Meropenem is an intravenous semisynthetic carbapenem antibiotic. Although similar to imipenem, meropenem does not require concomitant administration of a renal enzyme inhibitor (e.g., cilastatin). Meropenem is used for the treatment of complicated intraabdominal infections and skin and skin structure infections in adult and pediatric patients and for bacterial meningitis in children. The spectrum of activity of meropenem is very similar to imipenem although meropenem is more active against Enterobacteriaceae, Haemophilus influenzae, gonococcus, and Pseudomonas aeruginosa. Meropenem may also have a lower incidence of adverse drug reactions than imipenem. Meropenem was approved by the FDA in June 1996.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Tuberculosis patients*
-Directly observed therapy (DOT) is recommended for all children as well as adolescents and adults living with HIV.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Intermittent Intravenous (IV) Infusion
Powder Vials for Injection
Reconstitution
-Reconstitute 500 mg or 1 g vials with 10 or 20 mL of Sterile Water for Injection, respectively, for a resultant concentration of approximately 50 mg/mL. Shake to dissolve and let stand until clear.
-Alternatively, vials may be directly reconstituted with 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a concentration ranging from 1 to 20 mg/mL.
-Storage: Storage requirements for reconstituted solutions are dependent on the diluent used. Do not freeze.
-Sterile Water for Injection: Stable up to 3 hours at controlled room temperature 25 degrees C (77 degrees F) or up to 13 hours at 5 degrees C (41 degrees F).
-0.9% Sodium Chloride Injection: Stable up to 1 hour at controlled room temperature 25 degrees C (77 degrees F) or up to 15 hours at 5 degrees C (41 degrees F).
-5% Dextrose Injection: Use immediately.
Dilution
-If reconstituted with Sterile Water for Injection, further dilute the reconstituted solution 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a concentration ranging from 1 to 20 mg/mL.
-Storage: Storage requirements for reconstituted solutions are dependent on the diluent used. Do not freeze.
-0.9% Sodium Chloride Injection: Stable up to 1 hour at controlled room temperature 25 degrees C (77 degrees F) or up to 15 hours at 5 degrees C (41 degrees F).
-5% Dextrose Injection: Use immediately.
Duplex Drug Delivery System
-For administration in patients who require the entire 500 mg or 1 g dose and not any fraction of the dose.
-Use only if container and seals are intact.
-To inspect the drug powder for foreign matter or discoloration, peel the foil strip from the drug chamber. Protect from light after removal of foil strip.
-Allow the product to reach room temperature before patient use.
-Unfold Duplex container and point the set port downward. Starting at the hanger tab end, fold the Duplex container just below the diluent meniscus trapping all air above the fold.
-To activate, squeeze the folded diluent chamber until the seal between the diluent and powder opens, releasing diluent into the drug powder chamber.
-Agitate the liquid-powder mixture until the drug powder completely dissolves.
-Storage: If the foil strip is removed and the container will not be used immediately, refold container and latch the side tab until ready to activate; use within 7 days at room temperature. After reconstitution (activation), use within 1 hour if stored at room temperature or within 15 hours if stored under refrigeration.
Intermittent IV Infusion
-Infuse IV over 15 to 30 minutes.
-Do not use in series connections.
Intermittent Extended IV Infusion*
NOTE: Administration by extended infusion is not FDA-approved.
-Administering as an extended infusion (3- to 4-hour infusion) may increase the likelihood of pharmacodynamic target achievement in difficult to treat infections.
Intravenous (IV) Push
Powder Vials for Injection
Reconstitution
-Reconstitute 500 mg or 1 g vials with 10 or 20 mL of Sterile Water for Injection, respectively, for a resultant concentration of approximately 50 mg/mL.
-Shake to dissolve and let stand until clear.
-Storage: Stable for up to 3 hours at controlled room temperature 25 degrees C (77 degrees F) or up to 13 hours at 5 degrees C (41 degrees F).
Intermittent IV Push
-Inject doses up to 1 g (Max concentration: 50 mg/mL) IV over 3 to 5 minutes.
Continuous Intravenous (IV) Infusion*
NOTE: Meropenem is not FDA-approved for administration as a continuous intravenous infusion.
Powder Vials for Injection
Reconstitution
-Reconstitute 1 g vials with 20 mL of Sterile Water for Injection, respectively, for a resultant concentration of approximately 50 mg/mL. Shake to dissolve and let stand until clear.
Dilution
-3 g/day continuous IV infusion: Further dilute in 50 mL or 250 mL of 0.9% Sodium Chloride Injection and administer over 8 hours. For continuous infusion, administer a new infusion bag every 8 hours.
-4 g/day continuous IV infusion: Further dilute in 100 mL of 0.9% Sodium Chloride Injection and administer over 6 hours. For continuous infusion, administer a new infusion bag every 6 hours.
-3 g/day IV continuous infusion in ambulatory infusion pump with freezer packs: Reconstitute 1 g vial according to manufacturer recommendations by adding 20 mL of 0.9% Sodium Chloride Injection to each vial. Add 3 g (60 mL) to a 100 mL medication cassette reservoir and bring the final volume to 100 mL (final concentration, 30 mg/mL). Administer over 24 hours.
Stability of Continuous IV Infusion Solutions
-Although specific stability studies were not completed, clinical studies comparing continuous infusion to intermittent infusions of meropenem suggest similar serum concentrations between the 2 groups and possibly more therapeutic benefit.
-A stability study of meropenem diluted to 1 mg/mL and 20 mg/mL with Sterile Water for Injection or 0.9% Sodium Chloride Injection found that concentrations did not decrease below the allowable concentrations (95% of initial concentration) when stored at room temperature in polyvinyl chloride bags, but did fall below 95% of initial concentrations by 8 hours. However, when these same solutions were stored at 4 to 5 degrees C, the concentration was more than 95% of initial at 24 hours. When stored at room temperature at a concentration of 2.5 mg/mL in 0.9% Sodium Chloride Injection in glass vials, more than 95% of the initial concentration was remaining at 8 hours; however, when mixed in Sterile Water for Injection or 5% Dextrose Injection in glass vials, more than 95% of the concentration was NOT remaining after 4 hours and 3 hours, respectively. When diluted in 0.9% Sodium Chloride Injection and stored in the Baxter Minibag Plus system at room temperature, more than 95% of the initial concentration remained at 4 hours. When stored at 4 to 5 degrees C, however, more than 95% of the initial concentration remained after 24 hours (20 mg/mL concentration). When diluted in 5% Dextrose Injection and stored in the Baxter Minibag Plus system at 4 to 5 degrees C, more than 95% of the initial concentration remained after 8 hours (2.5 mg/mL concentration only).
-Continuous ambulatory infusion pump with freezer packs: An open-label, multidose study in 7 cystic fibrosis patients analyzed the stability of meropenem administered via a continuous ambulatory infusion pump stored between 2 freezer packs designed to maintain a refrigerated temperature of 5 degrees C or less. Current manufacturer recommendations state that meropenem is stable in 0.9% Sodium Chloride Injection at 4 degrees C for 24 hours. The mean recovery of meropenem 30 mg/mL (starting concentration) at 12 to 16 hours was 102.9% with no cassette having a concentration of less than 90% of the original concentration. At 24 to 28 hours, the mean recovery of meropenem was 103.3%, but 1 cassette had a concentration of 86.3% of the initial concentration. The temperature of meropenem was not measured.
In a retrospective cohort study of 5,566 infants < 3 months old, the rates of overall laboratory adverse events (increased creatinine, hyperbilirubinemia, and increased liver enzymes) were higher with meropenem compared with imipenem; cilastatin (odds ratio (OR) 1.41; 95% CI: 1.28 to 1.55); however, the probability of severe adverse events such as death or the combined outcome of death or seizure was significantly lower in infants treated with meropenem compared with those treated with imipenem; cilastatin (OR 0.68; 95% CI: 0.5 to 0.88 and OR 0.77; 95% CI: 0.62 to 0.95, respectively).
The most commonly reported adverse reactions associated with meropenem use involve the gastrointestinal (GI) tract. The most common GI-related adverse reactions include diarrhea (4.8% to 7% adults; 3.5% to 6% pediatrics), nausea (3.6% to 7.8% adults; 0.8 to 4%% pediatrics), vomiting (3.6% adults; 0.8% to 3% pediatrics), and constipation (1.4% to 7% adults; 0.2% or less in pediatrics). Other GI-related events occurring in up to 1% of adults in clinical trials were abdominal pain, abdominal enlargement, anorexia, flatulence, ileus, dyspepsia, and GI obstruction. Unspecified gastrointestinal disorder was reported in more than 1% of adults.
Nervous system and psychiatric adverse events have been reported with meropenem therapy. Headache has been reported in up to 4% of pediatric patients in clinical trials; headache was also relatively common in adult clinical trials (2.3% to 7.8%). Other nervous system events occurring in > 0.1 % to <= 1% of adults in clinical trials include insomnia, agitation, delirium, confusion, dizziness, convulsion, nervousness, paresthesias, hallucinations, drowsiness (somnolence), anxiety, depression, and asthenia.
