Ertapenem is a 1-beta methyl carbapenem, structurally related to beta-lactam antibiotics. It is highly stable against beta-lactamases and has activity against a wide variety of gram-positive, gram-negative and anaerobic microorganisms, but has no activity against Pseudomonas aeruginosa. Ertapenem is administered parenterally once daily for complicated urinary tract infections, skin and skin-structure infections, acute pelvic infections, community-acquired pneumonia, and intraabdominal infections. It is also used for surgical prophylaxis in colorectal procedures. The FDA approved ertapenem in November 2001.
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. Ertapenem solution is colorless to pale yellow; variations of color within this range do not affect the potency of the product.
Intravenous Administration
Intravenous (IV) Infusion
Powder Vials for Injection
Reconstitution
-Reconstitute each 1 g vial with 10 mL of 0.9% Sodium Chloride Injection, Sterile Water for Injection, or Bacteriostatic Water for Injection using a syringe equipped with a 21-gauge or smaller diameter needle. Use with a needless IV system is not recommended. According to the manufacturer, the final concentration after reconstitution is 100 mg/mL.
-Shake well to dissolve.
-Further dilution is necessary for IV infusion.
-Storage: Immediately transfer the appropriate amount of the reconstituted vial to diluent. Discard vial with unused portion of the reconstituted solution.
Dilution
-For a 1 g dose: further dilute with 50 mL of 0.9% Sodium Chloride Injection.
-For a dose less than 1 g: further dilute the appropriate dose with 0.9% Sodium Chloride Injection to a concentration of 20 mg/mL or less.
-Storage: Use within 6 hours if stored at room temperature (25 degrees C). The diluted solution may be refrigerated for up to 24 hours (5 degrees C) and used within 4 hours after removal from refrigeration. Do not freeze.
Intermittent IV Infusion
-Complete the infusion within 6 hours of reconstitution.
-Infuse IV over 30 minutes.
-Do not co-infuse with other medications.
Intravenous (IV) Push*
NOTE: Ertapenem is not approved by the FDA for IV push administration.
Powder Vials for Injection
Reconstitution
-A study included 12 healthy adult volunteers who received ertapenem by IV push.
--Doses of 1 g were reconstituted with 0.9% Sodium Chloride Injection to a total volume of 10 mL (100 mg/mL).
-Stability:
--In the 12-person volunteer study, doses (100 mg/mL) were stored under refrigeration and used within 6 hours of preparation; stability was not assessed.
-In a stability study, ertapenem reconstituted in 0.9% Sodium Chloride Injection to a total volume of 10 mL (100 mg/mL) and stored in polypropylene syringes was stable for 30 minutes at room temperature (25 degrees C), for 24 hours under refrigeration (4 degrees C) followed by 4 hours at room temperature (25 degrees C), for 14 days frozen (-20 degrees C) followed by 5 hours at room temperature (25 degrees C), and for 28 days frozen (-20 degrees C) followed by 3 hours at room temperature (25 degrees C).
Intermittent IV Push
-Doses were administered IVP at a rate of 5 minutes in 12 healthy adult volunteers.
Intramuscular Administration
Reconstitution
-Reconstitute the 1 g vial with 3.2 mL of 1% lidocaine injection (without epinephrine) to a final concentration of approximately 280 mg/mL.
-Agitate well to form a solution.
-Storage: Use within 1 hour after preparation. Discard vial with unused portion of the reconstituted solution.
Intramuscular Injection
-The IM reconstituted formulation is not for IV use.
-IM administration may be used as an alternative to IV administration in the treatment of infections where IM therapy is appropriate; however, only administer via IM injection for 7 days.
-Immediately withdraw the appropriate dose and inject deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh).
-Storage: Use within 1 hour after preparation.
In general, ertapenem was well tolerated during adult clinical trials (n = 1954) with most adverse events reported as mild to moderate in severity. Evaluation of adverse events also included the time frame during which a switch to oral antimicrobial therapy occurred. Most adverse events were described as mild to moderate in severity. Ertapenem was discontinued due to adverse events in 4.7% of patients. The overall adverse event profile in pediatric patients is comparable to that in adults.
