Imipenem + Cilastatin

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Imipenem + Cilastatin: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Imipenem + Cilastatin

ATX code: J01DH51

Active ingredient: Imipenem (imipenem), cilastatin (cilastatin)

Producer: KRASFARMA, JSC (Russia)

Description and photo update: 18.10.2018

Prices in pharmacies: from 525 rubles.

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Powder for preparation of solution for infusion Imipenem + Cilastatin

Imipenem + Cilastatin - carbapenem, an antibacterial drug.

Release form and composition

Dosage form Imipenem + Cilastatin - powder for preparation of solution for infusion: dry mass of white with a yellow tint or white (in a bottle: in a cardboard box 1 bottle; in a cardboard box 10 bottles; for hospitals - in a cardboard box 50 or 1-50 bottles).

1 bottle contains:

active ingredients: imipenem (in the form of monohydrate) - 0.5 g, cilastatin (in the form of sodium cilastatin) - 0.5 g;
excipient: sodium bicarbonate.

Pharmacological properties

Pharmacodynamics

Imipenem + Cilastatin is a combined antibacterial drug that consists of two components.

Imipenem belongs to beta-lactam antibiotics of a new class - thienamycins, is an inhibitor of bacterial cell wall synthesis, has a bactericidal effect against a wide range of pathogenic gram-positive and gram-negative microorganisms, including aerobic and anaerobic.

Cilastatin sodium is a specific inhibitor enzyme, does not have its own antibacterial activity and does not inhibit the beta-lactamase of bacteria. It slows down the metabolism of imipenem in the kidneys and contributes to a significant increase in the level of unchanged imipenem in the urinary tract.

The drug is resistant to degradation by bacterial beta-lactamases, which makes it highly effective against many microorganisms, including Pseudomonas aeruginosa, Serratia spp. and Enterobacter spp.

Antimicrobial sensitivity of imipenem, established by in vitro and in vivo studies:

aerobic gram-positive microorganisms: Enterococcus faecium (only in vivo), Enterococcus faecalis, Staphylococcus aureus (including penicillinase-forming strains), Streptococcus pneumoniae, Streptococcus agalactiae (Streptococcus group B streptococci), Streptococcus epidermalis including Staphylococcus aureus (including Staphylococcus) Methicillin-resistant staphylococci are insensitive to imipenem;
aerobic gram negative microorganisms: Citrobacter spp., Acinetobacter spp., Enterobacter spp., Gardnerella vaginalis, Escherichia coli, Haemophilus parainfluenzae, Haemophilus influenzae, Morganella morganii, Serugiella spp., Proteus vulgaris, Ps. spp. In vitro imipenem is inactive against Stenotrophomonas maltophilia and some strains of Burkholderia cepacia;
anaerobic gram-positive microorganisms: Propionibacterium spp., Clostridium spp., Bifidobacterium spp., Eubacterium spp., Peptostreptococcus spp., Peptococcus spp.;
anaerobic gram-negative microorganisms: Fusobacterium spp., B. Fragilis and other Bacteroides spp.

Only in vitro is imipenem susceptible to the following bacteria:

aerobic gram-positive microorganisms: Listeria monocytogenes, Bacillus spp., Nocardia spp., Streptococcus spp. (group C, G and Viridans), Staphylococcus saprophyticus;
aerobic gram-negative microorganisms: Alcaligenes spp., Aeromonas hydrophila, Capnocytophaga spp., Neisseria gonorrhoeae (including penicillinase-forming strains), Providencia stuartii, Pasteurella spp., Haemophilus ducreyi;
anaerobic gram-negative microorganisms: Prevotella disiens, Prevotella bivia, Veillonella spp., Prevotella melaninogenica.

Synergism of action in vitro occurs in combination with aminoglycosides to some strains of Pseudomonas aeruginosa.

Pharmacokinetics

The maximum concentration (C _max) of the drug in the blood plasma after intravenous administration of the solution occurs in about 0.3 hours and for imipenem is from 0.021 to 0.058 mg / ml, for cilastatin - from 0.021 to 0.055 mg / ml. 4-6 hours after the infusion, the C _{max of} imipenem decreases to 0.001 mg / ml and below.

The half-life of Imipenem + Cilastatin is 1 hour.

Plasma protein binding for imipenem is 20%, cilastatin - 40%.

