Ertapenem

475.51

475.51

1533716-785-6

G32F6EID2H

DTXSID50165456

C61752

J01DH03|J - Antiinfectives for systemic use

182

0.3

1.55±0.1 g/cm3(Predicted)

813.9±65.0 °C(Predicted)

446.0±34.3 °C

1.700

soluble as sodium salt

Do not store lyophilized powder above 25 deg C (77 deg F).

3.56X10-24 mm Hg at 25 deg C (est)

Henry's Law constant = 7.68X10-29 atm-cu m/mol at 25 °C (est)

White to off-white hygroscopic, weakly crystalline powder. Soluble in water, 0.9% sodium chloride solution. Practically insoluble in ethanol; insoluble in isopropyl acetate /Ertapenem sodium salt/|Insoluble in tetrahydrofuran /Ertapenem sodium/|Hydroxyl radical reaction rate constant = 1.69X10-10 cu cm/molec-sec at 25 °C (est)

The reconstituted solution, immediately diluted in 0.9% Sodium Chloride Injection, may be stored at room temperature (25 deg C) and used within 6 hours or stored for 24 hours under refrigeration (5 deg C) and used within 4 hours after removal from refrigeration. Solutions of ertapenem should not be frozen.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including ertapenem sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Ertapenem sodium/

|Danger|H334 (100%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]|P261, P273, P285, P304+P341, P342+P311, P391, and P501|Aggregated GHS information provided by 35 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Mild, transient, asymptomatic elevations in serum aminotransferase levels occur in about 5% of patients receiving parenteral ertapenem for 5 to 14 days. These abnormalities are usually self-limited and asymptomatic. In the limited period that it has been available, no cases of hepatitis with jaundice have been reported. Nevertheless, several instances of cholestatic jaundice arising during or shortly after therapy have been reported with other carbapenems. The latency to onset has been within 1 to 3 weeks and the pattern of enzyme elevations is usually cholestatic. Immunoallergic features can occur but autoantibodies are rare. The course is usually self-limiting, but at least one case of vanishing bile duct syndrome related to a carbapenem has been reported. Ertapenem and other carbapenems have not been linked to cases of acute liver failure.

When ertapenem is co-administered with probenecid (500 mg p.o. every 6 hours), probenecid competes for active tubular secretion and reduces the renal clearance of ertapenem. Based on total ertapenem concentrations, probenecid increased the AUC of ertapenem by 25%, and reduced the plasma and renal clearance of ertapenem by 20% and 35%, respectively. The half-life of ertapenem was increased from 4.0 to 4.8 hours.|Case reports in the literature have shown that co-administration of carbapenems, including ertapenem, to patients receiving valproic acid or divalproex sodium results in a reduction of valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid|In vitro studies indicate that ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin or vinblastine and that ertapenem is not a substrate for P-glycoprotein-mediated transport.|Divalproex sodium is an anticonvulsant widely prescribed to treat several types of seizure disorders, including tonic-clonic and simple or complex partial seizures. /Investigators/ describe a 41-year-old man who experienced recurring tonic-clonic seizures after a drug interaction between divalproex sodium and ertapenem, a carbapenem antibiotic. The patient's valproic acid serum concentration was 130 ug/mL approximately 3 months before he started ertapenem 2000 mg/day (20.6 mg/kg/day). On day 7 of ertapenem therapy, the patient was brought to the emergency department with tonic-clonic seizures; his valproic acid serum concentration was 70 ug/mL. His divalproex sodium dosage was increased, and he was released from the emergency department only to return 4 days later with recurring seizures. This time his valproic acid serum concentration was 10.7 ug/mL. Ertapenem was discontinued, and his divalproex sodium dosage was increased further. The patient's valproic acid level rapidly returned to a therapeutic level 2 days after ertapenem discontinuation, and he had no further seizures. Using the Naranjo adverse drug reaction probability scale to determine the probability of the drug interaction, we found that the likelihood of the interaction was probable (score of 7). Similar interactions have been reported between other carbapenem antibiotics and valproic acid. Clinicians should be aware of this potential interaction between divalproex sodium and ertapenem; concurrent administration of these two drugs should be approached with caution. In patients prescribed this combination, the valproic acid serum concentration should be carefully monitored to prevent recurring seizures.