During clinical trials, skin and skin appendage adverse effects that occurred in more than 1% of patients who received ertapenem included rash (2.3% to 2.5% adults; 2.9% pediatrics) and pruritus (1% to 2% adults; more than 0.5% pediatrics). Other skin and skin appendage events that occurred in more than 0.1% of adult patients included erythema, sweating or hyperhidrosis, dermatitis, desquamation, flushing, and urticaria. Diaper dermatitis occurred in 4.7% of pediatric patients. Other events that occurred in more than 0.5% of pediatric patients included dermatitis, erythematous rash, and skin lesions. Postmarketing reports have noted Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and hypersensitivity vasculitis.
Adverse events occurring in 1% or more of adult patients (n = 1,954) in ertapenem comparator trials included injection site reaction, such as infused vein complication, (3.7% to 7.1%), extravasation (more than 0.1%), phlebitis/thrombophlebitis (more than 0.1%), injection site induration (more than 0.1%), and injection site pain (more than 0.1%). Drug-related adverse events in pediatric patients included injection site reaction such as infusion site pain (5.5% to 7%), infusion site erythema (2.6% to 3.9%), infusion site induration (more than 0.5%), infusion site phlebitis (more than 0.5%), infusion site swelling (more than 0.5%), infusion site warmth (more than 0.5%), and infusion site itching (more than 0.5%).
Elevated hepatic enzymes occurred during ertapenem clinical trials. This included elevated AST (5.2% to 8.4% adults; 2.1% to 3.8% pediatrics), elevated ALT (6% to 8.8% adults; 2.2% to 3.8% pediatrics), increased alkaline phosphatase (3.4% to 6.6% adults; more than 0.5% pediatrics), and elevated total bilirubin or hyperbilirubinemia (more than 0.1%). Ertapenem therapy was discontinued due to a drug-related elevation in transaminases in a single patient. Cholelithiasis and jaundice were reported in more than 0.1% of adult patients during clinical trials.
Adverse gastrointestinal (GI) effects are common with many antibiotics, including ertapenem. Adverse events that occurred during ertapenem comparator trials included diarrhea (5.5% to 10.3% adults; 6.5% to 11.7% pediatrics), nausea (3.1% to 8.5% adults; more than 0.1% pediatrics), vomiting (3.7% to 4% adults; 2.1% to 10.2% pediatrics), constipation (3.3% to 4% adults; 2.3% pediatrics), abdominal pain (3.6% to 4.3% adults; more than 0.5% to 4.7% pediatrics), and loose stools (2.1% pediatrics). Infusion of doses more than 1 g daily resulted in an increased incidence of nausea. Other GI-related events that occurred in more than 0.1% of adult patients included acid regurgitation, dyspepsia, GI hemorrhage (GI bleeding), anorexia, flatulence, stomatitis, dysphagia, hemorrhoids, ileus, duodenitis, esophagitis, gastritis, mouth ulcer (oral ulceration), pancreatitis, pyloric stenosis, abdominal distention, weight loss, and taste perversion (dysgeusia). Dry mouth (xerostomia) and hematochezia were noted in more than 0.5% of adults. Decreased appetite was reported in more than 0.5% of pediatric patients. Small intestine obstruction (GI obstruction) was reported in 2.1% of adults during colorectal surgery prophylaxis trials. Cases of tooth discoloration (staining) have been noted in postmarketing reports.
Cardiovascular adverse events that occurred in more than 1% of adult patients treated with ertapenem in clinical trials included edema/swelling (2.9% to 3.4%) and hypotension (1% to 2%). Chest pain (unspecified) was reported in more than 0.1% of adults and more than 0.5% of pediatric patients. Other cardiovascular events that occurred in more than 0.1% of adult patients included heart failure, hematoma, hypertension, sinus tachycardia, cardiac arrest, bradycardia, arrhythmia, atrial fibrillation, heart murmur, ventricular tachycardia, asystole, and subdural hemorrhage.