Hematologic adverse events have been reported with meropenem use in both pediatric and adult patients. In a trial of 53 pediatric patients, 2 (3.8%) patients developed thrombocytosis and 1 (1.9%) developed eosinophilia. In other clinical trials in pediatric patients, these adverse events were not reported ; therefore the true incidence of these effects in pediatric patients is not known. In adults being treated with meropenem, anemia occurred in 0.1% to 5.5% of patients. Other hematologic adverse events occurring in > 0.1% to <= 1% of adults in clinical trials include epistaxis (0.2%), GI bleeding (0.5%), hemoperitoneum (0.2%), melena (0.3%), and hypochromic anemia. Eosinophilia, leukocytosis, increased or decreased platelets, decreased white blood cells, decreased hemoglobin and hematocrit, shortened prothrombin time, and shortened partial thromboplastin time were all reported in > 0.2% of patients. Agranulocytosis, positive direct or indirect Coombs test, hemolytic anemia, neutropenia, and leukopenia were reported in worldwide post-marketing surveillance reports. Thrombocytopenia has been reported in patients with renal impairment, but no clinical bleeding has been reported.
An injection site reaction may occur with meropenem administration; monitor the site of administration for irritation and phlebitis. During clinical trials of immunocompetent adults treated for infections outside the CNS, the following local adverse reactions were reported: inflammation at the injection site (2.4%), injection site reaction (0.9%), phlebitis/thrombophlebitis (0.8%), pain at the injection site (0.4%), and edema at the injection site (0.2%).
During clinical trials with meropenem, rash (unspecified) was reported in 1.9% of adults and 1.6% to 6% of pediatric patients, and pruritus was reported in 1.2% of adults. Diaper dermatitis (moniliasis) is the most common type of rash in young patients. Other hypersensitivity or skin adverse events occurring in up to 1% of adults in clinical trials include urticaria, sweating/diaphoresis, and skin ulcer. Severe cutaneous adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme, and acute generalized exanthematous pustulosis (AGEP) have occurred in patients receiving meropenem. Discontinue meropenem immediately and consider alternative therapy if signs and symptoms suggestive of these reactions occur. Angioedema has also been reported in postmarketing experience with meropenem. Anaphylactoid reactions have been reported in patients receiving beta-lactam therapy.
Hepatic adverse events have been reported with meropenem therapy. During adult clinical trials, hepatic adverse events that were reported in > 0.1% to <= 1% of patients include cholestasis with jaundice and hepatic failure. Elevated hepatic enzymes were reported in > 0.2% of adult patients and include ALT, AST, alkaline phosphatase, LDH, and bilirubin. Elevated hepatic enzymes is 1 of the more common laboratory adverse effects reported with meropenem use in pediatric patients. In a clinical study of 200 neonates and infants < 91 days of age with suspected or confirmed complicated intra-abdominal infections, elevated hepatic enzymes (increased AST) were reported in 3% of patients who received meropenem. Hyperbilirubinemia was noted in 5% of patients. In another retrospective cohort study of 5,566 infants < 3 months old, elevated hepatic enzymes (increased AST or ALT) were reported in 6.9% of the 3,479 infants who received meropenem. Hyperbilirubinemia was also reported (30.2/1,000 infant days), and was the most commonly observed laboratory adverse event with meropenem. In a study in children with cystic fibrosis (n = 102), increased AST and ALT were reported in 14% and 12% of patients who received meropenem/tobramycin, respectively, and increased alkaline phosphatase was reported in 8% of patients. The contribution of the patients' cystic fibrosis to these elevations is unclear. In another trial of 53 pediatric patients with serious bacterial infections, elevated hepatic enzymes occurred in 3.8% to 7.5% of patients.
In general, cardiovascular adverse events are not common with meropenem therapy. In a clinical study of 200 neonates and infants < 91 days of age with suspected or confirmed complicated intra-abdominal infections, hypotension was noted in 3% of patients who received meropenem. During adult clinical trials, shock was reported in 1.2% of patients. Other cardiovascular adverse events that were reported in > 0.1% to <= 1% of adult patients include bradycardia, chest pain (unspecified), heart failure, cardiac arrest, hypertension, hypervolemia, myocardial infarction, peripheral edema, sinus tachycardia, and syncope. Peripheral vascular disorder was reported in > 1% of adult patients in trials.
Respiratory adverse events have been reported with meropenem therapy. During clinical trials of immunocompetent adults treated for infections outside the CNS, apnea was reported in 1.3% of patients. Respiratory adverse events that were reported in > 0.1% to <= 1% of adult patients include asthma, increased cough, dyspnea, hypoxia, pulmonary edema, pulmonary embolism, pleural effusion, and respiratory disorder (unspecified).
Renal adverse events have been reported with meropenem therapy. Dysuria, renal failure (unspecified), and urinary incontinence were reported in > 0.1% to <= 1% of adult patients in clinical trials. An increase in creatinine and BUN (azotemia) was reported in > 0.2% of adult patients in trials. Increased creatinine (> 1.7 mg/dL) was commonly reported (24/1,000 infant days) in patients who received meropenem (n = 3,479; 38,705 infant days) in a retrospective cohort study of 5,566 infants < 3 months old. Because dosage adjustments are necessary in patients with renal impairment, renal function should be periodically monitored during therapy to avoid toxicity.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with meropenem. 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. During adult clinical trials, sepsis was reported in 1.6% of patients. Other infection-related adverse events that were reported in up to 1% of adult patients include chills and fever. Pharyngitis and pneumonia were noted in more 1% of adult patients. Candidiasis (oral and vaginal) was reported in up to 1% of adults, diaper area candidiasis was noted in 3.1% of pediatric patients, and oral candidiasis occurred in 1.9% of pediatric patients. Glossitis was reported in 1% of pediatric patients. In a trial of 200 neonates and infants younger than 91 days of age with suspected or confirmed complicated intra-abdominal infections, 6% of patients who received meropenem developed sepsis. Pharyngitis was reported in 6% of children with cystic fibrosis who received meropenem/tobramycin in a clinical study (n = 102).
During clinical trials of meropenem in adults, pain (unspecified) was reported in 5.1% of patients and back pain and pelvic pain were reported in <= 1% but > 0.1% of patients. Accidental injury was noted in > 1% of patients.
Seizures and other CNS adverse experiences have been reported during treatment with meropenem and have occurred most commonly in patients with CNS disorders (e.g., brain lesions or history of seizures) or with bacterial meningitis and/or compromised renal function. According to the manufacturer, during clinical trials of 2904 immunocompetent adults treated for infections outside the CNS, seizure was reported in 0.7% of patients (20 patients). All patients who experienced a seizure had a preexisting contributing factor such as prior history of seizure disorder, CNS abnormality, or concomitant therapy with medications with seizure potential. In a safety review of over 6000 patients treated with meropenem, one seizure was reported in patients with infections other than meningitis, which was determined by investigators not to be treatment-related. In a pediatric bacterial meningitis study involving 137 children, there were no reports of seizures that were considered treatment-related. According to the manufacturer, in pediatric meningitis patients, the rates of seizure activity during meropenem therapy in patients with no CNS abnormalities were comparable to those who received comparator agents (ceftriaxone or cefotaxime). In patients with known predisposing factors for seizure activity, close adherence to the recommended dosage regimen is encouraged. Dosage adjustment is recommended for patients with reduced renal function (see Dosage). Anticonvulsant therapy should be continued in patients with known seizure disorders. If focal tremors, myoclonus, or seizures occur, patients should be evaluated neurologically, placed on anticonvulsant therapy if not already instituted; additionally, the dose of meropenem should be evaluated to determine if a decrease in dose or discontinuation of therapy is warranted.
Hypoglycemia was reported in > 1% and hypokalemia in > 0.1% to <= 1% of adults in meropenem clinical trials. In a clinical trial of 200 neonates and infants < 91 days of age with suspected or confirmed complicated intra-abdominal infections, hyperglycemia and hypoglycemia were each reported in 3% of patients who received meropenem; hypokalemia was reported in 5%.
Meropenem is contraindicated in persons with known meropenem hypersensitivity, a history of carbapenem hypersensitivity, or a previous anaphylactic reaction to beta-lactams. Because of the potential for cross-sensitivity, caution is advised in persons with cephalosporin hypersensitivity, penicillin hypersensitivity, or hypersensitivity to any beta-lactam antibiotic. Serious and occasionally fatal hypersensitivity reactions have been reported in persons receiving therapy with beta-lactams and are more likely to occur in persons with a history of sensitivity to multiple allergens.
Use meropenem cautiously in patients with brain lesions, a history of seizure disorder, or other neurological disease or condition that may lower the seizure threshold, such as head trauma or bacterial meningitis. Seizures have been reported with meropenem use and have occurred most commonly in patients with these types of conditions; however, the risk of seizures appears to be low and is thought to be less than the risk associated with imipenem; cilastatin. The risk of seizures increases in patients given meropenem doses higher than recommended (e.g., patients with compromised renal function) or patients receiving concomitant medications with seizure potential.
