Invanz 1g injection powder MSD treats average to severe infections (15ml)

Pharmacological

Ertapenem has anti -vitro anti -energy and anaerobic bacteria, both gram -positive and gram negative. Ertapenem's bactericidal effect is due to the synthesis of bacterial walls: Ertapenem attaches to penicillin (PBP) proteins. In E.coli, Ertapenem has strong affinity for PBP La, 1B, 2, 3, 4 and 5, mainly with PBP2 and PBP3. Ertapenem is very sustainable, not hydrolyzed by most ß-lactamase types, including penicillinase, cephalosporinase and ß-lactamase broad spectrum but not against metallo-ß-lactamase.

Invanz has the activity against most of the following bacteria both in vitro and in clinical infections (see indicators):

Gram -positive and anaerobic bacteria:

Gram -negative and anaerobic bacteria:

The minimum inhibitory concentration (mic) Invanz of Invanz is ≤ 1 mcg/ml for the majority (≥ 90%) The strains of the streptococcus include Streptococcus pneumoniae, concentration ≤ 0.5 mcg/ml against the majority (≥ 90%) of Haemophilus strains, ≤ 2 mcg/ml resistant to large parts (≥ ≥ ≥ ≥ ≥ ≥ ≥ ≥ ≥ ≥ ≥ 90%) Mandatory and concentration ≤ 4 mcg/ml are against most (≥ 90%) strains of mandatory anaerobic bacteria in the list below; However, the effect and safety of Invanz in the treatment of clinical bacterial infections due to the infection of the above bacteria has not been proved in clinical studies with good and appropriate control:

Gram -positive and anaerobic bacteria:

Gram -negative and anaerobic bacteria:

Anaerobic bacteria:

Clinical studies

Adults

Ertapenem has been evaluated in a clinical trial in 665 adults treating infections in the abdominal cavity with complications: comparing Ertapenem (once a day 1 g of intravenous infusion) with piperacillin/tazobactam (intravenous 3.375 g every 6 hours), used for 5-14 days. At 1-2 weeks after the treatment period, the clinical and microbiological success rate is 89.6% (190/212) with Ertapenem and 82.7% (162/196) with piperacillin/lazobactam; After 4-6 weeks of treatment (evaluation), the success rate is 86.7% (176/203) with ERTAPENEM and 81.3% (157/193) with Piperacillin/Tazobactam.

In clinical trials, Ertapenem evaluation in 540 adults treating dermatitis and complicated skin structure, comparing Ertapenem (daily intravenous infusion 1 g) with piperacillin/tazobactam (intravenous infusion every 6 hours; each time 3.375 g) for 7-14 days, including lower limb infection due to diabetes, soft tissue infection, bacteria Pus drainage. The clinical success rate in 10-21 days after the treatment period (evaluation) is 82.2% (152/185) with ERTAPENEM and 84.5% (147/174) with Piperacillin/Tazobactam.

Ertapenem is evaluated effectively in the treatment of diabetes with diabetes in a clinical test with control, double blindness, multicolored, random groups. This study compares (1 g IV once a day) with piperacillin/tazobactam (3,375 g IV every 6 hours) on 586 patients. Both treatment regimen allows to switch to amoxicillin/clavuclanate therapy with oral treatment with a total treatment time of 5-28 days (both injection and orally). The clinical success rate within 10 days after treatment is 87.4% (180/206) for Ertapenem and 82.7% (162/196) for piperacillin/tazobactam.

In two clinical trials on 866 adults treating pneumonia in the community, Ertapenem (once a day injected 1 g) is compared to Ceftriaxone (1 g in injection a day). Both regimen allows to switch to amoxicillin/clavulanate therapy with oral treatment with a total treatment time of 10-14 days (both injection and oral). The clinical success rate (2 studies) at 7-14 days after the treatment period (evaluation) is 92% (335/364) with ERTAPENEM and 91.8% (270/294) with Ceftriaxone.