During clinical trials plus a 14-day follow-up period, seizures occurred in 0.5% of patients who received ertapenem. Comparatively, seizures occurred in 0.3% of patients treated with piperacillin; tazobactam and 0% of those treated with ceftriaxone. Other CNS and psychiatric adverse events that occurred during ertapenem clinical trials included insomnia (3% to 3.2%, adults; more than 0.5% pediatrics), dizziness (1.5% to 2.1% adults; more than 0.5% pediatrics), and headache (2.2% to 6.8% adults; 4.4% of pediatrics). Altered mental status such as agitation, confusion, disorientation, decreased mental acuity, changed mental status, drowsiness (somnolence), or stupor occurred in 3.3% to 5.1% of adults. Drowsiness was reported in more than 0.5% of pediatric patients. Other CNS and psychiatric events that occurred in more than 0.1% of adults included asthenia or fatigue, anxiety, nervousness, tremor, depression, hypesthesia/hypoesthesia, spasm, paresthesias, aggressive behavior, syncope, and vertigo. Cerebrovascular accident (stroke) was reported in more than 0.5% of adults. Dyskinesia, hallucinations, myoclonia, abnormal coordination, gait disturbances, encephalopathy (with prolonged recovery in patients with renal impairment), and altered mental status (including aggression, delirium, and decreased consciousness) all occurred during postmarketing experience with ertapenem.
During clinical trials, respiratory system adverse effects that occurred in patients who received ertapenem included dyspnea (1% to 2.6%, adults) and cough (more than 0.1%, adults; 4.4%, pediatrics). Other respiratory system events that occurred in more than 0.1% of adult patients included rales/rhonchi, respiratory distress, hypoxemia, bronchoconstriction, pharyngeal discomfort, epistaxis, pleuritic pain, asthma, hemoptysis, hiccups, and voice disturbance. Adverse events reported in more than 0.5% of adult patients include pulmonary crackles, pulmonary infiltration, pulmonary congestion, and pulmonary embolism. Atelectasis was noted in 3.4% of adult patients during colorectal surgery prophylaxis trials. Wheezing was reported in more than 0.5% of adult and pediatric patients. Pleural effusion and nasopharyngitis/pharyngitis occurred in more than 0.1% of adults and more than 0.5% of pediatric patients. Other events noted in more than 0.5% of pediatric patients include rhinitis and rhinorrhea.
During clinical trials, urogenital system adverse events that occurred in more than 0.1% of adult patients who received ertapenem included renal impairment, oliguria/anuria, vaginal pruritus, hematuria, urinary retention, and bladder dysfunction. Vaginitis occurred in 1.4% to 3.3% of adult female patients. Pollakiuria (increased urinary frequency) and dysuria were reported in more than 0.5% of adult patients. Genital rash was noted in more than 0.5% of pediatric patients. Laboratory abnormalities included increased serum creatinine (more than 0.1%), increased BUN/azotemia (more than 0.1%), increased urine red blood cells (1.1% to 2.5%), and increased urine white blood cells (1.6% to 2.5%).
Fatal hypersensitivity reactions, including anaphylaxis or anaphylactoid reactions have been reported with beta-lactams, including ertapenem. Facial edema (angioedema) has been reported in more than 0.1% of patients.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with ertapenem (more than 0.1% of adults). 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. Candidiasis, including oral candidiasis, unspecified candidiasis, and vaginal candidiasis, has been reported in more than 0.1% of patients. Septic shock and septicemia were reported in more than 0.1% of adults. Infection (cellulitis, abdominal abscess, fungal rash, pelvic abscess, pneumonia, UTI, wound infection, postoperative infection) occurred in more than 0.5% to 6.5% of adults receiving ertapenem for prophylaxis in clinical studies. Abdominal abscess, herpes simplex, ear infection, and viral pharyngitis occurred in more than 0.5% of pediatric patients in clinical trials. Upper respiratory tract infections occurred in 2.3% of pediatric patients in clinical trials.
In adult colorectal surgery prophylaxis trials, surgical complications were reported with ertapenem. Wound complication was reported in 2.9% of patients. Anastomotic leak, seroma, wound dehiscence, wound secretion, incision site complications, incision site hemorrhage (bleeding), and intestinal stoma complications were reported in more than 0.5% of patients.
General adverse events were reported during ertapenem clinical trials, including fever (2.3% to 5% adults; 4.9% pediatrics). Other adverse events that occurred in more than 0.1% of adult patients included pain, chills, dehydration, gout, malaise, necrosis, and flank pain. Crepitations were reported in more than 0.5% of adults. Hypothermia was reported in more than 0.5% of pediatric patients. Death was reported in 1.3% to 2.5% of adult patients overall in trials. However, deaths occurred in 4.7% of patients receiving ertapenem for complicated intraabdominal infections vs. 2.6% of patients receiving a comparator drug, such as piperacillin; tazobactam. According to investigators, deaths were unrelated to the study drugs.