Use meropenem cautiously in patients with renal impairment or renal failure because the drug is primarily eliminated by the kidneys. These patients are at higher risk for developing seizures while receiving meropenem. Thrombocytopenia has also been reported in patients with renal function impairment, although clinical bleeding has not been reported. Dosage adjustments are required in patients with renal impairment.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including meropenem, 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.
Meropenem may be associated with laboratory test interference. Positive Coombs' tests have been reported in patients receiving meropenem. In patients receiving meropenem and undergoing hematologic testing, a positive Coombs' test should be considered as possibly being caused by the antibiotic. A false-positive reaction for glucose in the urine has been observed in patients receiving beta-lactam antibiotics, including carbapenems, and using copper-reduction tests (e.g., Benedict's solution, Fehling's solution, and Clinitest tablets). This reaction, however, has not been observed with glucose oxidase tests (e.g., Tes-tape, Clinistix, Diastix).
Neuromotor impairment, including seizures, delirium, headache, and/or paresthesias may occur in patients receiving meropenem. Patients should avoid driving or operating machinery until drug tolerability has been established.
There are insufficient data to establish whether there is a drug-associated risk of major birth defects or miscarriages with meropenem use in human pregnancy. No teratogenic effects have been demonstrated in animals given meropenem intravenously at doses up to 3.2 times the maximum recommended human dose (MRHD) based on body surface area comparison.
Avoid sodium-containing meropenem formulations in patients who are particularly sensitive to sodium intake (e.g., elderly, patients with heart failure) or who may require sodium restriction.
Meropenem is excreted in human breast milk; however, no information is available on the effects of meropenem on the breast-fed child or on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for meropenem and any potential adverse effects on the breast-fed child from meropenem or the underlying maternal condition. In case reports in which meropenem was used during breast-feeding, no adverse events were reported in the infants.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Aeromonas hydrophila, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus, Campylobacter jejuni, Citrobacter freundii, Citrobacter koseri, Clostridioides difficile, Clostridium perfringens, Cutibacterium acnes, Eggerthella lenta, Enterobacter cloacae, Enterococcus faecalis, Escherichia coli, Fusobacterium sp., Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Morganella morganii, Neisseria meningitidis, Parabacteroides distasonis, Pasteurella multocida, Peptostreptococcus sp., Porphyromonas asaccharolytica, Prevotella bivia, Prevotella intermedia, Prevotella melaninogenica, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Viridans 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 intraabdominal infections, including peritonitis, appendicitis, intraabdominal abscess, biliary tract infections (cholecystitis, cholangitis), neonatal necrotizing enterocolitis, spontaneous bacterial peritonitis*, and peritoneal dialysis-related peritonitis*:
-for the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections with adequate source control:
Intravenous dosage:
Adults: 1 to 2 g IV every 8 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 3 to 7 days. Higher doses (40 mg/kg/dose IV every 8 hours) have been used in patients with severe infections. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours for 7 to 10 days. Meropenem is an option for necrotizing enterocolitis.
-for the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections with adequate source control due to resistant gram-negative organisms using extended-infusion dosing*:
Intravenous dosage:
Adults: 2 g administered over 3 hours IV every 8 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) administered over 3 to 4 hours IV every 8 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*:
Intravenous dosage:
Adults: 1 to 2 g IV every 8 hours. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. 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 spontaneous bacterial peritonitis*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for at least 5 to 7 days.
-for the treatment of peritoneal dialysis-related peritonitis*:
Intermittent Intraperitoneal dosage*:
Adults: 1 g intraperitoneally every 24 hours for 21 to 28 days.
For the treatment of meningitis and ventriculitis*, including infections due to resistant gram-negative organisms*:
-for the treatment of meningococcal meningitis as well as meningitis due to H. influenzae:
Intravenous dosage:
Adults*: 2 g IV every 8 hours for 7 days.
Infants, Children, and Adolescents 3 months to 17 years: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 7 days.
Infants 1 to 2 months*: 40 mg/kg/dose IV every 8 hours for 7 days.
Neonates 32 weeks gestation and older*: 40 mg/kg/dose IV every 8 hours for 7 days.
Neonates younger than 32 weeks gestation and 14 days and older*: 40 mg/kg/dose IV every 8 hours for 7 days.
Neonates younger than 32 weeks gestation and 0 to 13 days*: 40 mg/kg/dose IV every 12 hours for 7 days.
-for the treatment of pneumococcal meningitis or ventriculitis*:
Intravenous dosage:
Adults*: 2 g IV every 8 hours for 10 to 14 days.
Infants, Children, and Adolescents 3 months to 17 years: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 10 to 14 days.
Infants 1 to 2 months*: 40 mg/kg/dose IV every 8 hours for 10 to 14 days.
Neonates 32 weeks gestation and older*: 40 mg/kg/dose IV every 8 hours for 10 to 14 days.
Neonates younger than 32 weeks gestation and 14 days and older*: 40 mg/kg/dose IV every 8 hours for 10 to 14 days.
Neonates younger than 32 weeks gestation and 0 to 13 days*: 40 mg/kg/dose IV every 12 hours for 10 to 14 days.
-for the treatment of meningitis due to L. monocytogenes*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for at least 21 days.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for at least 21 days.
Neonates 32 weeks gestation and older: 40 mg/kg/dose IV every 8 hours for at least 21 days.
Neonates younger than 32 weeks gestation and 14 days and older: 40 mg/kg/dose IV every 8 hours for at least 21 days.
Neonates younger than 32 weeks gestation and 0 to 13 days: 40 mg/kg/dose IV every 12 hours for at least 21 days.
-for the treatment of meningitis or ventriculitis due to methicillin-sensitive S. aureus (MSSA)*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 10 to 14 days.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 10 to 14 days.
Neonates 32 weeks gestation and older: 40 mg/kg/dose IV every 8 hours for 10 to 14 days.
Neonates younger than 32 weeks gestation and 14 days and older: 40 mg/kg/dose IV every 8 hours for 10 to 14 days.
Neonates younger than 32 weeks gestation and 0 to 13 days: 40 mg/kg/dose IV every 12 hours for 10 to 14 days.
-for the treatment of meningitis or ventriculitis due to susceptible gram-negative organisms*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 10 to 21 days.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 10 to 21 days.
Neonates 32 weeks gestation and older: 40 mg/kg/dose IV every 8 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Neonates younger than 32 weeks gestation and 14 days and older: 40 mg/kg/dose IV every 8 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Neonates younger than 32 weeks gestation and 0 to 13 days: 40 mg/kg/dose IV every 12 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
-for the treatment of meningitis or ventriculitis due to resistant gram-negative organisms*:
Intravenous dosage:
Adults: 2 g IV administered over 3 hours every 8 hours for 10 to 21 days.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV administered over 3 hours every 8 hours for 10 to 21 days.
Neonates 32 weeks gestation and older: 40 mg/kg/dose IV administered over 3 hours every 8 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Neonates younger than 32 weeks gestation and 14 days and older: 40 mg/kg/dose IV administered over 3 hours every 8 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Neonates younger than 32 weeks gestation and 0 to 13 days: 40 mg/kg/dose IV administered over 3 hours every 12 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
For the treatment of complicated skin and skin structure infections, including cellulitis, erysipelas, necrotizing infections, diabetic foot ulcer, pyomyositis, and surgical incision site infections:
-for the treatment of severe complicated skin and skin structure infections, such as cellulitis and erysipelas:
Intravenous dosage:
Adults: 500 mg to 1 g IV every 8 hours for 5 to 14 days.
Infants, Children, and Adolescents 3 months to 17 years: 10 to 20 mg/kg/dose (Max: 1 g/dose) IV every 8 hours for 5 to 14 days.
Infants 1 to 2 months*: 10 to 20 mg/kg/dose IV every 8 hours for 5 to 14 days.
Neonates 32 weeks gestation and older and 14 days and older*: 30 mg/kg/dose IV every 8 hours for 5 to 14 days.
Neonates 32 weeks gestation and older and 0 to 13 days*: 20 mg/kg/dose IV every 8 hours for 5 to 14 days.
Neonates younger than 32 weeks gestation and 14 days and older*: 20 mg/kg/dose IV every 8 hours for 5 to 14 days.
Neonates younger than 32 weeks gestation and 0 to 13 days*: 20 mg/kg/dose IV every 12 hours for 5 to 14 days.
-for the treatment of complicated skin and skin structure infections due to resistant gram-negative organisms using extended infusion dosing*:
Intravenous dosage:
Adults: 2 g administered over 3 hours IV every 8 hours.
-for the treatment of necrotizing infections of the skin, fascia, and muscle:
Intravenous dosage:
Adults: 1 g IV every 8 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, Children, and Adolescents 3 months to 17 years: 20 mg/kg/dose (Max: 1 g/dose) IV every 8 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*: 20 mg/kg/dose IV every 8 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.