In two clinical trials on 850 adults treating complicated urinary tract infections, including nephritis - pyelonephritis, Ertapenem (daily injection 1 g) is compared to ceftriaxone (once a day 1 g). Both regimen allows to switch to oral ciprofloxacin (500 mg, taken 2 times a day) with a total treatment time of 10-14 days (both injection and oral). Microbiological success rate (2 studies) at 5-9 days after the treatment period (evaluation) is 89.5% (229/256) with Ertapenem and 91.1% (204/224) with Ceftriaxone.

In a clinical trial, Ertapenem evaluation (1 g intravenously, once a day) compared to piperacillin/ tazobactam (3,375 g of intravenous injection every 6 hours) used for 3-10 days in the treatment of higher level pelvic inflammatory disease of 412 adults including 350 infected people at birth/ after birth and 45 infections. The clinical success rate in 2-4 weeks after the treatment period (evaluation) is 93.9% (153/163) with Ertapenem and 91.5% (140/153) with Piperacillin/Tazobactam.

A multi -center test, double blindness, random groups to evaluate the effectiveness of the surgery in over 1002 adults, compare Invanz IV (1 g) with Cefotetan IV (2 g) of the infusion lasting 30 minutes at 1 hour before colorectal surgery under the program. The beneficial clinical response rate in general 4 weeks after surgery (the main criterion is effective) is 72.0% for the patient group using Ertapenem (N = 338) and 57.2% in the group using cefotetan (n = 334) (difference 14.8%, [95% Ci is 7.5% -21.9%]), showing the outstanding effect Colorectal surgery by program.

Children

Ertapenem is assessed in two multi -central, double clinical trials, random subgroups on children from 3 months to 17 years old. The first test is admitted 404 children, comparing Ertapenem (15 mg/kg intravenously every 12 hours on children from 3 months to 12 years old and 1g of intravenous infusion once a day for children 13 years old to 17 years old) with ceftriaxone (50 mg/kg/day of intravenous transmission 2 times on dual disease from 3 months to 12 years old and 50 mg/kg/day daily infection from 17 years old) There are complications, skin and soft tissue infections or pneumonia in the community. Both regimen allow to switch to oral amoxicillin/clavulanate with a total time of 14 days (injection and oral). Bacterial success rate is assessed in a protocol -based analysis in urinary -infected children with complications that is 87.0% (40/46) for Ertapenem and 90.0% (18/20) for Ceftriazone. The success rate in a protocol -based analysis in children treated with skin and soft tissue is 95.5% (64/67) for Ertapenem and 100% (26/26) for ceftriaxone and in patients received by the community is 96.1% (74/77) for Ertapenem and 96.4% (27/2) for 27/28) for 27/28) ceftriaxone.

The second test is admitted 112 children and compares Ertapenem (15 mg/kg intravenously every 12 hours on patients from 3 months to 12 years old and LG intravenously once a day on children from 13 years old to 17 years old) with ticarcillin/clavulanate (50 mg/kg for children 60 kg, 6 times or 6 days) Acute pelvic and infections. On patients treated with complications of abdominal infections (those who have previously had a hole or appendicitis with complications) clinical success rate of 83.7% (36/43) for Ertapenem and 63.6% (7/11) for Ticarcillin/Clavulanate in an analysis based on protocol. On patients treated for acute pelvic infections (postoperative or endometritis spontaneous or abortion infection) of clinical success rate of 100% (23/23) for Ertapenem and 100% (4/4) for Ticarcillin/Clavulanate in an analysis based on protocol.

Dynamic pharmacokinetics

absorption

Ertapenem injection mixed with 1% lidocaine injection solution (American pharmacopoeia) mixed in salt water without epinephrine, is easy to absorb after intramuscular injection with the recommended dose of 1 g. The average bioavailability is about 92%. After an intramuscular injection of 1 g/day, the average peak concentration in plasma (cmax) reaches about 2 hours (TMAX).

Distribution

Ertapenem is heavily associated with blood protein. In healthy young adults, Ertapenem's protein cohesion will decrease as plasma concentrations increase. When plasma concentration

Table 3 The following seven medium plasma concentrations (MCG/mL) of Ertapenem after an intravenous infusion 1 dose 1 g or 2 g last 30 minutes and only 1 g intramuscular injection for healthy young adults.