Total and unbound fractions of ertapenem pharmacokinetics were investigated in 26 adult subjects (31 to 80 years of age) with varying degrees of renal impairment. Following a single 1 g iv dose of ertapenem, the unbound AUC increased 1.5-fold and 2.3-fold in subjects with mild renal impairment (CLCR 60-90 mL/min/1.73 sq m) and moderate renal impairment (CLCR 31-59 mL/min/1.73 sq m), respectively, compared with healthy young subjects (25 to 45 years of age). No dosage adjustment is necessary in patients with CLCR greater than or equal to 31 mL/min/1.73 sq m. The unbound AUC increased 4.4-fold and 7.6-fold in subjects with advanced renal impairment (CLCR 5-30 mL/min/1.73 sq m) and end-stage renal disease (CLCR <10 mL/min/1.73 sq m), respectively, compared with healthy young subjects. The effects of renal impairment on AUC of total drug were of smaller magnitude. The recommended dose of ertapenem in adult patients with CLCR less than or equal to 30 mL/min/1.73 sq m is 0.5 grams every 24 hours. Following a single 1 g iv dose given immediately prior to a 4 hour hemodialysis session in 5 adult patients with end-stage renal disease, approximately 30% of the dose was recovered in the dialysate. Dose adjustments are recommended for patients with severe renal impairment and end-stage renal disease. There are no data in pediatric patients with renal impairment.|The impact of age on the pharmacokinetics of ertapenem was evaluated in healthy male (n=7) and healthy female (n=7) subjects >/=65 years of age. The total and unbound AUC increased 37% and 67%, respectively, in elderly adults relative to young adults. These changes were attributed to age-related changes in creatinine clearance. No dosage adjustment is necessary for elderly patients with normal (for their age) renal function.|/Ertapenem is contraindicated in patients with/ known hypersensitivity to ertapenem, other carbapenems, or any ingredient in the formulation; history of anaphylactic reaction to beta-lactams. Patients with known hypersensitivity to local anesthetics of the amide type should not receive ertapenem sodium reconstituted with lidocaine hydrochloride for im injection.|Seizures and other central nervous system (CNS) adverse experiences have been reported during treatment with ertapenem. During clinical investigations in adult patients treated with ertapenem (1 g once a day), seizures, irrespective of drug relationship, occurred in 0.5% of patients during study therapy plus 14-day follow-up period. These experiences have occurred most commonly in patients with CNS disorders (e.g., brain lesions or history of seizures) and/or compromised renal function. Close adherence to the recommended dosage regimen is urged, especially in patients with known factors that predispose to convulsive activity. 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, and the dosage of ertapenem re-examined to determine whether it should be decreased or discontinued.|Plasma concentrations at the midpoint of the dosing interval following a single 15 mg/kg iv dose of ertapenem in patients 3 months to 12 years of age are comparable to plasma concentrations at the midpoint of the dosing interval following a 1 g once daily iv dose in adults. The plasma clearance (mL/min/kg) of ertapenem in patients 3 months to 12 years of age is approximately 2-fold higher as compared to that in adults. At the 15 mg/kg dose, the AUC value (doubled to model a twice daily dosing regimen, i.e., 30 mg/kg/day exposure) in patients 3 months to 12 years of age was comparable to the AUC value in young healthy adults receiving a 1 g iv dose of ertapenem.

Ertapenem is highly bound to human plasma proteins, primarily albumin, in a concentration-dependent manner. The protein binding of ertapenem decreases as plasma concentrations increase. At a plasma concentration of <100 µg/mL, approximately 95% of ertapenem is protein bound. Protein binding of ertapenem decreases to approximately 85% at an approximate plasma concentration of 300 µg/mL.

