Tienam

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

Tienam: 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: Tienam

ATX code: J01DH51

Active ingredient: Imipenem (Imipenem) + Cilastatin (Cilastatin)

Manufacturer: Merck Sharp and Dome Corp. (Merck Sharp & Dohme Corp.) (USA); Neopharmed (Italy); Merck Sharp and Dome B. V. (Merck Sharp & Dohme, BV) (Netherlands); Ortat, JSC (Russia)

Description and photo updated: 28.08.

Powder for preparation of solution for infusion Tienam

Tienam is a two-component highly effective antibiotic with bactericidal action, active against a wide range of aerobic and anaerobic pathogenic microorganisms, both gram-positive and gram-negative.

Release form and composition

powder for preparation of suspension / solution for intramuscular (i / m) administration: powdery mass from yellowish-white to white (in glass vials, in a cardboard box 1 vial);
powder for preparation of solution for infusion [intravenous (i / v) administration]: powdery mass from light yellow to white (in glass vials with a volume of 20 ml, 10 vials in plastic trays or 25 vials in cardboard boxes; in glass vials with a volume of 115 ml, complete with connecting tubes, in a cardboard box 5 sets).

Each pack also contains instructions for using Tienam.

Active ingredients in 1 powder bottle for preparation of suspension for intramuscular administration: sterile imipenem - equivalent to 0.5 g of anhydrous thienamycin formamide monohydrate; sterile cilastatin sodium is equivalent to 0.5 g of cilastatin acid.

Contents of 1 bottle for preparation of solution for infusion:

active ingredients: sterile imipenem - 0.5 g, sterile sodium cilastatin - 0.5 g;
auxiliary component: sterile sodium bicarbonate / sodium bicarbonate - 0.02 g.

Pharmacological properties

Pharmacodynamics

Tienam has antibacterial, bactericidal and antimicrobial efficacy. Its therapeutic effect is due to the properties of two active components that make up the drug:

imipenem: the first representative of thienamycins (carbapenems) of a new class, extremely effective β-lactam antibiotics;
cilastatin sodium: a specific inhibitor enzyme that inhibits the renal metabolism of imipenem and significantly increases the level of unchanged imipenem in the urinary tract.

Being a highly effective inhibitor of bacterial cell wall synthesis, imipenem exhibits bactericidal action against a wide range of various aerobic and anaerobic pathogenic microorganisms, both gram-positive and gram-negative.

Thienam is resistant to degradation by bacterial β-lactamases, which ensures its high activity against many microorganisms (for example, Pseudomonas aeruginosa, Enterobacter spp., Serratia spp.) Resistant to most other β-lactam antibiotics.

Cilastatin does not possess its own antibacterial activity and does not inhibit the β-lactamase of bacteria.

The antibacterial spectrum of Tienam includes most of the clinically significant pathogenic microflora. According to confirmed experimental studies, the following microorganisms are susceptible to imipenem in vivo and in vitro:

gram-positive aerobes: Enterococcus faecalis (in vitro Enterococcus faecium is resistant); Staphylococcus aureus, including strains that form penicillinase; Staphylococcus epidermidis, including strains that form penicillinase (methicillin-resistant staphylococcus insensitive to imipenem); Streptococcus pneumoniae; streptococci belonging to group B (Streptococcus agalactiae); Streptococcus pyogenes;
gram-negative aerobes: Acinetobacter spp.; Enterobacter spp.; Citrobacter spp.; Escherichia coli; Haemophilus influenzae; Gardnerella vaginalis; Haemophilus parainfluenzae; Morganella morganii; Klebsiella spp.; Providencia rettgeri; Proteus vulgaris; Pseudomonas aeruginosa [imipenem is inactive in vitro against Stenotrophomonas (formerly Xanthomonas, formerly Pseudomonas) maltophilia and some Burkholderia cepacia strains]; Serratia spp. Including S. marcescens;
gram-positive anaerobes: Clostridium spp.; Bifidobacterium spp.; Eubacterium spp.; Peptostreptococcus spp.; Peptococcus spp.; Propionibacterium spp.;
gram-negative anaerobes: Fusobacterium spp.; Bacteroides spp., Including B. fragilis.