Neonates 32 weeks gestation and older and 14 days and older*: 30 mg/kg/dose IV every 8 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.
Neonates 32 weeks gestation and older and 0 to 13 days*: 20 mg/kg/dose IV every 8 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.
Neonates younger than 32 weeks gestation and 14 days and older*: 20 mg/kg/dose IV every 8 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.
Neonates younger than 32 weeks gestation and 0 to 13 days*: 20 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 diabetic foot ulcer:
Intravenous dosage:
Adults: 500 mg to 1 g IV every 8 hours for 7 to 14 days for moderate or severe infections in patients with risk factors for resistant gram negative rods, ischemic limb/necrotizing/gas forming infections, or a macerated ulcer or in a warm climate. 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: 500 mg to 1 g IV every 8 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.
Infants, Children, and Adolescents 3 months to 17 years: 10 to 20 mg/kg/dose (Max: 1 g/dose) IV every 8 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.
Infants 1 to 2 months*: 10 to 20 mg/kg/dose IV every 8 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 8 hours for incisional surgical site infections of the intestinal or genitourinary tract.
For the empiric treatment of febrile neutropenia*:
-for the treatment of febrile neutropenia in adults*:
Intravenous dosage:
Adults: 1 gram IV every 8 hours has been studied for febrile neutropenia. Guidelines recommend an antipseudomonal beta-lactam, such as meropenem, as a first line therapy option with or without an aminoglycoside and/or vancomycin as a treatment option for febrile neutropenia. Alternatively, 500 mg IV every 6 hours has shown similar clinical efficacy in hospitalized patients with a variety of infections (including febrile neutropenia) and based on Monte Carlo simulations, achieves pharmacodynamic endpoints equivalent to the manufacturer's recommended dose.
-for the treatment of febrile neutropenia in pediatric patients*:
Intravenous dosage:
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 1 g/dose) IV every 8 hours. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.
-for the treatment of febrile neutropenia due to resistant gram-negative organisms using extended infusion dosing*:
Intravenous dosage:
Adults: 2 g IV administered over 3 hours every 8 hours.
For the treatment of bacteremia*, catheter-associated infections*, and sepsis*, including infections with difficult-to-treat resistance*:
-for the treatment of unspecified bacteremia* and catheter-associated infections*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for 7 to 14 days.
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours. Consider 40 mg/kg/dose IV every 12 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
-for the treatment of unspecified sepsis*:
Intravenous dosage:
Adults: 2 g IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours. Consider 40 mg/kg/dose IV every 12 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
-for the treatment of bacteremia* and catheter-associated infections* due to infections with difficult-to-treat resistance using extended-infusion dosing*:
Intravenous dosage:
Adults: 2 g IV administered over 3 hours every 8 hours for 7 to 14 days.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV administered over 3 to 4 hours every 8 hours.
-for the treatment of sepsis* due to infections with difficult-to-treat resistance using extended-infusion dosing*:
Intravenous dosage:
Adults: 2 g IV administered over 3 hours every 8 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV administered over 3 to 4 hours every 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
For the treatment of anthrax*:
-for the treatment of cutaneous anthrax* without aerosol exposure or signs and symptoms of meningitis:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy.
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy.
Neonates 34 weeks gestation and older: 20 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy.
Neonates 32 to 33 weeks gestation and 7 days and older: 20 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy.
Neonates 32 to 33 weeks gestation and 0 to 6 days: 13.3 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy.
- for the treatment of cutaneous anthrax* with aerosol exposure and without signs and symptoms of meningitis:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 42- to 60-day total treatment course depending on vaccine status and immunocompetence.
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 34 weeks gestation and older: 20 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 32 to 33 weeks gestation and 7 days and older: 20 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 32 to 33 weeks gestation and 0 to 6 days: 13.3 mg/kg/dose IV every 8 hours for 7 to 10 days or until clinical criteria for stability are met; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
-for the treatment of systemic anthrax* without aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous dosage:
Adults: 2 g IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Neonates 34 weeks gestation and older: 20 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Neonates 32 to 33 weeks gestation and 7 days and older: 20 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Neonates 32 to 33 weeks gestation and 0 to 6 days: 13.3 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
-for the treatment of systemic anthrax* with aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous dosage:
Adults: 2 g IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Immunocompromised Adults: 2 g IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Immunocompromised Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Neonates 34 weeks gestation and older: 20 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Neonates 32 to 33 weeks gestation and 7 days and older: 20 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Neonates 32 to 33 weeks gestation and 0 to 6 days: 13.3 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
For the treatment of community-acquired pneumonia* (CAP), nosocomial pneumonia*, and pleural empyema*:
-for the treatment of community-acquired pneumonia (CAP)*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for at least 7 days.
Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 5 to 7 days.
-for the treatment of nosocomial pneumonia*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for 7 days.
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours. Consider 40 mg/kg/dose IV every 12 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections.
-for the treatment of hospital-acquire or postprocedural pleural empyema*:
Intravenous dosage:
Adults: 1 g IV every 8 hours. Use in combination with vancomycin for at least 2 weeks after drainage and defervescence.
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. Use in combination with vancomycin for at least 2 weeks after drainage and defervescence.
-for the treatment of pneumonia, including infections due to resistant gram-negative organisms, using extended-infusion dosing*:
Intravenous dosage:
Adults: 2 g administered over 3 hours IV every 8 hours for at least 7 days.
Infants, Children, and Adolescents: 40 mg/kg/dose (Max: 2 g/dose) administered over 3 to 4 hours IV every 8 hours.
For the treatment of drug-resistant tuberculosis infection* paired with clavulanic acid as part of combination therapy:
Intravenous dosage:
Adults: 1 g IV every 8 hours or 2 g IV every 8 to 12 hours.
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.
For the treatment of severe or complicated extensively drug-resistant typhoid fever*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for 10 to 14 days. Consider adding azithromycin for patients who do not improve.
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 1 g/dose) IV every 8 hours for 10 to 14 days. Consider adding azithromycin for patients who do not improve.
For the treatment of urinary tract infection (UTI)*, including cystitis*, pyelonephritis*, catheter-associated urinary tract infection*, and infections with difficult-to-treat resistance*:
-for the treatment of uncomplicated cystitis due to infections with difficult-to-treat resistance*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for 3 to 7 days.
-for the treatment of complicated UTI, including pyelonephritis*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for 7 to 14 days.
Adults with obesity: 1 to 2 g IV administered over 3 hours every 8 hours for 7 to 14 days.
-for the treatment of complicated UTI, including pyelonephritis, due to infections with ESBL or Amp-C-related resistance*:
Intravenous dosage:
Adults: 1 to 2 g IV every 8 hours for 7 to 14 days.
Adults with obesity: 1 to 2 g IV administered over 3 hours every 8 hours for 7 to 14 days.
-for the treatment of complicated UTI, including pyelonephritis, due to infections with CRE or CRAB-related resistance using extended infusion dosing*:
Intravenous dosage:
Adults: 2 g IV administered over 3 hours every 8 hours for 7 to 14 days.
-for the treatment of catheter-associated UTI*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for 7 to 14 days. A single dose prior to oral therapy may be used in patients not requiring hospitalization.
Adults with obesity: 1 to 2 g IV administered over 3 hours every 8 hours for 7 to 14 days. A single dose prior to oral therapy may be used in patients not requiring hospitalization.
For the treatment of bone and joint infections*, including osteomyelitis*, infectious arthritis*, orthopedic device-related infection*, and infections with difficult-to-treat resistance:
-for the treatment of unspecified osteomyelitis*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for 4 to 6 weeks.
Infants, Children, and Adolescents 3 months to 17 years: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Infants 1 to 2 months: 20 to 40 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours. Consider 40 mg/kg/dose IV every 12 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
-for the treatment of native vertebral osteomyelitis*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for 6 weeks as first-line therapy for infections due to P. aeruginosa. May consider addition of ciprofloxacin or aminoglycoside for P. aeruginosa infections.
-for the treatment of infectious arthritis*:
Intravenous dosage:
Adults: 1 g IV every 8 hours. Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks.
Infants, Children, and Adolescents 3 months to 17 years: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Infants 1 to 2 months: 20 to 40 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 14 days and older: 30 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 0 to 13 days: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 32 weeks gestation and 14 days and older: 20 mg/kg/dose IV every 8 hours. Consider 40 mg/kg/dose IV every 8 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 32 weeks gestation and 0 to 13 days: 20 mg/kg/dose IV every 12 hours. Consider 40 mg/kg/dose IV every 12 hours for severe infections due to Pseudomonas sp. or other more resistant organisms; pharmacokinetic data in neonates (including premature neonates) have suggested the need for the higher dose to achieve optimal pharmacodynamic targets for these infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
-for the treatment of prosthetic joint infections*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for 4 to 6 weeks, which may be followed by long-term suppressive therapy. May consider addition of an aminoglycoside for P. aeruginosa infections; if aminoglycoside is in spacer and organism is aminoglycoside-susceptible, then double coverage is provided with IV or oral monotherapy.