The concentration of ertapenem in breast milk from 5 lactating women with pelvic infections (5 to 14 days postpartum) was measured at random time points daily for 5 consecutive days following the last 1 g dose of intravenous therapy (3-10 days of therapy). The concentration of ertapenem in breast milk within 24 hours of the last dose of therapy in all 5 women ranged from <0.13 (lower limit of quantitation) to 0.38 ug/mL; peak concentrations were not assessed. By day 5 after discontinuation of therapy, the level of ertapenem was undetectable in the breast milk of 4 women and below the lower limit of quantitation (<0.13 ug/mL) in 1 woman.

The concentration of ertapenem in breast milk from 5 lactating women with pelvic infections (5 to 14 days postpartum) was measured at random time points daily for 5 consecutive days following the last 1 g dose of intravenous therapy (3-10 days of therapy). The concentration of ertapenem in breast milk within 24 hours of the last dose of therapy in all 5 women ranged from <0.13 (lower limit of quantitation) to 0.38 ug/mL; peak concentrations were not assessed. By day 5 after discontinuation of therapy, the level of ertapenem was undetectable in the breast milk of 4 women and below the lower limit of quantitation (<0.13 ug/mL) in 1 woman.|Ertapenem is highly bound to plasma protein. The protein binding changes from approximately 95% bound at concentrations of <50 ug/mL to approximately 92% bound at concentrations of 150 ug/mL (concentration at the end of a 30-min infusion following the 1-g dose). The nonlinear protein binding of ertapenem resulted in a slightly less than dose proportional increase in the area under the curve from 0 hr to infinity (AUC(0- infinity )) of total ertapenem. The single-dose AUC(0- infinity ) of unbound ertapenem was nearly dose proportional over the dose range of 0.5 to 2 g. The mean concentration of ertapenem in plasma ranged from approximately 145 to 175 ug/mL at the end of a 30-min infusion, from approximately 30 to 34 ug/mL at 6 hr, and from approximately 9 to 11 ug/mL at 12 hr. The mean plasma t(1/2) ranged from 3.8 to 4.4 hr. About 45% of the plasma clearance (CL(P)) was via renal clearance.

For the treatment the following moderate to severe infections caused by susceptible isolates of the designated microorganisms: (1) complicated intra-abdominal infections due to Escherichia coli, Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus species, Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides uniformis, (2) complicated skin and skin structure infections, including diabetic foot infections without osteomyelitis due to Staphylococcus aureus (methicillin susceptible isolates only), Streptococcus agalactiae, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Bacteroides fragilis, Peptostreptococcus species, Porphyromonas asaccharolytica, or Prevotella bivia, (3) community acquired pneumonia due to Streptococcus pneumoniae (penicillin susceptible isolates only) including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase negative isolates only), or Moraxella catarrhalis, (4) complicated urinary tract infections including pyelonephritis due to Escherichia coli, including cases with concurrent bacteremia, or Klebsiella pneumoniae, (5) acute pelvic infections including postpartum endomyometritis, septic abortion and post surgical gynecologic infections due to Streptococcus agalactiae, Escherichia coli, Bacteroides fragilis, Porphyromonas asaccharolytica, Peptostreptococcus species, or Prevotella bivia.|FDA Label|TreatmentTreatment of the following infections when caused by bacteria known or very likely to be susceptible to ertapenem and when parenteral therapy is required:intra-abdominal infections;community-acquired pneumonia;acute gynaecological infections;diabetic foot infections of the skin and soft tissue.PreventionInvanz is indicated in adults for the prophylaxis of surgical site infection following elective colorectal surgery.Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Ertapenem is a broad spectrum carbapenem antibiotic used primarily for the treatment of aerobic gram-negative bacterial infections. Ertapenem, like other carbapenems, is associated with transient and asymptomatic elevations in serum enzymes. The carbapenems have also been linked to rare instances of clinically apparent, acute cholestatic liver injury.

