours after the dose, but the peak concentrations occurred at various times between 1 and 4 hours. Peak plasma concentrations of aztreonam after nebulization are approximately 1% of peak concentrations observed after aztreonam 500 mg IV administration. There are no data on the effects of aztreonam on the breast-fed infant or on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for aztreonam and any potential adverse effects on the breast-fed child from aztreonam or the underlying maternal condition.
Clinical studies of systemic and nebulized aztreonam in geriatric patients have not included sufficient numbers of patients over 65 years of age to determine if they respond differently to treatment than younger adults. However, clinical experience has not identified differences between older and younger patients. In general, systemic aztreonam dosage selection for elderly patients should be cautious, starting at the lower end of the dosage range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and concomitant disease. Because elderly patients are more likely to have decreased renal function that will decrease aztreonam elimination, renal function should be monitored;systemic dosage adjustments made accordingly. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.
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: Aeromonas hydrophila, Citrobacter freundii, Citrobacter sp., Enterobacter cloacae, Enterobacter sp., Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Neisseria gonorrhoeae, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Serratia marcescens, Serratia sp., Yersinia enterocolitica
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.
This drug may also have activity against the following microorganisms: Salmonella enterica serotype Typhi
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of pulmonary exacerbation or improvement of respiratory symptoms in persons with cystic fibrosis:
-for the treatment of pulmonary exacerbation in persons with cystic fibrosis:
Intravenous dosage:
Adults: 2 g IV every 6 to 8 hours; doses of 2 to 3 g IV every 6 hours may be necessary to maintain adequate serum concentrations in the treatment of pseudomonal isolates with higher MICs.
Children and Adolescents 2 to 17 years: 150 to 200 mg/kg/day (Max: 8 g/day) IV divided every 6 to 8 hours; doses of 200 to 300 mg/kg/day (Max: 12 g/day) IV divided every 6 hours may be necessary to maintain adequate serum concentrations in the treatment of pseudomonal isolates with higher MICs.
Infants and Children 9 months to 1 year: 90 to 150 mg/kg/day IV divided every 6 to 8 hours; doses of 200 to 300 mg/kg/day IV divided every 6 hours may be necessary to maintain adequate serum concentrations in the treatment of pseudomonal isolates with higher MICs.
Infants 1 to 8 months*: 90 to 150 mg/kg/day IV divided every 6 to 8 hours; doses of 200 to 300 mg/kg/day IV divided every 6 hours may be necessary to maintain adequate serum concentrations in the treatment of pseudomonal isolates with higher MICs.
-for the improvement of respiratory symptoms in persons with cystic fibrosis with chronic P. aeruginosa:
Respiratory (Inhalation) dosage:
NOTE: The FDA has designated aztreonam solution for inhalation as an orphan drug for control of gram-negative bacteria in the respiratory tract of patients with cystic fibrosis and for the improvement of respiratory symptoms in patients with bronchiectasis and gram-negative bacteria in the airways.
Adults: 75 mg inhaled by nebulizer 3 times daily (at least 4 hours apart) for 28 days in alternating 28-day periods. Aztreonam inhalation solution is FDA-approved for persons with an FEV1 of 25% to 75% predicted.
Children and Adolescents 7 to 17 years: 75 mg inhaled by nebulizer 3 times daily (at least 4 hours apart) for 28 days in alternating 28-day periods. Aztreonam inhalation solution is FDA-approved for persons with an FEV1 of 25% to 75% predicted.
For the treatment of bacteremia:
-for the treatment of bacteremia using conventional dosing:
Intravenous dosage:
Adults: 2 g IV every 6 to 8 hours.
Infants, Children, and Adolescents 9 months to 17 years: 30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours.
Infants 1 to 8 months*: 30 mg/kg/dose IV every 6 to 8 hours.
Neonates 34 weeks gestation and older and 8 days and older*: 30 mg/kg/dose IV every 6 hours.