-for the treatment of bone and joint infections with difficult-to-treat resistance using extended infusion dosing*:
Intravenous dosage:
Adults: 2 g administered over 3 hours IV every 8 hours.
For the treatment of bronchiectasis*:
-for the treatment of acute exacerbations of bronchiectasis*:
Intravenous dosage:
Adults: 1 to 2 g IV every 8 hours for 14 days with or without an aminoglycoside.
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 14 days with or without an aminoglycoside.
-for the eradication of first or new isolates of Pseudomonas aeruginosa in patients with bronchiectasis*:
Intravenous dosage:
Adults: 1 to 2 g IV every 8 hours for 14 days with or without a systemic aminoglycoside or inhaled antibiotics, followed by inhaled antibiotics for 4 to 12 weeks.
Infants, Children, and Adolescents: 20 to 40 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 14 days with or without a systemic aminoglycoside or inhaled antibiotics, followed by inhaled antibiotics for 4 to 12 weeks.
For the treatment of invasive listeriosis* with bacteremia:
NOTE: For CNS disease, see meningitis indication.
Intravenous dosage:
Adults: 1 to 2 g IV every 8 hours for at least 14 days.
Maximum Dosage Limits:
-Adults
3 g/day IV is FDA-approved maximum; however, doses up to 6 g/day IV have been used off-label.
-Geriatric
3 g/day IV is FDA-approved maximum; however, doses up to 6 g/day IV have been used off-label.
-Adolescents
120 mg/kg/day (Max: 6 g/day) IV.
-Children
120 mg/kg/day (Max: 6 g/day) IV.
-Infants
3 to 11 months : 120 mg/kg/day IV.
1 to 2 months: 90 mg/kg/day IV is FDA-approved maximum; however, doses up to 120 mg/kg/day IV have been used off-label.
-Neonates
Neonates 32 weeks gestation and older and 14 days and older: 90 mg/kg/day IV is FDA-approved maximum; however, doses up to 120 mg/kg/day IV have been used off-label.
Neonates 32 weeks gestation and older and 0 to 13 days: 60 mg/kg/day IV is FDA-approved maximum; however, doses up to 120 mg/kg/day IV have been used off-label.
Neonates younger than 32 weeks gestation and 14 days and older: 60 mg/kg/day IV is FDA-approved maximum; however, doses up to 120 mg/kg/day IV have been used off-label.
Neonates younger than 32 weeks gestation and 0 to 13 days: 40 mg/kg/day IV is FDA-approved maximum; however, doses up to 80 mg/kg/day IV have been used off-label.
Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.
Patients with Renal Impairment Dosing
The following is for dosage adjustment in adults with renal impairment; there is no experience with this drug in children with renal impairment.
CrCl > 50 ml/min: no dose adjustment needed.
CrCl 26-50 ml/min: give the recommended dose every 12 hours.
CrCl 10-25 ml/min: give one-half the recommended dose every 12 hours.
CrCl < 10 ml/min: give one-half the recommended dose every 24 hours.
Intermittent hemodialysis
Meropenem and its metabolite are readily dialyzable and effectively removed by hemodialysis. Supplemental doses should be given after hemodialysis sessions.
Continuous hemodialysis (CVVHD, CVVHDF)
Meropenem and its metabolite are readily dialyzable and effectively removed by hemodialysis. Effective dosing regimens for patients receiving continuous hemodialysis vary from 500 mg IV every 12 hours to 1 g IV every 8 hours. Conflicting data exist regarding the most appropriate meropenem dosing regimen for patients receiving continuous hemodialysis. Differing operational characteristics of continuous hemodialysis (e.g., dialysate flow rate, membrane or filter type) at various centers involved in the studies and whether the goal of the study was to treat infections caused by susceptible or intermediate microorganisms may explain the variable dosing recommendations for continuous hemodialysis.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with meropenem. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and meropenem is a P-gp inhibitor.
Acetaminophen; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with meropenem is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If meropenem is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Meropenem is a weak CYP3A inducer. Concomitant use with meropenem can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Acetaminophen; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of hydrocodone as needed. If meropenem is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of oxycodone as needed. If meropenem is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Afatinib: (Major) Increase the daily dose of afatinib by 10 mg as tolerated if the concomitant use with meropenem is necessary; resume the previous dose of afatinib 2 to 3 days after discontinuation of meropenem. Afatinib is a P-gp substrate and meropenem is a P-gp inducer; coadministration may decrease plasma concentrations of afatinib. Pre-treatment with another strong P-gp inducer decreased afatinib exposure by 34%.
Alfentanil: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with meropenem is necessary. If meropenem is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like meropenem with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Anagrelide: (Moderate) Monitor for decreased efficacy of anagrelide and adjust dose accordingly if concomitant use of meropenem is necessary. Concomitant use may decrease anagrelide exposure; anagrelide is a CYP1A2 substrate and meropenem is a CYP1A2 inducer.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with meropenem is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If meropenem is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Meropenem is a weak CYP3A inducer. Concomitant use with meropenem can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of oxycodone as needed. If meropenem is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atogepant: (Major) Avoid use of atogepant and meropenem when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with meropenem. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and meropenem is a weak CYP3A inducer. Coadministration with a weak CYP3A inducer resulted in a 25% reduction in atogepant overall exposure and a 24% reduction in atogepant peak concentration.
Avanafil: (Major) Coadministration of avanafil with meropenem is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and meropenem is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Avatrombopag: (Major) In patients with chronic immune thrombocytopenia (ITP), increase the starting dose of avatrombopag to 40 mg PO once daily when used concomitantly with meropenem. In patients starting meropenem while receiving avatrombopag, monitor platelet counts and adjust the avatrombopag dose as necessary. Dosage adjustments are not required for patients with chronic liver disease. Avatrombopag is a CYP2C9 and CYP3A substrate, and dual moderate or strong inducers such as meropenem decrease avatrombopag exposure, which may reduce efficacy.
Baricitinib: (Major) Coadministration of baricitinib with meropenem is not recommended due to the potential for increased baricitinib exposure. Baricitinib is an OAT3 substrate and meropenem is a OAT3 inhibitor. In a drug interaction study, coadministration of another strong OAT3 inhibitor increased baricitinib exposure by 2-fold.
Bendamustine: (Major) Consider the use of an alternative therapy if meropenem treatment is needed in patients receiving bendamustine. Concomitant use of meropenem may decrease bendamustine exposure, which may result in decreased efficacy. Bendamustine is a CYP1A2 substrate and meropenem is a CYP1A2 inducer.
Benzhydrocodone; Acetaminophen: (Moderate) Monitor for reduced efficacy of benzhydrocodone and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of benzhydrocodone as needed. If meropenem is discontinued, consider a dose reduction of benzhydrocodone and frequently monitor for signs of respiratory depression and sedation. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Berotralstat: (Major) Avoid coadministration of berotralstat and meropenem. Concurrent use may decrease berotralstat exposure, leading to reduced efficacy. Berotralstat is a P-gp substrate and meropenem is a P-gp inducer.
Betrixaban: (Major) Avoid coadministration of betrixaban and meropenem due to the risk of decreased betrixaban exposure and reduced efficacy. Betrixaban is a P-gp substrate and meropenem is a P-gp inducer.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with meropenem may result in decreased tenofovir exposure, which may result in potential loss of virologic control. Tenofovir alafenamide is a P-gp substrate and meropenem is a P-gp inducer.
Bupivacaine; Lidocaine: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with meropenem is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP1A2 substrate and meropenem is a CYP1A2 inducer.
Buprenorphine: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with meropenem is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If meropenem is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A substrate and meropenem is a CYP3A inducer.
Buprenorphine; Naloxone: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with meropenem is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If meropenem is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A substrate and meropenem is a CYP3A inducer.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with meropenem is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If meropenem is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Meropenem is a weak CYP3A inducer. Concomitant use with meropenem can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with meropenem is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If meropenem is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Meropenem is a weak CYP3A inducer. Concomitant use with meropenem can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Carbamazepine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of meropenem; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A substrate and meropenem is a CYP3A inducer.
Cariprazine: (Major) Coadministration of cariprazine with meropenem is not recommended as the net effect of CYP3A induction on cariprazine and its metabolites is unclear. Cariprazine is a CYP3A substrate and meropenem is a weak CYP3A inducer. Coadministration of cariprazine with CYP3A inducers has not been evaluated.
Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of tramadol as needed. If meropenem is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with meropenem is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If meropenem is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Meropenem is a weak CYP3A inducer. Concomitant use with meropenem can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of hydrocodone as needed. If meropenem is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Clozapine: (Moderate) Monitor for loss of clozapine effectiveness if coadministered with meropenem. Consideration should be given to increasing the clozapine dose if necessary. When meropenem is discontinued, reduce the clozapine dose based on clinical response. Clozapine is a CYP1A2 and CYP3A substrate and meropenem is a weak CYP1A2 and weak CYP3A inducer.
Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with meropenem is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If meropenem is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Meropenem is a weak CYP3A inducer. Concomitant use with meropenem can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Guaifenesin: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with meropenem is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If meropenem is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Meropenem is a weak CYP3A inducer. Concomitant use with meropenem can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with meropenem is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If meropenem is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Meropenem is a weak CYP3A inducer. Concomitant use with meropenem can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with meropenem is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If meropenem is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Meropenem is a weak CYP3A inducer. Concomitant use with meropenem can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Promethazine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with meropenem is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If meropenem is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Meropenem is a weak CYP3A inducer. Concomitant use with meropenem can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Cyclosporine: (Moderate) Closely monitor cyclosporine concentrations and adjust the dose of cyclosporine as appropriate if coadministration with meropenem is necessary. Concurrent use may decrease cyclosporine exposure resulting in decreased efficacy. Cyclosporine is a CYP3A and P-gp substrate and meropenem is a weak CYP3A and P-gp inducer.
Dabigatran: (Major) Coadministration of dabigatran with meropenem should generally be avoided due to the risk of deceased dabigatran exposure which may reduce its efficacy. Dabigatran is a P-gp substrate and meropenem is a P-gp inducer.
Daprodustat: (Moderate) Monitor for a decrease in daprodustat efficacy during concomitant use of daprodustat and meropenem. Concomitant use may decrease daprodustat exposure. Daprodustat is a CYP2C8 substrate and meropenem is a CYP2C8 inducer.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with meropenem may result in decreased tenofovir exposure, which may result in potential loss of virologic control. Tenofovir alafenamide is a P-gp substrate and meropenem is a P-gp inducer.
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.
Diazepam: (Moderate) Monitor patients for decreased efficacy of diazepam if coadministration with meropenem is necessary. Concurrent use may decrease diazepam exposure. Diazepam is a CYP2C19 and CYP3A substrate and meropenem is a CYP2C19 and CYP3A inducer.
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.
Digoxin: (Moderate) Increase monitoring of serum digoxin concentrations when starting, adjusting, or discontinuing meropenem. Concurrent use may decrease digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and meropenem is a P-gp inducer.
Dolutegravir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with meropenem. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and meropenem is a P-gp inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with meropenem. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and meropenem is a P-gp inhibitor.
Dolutegravir; Rilpivirine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with meropenem. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and meropenem is a P-gp inhibitor.
Doravirine: (Minor) Concurrent administration of doravirine and meropenem may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; meropenem is a weak CYP3A inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Concurrent administration of doravirine and meropenem may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; meropenem is a weak CYP3A inducer.
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.
Edoxaban: (Moderate) Monitor for decreased efficacy of edoxaban if coadministration with meropenem is necessary; decreased concentrations of edoxaban may occur with concomitant use. Edoxaban is a P-gp substrate and meropenem is a P-gp inducer.
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.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with meropenem may result in decreased tenofovir exposure, which may result in potential loss of virologic control. Tenofovir alafenamide is a P-gp substrate and meropenem is a P-gp inducer.
Empagliflozin; Linagliptin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and meropenem if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and meropenem is a P-gp inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and meropenem if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and meropenem is a P-gp inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with meropenem may result in decreased tenofovir exposure, which may result in potential loss of virologic control. Tenofovir alafenamide is a P-gp substrate and meropenem is a P-gp inducer.
Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with meropenem may result in decreased tenofovir exposure, which may result in potential loss of virologic control. Tenofovir alafenamide is a P-gp substrate and meropenem is a P-gp inducer.
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.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of meropenem is necessary. If meropenem is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A inducer like meropenem with fentanyl, a CYP3A substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Fezolinetant: (Contraindicated) Concomitant use of fezolinetant and meropenem is contraindicated due the risk of increased fezolinetant exposure which may increase the risk of fezolinetant-related adverse effects. Fezolinetant is a CYP1A2 substrate; meropenem is a weak CYP1A2 inhibitor. Concomitant use with another strong CYP1A2 inhibitor increased fezolinetant overall exposure by 100%.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with coadministration of glecaprevir and meropenem as decreased plasma concentrations of glecaprevir may occur resulting in the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of P-gp and meropenem is a P-gp inducer. (Moderate) Caution is advised with coadministration of pibrentasvir and meropenem as decreased plasma concentrations of pibrentasvir may occur resulting in the potential loss of efficacy of pibrentasvir. Pibrentasvir is a substrate of P-gp and meropenem is a P-gp inducer.
Homatropine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of hydrocodone as needed. If meropenem is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of hydrocodone as needed. If meropenem is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Ibuprofen: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of hydrocodone as needed. If meropenem is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of oxycodone as needed. If meropenem is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Iptacopan: (Moderate) Monitor for a decrease in iptacopan efficacy during concomitant use of iptacopan and meropenem; discontinue use of meropenem if loss of efficacy of iptacopan is evident. Concomitant use may decrease iptacopan exposure. Iptacopan is a CYP2C8 substrate and meropenem is a CYP2C8 inducer.
Isradipine: (Minor) Monitor for decreased efficacy of isradipine if coadministration with meropenem is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A substrate and meropenem is a weak CYP3A inducer.
Ledipasvir; Sofosbuvir: (Major) Coadministration of ledipasvir with meropenem is not recommended. Taking these drugs together may decrease ledipasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Ledipasvir is a P-gp substrate and meropenem is a P-gp inducer. (Major) Coadministration of sofosbuvir with meropenem is not recommended. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Sofosbuvir is a P-gp substrate and meropenem is a P-gp inducer.
Lefamulin: (Major) Avoid coadministration of lefamulin with meropenem unless the benefits outweigh the risks as concurrent use may decrease lefamulin exposure and efficacy. Lefamulin is a P-gp substrate; meropenem is a P-gp inducer. Coadministration of a combined P-gp and strong CYP3A inducer decreased the mean AUC of lefamulin oral tablets by 72% and the mean AUC of lefamulin injection by 28%.
Letermovir: (Major) Concurrent administration of letermovir and meropenem is not recommended due to the risk of decreased letermovir exposure which may reduce its efficacy. Letermovir is a P-gp substrate and meropenem is a P-gp inducer.
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.
Lidocaine: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with meropenem is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP1A2 substrate and meropenem is a CYP1A2 inducer.
Lidocaine; Epinephrine: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with meropenem is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP1A2 substrate and meropenem is a CYP1A2 inducer.
Lidocaine; Prilocaine: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with meropenem is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP1A2 substrate and meropenem is a CYP1A2 inducer.
Linagliptin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and meropenem if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and meropenem is a P-gp inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Linagliptin; Metformin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and meropenem if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and meropenem is a P-gp inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Lopinavir; Ritonavir: (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with meropenem. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and meropenem is a weak CYP3A inducer.
Lumateperone: (Major) Avoid coadministration of lumateperone and meropenem as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A substrate; meropenem is a weak CYP3A inducer.
Mefloquine: (Moderate) Monitor for a decrease in mefloquine efficacy if concurrent use of meropenem is necessary. Concurrent use may decrease mefloquine exposure. Mefloquine is a CYP3A and P-gp substrate and meropenem is a weak CYP3A and P-gp inducer.
Meperidine: (Moderate) Monitor for reduced efficacy of meperidine and signs of opioid withdrawal if coadministration with meropenem is necessary. Consider increasing the dose of meperidine as needed. If meropenem is discontinued, consider a dose reduction of meperidine and frequently monitor for signs of respiratory depression and sedation. Meperidine is a substrate of CYP3A; meropenem is a weak CYP3A inducer. Concomitant use can decrease meperidine exposure resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Methadone: (Moderate) Monitor for reduced efficacy of methadone and signs of opioid withdrawal if coadministration with meropenem is necessary. Consider increasing the dose of methadone as needed. If meropenem is discontinued, consider a dose reduction of methadone and frequently monitor for signs of respiratory depression and sedation. Methadone is a substrate of CYP3A, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; meropenem is a weak CYP2C9, weak CYP2C19, and weak CYP3A inducer. Concomitant use can decrease methadone exposure resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Mexiletine: (Moderate) Monitor for decreased efficacy of mexiletine if coadministered with meropenem. Coadministration may decrease serum concentrations of mexiletine. Mexiletine is a CYP1A2 substrate and meropenem is a CYP1A2 inducer.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with meropenem is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 and CYP3A substrate and meropenem is a weak CYP2C8 and weak CYP3A inducer.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and meropenem as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and meropenem is a weak CYP3A and P-gp inducer.
Nimodipine: (Moderate) Monitor for decreased efficacy of nimodipine if coadministration with meropenem is necessary as concomitant use may decrease plasma concentrations of nimodipine. Nimodipine is a CYP3A substrate and meropenem is a weak CYP3A inducer.
Nintedanib: (Major) Avoid concurrent use of nintedanib and meropenem. Coadministration may decrease nintedanib exposure resulting in decreased efficacy. Nintedanib is a P-gp substrate, and a minor substrate of CYP3A and meropenem is a dual P-gp and CYP3A inducer. Coadministration with another dual P-gp and CYP3A inducer decreased the AUC of nintedanib by 50%.