Antiinfective Agents

beta-Lactams; Anti-Bacterial Agents|Ertapenem sodium is indicated for the treatment of adult patients and pediatric patients (3 months of age and older) with ... moderate to severe infections caused by susceptible isolates of the designated microorganisms. /Included in US product label/|Ertapenem sodium is indicated for the treatment of complicated intra-abdominal infections due to Escherichia coli, Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus species, Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides uniformis. /Included in US product label/|Ertapenem sodium is indicated for the treatment of complicated skin and skin structure infections, including diabetic foot infections without osteomyelitis due to Staphylococcus aureus (methicillin susceptible isolates only), Streptococcus agalactiae, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Bacteroides fragilis, Peptostreptococcus species, Porphyromonas asaccharolytica, or Prevotella bivia. Ertapenem sodium has not been studied in diabetic foot infections with concomitant osteomyelitis. /Included in US product label/|For more Therapeutic Uses (Complete) data for Ertapenem (8 total), please visit the HSDB record page.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ertapenem sodium and other antibacterial drugs, ertapenem sodium should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.|/Ertapenem is contraindicated in patients with/ known hypersensitivity to ertapenem, other carbapenems, or any ingredient in the formulation; history of anaphylactic reaction to beta-lactams. Patients with known hypersensitivity to local anesthetics of the amide type should not receive ertapenem sodium reconstituted with lidocaine hydrochloride for im injection.|Ertapenem is not recommended in the treatment of meningitis in the pediatric population due to lack of sufficient CSF penetration.|Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. These reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam. Before initiating therapy with ertapenem, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams and other allergens. If an allergic reaction to ertapenem occurs, discontinue the drug immediately. Serious anaphylactic reactions require immediate emergency treatment as clinically indicated.|For more Drug Warnings (Complete) data for Ertapenem (16 total), please visit the HSDB record page.

Ertapenem has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

Ertapenem is almost completely absorbed following intramuscular administration. The bioavailability of a 1 g intramuscular dose approximated 92% in 26 healthy subjects [77% male; median (range) age, 29 (22–41) years]. Plasma concentrations of total ertapenem were similar whether given intramuscularly or intravenously.|Of the 80% recovered in urine, approximately 38% is excreted as unchanged drug and approximately 37% as the ring-opened metabolite.|0.12 liter/kg [adults]|1.8 L/h|Ertapenem, reconstituted with 1% lidocaine HCl injection, USP (in saline without epinephrine), is almost completely absorbed following intramuscular (IM) administration at the recommended dose of 1 g. The mean bioavailability is approximately 90%. Following 1 g daily IM administration, mean peak plasma concentrations (Cmax) are achieved in approximately 2.3 hours (Tmax).|Ertapenem is highly bound to human plasma proteins, primarily albumin. In healthy young adults, the protein binding of ertapenem decreases as plasma concentrations increase, from approximately 95% bound at an approximate plasma concentration of <100 micrograms (ug)/mL to approximately 85% bound at an approximate plasma concentration of 300 ug/mL.|The apparent volume of distribution at steady state (Vss) of ertapenem in adults is approximately 0.12 liter/kg, approximately 0.2 liter/kg in pediatric patients 3 months to 12 years of age and approximately 0.16 liter/kg in pediatric patients 13 to 17 years of age.|The concentration of ertapenem in breast milk from 5 lactating women with pelvic infections (5 to 14 days postpartum) was measured at random time points daily for 5 consecutive days following the last 1 g dose of intravenous therapy (3-10 days of therapy). The concentration of ertapenem in breast milk within 24 hours of the last dose of therapy in all 5 women ranged from <0.13 (lower limit of quantitation) to 0.38 ug/mL; peak concentrations were not assessed. By day 5 after discontinuation of therapy, the level of ertapenem was undetectable in the breast milk of 4 women and below the lower limit of quantitation (<0.13 ug/mL) in 1 woman.|For more Absorption, Distribution and Excretion (Complete) data for Ertapenem (18 total), please visit the HSDB record page.