Neonates 34 weeks gestation and older and 0 to 7 days*: 30 mg/kg/dose IV every 8 hours.
Neonates younger than 34 weeks gestation and 8 days and older*: 30 mg/kg/dose IV every 8 hours.
Neonates younger than 34 weeks gestation and 0 to 7 days*: 30 mg/kg/dose IV every 12 hours.
-for the treatment of bacteremia due to resistant gram-negative organisms using extended infusion dosing*:
Intravenous dosage:
Adults: 2 g IV every 8 hours administered over 3 hours plus ceftazidime; avibactam.
For the treatment of uncomplicated and complicated urinary tract infection (UTI), including cystitis and pyelonephritis:
-for the treatment of mild to moderate UTI, including cystitis:
Intravenous or Intramuscular dosage:
Adults: 500 mg to 1 g IV or IM every 8 to 12 hours. Treat for at least 48 hours after patient becomes asymptomatic or evidence of bacterial eradication.
Infants, Children, and Adolescents 9 months to 17 years: 30 mg/kg/dose (Max: 1 g/dose) IV every 8 hours.
Infants 2 to 8 months*: 30 mg/kg/dose IV every 6 to 8 hours.
-for the treatment of moderate to severe UTI, including pyelonephritis:
Intravenous or Intramuscular dosage:
Adults: 1 g IV or IM every 8 to 12 hours or 2 g IV every 6 to 12 hours for 7 to 14 days with or without an aminoglycoside.
Infants, Children, and Adolescents 9 months to 17 years: 30 mg/kg/dose (Max: 1 g/dose) IV every 6 to 8 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
Infants 2 to 8 months*: 30 mg/kg/dose IV every 6 to 8 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
Infants younger than 2 months*: 30 mg/kg/dose IV every 6 to 8 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 34 weeks gestation and older and 8 days and older*: 30 mg/kg/dose IV every 6 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 34 weeks gestation and older and 0 to 7 days*: 30 mg/kg/dose IV every 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates younger than 34 weeks gestation and 8 days and older*: 30 mg/kg/dose IV every 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates younger than 34 weeks gestation and 0 to 7 days*: 30 mg/kg/dose IV every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
For surgical infection prophylaxis*:
Intravenous dosage:
Adults: 2 g IV as a single dose within 60 minutes prior to the surgical incision; or alternately, 1 g IV as a single dose for gynecologic procedures. Intraoperative redosing 4 hours from the first preoperative dose and a duration of prophylaxis less than 24 hours for most procedures are recommended by clinical practice guidelines. Clinical practice guidelines recommend aztreonam in combination with cefazolin, or for beta-lactam allergic patients, clindamycin or vancomycin, for urologic procedures involving implanted prosthesis. Aztreonam in combination with an appropriate antimicrobial with gram-positive activity (i.e., clindamycin or vancomycin) is also recommended as an alternate therapy for patients with a beta-lactam allergy undergoing gastrointestinal, biliary tract, uncomplicated appendectomy, colorectal, hysterectomy, or abdominal transplantion procedures.
Infants, Children, and Adolescents: 30 mg/kg/dose IV as a single dose (Max: 2 g/dose) within 60 minutes prior to the surgical incision. Intraoperative redosing 4 hours from the first preoperative dose and a duration of prophylaxis less than 24 hours for most procedures are recommended by clinical practice guidelines. Clinical practice guidelines recommend aztreonam in combination with cefazolin, or for beta-lactam allergic patients, clindamycin or vancomycin, for urologic procedures involving implanted prosthesis. Aztreonam in combination with an appropriate antimicrobial with gram-positive activity (i.e., clindamycin or vancomycin) is also recommended as an alternate therapy for patients with a beta-lactam allergy undergoing gastrointestinal, biliary tract, uncomplicated appendectomy, colorectal, or abdominal transplantion procedures.