The area under the curve (AUC) of Ertapenem increases almost proportional to the dose of 0.5-2g.

There is no accumulation of Ertapenem in adults after intravenous infusion, 0.5-2 g per day or intramuscularly 1 g.

Please see more information about drugs in the instructions for the use of drugs attached.

Ertapenem content in breast milk, collected in 5 nursing mothers are measured at random selection times of the day, continuous testing 5 days after the last Ertapenem intravenous infusion. Ertapenem concentration in milk of all 5 mothers on the final day of treatment (5-14 days after birth) is

In vitro research shows that Enapenem does not inhibit the transportation of digoxin or vinblastin through p-glycoprotein and ertapenem intermediaries are not the substrate in the metabolism through P-Glycoprotein intermediaries (see drug interactions).

transformation

In healthy young adults after 1 g Ertapenem intravenously marked radioactive, radioactive properties in plasma are mainly Ertapenem (94%). The main metabolite of Ertapenem is the derivative of ß-lactam open after this round is hydrolyzed.

In vitro research on human liver cell microsom shows that Ertapenem does not inhibit the metabolism of drugs through the catalysts of the 6 -form Cytochrom P450 (CYP) mainly 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (see drug interaction).

reversal

Ertapenem excreted mainly through the kidneys. In young, healthy adults and patients aged 13-17 years old, the sale time in plasma is about 4 hours and about 2.5 hours in children from 3 months to 12 years old.

After 1 g Ertapenem intravenously marked radioactive, about 80% discharged through the urine, 10% in fertilizer.

Of the 80% of the drug found in the urine, about 38% of the drug in the form of constant and about 37% is an open ß-lactam metabolitus.

In healthy young adults, 1 g intravenously, the average concentration of Ertapenem in the urine exceeds 984 mcg/ml for 0-2 hours after the injection and exceeds 52 mcg/ml for 12-24 hours after injection.

Characteristics of patients

gender

Ertapenem/plasma concentration does not depend on gender.

Elderly

Plasma concentrations after intravenous infusion of 1 g and 2 g of Ertapenem to the 265 -year -old are about 39% and 22%, slightly higher than the young adults (

Children

The plasma concentration of Ertapenem in children 13-17 years old is equivalent to adults taking a dose of 1 g of intravenous injection once a day.

The value of kinetic parameters in children from 13-17 years old when taking a dose of 20 mg/kg (maximum 1 g) is generally similar in healthy young adults. Three out of six patients aged 13-17 years of doses are less than 1 g. To estimate pharmacokinetic data when all patients in this age group take a dose of 1 g, the pharmacokinetic data is adjusted in the dose of 1 g, with a linear router according to the dose. Comparing the results shows that patients from 13-17 years old take the dose of 1 g Ertapenem once a day to achieve the same pharmacokinetic properties in adults. The ratio (group 13-17 years/ adult) of AUC values ​​is 0.99, the concentration at the end of the infusion is 1.20 and the concentration at the middle point of the distance of the doses is 0.84.

Plasma concentration at the middle of the distance of the doses when intravenous injection Ertapenem single dose 15 mg/kg for children from 3 months to 12 years old is equivalent to plasma concentration at the middle of the distance of the doses when the intravenous injection 1 g once a day in adults (see distribution). Ertapenem clearance in plasma (ml/min/kg) in children from 3 months to 12 years old is approximately 2 times higher than adults.

When using a dose of 15 mg/kg, AUC value (double for treatment 2 times/day, meaning 30 mg/kg/day) in children from 3 months to 12 years old, similar to AUC value in healthy young adults with single -dose inferior to 1 g Ertapenem.

liver failure

Not determined Ertapenem's pharmacokinetics in liver failure people. Because this drug is less metabolic through the liver, the dynamics of the drug are most likely not affected when liver failure. Therefore, there is no need to adjust the dose when liver failure.

kidney failure

After an intravenous infusion of a single 1 g of adults, AUC in mild kidney failure (creatinine purification from 60-90 ml/min/1.73 m2) is equivalent to AUC in healthy people (25-82 years old). But in medium renal failure (creatinine purification from 31-59 ml/minute/1.73 m2), AUC increased by 1.5 times compared to healthy people.