The major metabolite is the inactive ring-opened derivative formed by hydrolysis of the β-lactam ring. Ertapenem did not inhibit metabolism mediated by cytochrome P450 (CYP) isoforms 1A2, 2C9, 2C19, 2D6, 2E1, or 3A4 when evaluated by in vitro studies in human liver microsomes. Ertapenem is neither a substrate nor an inhibitor of P-glycoprotein or cytochrome P450 enzymes; significant drug interactions between ertapenem and drugs handled by these systems are not expected [PMID: 15150180]|The disposition and metabolism of ertapenem, a carbapenem antibiotic, was examined in rat, monkey and man. Sprague-Dawley rats and Rhesus monkeys were given, by intravenous administration, radiolabelled doses of ertapenem (60 and 30 mg kg(-1), respectively), and healthy normal volunteers received a single fixed dose of 1000 mg. Urine and feces were collected for determination of total radioactivity. In healthy volunteers, (14)C-ertapenem was eliminated by a combination of hydrolytic metabolism to a beta-lactam ring-opened derivative and renal excretion of unchanged drug. Approximately equal amounts were excreted as a beta-lactam ring-opened metabolite and unchanged drug (36.7 and 37.5% of dose, respectively). A secondary amide hydrolysis product accounted for about 1% of the dose in man. About 10% of the administered radioactivity was recovered in feces, which suggested that a minor fraction underwent biliary and/or intestinal excretion. In animals, a greater fraction of the dose was eliminated via metabolism; excretion of unchanged drug accounted for 17 and 5% of dose in rats and monkeys, respectively. In monkeys, the beta-lactam ring-opened and amide hydrolysis metabolites accounted for 74.8 and 7.59% of the dose, respectively, whereas in rats, these metabolites accounted for 31.9 and 20% of dose, respectively. In vitro studies with fresh rat tissue homogenates indicated that lung and kidney were the primary organs involved in mediating formation of the beta-lactam ring-opened metabolite. The specific inhibitor of dehydropeptidase-I, cilastatin, inhibited the in vivo and in vitro metabolism of ertapenem in rats, which suggested strongly that the hydrolysis of ertapenem in lung and kidney was mediated by this enzyme.|Ertapenem is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Ertapenem is hydrolyzed by metallo-beta-lactamases.|In healthy young adults, after infusion of 1 g IV radiolabeled ertapenem, the plasma radioactivity consists predominantly (94%) of ertapenem. The major metabolite of ertapenem is the inactive ring-opened derivative formed by hydrolysis of the beta-lactam ring.

The mean plasma half-life is approximately 4 hours.|The drug has a mean plasma half-life of approximately 4 hours and may be administered once daily.|The mean plasma half-life in pediatric patients 13 to 17 years of age is approximately 4 hours and approximately 2.5 hours in pediatric patients 3 months to 12 years of age.|The mean plasma t(1/2) ranged from 3.8 to 4.4 hr.