For the empiric treatment of febrile neutropenia*:
-for the treatment of febrile neutropenia in adults:
Intravenous dosage:
Adults: 2 g IV every 6 to 8 hours or 1.5 g IV every 4 hours has been studied in combination with vancomycin or clindamycin. Aztreonam in combination with vancomycin is recommended in guidelines as an alternative in patients that have significant beta-lactam allergy.
-for the treatment of febrile neutropenia in pediatric patients:
Intravenous dosage:
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours in combination with other antimicrobials. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent, such as aztreonam, is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.
For the treatment of lower respiratory tract infections (LRTIs), including bronchitis, pneumonia, community-acquired pneumonia (CAP), and nosocomial pneumonia:
-for the treatment of LRTIs, including nonspecific pneumonia and bronchitis:
Intravenous or Intramuscular dosage:
Adults: 1 to 2 g IV or IM every 8 to 12 hours for moderately severe systemic infections. For severe, life-threatening infections, 2 g IV every 6 to 8 hours (Max: 8 g/day).
Infants Children, and Adolescents 9 months to 17 years: 30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours.
Infants 1 to 8 months*: 30 mg/kg/dose IV every 6 to 8 hours.
Neonates 34 weeks gestation and older and 8 days and older*: 30 mg/kg/dose IV every 6 hours.
Neonates 34 weeks gestation and older and 0 to 7 days*: 30 mg/kg/dose IV every 8 hours.
Neonates younger than 34 weeks gestation and 8 days and older*: 30 mg/kg/dose IV every 8 hours.
Neonates younger than 34 weeks gestation and 0 to 7 days*: 30 mg/kg/dose IV every 12 hours.
-for the treatment of acute bacterial exacerbations of chronic bronchitis:
Intravenous or Intramuscular dosage:
Adults: 1 to 2 g IV or IM every 8 to 12 hours for 5 to 7 days.
-for the treatment of community-acquired pneumonia (CAP):
Intravenous dosage:
Adults: 2 g IV every 8 hours for at least 7 days.
Adolescents: 30 mg/kg/dose IV (Max: 2 g/dose) every 6 to 8 hours for 5 to 7 days.
-for the treatment of nosocomial pneumonia:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 7 days.
-for the treatment of pneumonia due to resistant gram-negative organisms using extended-infusion dosing*:
Intravenous dosage:
Adults: 2 g administered over 3 hours IV every 8 hours for at least 7 days plus ceftazidime; avibactam.
For the treatment of quinolone-resistant severe typhoid fever*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 7 to 14 days as an alternative in cephalosporin-allergic patients; treat for at least 7 days after defervescence.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 7 to 14 days as an alternative in cephalosporin-allergic patients; treat for at least 7 days after defervescence.
For the treatment of intraabdominal infections, including peritonitis, appendicitis, intraabdominal abscess, and peritoneal dialysis-related peritonitis*:
-for the treatment of uncomplicated intraabdominal infections:
Intravenous dosage:
Adults: 1 to 2 g IV every 6 to 8 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
Infants, Children, and Adolescents 9 months to 17 years: 30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
Infants 1 to 8 months*: 30 mg/kg/dose IV every 6 to 8 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
-for the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections with adequate source control using conventional dosing:
Intravenous dosage:
Adults: 1 to 2 g IV every 6 to 8 hours for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Infants, Children, and Adolescents 9 months to 17 years: 30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Infants 1 to 8 months*: 30 mg/kg/dose IV every 6 to 8 hours for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Neonates 34 weeks gestation and older and 8 days and older*: 30 mg/kg/dose IV every 6 hours for 7 to 10 days.
Neonates 34 weeks gestation and older and 0 to 7 days*: 30 mg/kg/dose IV every 8 hours for 7 to 10 days.
Neonates younger than 34 weeks gestation and 8 days and older*: 30 mg/kg/dose IV every 8 hours for 7 to 10 days.
Neonates younger than 34 weeks gestation and 0 to 7 days*: 30 mg/kg/dose IV every 12 hours for 7 to 10 days.