During ertapenem clinical trials, muscle spasms or muscle cramps were reported in more than 0.5% of adult patients, leg pain was reported in more than 0.1% of adults, and arthralgia was noted in more than 0.5% of pediatric patients.
Hematologic abnormalities reported during ertapenem clinical trials included decreased serum albumin (more than 0.1%, adults), increased eosinophils (1.1% to 2.1%, adults; more than 0.5%, pediatrics), decreased hematocrit (3% to 3.4%, adults), decreased hemoglobin (4.5% to 4.9%, adults), decreased platelet count (more than 0.1%, adults), increased platelet count (4.3% to 6.5%, adults; more than 0.5%, pediatrics), decreased neutrophils (more than 0.1%, adults; 3% to 5.8%, pediatrics), increased PT and PTT (more than 0.1%, adults), and decreased white blood cells (more than 0.1%, adults; more than 0.5% pediatrics). During colorectal surgery prophylaxis trials, anemia was reported in 5.7% of adults.
General laboratory abnormalities that occurred in more than 0.1% of adults during ertapenem clinical trials included hyperglycemia, hypernatremia, hypokalemia, and hyperkalemia.
Lidocaine is the diluent for IM administration of ertapenem. IM use is contraindicated in patients with an amide local anesthetic hypersensitivity.
Ertapenem is contraindicated in any patient who has exhibited hypersensitivity to ertapenem, other drugs in the same class (e.g., carbapenem hypersensitivity) or in patients who have demonstrated anaphylactic reactions to beta-lactams. Prior to initiating ertapenem therapy, the patient should be carefully questioned about previous penicillin hypersensitivity, cephalosporin hypersensitivity, allergic reactions to other beta-lactams (e.g., aztreonam) and other allergens. Patients who have experienced anaphylactic reactions to penicillins or cephalosporins should not receive ertapenem. Ertapenem is structurally similar to the penicillins and cephalosporins and these patients may be more susceptible to hypersensitivity reactions. If an allergic reaction occurs, discontinue the drug and initiate appropriate emergency treatment with epinephrine, oxygen, IV steroids, intubation or other therapy as indicated.
Patients with renal impairment or renal failure (CrCl <= 30 mL/min) will require a dosage adjustment of ertapenem. A supplemental dose may or may not be required following dialysis.
Use ertapenem cautiously in patients with brain lesions or brain tumor, a history of seizure disorder, or other neurological disease or condition that may lower the seizure threshold, such as head trauma. Seizures have been reported with ertapenem use and have occurred most commonly in patients with these types of conditions. The risk of seizures increases in patients given ertapenem doses higher than recommended (e.g., patients with compromised renal function). Close adherence to the recommended dose regimen is recommended, particularly for patients with known risk factors for seizures. Anticonvulsant therapy should be continued in patients with a known seizure disorder. If focal tremor or myoclonic seizures occur, patients should be evaluated neurologically. Anticonvulsant therapy should be initiated if indicated and the dose of ertapenem should be re-evaluated based on the patient's renal function.
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 ertapenem, 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.
Available data from a small number of postmarketing cases with ertapenem use in pregnancy are insufficient to inform any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies evaluating doses 1.2 and 3 times the recommended human dose of 1 g, there was no evidence of fetal developmental toxicity; however, slight decreases in fetal weights and numbers of ossified sacrocaudal vertebrae were observed.
Ertapenem is excreted in human breast milk. The concentration in breast milk 24 hours after a 1 g dose ranged from less than 0.13 mcg/mL (lower limit of quantitation) to 0.38 mcg/mL in 5 lactating women. By day 5 after discontinuation, the concentration in breast milk was undetectable. There are no data on the effects of ertapenem on the breast-fed infant or on milk production. In general, unless the infant is allergic to ertapenem, breast-feeding is likely safe during maternal carbapenem therapy; observe the infant for potential effects. Consider the benefits of breast-feeding along with the mother's clinical need for ertapenem and any potential adverse effects on the breast-fed infant from ertapenem or the underlying maternal condition.
Clinical trial data and other reported clinical experience has not identified differences in responses between geriatric adults and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out. Ertapenem is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because older adults are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
FDA-approved labeling recommends that intramuscular administration may be used for up to 7 days.