Nirmatrelvir; Ritonavir: (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of meropenem is necessary. Concomitant use of nirmatrelvir and meropenem may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and meropenem is a CYP3A inducer. (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with meropenem. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and meropenem is a weak CYP3A inducer.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with meropenem as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and meropenem is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
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.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of oxycodone as needed. If meropenem is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Paclitaxel: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with meropenem is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP2C8 and CYP3A substrate and meropenem is a weak CYP2C8 and weak CYP3A inducer.
Posaconazole: (Major) Avoid concurrent use of posaconazole and meropenem due to the possibility of decreased posaconazole plasma concentrations unless the benefit outweighs the risk. Closely monitor for breakthrough fungal infections if concurrent use is necessary. Posaconazole is a P-gp substrate and meropenem is a P-gp inducer.
Probenecid: (Major) Avoid concomitant use of meropenem and probenecid due to the risk for increased meropenem exposure which may increase the risk for meropenem-related adverse effects. Concurrent use has been observed to increase the mean systemic exposure and half-life of meropenem by 56% and 38%, respectively.
Probenecid; Colchicine: (Major) Avoid concomitant use of meropenem and probenecid due to the risk for increased meropenem exposure which may increase the risk for meropenem-related adverse effects. Concurrent use has been observed to increase the mean systemic exposure and half-life of meropenem by 56% and 38%, respectively.
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.
Riluzole: (Moderate) Coadministration of riluzole with meropenem may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and meropenem is a CYP1A2 inducer.
Ritonavir: (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with meropenem. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and meropenem is a weak CYP3A inducer.
Rosiglitazone: (Moderate) Monitor for a decrease in rosiglitazone efficacy during concomitant use with meropenem; adjust the dose of rosiglitazone based on clinical response. Coadministration may decrease the exposure of rosiglitazone. Rosiglitazone is a CYP2C8 substrate and meropenem is a weak CYP2C8 inducer.
Saquinavir: (Moderate) Monitor for decreased efficacy of saquinavir if concurrent use of meropenem is necessary. Concurrent use may decrease saquinavir plasma concentrations reducing antiretroviral efficacy and increasing the risk for antiretroviral resistance. Saquinavir is a P-gp substrate and meropenem is a P-gp inducer.
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.
Sildenafil: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with meropenem is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and meropenem is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of meropenem. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and meropenem is a weak CYP3A and P-gp inducer.
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.
Sofosbuvir: (Major) Coadministration of sofosbuvir with meropenem is not recommended. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Sofosbuvir is a P-gp substrate and meropenem is a P-gp inducer.
Sofosbuvir; Velpatasvir: (Major) Coadministration of sofosbuvir with meropenem is not recommended. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Sofosbuvir is a P-gp substrate and meropenem is a P-gp inducer. (Major) Concomitant use of velpatasvir with meropenem is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a P-gp substrate and meropenem is a P-gp inducer.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Coadministration of sofosbuvir with meropenem is not recommended. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Sofosbuvir is a P-gp substrate and meropenem is a P-gp inducer. (Major) Concomitant use of velpatasvir with meropenem is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a P-gp substrate and meropenem is a P-gp inducer. (Major) Concomitant use of voxilaprevir with meropenem is not recommended due to the risk of decreased plasma concentrations of voxilaprevir, which may result in loss of antiviral efficacy. Voxilaprevir is a P-gp substrate and meropenem is a P-gp inducer.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if meropenem must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of sufentanil injection as needed. If meropenem is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate if coadministration with meropenem is necessary; a tacrolimus dose adjustment may be needed. Concurrent administration may decrease tacrolimus concentrations. Tacrolimus is a sensitive CYP3A substrate with a narrow therapeutic range; meropenem is a weak CYP3A inducer.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with meropenem may result in decreased tenofovir exposure, which may result in potential loss of virologic control. Tenofovir alafenamide is a P-gp substrate and meropenem is a P-gp inducer.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with meropenem may result in decreased tenofovir exposure, which may result in potential loss of virologic control. Tenofovir alafenamide is a P-gp substrate and meropenem is a P-gp inducer.
Theophylline, Aminophylline: (Moderate) Monitor theophylline concentrations and watch for decreased efficacy of theophylline if coadministration with meropenem is necessary; a theophylline dose increase may be necessary. Theophylline is a CYP1A2 substrate with a narrow therapeutic index and meropenem is a CYP1A2 inducer.
Tipranavir: (Moderate) Monitor for decreased efficacy of tipranavir if coadministered with meropenem. Concurrent use may decrease the plasma concentrations of tipranavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Tipranavir is a P-gp substrate and meropenem is a P-gp inducer.
Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of tramadol as needed. If meropenem is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with meropenem is necessary; consider increasing the dose of tramadol as needed. If meropenem is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and meropenem is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with meropenem as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A substrate; meropenem is a weak CYP3A inducer.
Ulipristal: (Major) Avoid coadministration of ulipristal with meropenem. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal. Ulipristal is a substrate of CYP3A and meropenem is a CYP3A inducer.
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.
Vincristine Liposomal: (Major) Avoid coadministration of vincristine and meropenem due to the risk of decreased vincristine exposure which may reduce its efficacy. Vincristine is a P-gp substrate and meropenem is a P-gp inducer.
Vincristine: (Major) Avoid coadministration of vincristine and meropenem due to the risk of decreased vincristine exposure which may reduce its efficacy. Vincristine is a P-gp substrate and meropenem is a P-gp inducer.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with meropenem is necessary as concurrent use may have an unpredictable effect on INR. There have been reports of changes in INR with concomitant use, but studies have not shown consistent effects. The active metabolite of warfarin, the S-enantiomer, is a CYP2C9 substrate and meropenem is a CYP2C9 inducer. Additionally, the R-enantiomer of warfarin is a CYP1A2 and CYP3A substrate and meropenem is CYP1A2 and CYP3A inducer. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Meropenem, a carbapenem beta-lactam antibiotic, is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. PBPs are responsible for several steps in 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. Meropenem readily penetrates the outer membrane of bacteria cells. After penetrating the bacterial cell wall, it binds to several PBPs. Meropenem has a high affinity for PBP-2, PBP-3, and PBP-4 of E. coli and P. aeruginosa and PBP-1, PBP-2, and PBP-4 of S. aureus. The rapid bactericidal activity of the carbapenems against gram-negative bacteria is associated with their great affinity for PBP-1a, PBP-1b, and PBP-2, rather than PBP-3 (the primary target for other beta-lactams). There are differences in preferential binding sites between the carbapenems. Imipenem preferentially binds to PBP-2, then PBP-1a and PBP-1b, with a weak affinity for PBP-3. Meropenem and ertapenem preferentially bind to PBP-2, then PBP-3, but also have a strong affinity for PBP-1a and PBP-1b. Doripenem has a strong affinity for PBP-3 in P. aeruginosa, PBP-1, PBP-2, and PBP-4 in S. aureus, and PBP-2 in E. coli. Cell lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.
Beta-lactams, including meropenem, 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. 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. PAE has been reported to be 1.3 to 4 hours with imipenem, 4 to 5 hours with meropenem, and 1.5 hours with ertapenem.
The susceptibility interpretive criteria for meropenem are delineated by pathogen. Breakpoints for Enterobacterales, P. aeruginosa, Aeromonas sp., and Vibrio sp. are based on a dosage regimen of 1 g IV every 8 hours while breakpoints for Acinetobacter sp. are based on a dosage regimen of 1 g IV every 8 hours or 500 mg IV every 6 hours. The MICs are defined for Enterobacterales, Lactobacillus sp., Aeromonas sp., and Vibrio sp. 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 Acinetobacter sp. and P. aeruginosa 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 B. cepacia complex, other non-Enterobacterales, anaerobes, Aggregatibacter sp., and Bacillus sp. (excluding B. anthracis) and related genera as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more. The MICs are defined for H. influenzae, H. parainfluenzae, beta-hemolytic streptococci, S. viridans group, Aerococcus sp., and as E. rhusiopathiae susceptible at 0.5 mcg/mL or less. The MICs are defined for S. pneumoniae, Corynebacterium sp., and Lactococcus sp. as susceptible at 0.25 mcg/mL or less, intermediate at 0.5 mcg/mL, and resistant at 1 mcg/mL or more. The MICs are defined for N. meningitidis and L. monocytogenes as susceptible at 0.25 mcg/mL or less. The MICs are defined for Cardiobacterium sp., E. corrodens, Kingella sp., Gemella sp., Abiotrophia sp. and Granulicatella sp. as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more. Considering site of infection and appropriate meropenem dosing, oxacillin-susceptible staphylococci may be considered susceptible to meropenem.
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. Decreased porin OprD in combination with activity of a chromosomal AmpC beta-lactamase is associated with imipenem, doripenem, and to a lesser extent meropenem resistance. Doripenem and meropenem may also require over-expression of efflux pumps for resistance to emerge; imipenem is not subject to efflux. 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.
