Thienam

Tienam is a systemic antibacterial drug.

Indications Thienam

It is used to eliminate infectious lesions of the skin, lower respiratory system, joints with soft tissues, and in addition to this, organs in the pelvic area. It is also used in the treatment of sepsis, infections that have arisen inside the peritoneum, nosocomial infections, bacterial endocarditis, and also in mixed infectious processes and to prevent the occurrence of inflammation in the period after surgical interventions.

Release form

It is released as a lyophilisate for a solution used for intramuscular injections. The glass bottle contains 1 g of lyophilisate (0.5 g of imipenem and sodium cilastatin). Inside the package is 1 bottle with powder.

Pharmacodynamics

The active ingredients of the drug are imipenem with cilastatin. The drug has a wide range of antimicrobial effects. Tienam has a bactericidal effect on gram-negative flora, gram-positive microbes, as well as aerobes and anaerobes. It acts by inhibiting the binding processes inside the cell walls of bacteria.

Imipenem belongs to the carbapenem category and is also a derivative of the component thienamycin.

Sodium cilastatin slows down the activity of the enzyme that exposes imipenem to renal metabolism, increasing its values in the urinary system in an unchanged form. Cilastatin does not affect the activity of microbial β-lactamase, and does not have its own antibacterial effect.

The medicine has an effect on staphylococci with streptococci, as well as enterobacteria, neisseria, campylobacter, mycobacteria, yersinia with gardnerella, and listeria with klebsiella. The drug actively affects flora that is resistant to aminoglycosides with penicillins, as well as cephalosporins. Synergistic action is noted when combined with aminoglycosides - in relation to Pseudomonas aeruginosa (in vitro tests).

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Pharmacokinetics

When the solution was administered intramuscularly with 1% lidocaine (0.5 g), peak plasma levels of imipenem were observed after 2 hours and their average value was 10 μg/ml. Compared with the intravenous form of the drug, imipenem demonstrated approximately 75% bioavailability. The component was absorbed from the injection site over 6-8 hours, resulting in the imipenem value in plasma being greater than 2 μg/ml for approximately 6 hours after injection. Administration of the drug at a dose of 0.5 g every 12 hours caused slight accumulation of the substance. The imipenem values in urine were greater than 10 μg/ml for 12 hours after intramuscular injection of the solution. The average excretion of the component with urine was 50%.

Maximum plasma values of cilastatin when using the drug by the intramuscular method at a dosage of 0.5 g averaged 24 mcg/ml and were noted after 1 hour. Bioavailability of the substance compared to intravenous injection was approximately 95%. Absorption of the substance from the injection site was almost complete after 4 hours. No accumulation of the substance was noted when using the solution 2 times a day (at a dosage of 0.5 g). The average level of cilastatin excretion with urine was 75%.

Cilastatin is a specific inhibitor of the enzyme dehydropeptidase-I. The substance effectively inhibits the process of imipenem metabolism, which allows for the combined use of these components to obtain medicinally effective antibacterial values of imipenem in plasma with urine. Peak plasma levels of cilastatin after 20 minutes after the administration of the solution (0.5 g) fluctuated within 21-55 μg / ml. The plasma half-life of cilastatin is approximately 1 hour. About 70-80% of the substance dosage is excreted unchanged in the urine 10 hours after administration. Subsequently, cilastatin is not observed in the urine. About 10% was noted in the form of a decay product - N-acetyl substance, which has a suppressive effect on dehydropeptidase (it can be compared with a similar effect of the original component).

The combination of the drug with probenecid increases the plasma level and half-life of cilastatin by 2 times, but does not affect its excretion in urine. Cilastatin is synthesized with serum protein by approximately 40%.

Dosing and administration

The solution can be administered both intramuscularly and intravenously. No more than 4000 mg of the drug can be administered per day (calculated at a ratio of 50 mg/kg). The dosage can be changed taking into account renal function, the severity of the disease and the patient's weight.

To prevent the development of complications after surgical procedures: a solution is administered intravenously at a dose of 1000 mg (an anesthetic must be administered before this), and then, after 3 hours, it is administered again.

Injections of the substance by the intramuscular method are carried out in the amount of 500-750 mg, the procedure is performed twice a day (the maximum permitted daily dose is 1.5 g).

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Use Thienam during pregnancy

The use of Tienam in pregnant women has not been adequately studied, therefore its use during this period is permitted only if there is confidence that the benefit from its administration outweighs possible complications for the fetus.

Imipenem penetrates into breast milk, so when using the drug, you must temporarily stop breastfeeding your child.

Contraindications

Main contraindications:

• hypersensitivity to carbapenems or β-lactam antibiotics;
• infants under 3 months of age;
• severe kidney disease;
• An intramuscular solution prepared with the addition of lidocaine is prohibited for use in cases of hypersensitivity to local amide anesthetics (cardiac conduction is impaired and a state of shock develops).

Caution is required when prescribing to elderly people, as well as to people with CNS diseases. Also in this case, a preliminary consultation with a specialized doctor is necessary.

Side effects Thienam

Injections of the solution may cause the following side effects:

• lesions of the urogenital system: occasionally, polyuria, oliguria, as well as acute renal failure and anuria are observed;
• nervous system disorders: occurrence of hallucinations, paresthesia, mental disorders, development of myoclonus, epileptic seizures, as well as a feeling of confusion;
• gastrointestinal dysfunction: drug-induced hepatitis is occasionally observed, as well as vomiting, pyelonephritis, nausea and diarrhea;
• damage to hemostasis and the hematopoietic system: development of agranulocytosis, eosinophilia, lymphocytosis, basophilia, monocytosis, or leuko-, thrombocyto-, or neutropenia. A positive Coombs test result, decreased hemoglobin levels, and prolongation of the PT level may also be observed;
• changes in laboratory test values: an increase in creatinine and bilirubin levels, as well as urea nitrogen and liver enzymes AST and ALT;
• allergy symptoms: development of Quincke's edema, TEN, urticaria, skin rash, erythema multiforme, itching, fever, and in addition, exfoliative dermatitis and manifestations of anaphylaxis;
• Others: candidiasis, skin hyperemia, pain due to the formation of an infiltrate at the site of drug administration, as well as thrombophlebitis and taste bud disorders may occur.

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Interactions with other drugs

Tienam is prohibited to be combined with other antibiotics, as well as lactate salt.

A cross-allergic reaction may occur in case of combination with penicillins and cephalosporins.

Shows antagonism towards other β-lactams (such as monobactams, as well as penicillins and cephalosporins).

Concomitant use with ganciclovir may result in generalized seizures.

Canalicular secretion blocking drugs can increase the levels of the antibiotic in the blood and also prolong the half-life of imipenem.

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Storage conditions

Tiens should be kept in a place out of reach of children. The temperature should not exceed 25°C.

Special instructions

Reviews

Tienam is considered to be a fairly effective medication, based on the reviews of most patients. But it is necessary to take into account that it has a very powerful effect, as a result of which it is prohibited to use it independently, without the supervision of a doctor.

Shelf life

Tienam can be used for a period of 3 years from the date of release of the drug.