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: Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Citrobacter freundii, Citrobacter koseri, Clostridium clostridioforme, Clostridium perfringens, Eggerthella lenta, Enterobacter cloacae, Escherichia coli, Fusobacterium sp., Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Haemophilus parainfluenzae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Morganella morganii, Parabacteroides distasonis, Peptostreptococcus sp., Porphyromonas asaccharolytica, Prevotella bivia, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marcescens, Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of community-acquired pneumonia, including cases with concurrent bacteremia and infections due to resistant gram-negative organisms:
Intravenous or Intramuscular dosage:
Adults: 1 g IV or IM once daily for 10 to 14 days. Consider transitioning to an appropriate oral therapy after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated.
Adolescents: 1 g IV or IM once daily for 10 to 14 days. Consider transitioning to an appropriate oral therapy after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated.
Infants and Children 3 months to 12 years: 15 mg/kg/dose IV or IM twice daily (Max: 1 g/day) for 10 to 14 days. Consider transitioning to an appropriate oral therapy after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated.
Infants 1 to 2 months*: 15 mg/kg/dose IV or IM twice daily.
For the treatment of intraabdominal infections, including peritonitis, appendicitis, intraabdominal abscess, biliary tract infections (cholecystitis), and peritoneal dialysis-related peritonitis*:
-for the treatment of unspecified complicated intraabdominal infections:
Intravenous or Intramuscular dosage:
Adults: 1 g IV or IM once daily for 5 to 14 days.
Adolescents: 1 g IV or IM once daily for 5 to 14 days.
Infants and Children 3 months to 12 years: 15 mg/kg/dose IV or IM every 12 hours (Max: 1 g/day) for 5 to 14 days.
Infants 1 to 2 months*: 15 mg/kg/dose IV or IM twice daily. FDA-labeling for other populations suggests a duration of 5 to 14 days.
-for the treatment of complicated community-acquired intraabdominal infections with adequate source control, including infections due to resistant gram-negative organisms:
Intravenous dosage:
Adults: 1 g IV every 24 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Adolescents: 1 g IV every 24 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Infants and Children 3 months to 12 years: 15 mg/kg/dose IV every 12 hours (Max: 1 g/day) for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Infants 1 to 2 months*: 15 mg/kg/dose IV every 12 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
-for the treatment of uncomplicated intraabdominal infections* with adequate source control:
Intravenous dosage:
Adults: 1 g IV once as a single dose as 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.
Adolescents: 1 g IV as a single dose as 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 and Children: 15 mg/kg/dose IV every 12 hours (Max: 1 g/day). 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 uncomplicated intraabdominal infections* without definitive source control:
Intravenous dosage:
Adults: 1 g IV every 24 hours for at least 48 hours, followed by oral step-down therapy for a total treatment duration of 5 to 10 days. 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.
Adolescents: 1 g IV every 24 hours for at least 48 hours, followed by oral step-down therapy for a total treatment duration of 5 to 10 days. 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 and Children: 15 mg/kg/dose IV every 12 hours (Max: 1 g/day) for at least 48 hours, followed by oral step-down therapy for a total treatment duration of 5 to 10 days. 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 peritoneal dialysis-related peritonitis*:
Intravenous dosage:
Adults: 500 mg IV every 24 hours for 21 days.
For the treatment of complicated skin and skin structure infections, including necrotizing infections, human bite wounds, diabetic foot ulcer, pyomyositis, and surgical incision site infections:
-for the treatment of unspecified skin and skin structure infections, including infections due to resistant gram-negative organisms:
Intravenous or Intramuscular dosage:
Adults: 1 g IV or IM every 24 hours for 7 to 14 days.
Adolescents: 1 g IV or IM every 24 hours for 7 to 14 days.
Infants and Children 3 months to 12 years: 15 mg/kg/dose (Max: 1 g/dose) IV or IM every 12 hours for 7 to 14 days.
Infants 1 to 2 months*: 15 mg/kg/dose IV or IM every 12 hours for 7 to 14 days.
-for the treatment of necrotizing infections of the skin, fascia, and muscle:
Intravenous dosage:
Adults: 1 g IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.
Adolescents: 1 g IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.
Infants and Children 3 months to 12 years: 15 mg/kg/dose (Max: 1 g/dose) IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.
Infants 1 to 2 months*: 15 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.
-for the treatment of human bite wounds:
Intravenous dosage:
Adults: 1 g IV every 24 hours.