In vitro sensitivity with unknown clinical efficacy to imipenem was shown by:

gram-positive aerobes: Bacillus spp.; Nocardia spp.; Listeria monocytogenes; Staphylococcus saprophyticus; Streptococcus spp. groups C and G, Streptococcus viridans;
gram-negative aerobes: Alcaligenes spp.; Aeromonas hydrophila; Capnocytophaga spp.; Neisseria gonorrhoeae, including Pasteurella spp. Strains that form penicillinase; Haemophilus ducreyi; Providencia stuartii;
gram-negative anaerobes: Prevotella melaninogenica; Prevotella disiens; Prevotella bivia; Veillonella spp.

Imipenem in vitro exhibits synergism with aminoglycosides against some strains of Pseudomonas aeruginosa.

Pharmacokinetics

Powder for solution for infusion (IV injection)

After intravenous administration of a solution prepared from Tienam powder, for both active components of the drug T _Cmax (time to reach the maximum plasma concentration) is 20 minutes. The Cmax (maximum plasma concentration) index for imipenem is 21–58 μg / ml, for cilastatin - 21–55 μg / ml. Within 4-6 hours after the administration of Tienam, Cmax of imipenem drops to 1 μg / ml and below.

T _1/2 (half-life) of each of the active substances of the drug is 1 hour. Imipenem binds to plasma proteins by 20%, cilastatin by 40%. About 70% of the imipenem administered by infusion is eliminated by the kidneys within 10 hours. Its concentration in urine above 10 μg / ml can persist for up to 8 hours after intravenous administration of the solution. Cilastatin is excreted by the kidneys by 70-80% in 10 hours.

Regular intravenous infusions of Tienam with a frequency of once every 6 hours in patients with normal renal function in plasma or urine did not detect accumulation of imipenem / cilastatin.

Average values of the level of imipenem in tissues and environments of the human body, recorded after infusion of 1 g of Tienam [concentration of imipenem / measurement time - μg / ml (μg / g) / h]:

vitreous body of the eyeball: 3.4 / 3.5;
intraocular fluid: 2.99 / 2.0;
pulmonary parenchyma: 5.6 / 1.0;
sputum: 2.1 / 1.0;
pleural fluid: 22.0 / 1.0;
peritoneal fluid: 23.9 / 2.0;
bile: 5.3 / 2.25;
CSF (not inflamed): 1.0 / 4.0;
CSF (inflamed): 2.6 / 2.0;
secret of the prostate gland: 0.2 / 1.0-1.5;
prostate tissue: 5.3 / 1.0–2.75;
fallopian tubes: 13.6 / 1.0;
endometrium: 11.0 / 1.0;
myometrium: 5.0 / 1.0;
bone tissue: 2.6 / 1.0;
interstitial fluid: 16.4 / 1.0;
leather: 4.4 / 1.0;
connective tissue: 4.4 / 1.0.

Powder for preparation of suspension / solution for intramuscular (i / m) administration

After injection of a suspension / solution of Tienam (0.5 g of imipenem + 0.5 g of cilastatin), the plasma T _Cmax for imipenem is 2 hours; for cilastatin - 1 hour. Cmax of imipenem reaches 10 μg / ml, for cilastatin - 24 μg / ml.

With intramuscular administration of Tienam, the bioavailability of imipenem is approximately 75% of that with intravenous administration, and cilastatin is 95%. It is absorbed by imipenem from the intramuscular injection area for about 6-8 hours, the absorption of cilastatin is 4 hours in this case. Prolonged absorption of imipenem due to intramuscular injection provides T _1/2 = 2-3 hours, with persistence for 6 hours after administration 0.5 g of imipenem in plasma Cmax of at least 2 μg / ml. This allows the drug to be dosed 2 times a day (1 time in 12 hours), the expected cumulation of imipenem is insignificant, and the accumulation of cilastatin in tissues and organs is not observed.