Meropenem is administered intravenously. Plasma protein binding is approximately 2%. After administration, it is distributed into most body fluids and tissues including cerebrospinal fluid (CSF). Higher CSF concentrations have been noted with increasing CSF white blood cells suggesting better penetration in the presence of meningeal inflammation. Meropenem is minimally metabolized to 1 microbiologically inactive metabolite. Approximately 70% (50% to 75%) of the dose is excreted unchanged in the urine over 12 hours and 28% excreted as the inactive metabolite; fecal elimination is minimal (2%). Urinary concentrations more than 10 mcg/mL are maintained for up to 5 hours in adults after a 500 mg dose. In adult patients with normal renal function, the elimination half-life is approximately 1 hour.
Affected cytochrome P450 isoenzymes and/or drug transporters: OAT1, OAT3
Meropenem is a substrate of OAT1 and OAT3 transporters in the proximal tubule of the kidney. Carbapenems have not shown the potential for CYP450 inhibition or induction.
-Route-Specific Pharmacokinetics
Intravenous Route
IV Push (over 5 minutes)
In healthy adults, the mean peak plasma concentration after a 500 mg dose is 45 mcg/mL (range, 18 to 65 mcg/mL) and after a 1 g dose is 112 mcg/mL (range, 83 to 140 mcg/mL).
Short Infusion (over 30 minutes)
In healthy adults, the mean peak plasma concentration after a 500 mg dose is 23 mcg/mL (range, 14 to 26 mcg/mL) and after a 1 g dose is 49 mcg/mL (range, 39 to 58 mcg/mL). Peak CSF concentrations in adult patients with uninflamed meninges have been reported to be 0.2 mcg/mL (range, 0.1 to 0.3 mcg/mL) 2 hours after a 1 g dose (data based on 4 samples). In pediatric patients (1 month to 15 years of age) with inflamed meninges who received meropenem 40 mg/kg IV, the mean peak CSF concentration was 3.3 mcg/mL (range, 0.9 to 6.5 mcg/mL) 3 hours after the dose.
Extended Infusion (over 3 to 4 hours)
Based on Monte Carlo simulations and population pharmacokinetic studies in adults, an extended infusion (3 to 4 hours) may increase the likelihood of pharmacodynamic target achievement (amount of time free drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism [%T more than the MIC]), particularly for bacteria with higher MICs (2 mcg/mL or greater), such as Pseudomonas. In 1 study, the 3-hour infusion achieved the pharmacodynamic target 99% of the time for bacteriostatic exposure and 93% of the time for bactericidal exposure. Additionally, this regimen had a higher probability of achieving the pharmacodynamic target than traditionally infused meropenem for intermediately resistant pathogens with an MIC of 8 mcg/mL (62% vs. less than 40%). Another study demonstrated that 2 g IV administered over 3 hours every 8 hours in combination with an aminoglycoside was able to suppress resistance and achieve the bacteriocidal pharmacodynamic parameter 79% of the time.
Based on Monte Carlo simulations and population pharmacokinetic studies in children, an extended infusion (3 to 4 hours) may increase the likelihood of pharmacodynamic target achievement (amount of time free drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism [%T more than the MIC]), particularly for bacteria with higher MICs (2 mcg/mL or greater), such as Pseudomonas. In 1 study using population pharmacokinetic modeling based on data from 50 children, the probability of target attainment (PTA; 50% T more than the MIC) against Pseudomonas was increased from 60.7% with a 30-minute infusion to 89.9% with a 4-hour infusion (40 mg/kg/dose every 8 hours). In another study using a Monte Carlo simulation, a 3-hour meropenem infusion was necessary to obtain bactericidal PTAs for organisms at the susceptibility breakpoint. PTA (40% T more than the MIC) for Pseudomonas aeruginosa isolates at the susceptibility breakpoint increased from 33% with a 30-minute infusion to 97% with a 3-hour infusion.
Peak concentrations are achieved at the end of infusion for extended infusion administration. In a pharmacokinetic trial in neonates, a lower Cmax and longer time to Cmax were observed with extended infusions compared to shorter infusions; all other pharmacokinetic parameters were similar between the 2 infusion methods. Unlike in older populations studied, meropenem infusions over 30 minutes are optimal for achieving a 40% T more than the MIC in the majority of very low birth weight neonates.
Continuous Infusion
To maximize the likelihood of pharmacodynamic target achievement, several studies, including population pharmacokinetic studies, and Monte Carlo simulations have reviewed meropenem as a continuous intravenous infusion (CI). A retrospective cohort study of 89 patients compared intermittent meropenem dosing (1 g IV every 6 hours) to CI dosing (4 g/day IV, given as four 1 g infusions, each over 6 hours). The CI group had a greater clinical cure rate (90.47% vs. 59.7%, p less than 0.001). In a randomized study of 10 patients, CI meropenem (500 mg IV load over 3 minutes, then 3 g/day IV, given as three 1 g infusions, each over 8 hours) achieved higher median trough concentrations than intermittent dosing (1.5 g IV load, then 1 g IV every 8 hours). Another prospective crossover study of 15 patients determined CI meropenem (2 g IV load, then 3 g/day IV, given as three 1 g infusions, each over 8 hours) was equivalent to intermittent dosing (2 g IV every 8 hours), but required a smaller total daily dose.
-Special Populations
Hepatic Impairment
A pharmacokinetic study with meropenem in patients with hepatic impairment has shown no effects of hepatic disease on the pharmacokinetics of meropenem.
Renal Impairment
The clearance of meropenem is significantly lower in patients with renal impairment; plasma clearance of meropenem correlates with creatinine clearance. In adult patients with renal failure, the elimination half-life of meropenem is prolonged to approximately 10 to 14 hours. In a pharmacokinetic study of 7 pediatric patients (1.4 to 17 years) with end-stage renal disease, the elimination half-life of meropenem off dialysis was approximately 7.3 hours (range, 4.9 to 11.7 hours). The elimination half-life on dialysis was approximately 1.3 hours (range, 1.1 to 1.7 hours).
Hemodialysis
Adult data have shown that approximately 50% of meropenem is removed by hemodialysis. In a pharmacokinetic study of 7 pediatric patients with end-stage renal disease, meropenem clearance was increased from 22.4 mL/minute/1.73 m2 to 90.7 mL/minute/1.73 m2 with hemodialysis. The elimination half-life on dialysis was approximately 1.3 hours (range, 1.1 to 1.7 hours).
Continuous renal replacement therapy (CRRT)
In adult patients, the removal of meropenem has been shown to be approximately 13% to 53% by CVVHDF and 25% to 50% by CVVHF. Data are unavailable in pediatric patients receiving meropenem and CRRT.
Pediatrics
Infants 3 months and older and Children
As with many other drugs that are primarily renally eliminated, the clearance of meropenem is slightly lower in infants compared to older children and adults and increases with age. An elimination half-life of approximately 1.5 hours has been reported in children 3 months to younger than 2 years, decreasing to approximately 1 hour in children 2 to 5 years and 0.8 hours in children 6 to 12 years. A volume of distribution of approximately 0.4 L/kg has been reported in infants and young children (i.e., 3 months to 5 years) and 0.3 L/kg in older children (6 to 12 years).
Neonates and Infants younger than 3 months
Neonates have a larger volume of distribution and slower clearance of meropenem compared to adults. The clearance of meropenem is lowest in premature neonates and increases with postmenstrual age (PMA) and postnatal age (PNA). The elimination half-life in premature and term infants is approximately 3 to 4 hours and 2 hours, respectively. Due to slower meropenem clearance, the extended infusion method of administration (over 3 to 4 hours) does not appear to have the same benefit in very low birth weight (VLBW) neonates as is seen in older age groups; infusions over 30 minutes are optimal for achieving a 40% T more than the MIC in the majority of VLBW neonates.
The following pharmacokinetic parameters were derived from a population pharmacokinetic analysis of neonates and infants younger than 3 months:
Gestational Age 32 weeks and older
Postnatal Age 2 weeks and older (30 mg/kg every 8 hours)
Vd (L/kg) = 0.451
AUC (mcg x hour/mL) = 444
t 1/2 (hours) = 1.58
Postnatal Age younger than 2 weeks (20 mg/kg every 8 hours)
Vd (L/kg) = 0.463
AUC (mcg x hour/mL) = 445
t 1/2 (hours) = 2.33
Gestational Age younger than 32 weeks
Postnatal Age 2 weeks and older (20 mg/kg every 8 hours)
Vd (L/kg) = 0.467
AUC (mcg x hour/mL) = 491
t 1/2 (hours) = 2.68
Postnatal Age younger than 2 weeks (20 mg/kg every 12 hours)
Vd (L/kg) =0.489
AUC (mcg x hour/mL) = 448
t 1/2 (hours) = 3.82
Geriatric
A pharmacokinetic study with meropenem in elderly patients with renal impairment shows a reduction in plasma clearance of meropenem that correlates with age-associated reduction in creatinine clearance.