-for the treatment of diabetic foot ulcer:
Intravenous or Intramuscular dosage:
Adults: 1 g IV or IM every 24 hours for 7 to 14 days for moderate or severe infections in patients with recent antibiotic exposure or infections with ischemic limb/necrosis/gas forming. 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 pyomyositis:
Intravenous dosage:
Adults: 1 g IV every 24 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.
Adolescents: 1 g IV every 24 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.
Infants and Children 3 months to 12 years: 15 mg/kg/dose (Max: 1 g/dose) IV every 12 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.
Infants 1 to 2 months*: 15 mg/kg/dose IV every 12 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.
-for the treatment of surgical incision site infections:
Intravenous dosage:
Adults: 1 g IV every 24 hours for incisional surgical site infections of the intestinal or genitourinary tract.
For the treatment of complicated urinary tract infection (UTI), including pyelonephritis and cases with concurrent bacteremia, as well as cystitis* and pyelonephritis due to infections with difficult-to-treat resistance:
-for the treatment of complicated urinary tract infection, including pyelonephritis and cases with concurrent bacteremia:
Intravenous or Intramuscular dosage:
Adults: 1 g IV or IM once daily for 7 to 14 days.
Adolescents: 1 g IV or IM once daily for 10 to 14 days.
Infants and Children 3 months to 12 years: 15 mg/kg/dose IV or IM twice daily (Max: 1 g/day) for 10 to 14 days.
Infants 1 to 2 months*: 15 mg/kg/dose IV or IM twice daily.
-for the treatment of complicated urinary tract infections, including pyelonephritis, due to infections with difficult-to-treat resistance:
Intravenous dosage:
Adults: 1 g IV once daily for 7 to 14 days.
-for the treatment of uncomplicated cystitis due to infections with difficult-to-treat resistance*:
Intravenous dosage:
Adults: 1 g IV once daily for 3 to 7 days.
For the treatment of acute pelvic infections, including postpartum endomyometritis, septic abortion, and postsurgical gynecologic infections:
Intravenous or Intramuscular dosage:
Adults: 1 g IV or IM once daily for 3 to 10 days.
Adolescents: 1 g IV or IM once daily for 3 to 10 days.
Infants and Children 3 months to 12 years: 15 mg/kg/dose IV or IM twice daily (Max: 1 g/day) for 3 to 10 days.
For surgical infection prophylaxis for elective colorectal surgery:
Intravenous dosage:
Adults: 1 g IV as a single dose within 60 minutes prior to the surgical incision. No intraoperative redosing is necessary. The duration of prophylaxis should not exceed 24 hours.
Infants*, Children*, and Adolescents*: 15 mg/kg/dose IV as a single dose (Max: 1 g/dose) within 60 minutes prior to the surgical incision. No intraoperative redosing is necessary. The duration of prophylaxis should not exceed 24 hours.
For the treatment of severe or complicated extensively drug-resistant typhoid fever*:
Intravenous dosage:
Adults: 1 g IV every 24 hours for 10 to 14 days. Consider adding azithromycin for patients who do not improve.
For the treatment of bone and joint infections*, including native vertebral osteomyelitis*, orthopedic device-related infection* (e.g., prosthetic joint infection), and infections with difficult-to-treat resistance:
-for the treatment of native vertebral osteomyelitis*, including infections with difficult-to-treat resistance:
Intravenous dosage:
Adults: 1 g IV every 24 hours for 6 weeks as first-line therapy for infections due to Enterobacterales.
-for the treatment of prosthetic joint infections*, including infections with difficult-to-treat resistance:
Intravenous dosage:
Adults: 1 g IV every 24 hours for 4 to 6 weeks as first-line therapy for infections due to Enterobacterales, which may be followed by chronic oral suppressive therapy.
For bacterial infection prophylaxis* after penetrating chest trauma with esophageal disruption or penetrating abdominal trauma:
Intravenous dosage:
Adults: 1 g IV as a single dose as an alternative.
Adolescents: 1 g IV as a single dose as an alternative.
Infants and Children: 15 mg/kg/dose (Max: 1 g/dose) IV as a single dose as an alternative.
For the treatment of chorioamnionitis* or intraamniotic infection*:
Intravenous dosage:
Adults: 1 g IV every 24 hours during the intrapartum period as an alternative. Give 1 additional dose after cesarean delivery; an additional dose is generally not needed after vaginal delivery. Other risk factors such as bacteremia or persistent postpartum fever may require additional therapy.
