The need to supplement the instructions for the use of medicines containing meropenem the following information:
1. In the section "With caution", the information should be revised to read:
"Simultaneous use with potentially nephrotoxic drugs.
Patients with gastrointestinal complaints (diarrhea), especially those suffering from colitis. "
2. In the section "Method of administration and dose" the information should be revised to read:
"Adults
The dose and duration of therapy should be determined depending on the type and severity of the infection and the condition of the patient.
The following daily doses are recommended:
500 mg intravenously every 8 hours for the treatment of pneumonia, urinary tract infections, gynecological infections such as endometritis, skin infections and skin structures;
1 g intravenously every 8 hours in the treatment of nosocomial pneumonia, peritonitis, suspected bacterial infection in patients with symptoms of neutropenia, and septicemia.
In the treatment of meningitis, the recommended dose is 2 g every 8 hours. In the treatment of certain infections, in particular, caused by less sensitive pathogens (such as Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp.), or with very severe infections, the recommended dose is up to 2 g every 8 hours. The safety of taking a dose of 2 g in the form of a bolus injection has not been sufficiently studied.
Dose in adult patients with impaired renal function
In patients with a creatinine clearance less than 51 mL / min, the dose should be reduced as follows
| Creatinine clearance (ml / min) | Dose (based on a unit dose of 500 mg, 1 g, 2 g) | Frequency of administration |
| 26-50 | one dose unit | every 12 hours |
| 10-25 | 0.5 unit dose | every 12 hours |
| <10 | 0.5 unit dose | every 24 hours |
Meropenem is excreted in hemodialysis and hemofiltration. If long-term treatment with meropenem is required, it is recommended that the drug (depending on the type and severity of the infection) be administered at the end of the hemodialysis procedure in order to restore the effective concentration in the blood plasma.
At present, there is no evidence of experience with the use of meropenem for administration to patients on peritoneal dialysis.
Dosing in adult patients with impaired hepatic function
In patients with hepatic insufficiency, there is no need for dose adjustment.
Elderly patients
In elderly patients with normal renal function or creatinine clearance greater than 50 mL / min, dose adjustment is not required.
Children
For children aged 3 months to 12 years, the recommended dose for intravenous administration is 10-20 mg / kg every 8 hours, depending on the type and severity of the infection,sensitivity of the pathogenic microorganism and the patient's condition.
Children weighing more than 50 kg should use doses for adults. With meningitis, the recommended dose is 40 mg / kg every 8 hours.
In the treatment of certain infections, in particular, caused by less sensitive pathogens (such as Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp.), or with very severe infections, the recommended dose is up to 40 mg / kg every 8 hours. The safety of taking a dose of 40 mg / kg as a bolus injection has not been sufficiently studied.
There is no experience of using the drug in children with impaired liver and kidney function.
Method of administration
Meropenem for intravenous administration can be administered as an intravenous bolus injection for at least 5 minutes, or as an intravenous infusion for 15-30 minutes; appropriate infusion liquids should be used for dilution.
The possibility of using meropenem in the regime of prolonged infusion (up to 3 hours) is based on pharmacokinetic and pharmacodynamic parameters. To date, clinical data and safety data supporting this regimen are limited.
To prepare a solution for intravenous bolus injections meropenem should be dissolved with sterile water for injection (5 ml per 250 mg of meropenem), with a solution concentration of 50 mg / ml. To prepare a solution for intravenous infusion meropenem should be dissolved 0.9% solution of sodium chloride for infusion or 5% solution of dextrose (glucose) for infusion, with the concentration of the solution should be from 1 to 20 mg / ml.
The solution of meropenem should not be frozen.
The prepared solution is recommended to be administered immediately after preparation (from the microbiological point of view), if the conditions for the preparation of the solution do not exclude the possibility of microbiological contamination. "
Information on storage of prepared solutions of meropenem with the use of sterile water for injection and 0.9% solution of sodium chloride for infusions may be added to the section if there is data confirming the stability of the prepared solutions under the stated storage conditions.
3. The section "Side effect" is to be presented in the following edition:
"Generally, meropenem is characterized by good tolerability. In rare cases, side effects led to the abolition of therapy. Serious adverse reactions are rare.
The frequency of adverse reactions is given in the form of the following gradation: very often (> 1/10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000), unspecified frequency (frequency can not be determined based on available data).
Hematology system *
Often: thrombocytosis;
Infrequently: eosinophilia, thrombocytopenia;
Rarely: leukopenia, neutropenia, agranulocytosis;
Rarely: hemolytic anemia.
Nervous system
Infrequently: headache, paresthesia, syncope **, hallucinations **, depression **, anxiety **, increased excitability **, insomnia **;
Rarely: convulsions.
Gastrointestinal tract
Often: nausea, vomiting, diarrhea, increased activity of "liver" transaminases, alkaline phosphatase, lactate dehydrogenase and serum bilirubin concentration;
Infrequently: constipation **, cholestatic hepatitis **;
Rarely: pseudomembranous colitis.
Skin and subcutaneous tissue
Infrequently: a rash, hives, itching;
Rarely: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis;
Unspecified frequency: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).
The immune system
Rarely: angioedema, manifestations of anaphylaxis.
The cardiovascular system
Infrequently: heart failure **, cardiac arrest **, tachycardia **, bradycardia **, myocardial infarction **, a decrease or increase in blood pressure (BP) **, thromboembolism of the branches of the pulmonary artery * *.
Kidneys and urinary tract
Infrequently: increasing the concentration of creatinine in the blood, increasing the concentration of urea in the blood.
Respiratory tract
Infrequently: dyspnea **.
Other
Often: local reactions - inflammation, thrombophlebitis, pain at the injection site;
Rarely: vaginal candidiasis and candidiasis of the oral mucosa.
* There were reported cases of positive direct or indirect Coombs test, as well as cases of partial thromboplastin time reduction.
** Cause-and-effect relationship with taking meropenem is not established. "