The bactericidal activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin binding proteins (PBPs). In Escherichia coli, it has strong affinity toward PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3. Ertapenem is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Ertapenem is hydrolyzed by metallo-beta-lactamases.|Ertapenem is a synthetic carbapenem beta-lactam antibiotic that is structurally and pharmacologically related to imipenem and meropenem. Like meropenem but unlike imipenem, ertapenem has a methyl group at position 1 of the 5-membered ring, which confers stability against hydrolysis by dehydropeptidase 1 (DHP 1) present on the brush border of proximal renal tubular cells, and therefore does not require concomitant administration with a DHP-1 inhibitor such as cilastatin.|Ertapenem has in vitro activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. The bactericidal activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin binding proteins (PBPs). In Escherichia coli, it has strong affinity toward PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3.|Antimicrobials are the most frequently implicated class of drugs in drug-induced seizure, with beta-lactams being the class of antimicrobials most often implicated. The seizure-inducing potential of the carbapenem subclass may be directly related to their beta-lactam ring structure. Data on individual carbapenems and seizure activity are scarce. To evaluate the available evidence on the association between carbapenem agents and seizure activity, /investigators/ conducted a literature search of the MEDLINE (1966-May 2010), EMBASE (1974-May 2010), and International Pharmaceutical Abstracts (1970-May 2010) databases. Reference citations from the retrieved articles were also reviewed. Mechanistically, seizure propensity of the beta-lactams is related to their binding to gamma-aminobutyric acid (GABA) receptors. There are numerous reports of seizure activity associated with imipenem-cilastatin, with seizure rates ranging from 3-33%. For meropenem, doripenem, and ertapenem, the seizure rate for each agent is reported as less than 1%. However, as their use increases and expands into new patient populations, the rate of seizures with these agents may increase. High-dose therapy, especially in patients with renal dysfunction, preexisting central nervous system abnormalities, or a seizure history increases the likelihood of seizure activity. ...

Ertapenem can be removed by hemodialysis; the plasma clearance of the total fraction of ertapenem was increased 30% in subjects with end-stage renal disease when hemodialysis (4 hour session) was performed immediately following administration. However, no information is available on the use of hemodialysis to treat overdosage.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ No specific information is available on the treatment of overdosage with ertapenem. Intentional overdosing of ertapenem is unlikely. Intravenous administration of ertapenem at a dose of 2 g over 30 min or 3 g over 1-2 hr in healthy adult volunteers resulted in an increased incidence of nausea. In clinical trials in adults, inadvertent administration of three 1 g doses of ertapenem in a 24 hour period resulted in diarrhea and transient dizziness in one patient. In pediatric clinical trials, a single intravenous dose of 40 mg/kg up to a maximum of 2 g did not result in toxicity.|/CASE REPORTS/ A 78-year old man was given, after surgery, 1 g ertapenem every 24 hr intravenously. His clinical evolution was favorable and on day 8 ertapenem was discontinued and the patient was put on a semi-solid diet. On day 9, abdominal distension was seen accompanied by epigastric pain. The laboratory tests on day 8 showed an altered pancreatic profile: amylase = 1823 U/L (normal value: 0-100); lipase = 8045 U/L (normal value: 0-60); C-reactive protein (CRP) = 16.09 mg/dL (normal value: 0-0.5). Full Blood Count (FBC) showed leukocytosis with an increase in neutrophils and eosinophils. The prior pancreatic parameters were normal without leukocytosis. The evolution of clinical symptoms after discontinuing ertapenem was rapid. Between days 11 and 16, the laboratory parameters returned to normal values; the eosinophilia persisted longer, decreasing between days 14 and 16. Clinicians should include monitoring the development of acute pancreatitis in the safety parameters in patients undergoing treatment with this carbapenem.|/CASE REPORTS/ Three patients presented seizures during ertapenem therapy. They were classified as probably-related in 1 case and as possible-related in the others. Convulsions appeared after 1 week of therapy at usual doses with 1 or 2 events, and were observed only among patients with CNS disorders and renal insufficiency.|/CASE REPORTS/ In the first case, a 47-year-old woman was brought to the emergency department (ED) with fever, pain, redness, swelling, and local heat in the tissue around her tracheostomy tube and left foot. One month prior she was hospitalized with pneumonia and had a generalized tonic-clonic seizure. She was given teicoplanin and amoxicillin-clavulanate potassium as empirical therapy for cellulitis. On day 3, the patient developed a fever. Amoxicillin-clavulanate potassium was discontinued and replaced by i.v. ertapenem. On day 5, due to a suspected drug-induced fever, carbamazepine was discontinued, and oral valproate sodium was initiated. On day 16, the patient was afebrile, so ertapenem was discontinued. Her serum valproic acid concentration was <1 mg/L, but seizures did not recur. Three days after ertapenem was discontinued, her serum valproic acid concentration increased to 33.6 mg/L. In the second case, a 72-year-old woman was brought to the ED after a sudden loss of consciousness and convulsive seizure. The patient was diagnosed with status epilepticus and admitted to the intensive care unit. A urine culture revealed Pseudomonas aeruginosa, and she was given cefpirome and valproate sodium. On day 15, cefpirome was replaced with ertapenem. On day 21, she had a seizure, and her serum valproic acid levels was found to be <1 mg/L. Ertapenem was discontinued after 14 days. Her serum valproic acid levels continued to increase until discharge on day 42.|For more Human Toxicity Excerpts (Complete) data for Ertapenem (7 total), please visit the HSDB record page.