-for the treatment of complicated intraabdominal infections due to resistant gram-negative organisms with adequate source control using extended-infusion dosing*:
Intravenous dosage:
Adults: 2 g administered over 3 hours IV every 8 hours for 3 to 7 days with ceftazidime; avibactam as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
-for the treatment of peritoneal dialysis-related peritonitis*:
Intermittent Intraperitoneal dosage*:
Adults: 2 g intraperitoneally every 24 hours for 21 to 28 days.
Continuous Intraperitoneal dosage*:
Adults: 1 g/L intraperitoneal loading dose, followed by 250 mg/L in each dialysate exchange. Treat for 21 to 28 days.
Infants, Children, and Adolescents: 1 g/L intraperitoneal loading dose, followed by 250 mg/L in each dialysate exchange. Treat for 14 to 21 days.
For the treatment of skin and skin structure infections, including burn wound infection, postoperative wounds, and diabetic foot ulcer:
-for the treatment of moderate skin and skin structure infections using conventional dosing:
Intravenous dosage:
Adults: 1 or 2 g IV every 8 to 12 hours.
Infants, Children, and Adolescents 9 months to 17 years: 30 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.
Infants 1 to 8 months*: 30 mg/kg/dose IV every 8 hours.
Neonates 34 weeks gestation and older and 8 days and older*: 30 mg/kg/dose IV every 6 hours.
Neonates 34 weeks gestation and older and 0 to 7 days*: 30 mg/kg/dose IV every 8 hours.
Neonates younger than 34 weeks gestation and 8 days and older*: 30 mg/kg/dose IV every 8 hours.
Neonates younger than 34 weeks gestation and 0 to 7 days*: 30 mg/kg/dose IV every 12 hours.
Intramuscular dosage:
Adults: 1 g IM every 8 to 12 hours.
-for the treatment of severe or life-threatening skin and skin structure infections using conventional dosing:
Intravenous dosage:
Adults: 2 g IV every 6 to 8 hours.
Infants, Children, and Adolescents 9 months to 17 years: 30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours.
Infants 1 to 8 months*: 30 mg/kg/dose IV every 6 to 8 hours.
Neonates 34 weeks gestation and older and 8 days and older*: 30 mg/kg/dose IV every 6 hours.
Neonates 34 weeks gestation and older and 0 to 7 days*: 30 mg/kg/dose IV every 8 hours.
Neonates younger than 34 weeks gestation and 8 days and older*: 30 mg/kg/dose IV every 8 hours.
Neonates younger than 34 weeks gestation and 0 to 7 days*: 30 mg/kg/dose IV every 12 hours.
-for the treatment of skin and skin structure infections due to resistant gram-negative organisms using extended-infusion dosing*:
Intravenous dosage:
Adults: 2 g administered over 3 hours IV every 8 hours plus ceftazidime; avibactam.
-for the treatment of diabetic foot ulcer:
Intravenous dosage:
Adults: 2 g IV every 6 to 8 hours for 7 to 14 days for severe infections as empiric therapy. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.
For the treatment of gynecologic infections, including endometritis and pelvic cellulitis:
-for the treatment of moderate gynecologic infections:
Intravenous dosage:
Adults: 1 or 2 g IV every 8 to 12 hours.
Adolescents: 30 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.
Intramuscular dosage:
Adults: 1 g IM every 8 to 12 hours.
-for the treatment of severe or life-threatening gynecologic infections:
Intravenous dosage:
Adults: 2 g IV every 6 to 8 hours.
Adolescents: 30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours.
For the treatment of bronchiectasis*:
-for the treatment of acute exacerbations of bronchiectasis*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 14 days with or without an aminoglycoside.
Infants, Children, and Adolescents: 30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours for 14 days with or without an aminoglycoside.
-for the eradication of first or new isolates of Pseudomonas aeruginosa in patients with bronchiectasis*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 14 days with or without a systemic aminoglycoside or inhaled antibiotics, followed by inhaled antibiotics for 4 to 12 weeks.