Within 10 hours, about 70% of imipenem is excreted by the kidneys. In urine, imipenem levels above 0.01 mg / ml can persist for 8 hours.

About 70–80% of cilastatin is excreted by the kidneys within 10 hours.

In patients with normal renal function, intravenous administration of the drug every 6 hours does not cause accumulation of imipenem or cilastatin in urine or blood plasma.

Indications for use

According to the instructions, Imipenem + Cilastatin is indicated for the treatment of infectious and inflammatory pathologies caused by microorganisms sensitive to it:

intra-abdominal infections;
lower respiratory tract infections;
gynecological infections;
urinary tract infections;
bacterial septicemia;
infectious diseases of the skin and soft tissues;
joint and bone infections;
bacterial endocarditis.

In addition, Imipenem + Cilastatin is prescribed for the prevention of infectious complications after surgery.

Contraindications

chronic renal failure with creatinine clearance (CC) less than 5 ml / min per 1.73 m ² in patients without hemodialysis;
age up to 3 months of life;
breast-feeding;
severe renal failure in children with a serum creatinine concentration of more than 2 mg / dL;
hypersensitivity to penicillins, cephalosporins, beta-lactam antibiotics, carbapenems or drug components.

With caution, Imipenem + Cilastatin should be prescribed for diseases of the gastrointestinal tract in history, pseudomembranous colitis, pathologies of the central nervous system (CNS), concomitant anticonvulsant therapy with valproic acid, CC less than 70 ml / min per 1.73 m ², hemodialysis use, pregnancy, sick in old age.

Instructions for use Imipenem + Cilastatin: method and dosage

The ready-made solution of the drug Imipenem + Cilastatin is used intravenously (iv) by drop.

The dose of the drug is prescribed on the basis of imipenem.

The duration of the infusion depends on the dose used, so for the introduction of doses of less than 0.5 g of the drug it takes 0.5 hour, for a dose of more than 0.5 g - 1 hour. If the patient develops nausea during the infusion, the drip rate of the drug should be reduced.

To prepare the solution, 100 ml of the infusion solution is required. To the contents of the vial, add 10–20 ml of an approved solvent and shake the vial until a homogeneous suspension is obtained. Do not use the resulting suspension for administration! It must be dissolved in a bottle in the remaining (80–90 ml) part of the infusion solution to obtain a total solution volume of 100 ml. For a complete collection of the remaining suspension from the walls of the vial, 20 ml of the resulting solution should be re-added to the vial, shaken well and combined with the total mass. Shake thoroughly again so that the resulting solution has a transparent structure. A ready-made solution for infusion in a volume of 100 ml with an imipenem concentration of 0.005 g per 1 ml may have a color from colorless to yellow. It remains stable for 4 hours at room temperature, 24 hours when stored in a refrigerator.

To prepare the solution, the following infusion solutions can be used: 0.9% sodium chloride solution, 5% or 10% dextrose solution, 5% dextrose solution and 0.45% sodium chloride solution, 0.9% sodium chloride solution and 5% dextrose solution, 5% dextrose solution and 0.225% sodium chloride solution, 0.15% potassium chloride solution and 5% dextrose solution.

The finished solution of the drug cannot be administered intramuscularly!

Recommended daily dosage, calculated using imipenem, for patients without renal impairment and body weight of 70 kg or more:

mild infection, uncomplicated urinary tract infections: 1 g - 0.25 g 4 times a day;
moderate form of infection: 1.5–2 g - 0.5 g 3 times a day or 1 g 2 times a day;
severe form of infection, complicated urinary tract infections: 2 g - 0.5 g 4 times a day;
infections that threaten the patient's life: 3-4 g - 1 g 3-4 times a day.

Prevention of postoperative infections is carried out by introducing 1 g of the drug during induction anesthesia, then 1 g after 3 hours. With a high degree of risk of infection (surgery on the colon and rectum), an additional administration of 0.5 g is prescribed 8 and 16 hours after general anesthesia.