Adolescents: 1 g IV every 24 hours during the intrapartum period as an alternative. Give 1 additional dose after cesarean delivery; an additional dose is generally not needed after vaginal delivery. Other risk factors such as bacteremia or persistent postpartum fever may require additional therapy.
Maximum Dosage Limits:
-Adults
1 g/day IV/IM.
-Geriatric
1 g/day IV/IM.
-Adolescents
1 g/day IV/IM.
-Children
30 mg/kg/day IV/IM (Max: 1 g/day).
-Infants
3 to 11 months: 30 mg/kg/day IV/IM.
1 to 2 months: Safety and efficacy have not been established; however, doses up to 30 mg/kg/day IV/IM are recommended off-label.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage guidelines are available; it appears no dosage adjustment is needed.
Patients with Renal Impairment Dosing
No data are available regarding use in pediatric patients with renal impairment.
FDA-approved dosage in renal failure for adults:
CrCl > 30 mL/min: No dosage adjustment needed.
CrCl <= 30 mL/min: 500 mg IV or IM once a day.
Other dosage adjustment guidelines for adults:
CrCl > 10 mL/min: No dosage adjustment needed.
CrCl < 10 mL/min: 500 mg IV or IM once a day.
Intermittent hemodialysis
Give recommended dose of 500 mg IV or IM once a day. If ertapenem is given 6 hours or more prior to hemodialysis, no supplemental dosing is required. If ertapenem is given within 6 hours of hemodialysis, a supplementary dose of 150 mg is recommended following the hemodialysis session.
Peritoneal dialysis
Administer 500 mg IV or IM once a day.
Continuous renal replacement therapy (CRRT)
No dosage adjustment is necessary unless anticipated clearance is < 30 mL/min.
*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.
Probenecid: (Minor) Probenecid inhibits the renal excretion of ertapenem by competing with them for active tubular secretion. In some instances, this effect is used therapeutically to increase availability of the antimicrobial agent. However, the elimination half-life of ertapenem is increased only from 4 to 4.8 hours. Concurrent administration of ertapenem with probenecid is not recommended.
Probenecid; Colchicine: (Minor) Probenecid inhibits the renal excretion of ertapenem by competing with them for active tubular secretion. In some instances, this effect is used therapeutically to increase availability of the antimicrobial agent. However, the elimination half-life of ertapenem is increased only from 4 to 4.8 hours. Concurrent administration of ertapenem with probenecid is not recommended.
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.
Valproic Acid, Divalproex Sodium: (Major) Avoid concomitant carbapenem and valproic acid use. Consider alternative antibacterial therapies other than carbapenems to treat infections in patients whose seizures are well controlled with valproic acid or divalproex sodium. If coadministered, monitor valproic acid concentrations. Coadministration of carbapenems with valproic acid or divalproex sodium may reduce the serum concentration of valproic acid potentially increasing the risk of breakthrough seizures. Carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing valproic acid serum concentrations.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including carbapenems, 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.
Ertapenem exhibits bactericidal activity due inhibition of cell wall synthesis mediated via binding to penicillin binding proteins (PBPs). It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific PBPs that are located inside the bacterial cell wall. PBPs 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. PBPs vary among different bacterial species. In E. coli, ertapenem has shown strong affinity towards PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3. PBP-1 is responsible for formation of the cell wall; PBP-2 is responsible for maintaining the rod-like shape, and PBP-3 is responsible for bacterial septum formation. Ertapenem is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. Like meropenem, but unlike imipenem, it has a 1-beta-methyl substituent and does not require protection with an inhibitor of human renal dihydropeptidase I.
Beta-lactams, including ertapenem, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T above the MIC). This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Carbapenems require free drug concentrations to exceed the MIC for 20% of the dosing interval for bacteriostatic activity and 40% of the dosing interval for maximal bactericidal activity. Carbapenems also are reported to have a post-antibiotic effect (PAE). PAE is defined as the suppression of bacterial growth that continues after the antibiotic concentration falls below the bacterial MIC. Ertapenem has a short PAE of 1.4 to 2.6 hours against gram-positive strains only.
The susceptibility interpretive criteria for ertapenem are delineated by pathogen. The MICs are defined for Enterobacterales and Aeromonas sp. as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more based on a dose of 1 gram every 24 hours. The MICs are defined for S. pneumoniae as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for Staphylococcus sp. as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. The MICs are defined for beta-hemolytic group Streptococcus sp. and Streptococcus sp. Viridans group as susceptible at 1 mcg/mL or less. The MICs are defined for H. influenzae and H. parainfluenzae as susceptible at 0.5 mcg/mL or less. The MICs are defined for anaerobes as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more.