Infants, Children, and Adolescents: 30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours for 14 days with or without a systemic aminoglycoside or inhaled antibiotics, followed by inhaled antibiotics for 4 to 12 weeks.
Maximum Dosage Limits:
-Adults
225 mg/day nebulized; 8 g/day IV/IM is FDA-approved; however, 12 g/day IV has been used.
-Geriatric
225 mg/day nebulized; 8 g/day IV/IM is FDA-approved; however, 12 g/day IV has been used.
-Adolescents
225 mg/day nebulized; 120 mg/kg/day (Max: 8 g/day) IV is the FDA-approved maximum dosage; however, up to 300 mg/kg/day (Max: 12 g/day) IV has been used in patients with cystic fibrosis.
-Children
7 to 12 years: 120 mg/kg/day (Max: 8 g/day) IV is the FDA-approved maximum dosage; however, up to 300 mg/kg/day (Max: 12 g/day) IV has been used in patients with cystic fibrosis. The maximum nebulized dosage is 225 mg/day.
1 to 6 years: 120 mg/kg/day IV is the FDA-approved maximum dosage; however, up to 300 mg/kg/day IV has been used in patients with cystic fibrosis. Safety and efficacy of nebulization have not been established.
-Infants
9 to 12 months: 120 mg/kg/day IV is the FDA-approved maximum dosage; however, up to 300 mg/kg/day IV has been used in patients with cystic fibrosis. Safety and efficacy of nebulization have not been established.
1 to 8 months: Safety and efficacy have not been established. Doses up to 120 mg/kg/day IV have been used off-label for most infections; up to 300 mg/kg/day IV has been used in patients with cystic fibrosis.
-Neonates
34 weeks gestation and older and 8 days and older: Safety and efficacy have not been established; however, doses up to 120 mg/kg/day IV have been used off-label.
34 weeks gestation and older and 0 to 7 days: Safety and efficacy have not been established; however, doses up to 90 mg/kg/day IV have been used off-label.
Younger than 34 weeks gestation and 8 days and older: Safety and efficacy have not been established; however, doses up to 90 mg/kg/day IV have been used off-label.
Younger than 34 weeks gestation and 0 to 7 days: Safety and efficacy have not been established; however, doses up to 60 mg/kg/day IV have been used off-label.
Patients with Hepatic Impairment Dosing
No dosage adjustment is needed. The half-life of systemically administered aztreonam is only slightly prolonged in patients with hepatic impairment. The low systemic exposure of aztreonam for inhalation would not warrant dosage adjustments.
Patients with Renal Impairment Dosing
Dosage adjustment due to renal impairment is necessary for systemic dosage only. Nebulized aztreonam does not require dosage adjustment due to low systemic exposure.
The FDA-labeled dosage adjustment in adults with renal impairment reduces the dose and maintains the fixed dosing intervals.
CrCl more than 30 mL/minute/1.73 m2: No dosage adjustment needed.
CrCl 10 to 30 mL/minute/1.73 m2: After a normal loading dose, administer 50% of the standard dose and give at standard dosing intervals.
CrCl less than 10 mL/minute/1.73 m2: After a normal loading dose, administer 25% of the standard dose and give at standard dosing intervals.
Dosage adjustments in pediatric patients:
According to the FDA-approved product labeling, there are insufficient data in pediatric patients with renal failure to determine appropriate dosage adjustments. However, other experts recommend the following dosage adjustments :
GFR 30 to 50 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 10 to 29 mL/minute/1.73 m2: 15 to 20 mg/kg/dose IV every 8 hours.
GFR less than 10 mL/minute/1.73 m2: 7.5 to 10 mg/kg/dose IV every 12 hours.
Intermittent hemodialysis
Aztreonam is cleared by hemodialysis with 27% to 58% of the dose removed. The FDA-approved dosage adjustment for adult hemodialysis patients is to give the normal loading dose followed by 25% of the usual dose given at the standard dosing interval. For serious or life-threatening infections, one-eighth of the initial dose should be given after each hemodialysis session in addition to maintenance dosing. For pediatric patients, 7.5 to 10 mg/kg/dose IV every 12 hours is recommended.