Comparison of the dynamics of the Cmax index for imipenem after i / m and i / v administration of Tienam (0.5 g of imipenem + 0.5 g of cilastatin), correlation of Cmax of imipenem in plasma (μg / ml) depending on the time elapsed after administration (in / in ÷ in / m):

25 min - 45.1 ÷ 6.0;
60 min (1 h) - 21.6 ÷ 9.4;
120 min (2 h) - 10.0 ÷ 9.9;
240 min (4 h) - 2.6 ÷ 5.6;
360 min (6 h) - 0.6 ÷ 2.5;
720 min (12 h) - n / a ¹ ÷ 0.5.

¹ n / a - substance in plasma is not detected.

After i / m administration of Tienam, the concentration of imipenem in the urine for 12 hours remains at a level of more than 10 μg / ml. During this time, 50% of imipenem and 75% of cilastatin are excreted by the kidneys from the dose received.

Due to the i / m administration of Tienam in healthy volunteers, Cmax in the interstitial fluid reaches 5.0 μg / ml approximately 3.5 hours after injection.

Indications for use

Thienam is used to treat moderate and severe infections caused by pathogenic microbes (including strains producing penicillinase) sensitive to thienamycins, as well as for empirical therapy (treatment of an infectious process before identifying the pathogen and determining its sensitivity to these drugs) with bacterial infection with the following localization:

urinary tract;
lower respiratory tract [pneumonia, bronchitis, exacerbation of chronic obstructive pulmonary disease (COPD)];
bones and joints;
organs of the abdominal cavity (intra-abdominal infections, including acute gangrenous and perforated appendicitis, including those complicated by peritonitis);
female genital organs (gynecological infections, including postpartum endomyometritis);
blood (bacterial septicemia);
skin and soft tissues (phlegmon, abscess, infected ulcers and wounds);
tissues of the valve apparatus of the heart and endothelium (infective endocarditis).

For prophylactic purposes, Tienam is used in the perioperative period in patients at risk with a high probability of developing intraoperative and postoperative infection.

Contraindications

Absolute:

renal failure with creatinine clearance (CC) <20 ml / min / 1.73 m ² (powder for preparing a suspension for intramuscular injection), CC <5 ml / min / 1.73 m ² (powder for preparing a solution for infusion);
children's age up to 3 months (powder for solution for infusion);
children under 12 years of age (powder for preparing a suspension for intramuscular injection);
hypersensitivity to drug components, other β-lactam antibiotics, cephalosporins, penicillins.

When using lidocaine hydrochloride to dilute Tienam powder, i / m administration of the resulting solution is contraindicated in cases of known hypersensitivity to local amide anesthetics, as well as in severe shock and intracardiac conduction blockade.

Relative (Tienam is used with caution):

pseudomembranous colitis;
history of diseases of the gastrointestinal tract;
hepatic failure with CC 20–70 ml / min / 1.73 m ²;
diseases of the central nervous system (CNS);
advanced age> 65 years.

The drug in the form of a solution for intravenous infusion is used with caution in patients on dialysis.

Since special studies of the teratogenic and embryogenic effects of Tienam have not been carried out, the appointment of Tienam during pregnancy is permissible only if the benefits of therapy for the mother exceed the potential risk to the fetus.

Imipenem passes into breast milk, therefore, if the use of Tienam is deemed necessary, breastfeeding is suspended or stopped.

Tienam, instructions for use: method and dosage

Tienam in the form of a solution for intramuscular administration should not be used for infusion, and the infusion solution should not be administered intramuscularly.

The dosage regimen and dosage form (route of administration) is determined by the attending physician, taking into account the severity of the infection, the sensitivity of the pathogenic microflora to Tienam, the location of the infection, kidney function and the patient's weight.

Tienam for intramuscular injections and for infusions (intravenous administration) should not be mixed with other antibiotics.

Powder for preparation of suspension / solution for intramuscular injection

Tienam is injected deeply intramuscularly into large muscles (such as the gluteus or lateral thigh muscles). To avoid intravascular administration, a trial aspiration must be performed before injection.