In people with progressive renal failure (creatinine purification from 5-30 ml/min/1.73 m2), AUC increased by about 2.6 times compared to healthy people. In people with end -stage renal failure (creatinine purification

The dose of Ertapenem is needed in adults with progressive renal failure or at the end (see the dose and how to use).

In the majority of clinical studies, injected antibiotics are followed by oral antibiotics (see pharmacological, clinical studies). During the treatment period and the 14 -day monitoring period after treatment, the reactions related to Invanz include the above -mentioned reactions, as well as rashes and vaginitis with the rate of 21.0% (common) and allergic reactions, uncomfortable and fungal infections with a rate of> 0.1% but

In a clinical study on the treatment of diabetes infections due to diabetes in 289 adult patients with diabetes treated with Ertapenem, the adverse adverse reaction characteristics are generally similar to the observed reactions in previous clinical trials.

In a clinical study on the use of Invanz in an interview with local infections after colorectal surgery under the program over 476 adult patients who use 1 g of Ertapenem before surgery, only sinus rhythms are an unfavorable adverse drug -related reaction that has not been seen in previous clinical trials that have been reported at a ratio of> 0.1% but Children

There are a total of 384 patients treated with Ertapenem in clinical trials. The overall safety characteristics of the drug in children are similar to adults. In clinical trials, clinical adverse reactions related to the most common drug throughout the therapy are reported as diarrhea (5.5%), pain at the injection site (5.5%) and the erythema at the injection site (2.6%).

The following adverse adverse reactions are reported during the time when the patient treats Ertapenem:

or meet (1/100,

In clinical studies in children, most patients treated with injection antibiotics and then switched to appropriate oral antibiotics. During treatment and monitoring time of 14 days after treatment, adverse reactions related to drugs in patients using Invanz are similar to the reactions listed above.

After -sales experience

The following adverse reactions have been reported when the drug is used on the market:

Notify the physician with unwanted effects when using the drug.

There is no recommendation to use Invanz in children under 3 months old because there is no data.

The effect of the drug on the ability to drive and operate machinery

No data shows that Invanz affects the ability to drive and operate machinery.

Use drugs for women during pregnancy and lactation

Pregnancy

There is no full research and good control in pregnant women. Only use Invanz during pregnancy if the benefit is more than the risk of being able to occur for the mother and for the fetus.

Breastfeeding period

Ertapenem excreted through breast milk (see pharmacokinetics, distribution). Be cautious when using Invanz for breastfeeding mothers.

Drug interaction

When combining Ertapenem with Probenecid, Probenecid competition leads to inhibition of active elimination of Ertapenem through the renal tubules, so it increases with little but has statistical significance of the sale time (up 19%) and the concentration of Ertapenem in the body (25%). No need to adjust the Ertapenem dose when combined with probenecid. Because of the significant effect on Ertapenem's disposal time, it is not recommended to use Probenecid to extend Ertapenem's semi -waste time.

In vitro research shows that Ertapenem does not inhibit the transportation of digoxin or vinblastin via intermediaries P-Glycoprotein and Ertapenem are not the substrate used in the transport via intermediary P-Glycoprotein. Research in vitro on the liver microsom people found that Ertapenem did not inhibit the metabolism of other drugs through the catalyst of the 6 -form Cytochrom P450 (CYP) mainly: 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. It is not sure to interact with Ertapenem through the mechanism of inhibiting medication clearance through p-glycoprotein or through the catalyst of Cytochrom P450. (See pharmacokinetics, distribution and metabolism).

In addition to Probenecid, have not conducted other specialized studies on clinical interactions.

The articles on the literature on individual cases show that the use of carbapenems, including Ertapenem simultaneously with Valproic acid or Divalproex sodium will reduce Valproic acid levels. Valproic acid levels may be reduced lower than this interaction, thus increasing the risk of outbreak of seizures. Although the mechanism of this interaction is not well known, data from animal studies and in vitro shows that carbapenems can inhibit the hydrolysis of glucuronide conversion of Valproic acid (VPA-G) into Valproic acid, thus reducing the serum level of Valproic acid (see carefully).