Dose adjustment of Imipenem + Cilastatin is required with the patient's body weight up to 70 kg, taking into account clinical indications:

maximum daily dose of 1 g: 60-69 kg - 0.25 g 3 times a day, 40-59 kg - 0.125 g 4 times a day, 30-39 kg - 0.125 g 3 times a day;
maximum daily dose of 1.5 g: 50-69 kg - 0.25 g 4 times a day, 40-49 kg - 0.25 g 3 times a day, 30-39 kg - 0.125 g 4 times a day;
maximum daily dose of 2 g: 60–69 kg - 0.5 g 3 times a day, 40–59 kg - 0.25 g 4 times a day, 30–39 kg - 0.25 g 3 times a day;
maximum daily dose of 3 g: 60-69 kg - 0.75 g 3 times a day, 50-59 kg - 0.5 g 4 times a day, 40-49 kg - 0.5 g 3 times a day, 30–39 kg - 0.25 g 4 times a day;
maximum daily dose 4 g: 60-69 kg - 1 g 3 times a day, 50-59 kg - 0.75 g 3 times a day, 40-49 kg - 0.5 g 4 times a day, 30 –39 kg - 0.5 g 3 times a day.

In case of impaired renal function (CC less than 70 ml / min per 1.73 m ²), the dose should be reduced in proportion to CC and the patient's weight according to clinical indications.

If CC is less than 5 ml / min / 1.73 m ^{2, the} drug can be administered only if the patient undergoes a hemodialysis session in the next two days.

In patients on hemodialysis, the use of the drug is recommended only if the benefits of therapy outweigh the potential threat of seizures.

With peritoneal dialysis, there is no experience with the drug.

In children over the age of 3 months and with a body weight of up to 40 kg, a single dose is determined at the rate of 0.015 g per 1 kg of the child's weight. The frequency of administration is 4 times a day. The maximum daily dose is 2 g.

In case of impaired liver function and treatment of patients in old age, dose adjustment is not required.

Side effects

parasitic pathologies and infections: rarely - candidiasis, pseudomembranous colitis; very rarely - gastroenteritis;
from the lymphatic system and blood: often - eosinophilia; infrequently - neutropenia, pancytopenia, leukopenia, thrombocytosis, thrombocytopenia; rarely - agranulocytosis; very rarely - suppression of bone marrow function, hemolytic anemia;
from the immune system: rarely - anaphylactic reactions;
on the part of the psyche: infrequently - hallucinations, confusion, other mental disorders;
from the nervous system: infrequently - drowsiness, dizziness, convulsions, myoclonus; rarely - taste perversion, encephalopathy, tremor, paresthesia; very rarely - headache, exacerbation of myasthenia gravis; frequency unknown - dyskinesia, agitation;
from the organ of hearing, labyrinth disorders: rarely - hearing loss; very rarely - ringing in the ears, vertigo;
from the side of the vessels: often - thrombophlebitis; infrequently - a decrease in blood pressure (BP); very rarely - hot flashes;
from the heart: very rarely - tachycardia, cyanosis, palpitations;
from the respiratory system, chest and mediastinal organs: very rarely - sore throat, shortness of breath, hyperventilation;
from the gastrointestinal tract: often - nausea, vomiting (more often with granulocytopenia), diarrhea; rarely - staining of the teeth and / or tongue; very rarely - heartburn, glossitis, abdominal pain, hemorrhagic colitis, hypersalivation, hypertrophy of the papillae of the tongue;
from the liver and biliary tract: rarely - hepatitis, liver failure; very rarely - fulminant hepatitis;
dermatological reactions: often - rash (including exanthematous); infrequently - urticaria, itchy skin; rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, angioedema; very rarely - changes in the structure of the skin, hyperhidrosis;
from the musculoskeletal and connective tissue: very rarely - polyarthralgia, spinal pain in the thoracic region;
from the urinary system: rarely - polyuria, acute renal failure, discoloration of urine, oliguria or anuria;
from the genital organs: very rarely - genital itching;
general disorders and local reactions: infrequently - thickening of the skin and pain at the injection site, erythema, fever; very rarely - a feeling of discomfort in the chest, asthenia or weakness;
laboratory indicators: often - increased activity of alkaline phosphatase, increased activity of serum transaminases; infrequently - a decrease in hemoglobin, a positive direct Coombs' test, an increase in the concentration of serum creatinine, an increase in prothrombin time, an increase in the content of urea nitrogen in the blood, an increase in the level of serum bilirubin.

Overdose

Symptoms: nausea, vomiting, convulsions, confusion, decreased blood pressure, bradycardia, tremor.

Treatment: since there are no special methods of therapy for drug overdose, symptomatic treatment, hemodialysis should be used, although the effectiveness of this procedure has not been established.

special instructions

It is not recommended to use Imipenem + Cilastatin for the treatment of meningitis.