The recommended doses of imipenem at a frequency of injections 1 time per 12 hours: infections of the skin and soft tissues, lower respiratory tract, female genital organs - 0.5 g each; intra-abdominal infections - 0.75 g each

The course of therapy depends on the type of pathogen and the severity of the infection. Treatment is usually continued for at least another 2 days after all symptoms disappear. The safety and efficacy of treatment duration over 2 weeks have not been established.

The total daily dose for intramuscular administration should not exceed 1.5 g of imipenem (3 vials of the drug). If higher doses are required, it is necessary to use an antibiotic in a dosage form for intravenous administration.

To obtain a dose of Tienam containing 0.5 g of imipenem, 2 ml of solvent are added to the powder bottle. The total volume of the resulting solution is 2.8 ml.

As a solvent for Tienam powder, you can use water for injection, saline or lidocaine hydrochloride solution 1% (without adrenaline). The prepared solution should be white or slightly yellowish, it should be used within an hour.

Powder for solution for infusion

Tienam is given by intravenous infusion. Single dose administration time ≤ 0.5 g - 20-30 minutes,> 0.5 g - 40-60 minutes. If during the infusion of the drug the patient complains of nausea, the rate of Tienam infusion should be slowed down.

The recommended average daily therapeutic dose, calculated on the basis of imipenem (divided into several injections in equal doses) - 1-2 g, divided into 3-4 injections. With infections of moderate severity, the daily dose may be 2 g for 2 injections.

For infections caused by less sensitive pathogenic microflora, the daily dose can be increased to a maximum - up to 4 g or 0.05 g / kg (of these two doses, the smaller is chosen).

For children from 3 months and older (with a body weight of up to 40 kg), the required dose is determined at the rate of 0.015 g / kg and administered once every 6 hours. For the treatment of children weighing more than 40 kg, the dosage regimen of adult patients is used. The maximum daily dose for children is 2 g.

As a solvent for Tienam powder for infusion are used: isotonic sodium chloride solution, 5% or 10% aqueous dextrose solution, 5% dextrose and 0.225%, 0.45% or 0.9% sodium chloride, 5% dextrose and 0.15 % potassium chloride, 5% or 10% mannitol solution.

To obtain a solution of Tienam for injection of average concentration - 0.005 g / ml of imipenem - add 100 ml of solvent to a vial of powder (0.5 g). The preparation of the Tienam solution for infusion is carried out as follows:

Take the solvent required to prepare the solution in a volume of 100 ml.
Introduce 10 ml of solvent into a 20 ml vial with a preparation and dilute the powder, shaking the vial well.
The resulting solution cannot be used for administration; it should be transferred to a vial or container with the rest of the solvent in a volume of 90 ml.

The period of stability (use) of the solution at room temperature up to 25 ° C is 4 hours; chilled to 4 ° C - 24 h.

Thienam is chemically incompatible with lactate (lactic acid), therefore, solvents containing lactate are not used to prepare the infusion solution. However, it is allowed to inject Tienam's solution intravenously using an infusion system through which a solution containing lactate was injected.

Side effects

Usually Tienam is well tolerated, side effects are transient, mild and, as a rule, do not require discontinuation of therapy. Serious adverse reactions are rare.

The following side effects from organs and systems were most often noted:

digestive system: nausea / vomiting, diarrhea, the risk of developing pseudomembranous colitis caused by Clostridium difficile (typical for the use of broad-spectrum antibacterial drugs), both during and after treatment, hepatitis (including fulminant), hemorrhagic colitis, liver failure, jaundice, pigmentation of the teeth and tongue, hypertrophy of the papillae of the tongue, gastroenteritis, glossitis, abdominal pain, heartburn, hypersalivation, increased levels of bilirubin, serum transaminases and / or alkaline phosphatase;
central nervous system: tremor, confusion, paresthesia, vertigo, myoclonus, headache, encephalopathy, mental disorders (including hallucinations);
sensory organs: noise and ringing in the ears, hearing loss, taste perversion;
respiratory system: hyperventilation, shortness of breath, chest discomfort, pain in the thoracic spine;
cardiovascular system: palpitations, tachycardia;
hypersensitivity reactions: rash, urticaria, itching, excessive sweating, cyanosis, Stevens-Johnson syndrome, angioedema, Lyell's syndrome (rarely), exfoliative dermatitis (rarely), fever (including drug), erythema multiforme, anaphylactic reactions;
electrolyte balance: a decrease in the serum concentration of chlorine and sodium, an increase in the concentration of potassium;
urinary system: polyuria, oliguria / anuria, proteinuria, leukocyturia, cylindruria, erythrocyturia, increased bilirubin concentration, change in urine staining (safe, should not be mistaken for hematuria), increased serum creatinine and urea concentrations, acute renal failure (rare);
laboratory parameters: inhibition of the function of the red line of bone marrow, agranulocytosis, pancytopenia, thrombocytopenia, leukopenia, hemolytic anemia, neutropenia, eosinophilia, leukocytosis, monocytosis, thrombocytosis, lymphocytosis, decrease in hemoglobin and hematocrit, increase in prothrombin time;
reactions at the injection site: pain, phlebitis / thrombophlebitis, erythema, vein compaction, infection at the injection site of Tienam;
other: sore throat, candidiasis, high levels of low density lipoprotein (LDL).

Overdose

Symptoms of a Tienam overdose are similar to the side effect profile of the drug and may include tremors, confusion, seizures, nausea / vomiting, hypotension, bradycardia.

There are no specific recommendations for the treatment of the condition. The parenteral administration of the solution should be discontinued and symptomatic and supportive treatment prescribed.

Imipenem and cilastatin sodium are excreted during hemodialysis, but the effectiveness of this procedure for treating an overdose of Tienam has not been studied.

special instructions

Since during infusion therapy the antibiotic enters directly into the circulatory system, it is preferable to use solution for intravenous administration at the beginning of treatment for endocarditis, bacterial sepsis, other severe / life-threatening infections (including lower respiratory tract infections caused by Pseudomonas aeruginosa), as well as with significant physiological violations such as shock.

Against the background of antibiotic therapy, life-threatening conditions can develop: seizures, anaphylaxis, severe clinical forms of pseudomembranous colitis (Clostridium difficile infection), and therefore the use of Tienam requires special attention of medical personnel and the availability of the possibility of providing emergency medical care if necessary.

Like other β-lactam antibiotics, Pseudomonas aeruginosa can develop resistance to Thienam rather quickly, therefore, during therapy, in accordance with the clinical situation, it is recommended to carry out tests for susceptibility to imipenem.

Patients should take into account the sodium content in 0.5 g of Tienam (depending on the dosage form):

powder for preparation of solution for infusion - 0.0375 g (1.6 meq);
powder for the preparation of a solution for intramuscular injections - 0.032 g (1.4 meq).

In the course of clinical studies, it was found that the safety and efficacy of Tienam in elderly patients> 65 years of age with intravenous administration did not differ from those in younger patients. But the disorders of the liver, kidneys, cardiovascular system characteristic of this age group, as well as the presence of concomitant diseases and drug therapy, require caution when choosing a dose. Patients over 65 are advised to adhere to the lower dose limit and periodically monitor renal excretory function.

There are insufficient data on the safety and efficacy of Tienam for intravenous infusion in children under 3 months of age, and in impaired renal function with a serum creatinine value of> 2 mg / dL.

Influence on the ability to drive vehicles and complex mechanisms

Since some of the adverse reactions recorded with the use of Tienam (such as confusion, vertigo, severe headache, mental disorders, including hallucinations) can affect the speed of psychomotor reactions and concentration, patients should refrain from driving and working with difficult, potentially dangerous mechanisms.

Application during pregnancy and lactation

Due to the lack of clinical studies of the effect of Tienam on the course of pregnancy and the condition of the fetus, the drug during gestation is prescribed only for strict indications, provided that the benefits of treatment for the mother are significantly exceeded over the potential risk for the fetus.

Imipenem passes into human breast milk, therefore, if it is necessary to use Tienam, breastfeeding should be stopped.