Peritoneal dialysis
For adults, administer 25% of the standard dose. For pediatric patients, 7.5 to 10 mg/kg/dose IV every 12 hours is recommended.
Continuous renal replacement therapy (CRRT)
For adults, a loading dose of 2 g IV is suggested for CRRT. Recommended doses for various types of CRRT include 1 to 2 g IV/IM every 12 hours for continuous venovenous hemofiltration (CVVH) and 1 g IV/IM every 8 hours or 2 g IV/IM every 12 hours for continuous venovenous hemodialysis (CVVHD) or continuous venovenous hemodiafiltration (CVVHDF). For pediatric patients, 100% of the dose is recommended.
*non-FDA-approved indication
Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
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.
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.
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.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including aztreonam, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. 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.
Unlike the penicillins and cephalosporins, aztreonam is a monobactam. It contains a sulfonic acid group that gives the beta-lactam of aztreonam its activity. Like the penicillins and cephalosporins, aztreonam is mainly bactericidal and 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. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. In particular, aztreonam preferentially binds to PBP-3 of the gram-negative rods, and the sulfonic acid group assists in the acetylation of PBP-3. Since PBP-3 is responsible for formation of the septum during cell division, aztreonam's inhibition of these proteins causes elongation of the bacteria, inhibition of bacterial cell division, and breakage of the cell wall, which results in cell lysis and death. Aztreonam has no affinity for the PBPs of gram-positive organisms and poor affinity for anaerobic PBPs. In vitro, aztreonam has little ability to induce chromosomally mediated beta-lactamase production, although the selection of preexisting resistant organisms is still possible during clinical use.
The susceptibility interpretive criteria for aztreonam are delineated by pathogen. The MICs are defined for Enterobacterales and Aeromonas sp. as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more (based on a dosage of 1 g IV every 8 hours). The MICs are defined for P. aeurginosa and non-Enterobacterales as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more (based on a dosage of 1 g IV every 6 hours or 2 g IV every 8 hours for P. aeurginosa). The MICs are defined for H. influenzae and H. parainfluenzae as susceptible at 2 mcg/mL or less.
Bacterial resistance to aztreonam occurs via hydrolysis by beta-lactamase, alteration of the PBP, and decreased intracellular permeability.
Aztreonam is administered via nebulization, intravenously, and intramuscularly. Approximately 56-65% of aztreonam is protein-bound. Systemic aztreonam is distributed into most body tissues and fluids including lungs, liver, kidneys, bone, uterus, ovary, intestine, saliva, sputum, bile, as well as peritoneal, pleural, pericardial, and synovial fluids. It reaches high enough concentrations within CSF to inhibit most Enterobacteriaceae when administered systemically, although it is not indicated for the treatment of meningitis. It also crosses the placenta.
Hepatic metabolism is a minor pathway of excretion. Aztreonam and the inactive metabolites are excreted primarily into the urine via tubular secretion and glomerular filtration. A small percentage is excreted in feces. The drug is also excreted in breast milk. The elimination half-life of aztreonam is 1.7 hours after systemic administration and 2.1 hours after nebulization in patients with normal renal function. Concomitant administration of probenecid or furosemide and aztreonam does not result in clinically significant increases in aztreonam serum concentrations.
-Route-Specific Pharmacokinetics
Oral Route
Aztreonam is poorly absorbed from the GI tract.
Intravenous Route
After single aztreonam 500-1000 mg IV doses, the serum levels exceeded the MIC90 for Neisseria sp, H. influenzae, most genera of Enterobacteriaceae and 80% of Enterobacter sp. for 8 hours. For P. aeruginosa, a single 2 g IV dose of aztreonam will maintain levels exceeding the MIC90 for 4-6 hours. The same doses of aztreonam result in urine concentrations of aztreonam that exceed the MIC90 for these organisms for up to 12 hours. Approximately 60-70% of an IV or IM dose of aztreonam is recovered in the urine in 8 hours. Urinary excretion of a single dose is essentially complete 12 hours after the injection.