Staining the urine reddish is safe and should not be feared or mistaken for hematuria.

The use of the drug Imipenem + Cilastatin should be started after determining the causative agent of the infection, given the severity of infection, resistance to other antibiotics. It is necessary to make sure that the patient does not have allergic reactions to beta-lactam antibiotics. If symptoms of an allergic reaction appear, immediate discontinuation of therapy and the provision of emergency emergency care are required.

The use of the drug should be accompanied by careful monitoring of liver function for the development of hepatotoxic reactions, especially in patients with impaired liver function.

Due to the risk of developing antibiotic-associated colitis and pseudomembranous colitis, which threatens the patient's life, with the development of diarrhea while using the drug, a thorough diagnosis of its cause should be carried out. Infusion should be discontinued and appropriate therapy should be prescribed that does not include peristalsis-inhibiting agents.

Since with reduced renal function, the accumulation of Imipenem + Cilastatin occurs, it is necessary to very carefully approach the appointment of the dose to patients with reduced creatinine clearance. Correctly selected dose reduces the risk of developing adverse reactions from the central nervous system.

In patients with a brain injury, a history of seizures during the entire period of use of the drug Imipenem + Cilastatin, simultaneous therapy with antiepileptic drugs is required.

The condition of children with a history of seizures and the presence of neurological symptoms should be especially carefully monitored, while the use of drugs that reduce the seizure threshold of sensitivity.

When involuntary muscle twitching, minor tremors or seizures appear, a neurologist must prescribe anticonvulsant therapy. In the absence of a therapeutic effect from the central nervous system, the dose of Imipenem + Cilastatin should be reduced or its use should be discontinued.

Influence on the ability to drive vehicles and complex mechanisms

Since the use of the drug can cause side effects that affect the speed of psychomotor reactions and the patient's psyche, during the period of treatment, one should not engage in potentially hazardous activities, including driving vehicles and mechanisms.

Application during pregnancy and lactation

During pregnancy, the use of the drug is indicated only in exceptional cases when the expected effect of therapy for the mother significantly exceeds the potential threat to the fetus.

Since both active substances of the drug penetrate into breast milk, during lactation, Imipenem + Cilastatin can be used only after the termination of breastfeeding.

Pediatric use

The use of Imipenem + Cilastatin for the treatment of infants under the age of three months is contraindicated.

In children over the age of three months and with a body weight of up to 40 kg, a single dose is determined at the rate of 0.015 g per 1 kg of the child's weight. The frequency of administration is 4 times a day. The maximum daily dose is 2 g.

Children weighing more than 40 kg are prescribed the standard doses prescribed for the treatment of adults.

With impaired renal function

In case of impaired renal function (CC less than 70 ml / min per 1.73 m ²) the dose of Imipenem + Cilastatin should be proportionally reduced according to clinical indications.

Recommended dosage for mild infections, uncomplicated urinary tract infections in patients with impaired renal function:

CC 41-70 ml / min / 1.73 m ²: with a weight of more than 70 kg - 0.25 g 3 times a day, 50-69 kg - 0.125 g 4 times a day, 30-49 kg - 0.125 g 3 once a day;
CC 21-40 ml / min / 1.73 m ²: with a weight of more than 60 kg - 0.25 g 2 times a day, 50-59 kg - 0.125 g 3 times a day, 30-49 kg - 0.125 g 2 once a day;
CC 6–20 ml / min / 1.73 m ²: with a weight over 70 kg - 0.25 g 2 times a day, 30–69 kg - 0.125 g 2 times a day.

Recommended dosage at a maximum daily dose of 1.5 g for impaired renal function:

CC 41-70 ml / min / 1.73 m ²: with a weight of more than 70 kg - 0.25 g 4 times a day, 50-69 kg - 0.25 g 3 times a day, 40-49 kg - 0.125 g 4 times a day, 30–39 kg - 0.125 g 3 times a day;
CC 21-40 ml / min / 1.73 m ²: with a weight of more than 60 kg - 0.25 g 3 times a day, 50-59 kg - 0.25 g 2 times a day, 30-49 kg - 0.125 g 3 times a day;
CC 6–20 ml / min / 1.73 m ²: with a weight over 50 kg - 0.25 g 2 times a day, 30–49 kg - 0.125 g 2 times a day.