Pediatric use

In pediatric practice, Tienam is used for the same indications as in adult patients, but taking into account the following age restrictions:

powder for the preparation of a solution for infusion (intravenous injection): it is allowed to use it to treat children over 3 months of age;
powder for preparation of suspension / solution for intramuscular injection: it is allowed to use it for the treatment of children over 12 years of age.

With impaired renal function

Patients with impaired renal function require correction of the dosage regimen, which is carried out by the attending physician, taking into account the patient's weight, the sensitivity of the pathogen to Tienam, the severity and localization of the infection, as well as the creatinine clearance rate (ml / min / 1.73 m ²).

Intravenous administration of Tienam at a dose of 0.5 g with creatinine clearance in the range of 6–20 ml / min / 1.73 m ² may increase the likelihood of seizures.

If creatinine clearance is less than 5 ml / min / 1.73 m ^2, Tienam infusions are permissible only if the hemodialysis procedure is carried out no later than 48 hours after them.

The appointment of Tienam for hemodialysis is permissible only if the benefits of treatment exceed the potential risk of seizures. During hemodialysis, imipenem and cilastatin are removed from the systemic circulation, therefore, Tienam infusions should be carried out after the hemodialysis procedure and then at intervals of 12 hours from the moment of its completion. Patients on hemodialysis, especially those with diseases of the central nervous system, during therapy with Tienam require careful medical supervision.

For violations of liver function

There is no need to adjust the dosage regimen of Tienam in patients with liver disease. But due to the presence of a risk of hepatotoxicity (liver failure, increased transaminase activity, fulminant hepatitis), careful monitoring of hepatic function is required.

Use in the elderly

Elderly patients with normal renal function do not require dose adjustment of Tienam.

With the intramuscular administration of Tienam, persons over 65 years of age should take into account the decrease in liver / kidney and cardiovascular system functions characteristic of this age, the presence of concomitant diseases, and their simultaneous drug treatment. The dose selection is required with caution, adhering to the lower recommended limits, if possible, it is necessary to monitor renal excretory function.

Drug interactions

Thienam for intramuscular and intravenous administration should not be mixed with other antibiotics or added to their solutions.

The combined use of ganciclovir and Tienam in the form of intravenous infusions can cause generalized convulsions, therefore their combined use is not recommended, except in cases where the potential benefits of therapy exceed the possible risks.

Probenecid slightly increases the plasma concentration and the half-life of Tienam; joint drug therapy is not recommended.

Tienam reduces the plasma concentration of valproic acid, increasing the risk of seizure activity (cases reported in clinical practice), it is recommended to monitor the level of valproic acid.

Simultaneous isolated administration of other antibiotics (aminoglycosides) with the infusion of Tienam is allowed.

Analogs

The analogues of Tienam are: Aquapenem, Grimipenem, Imipenem and Cilastatin Jodas, Imipenem and Cilastatin Spencer, Imipenem + Cilastatin, Imipenem + Cilastatin-Vial, Tiepenem, Cilapenem, Cilaspen, etc.

Terms and conditions of storage

Keep out of the reach of children at a temperature not exceeding 25 ° C.

Shelf life: powder for preparation of solution for infusion - 2 years, powder for preparation of suspension for intramuscular injection - 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Tienam

Most patients leave only positive reviews about Tienam. Due to its high antibacterial effectiveness, the drug copes if other drugs do not work. Cases are described when, due to the timely completion of the course of antibiotic therapy, it was possible to avoid surgical interventions. The broad spectrum of its antibacterial action is emphasized separately.

Despite the high cost of Tienam, if the doctor has prescribed this particular drug, patients recommend using it.

Price for Tienam in pharmacies

Estimated price of Tienam:

powder for preparation of solution for infusion (500 mg + 500 mg), 10 pcs. bottle (bottle) 20 ml, contour plastic packaging (pallets) 10, plastic film - 5313 rubles;
powder for preparation of a solution for intramuscular administration (500 mg + 500 mg), 20 ml 10 pcs. - 4700 rubles.

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!