Intramuscular Route
Peak plasma levels of aztreonam occur within 60 minutes after an IM dose. Serum concentrations are comparable between IM and IV dosing at 1 hour (1.5 hours from the start of the IV infusion) after the dose. Following single aztreonam 500-1000 mg IM doses, the serum levels exceeded the MIC90 for Neisseria sp, H. influenzae, most genera of Enterobacteriaceae, and 80% of Enterobacter sp. for 8 hours. The same doses of aztreonam result in urine concentrations of aztreonam that exceed the MIC90 for these organisms for up to 12 hours. Approximately 60-70% of an IV or IM dose of aztreonam is recovered in the urine in 8 hours. Urinary excretion of a single dose is essentially complete 12 hours after the injection.
Inhalation Route
Sputum and plasma concentrations exhibited considerable variability between patients receiving nebulized aztreonam in clinical trials. The mean sputum concentration 10 minutes after the first dose of nebulized aztreonam (75 mg) was 726 mcg/g. In patients receiving nebulized aztreonam 3 times daily, mean sputum concentrations 10 minutes after dose administration on days 0, 14, and 28 were 984 mcg/g, 793 mcg/g, and 715 mcg/g, respectively, indicating no drug accumulation. The mean peak plasma concentration one hour after the first dose of nebulized aztreonam was 0.59 mcg/mL. Mean peak plasma concentrations in patients receiving nebulized aztreonam 3 times daily were 0.55 mcg/mL, 0.67 mcg/mL, and 0.65 mcg/mL on days 0, 14, and 28, respectively. These are low systemic concentrations compared to peak serum concentrations after an IV dose (approximately 54 mcg/mL after a 500 mg dose). Evaluation of plasma and urine concentrations indicates a low systemic absorption of nebulized aztreonam. Approximately 10% of the total nebulized dose is excreted in the urine as unchanged drug compared to 60-65% after IV administration. The elimination half-life of nebulized aztreonam is 2.1 hours.
-Special Populations
Hepatic Impairment
The half-life of aztreonam is only slightly prolonged in patients with hepatic impairment.
Renal Impairment
Due to minimal systemic concentrations with the use of inhaled aztreonam, decreased renal function does not alter dosing. With declining renal function, the elimination half-life of systemically administered aztreonam is prolonged will increase up to 6-8 hours in patients with end-stage renal disease. Systemic dosages need to be adjusted accordingly. Aztreonam is removed by hemodialysis with 27-58% of the dose removed. Approximately 10% of the dose is removed by a 6 hour peritoneal dialysis dwell. Aztreonam given IV rapidly reaches therapeutic concentrations in peritoneal dialysis fluid; conversely, aztreonam administered intraperitoneally in dialysis fluid rapidly produces therapeutic serum concentrations.
Pediatrics
Infants, Children, and Adolescents
In general, aztreonam pharmacokinetics in pediatric patients >= 9 months of age are comparable to adults in studies. Serum half-life ranges from 1.2-2.7 hours and the volume of distribution ranges from 0.2-0.29 L/kg.
Neonates
The half-life of aztreonam ranges from 2.2-9.9 hours in premature neonates and neonates and appears to shorten with increased gestational and post-natal age. The volume of distribution tends to correspond to the higher extracellular water content in these patients and generally ranges from 0.24-0.58 L/kg. One study in premature neonates had 14 patients with a mean gestational age of 27.6 weeks and mean birth weight of 1060 g and an additional 16 patients with a mean gestational age of 32.4 weeks and a mean birth weight of 1639 g. The patients in this study had a higher volume of distribution that ranged from 0.64-1 L/kg.
Geriatric
In elderly patients, the mean serum half-life of aztreonam increased and the renal clearance decreased, consistent with the age-related decrease in creatinine clearance.