There are 4 general mechanisms of carbapenem resistance including decreased permeability of the outer membrane of gram-negative organisms due to decreased porin channel production, decreased affinity for the target PBPs, over-expression of efflux pumps, and enzymatic degradation. Generally, carbapenems show stability to the majority of beta-lactamases, including AmpC beta-lactamases and extended-spectrum beta-lactamases (ESBLs). However, specific intrinsic or acquired beta-lactamases, generally called carbapenemases, can hydrolyze the carbapenems. These include some class A enzymes, several class D (OXA) enzymes, and the class B metallo-beta-lactamases. A deficiency in the outer membrane porin protein (Opr) D2 is associated with decreased carbapenem susceptibility in gram-negative bacteria. However, it is theorized that a combination of resistance mechanisms is required for significant carbapenem resistance. Theoretically, efflux activity plus loss of membrane permeability is less likely to happen in vivo than AmpC beta-lactamase expression and loss of membrane permeability.
Ertapenem is administered via intravenous (IV) or intramuscular (IM) routes. Ertapenem exhibits non-linear pharmacokinetics due to a high level of concentration-dependent plasma protein binding to albumin. Protein binding averages 95% at an approximate plasma concentration of less than 100 mcg/mL and decreases to approximately 85% at a plasma concentration of 300 mcg/mL. However, protein binding is not deleterious to ertapenem's in-vivo efficacy against organisms for which the MICs are low. Ertapenem distributes into human breast milk and crosses the rat placental barrier. Activity is maintained by the parent drug until the beta-lactam ring is hydrolyzed resulting in an inactive metabolite. Ertapenem is not a substrate for P-glycoprotein-mediated transport. It is eliminated via the kidney. Approximately 80% is recovered in the urine, roughly 38% as unchanged drug and 37% as the inactive metabolite; 10% is recovered in the feces. The elimination half-life of ertapenem in healthy young adults in approximately 4 hours.
Affected cytochrome P450 isoenzymes: none
In vitro studies have shown that ertapenem does not inhibit metabolism mediated by cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4. In vitro studies have also shown that it does not inhibit P-glycoprotein-mediated transport of digoxin or vinblastine.
-Route-Specific Pharmacokinetics
Intravenous Route
Accumulation of ertapenem does not occur following multiple IV doses in healthy adults.
Intramuscular Route
Absorption of ertapenem is almost complete following IM administration with mean bioavailability of 90%. Peak plasma concentrations following a 1 g dose are achieved in roughly 2.3 hours. Accumulation does not occur following multiple IM doses in healthy adults.
-Special Populations
Hepatic Impairment
The pharmacokinetics of ertapenem in patients with hepatic impairment have not been established; however, ertapenem does not appear to undergo hepatic metabolism based on studies.
Renal Impairment
The unbound AUC of ertapenem increased 1.5- and 2.3-fold in adult patients with mild and moderate renal impairment, respectively. The unbound AUC increased 4.4- and 7.6-fold in adult patients with advanced renal impairment and end-stage renal disease, respectively. Approximately 30% of a dose given immediately prior to dialysis is cleared by a 4-hour hemodialysis session. There are no pharmacokinetic data in pediatric patients with renal impairment.
Pediatrics
Adolescents
In pediatric patients 13 to 17 years of age, the pharmacokinetic parameters of ertapenem are similar to those of young, healthy adults. The mean half-life is approximately 4 hours. The volume of distribution is 0.16 L/kg, which is comparable to the adult volume of distribution of 0.12 L/kg.
Infants and Children
In pediatric patients 3 months to 12 years of age, the plasma clearance of ertapenem is approximately 2-fold higher than adults; the mean half-life is approximately 2.5 hours. The volume of distribution is approximately 0.2 L/kg.
Geriatric
The total and unbound AUC increased 37% and 67%, respectively, in elderly adults (n = 14) as compared to young adults in clinical trials. These changes were likely due to age-related changes in creatinine clearance. No dosage adjustments are recommended based on age.
Gender Differences
Differences observed in the pharmacokinetics of ertapenem between healthy male and female patients could be attributed to body size when body weight was taken into consideration. No dosage adjustment are recommended.