ertapenem

Table: Ertapenem Sodium Preparations [Table#7977]

Stability-indicative determination of ertapenem (E(RTM)) and imipenem (I(MPM)) in the presence of their corresponding open-ring degradation products, the metabolites, is investigated. The degradation products have been isolated via acid-degradation, characterized, and confirmed. Selective quantification of E(RTM) or I(MPM) singly in bulk form, pharmaceutical formulations, and/or in the presence of their corresponding degradants is demonstrated. The indication of stability has been undertaken under conditions likely to be expected at normal storage conditions. Among the chromatographic techniques adopted for quantification are coupled thin layer chromatography-densitometry and high-performance liquid chromatography.

A sensitive assay for the determination of unbound ertapenem in human plasma and bronchoalveolar lavage (BAL) was developed using ultrafiltration of plasma and BAL samples. A rapid HPLC method was used with ultraviolet detection set at a wavelength of 305 nm and a separation on a Prontosil AQ C18 column, with imipenem used as internal standard. This assay was linear over the concentration range of 0.5-100 microg/mL and 0.25-50 microg/mL in plasma and BAL, respectively. Limits of detection and quantitation were respectively 0.05 and 0.25 microg/mL. Validation data for accuracy and precision were CV<2.48 and 8.25%, accuracy in the range 98.1-104.2% and 102.2-108.4%, respectively, for intra and inter-day.|... A new HPLC/UV method based on narrow-bore column design using sample pre-cleaning by liquid-liquid extraction has been developed. The assay is rapid for specimen concentrations > or =1 mg/L and is easily tuned to achieve low quantification limits at high chromatographic resolution for lower concentrated samples. The method has been successfully applied to plasma, serum, lung tissue or cell homogenates, and broncho-alveolar lavage fluid with lower limits of quantification of 40 and 20 microg/L, respectively. It was also used for the pharmacokinetic monitoring of ertapenem in humans.|A column-switching, reversed-phase high-performance liquid chromatographic (HPLC) assay for a new structurally unique carbapenem antibiotic, ertapenem, in urine has been improved for selectivity and automated using a Packard MultiPROBE II EX pipetting station. The method uses column-switching for on-line extraction of the urine sample. The extraction column, analytical column, mobile phase, and timing of the column-switching valve have been changed to enhance selectivity for the analyte over endogenous background material. Sample transfer and dilution prior to direct-injection into the HPLC system have been accomplished using a Packard MultiPROBE II EX robotic liquid handling system.|A simple chromatographic assay based on ultra high performance liquid chromatography with ultraviolet detection at 295 nm is proposed to determinate simultaneously human plasma concentrations of imipenem, doripenem, meropenem and ertapenem. After deproteinization by acetonitrile, carbapenems are separated on a PentaFluoroPhenyl column with a binary gradient elution. This method is specific, accurate, precise (the intra-day and inter-day imprecision and inaccuracy are lower than 15%), sensitive (the limit of quantitation is equal to 0.50 mg/L for imipenem, doripenem, ertapenem, meropenem) and not time consuming (run time=7 min). An application of this method to measure ertapenem plasma concentrations in burn patients is presented.|For more Clinical Laboratory Methods (Complete) data for Ertapenem (6 total), please visit the HSDB record page.

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