Recommended dosage at a maximum daily dose of 2 g for impaired renal function:

CC 41-70 ml / min / 1.73 m ²: with a weight of more than 70 kg - 0.5 g 3 times a day, 50-69 kg - 0.25 g 4 times a day, 40-49 kg - 0, 25 g 3 times a day, 30–39 kg - 0.125 g 4 times a day;
CC 21-40 ml / min / 1.73 m ²: with a weight over 70 kg - 0.25 g 4 times a day, 50-69 kg - 0.25 g 3 times a day, 40-49 kg - 0, 25 g 2 times a day, 30–39 kg - 0.125 g 3 times a day;
CC 6–20 ml / min / 1.73 m ²: with a weight of more than 40 kg - 0.25 g 2 times a day, 30–39 kg - 0.125 g 2 times a day.

Recommended dosage at a maximum daily dose of 3 g for impaired renal function:

CC 41-70 ml / min / 1.73 m ²: with a weight of more than 70 kg - 0.5 g 4 times a day, 50-69 kg - 0.5 g 3 times a day, 40-49 kg - 0, 25 g 4 times a day, 30–39 kg - 0.25 g 3 times a day;
CC 21-40 ml / min / 1.73 m ²: with a weight of more than 60 kg - 0.5 g 3 times a day, 50-59 kg - 0.25 g 4 times a day, 30-49 kg - 0, 25 g 3 times a day;
CC 6–20 ml / min / 1.73 m ²: with a weight of more than 60 kg - 0.5 g 2 times a day, 30–59 kg - 0.25 g 2 times a day.

Recommended dosage at a maximum daily dose of 4 g for impaired renal function:

CC 41-70 ml / min / 1.73 m ²: with a weight of more than 60 kg - 0.75 g 3 times a day, 50-59 kg - 0.5 g 4 times a day, 40-49 kg - 0, 5 g 3 times a day, 30–39 kg - 0.25 g 4 times a day;
CC 21-40 ml / min / 1.73 m ²: with a weight of more than 70 kg - 0.5 g 4 times a day, 50-69 kg - 0.5 g 3 times a day, 40-49 kg - 0, 25 g 4 times a day; 30–39 kg - 0.25 g 3 times a day;
CC 6–20 ml / min / 1.73 m ²: with a weight of more than 50 kg - 0.5 g 2 times a day, 40–49 kg - 0.25 g 2 times a day, 30–39 kg - 0.125 each d 2 times a day.

If CC is less than 5 ml / min / 1.73 m ^{2, the} drug can be administered only if the patient undergoes a hemodialysis session in the next two days.

Patients on hemodialysis (CC up to 5 ml / min / 1.73 m ²) are prescribed a dose of the drug as with CC 6–20 ml / min / 1.73 m2, it is administered immediately after a hemodialysis session, then every 12 hours. Patients on hemodialysis, especially with concomitant pathologies of the central nervous system, require careful medical supervision.

In patients on hemodialysis, the use of the drug is recommended only if the benefits of therapy outweigh the potential threat of seizures.

With peritoneal dialysis, there is no experience with the drug.

For violations of liver function

No dose adjustment is required in patients with impaired liver function.

Use in the elderly

When treating elderly patients with CC above 70 ml / min per 1.73 m ^{2, the} usual doses of Imipenem + Cilastatin are used.

Drug interactions

With the simultaneous use of the drug Imipenem + Cilastatin:

ganciclovir can cause generalized seizures;
probenecid increases the plasma concentration and half-life of imipenem;
valproic acid or sodium valproate reduces its concentration in blood plasma, causing an increased risk of developing a seizure;
warfarin and other oral anticoagulants increase their effect.

The solution should not be mixed in the same vial with other antibiotics; while prescribing another antibiotic, it should be used in isolation.

Analogs

Analogs of Imipenem + Cilastatin: Imipenem + Cilastatin-Vial, Tienam, Imipenem and cilastatin sodium, Aquapenem, Grimipenem, Tiepenem, Cilaspen, Tsilapenem.

Terms and conditions of storage

Keep out of the reach of children.

Store at temperatures up to 25 ° C.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Imipenem + Cilastatin

According to a few reviews, Imipenem + Cilastatin has established itself as a highly effective drug.

Price for Imipenem + Cilastatin in pharmacies

The price of Imipenem + Cilastatin can be 660 rubles for 1 bottle.