Carbenicillin (Carbenicillinum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Penicillins

Included in the formulation
АТХ:

J.01.C.A.03   Carbenicillin

Pharmacodynamics:The formation of an acyl bond with the active center of transpeptidase of bacteria (the breakdown of the -CO-N- bond in β-lactamring): irreversible inhibition of penicillin-binding bacteria proteins, including transpeptidases involved in the last (third) stage of cell wall formation. Activation of (relative) endogenous peptidohydrolases (autolysins) of bacteria. The death of bacteria from osmotic shock. Effects - antibacterial, bactericidal.

Spectrum of antimicrobial activity

Refers to anti-synergic penicillins. Gram-positive microorganisms are inferior to natural penicillins and aminopenicillins. Gram-negative bacteria, including: Pseudomonas aeruginosa Enterobacter spp., Morganella spp., Providencia spp.; for action on Haemophilus spp., Neisseria meningitidis and N. gonorrhoeae, not producing β-lactamase, are comparable with ampicillin; are inferior to him in relation to streptococci and enterococci. They destroy β-lactamase of gram-positive and some gram-negative microorganisms. By action on P. aeruginosa Carbenicillin is 2-4 times inferior to ticarcillin and piperacillin.

Pharmacokinetics:Bioavailability is 30%. The maximum concentration in the blood - after 1 h. Connection with plasma proteins 50%. Penetrates into tissues and body fluids, including peritoneal fluid, bile, pleural effusion, middle ear fluid, intestinal mucosa, gallbladder, lungs, genital organs.Biotransformation in the liver (0-2%). The half-life is 1.0-1.5 hours, with creatinine clearance of 10-30 ml / min - 9.6 hours, <10 ml / min - 18.2 hours. Elimination of the kidneys in unchanged form: when applied inside - 36% with intravenous administration through the kidneys, 75-95% of the drug is excreted, creating a high concentration in the urine, which is important for urological infections. Removed from the body by hemodialysis. Passes through the placenta and penetrates into breast milk (in low concentrations).
Indications:Bacterial infections caused by sensitive microflora (including mixed aerobic-anaerobic infections of severe course):

- sepsis. Monotherapy with β-lactam antibacterial agents with a wide activity spectrum is recommended;

- peritonitis;

- Urinary tract infections, bacteriuria in pregnant women, infection of the pelvic organs;

- hospital pneumonia caused by gram-negative microorganisms, cystic fibrosis;

- bile duct infection, enterocolitis;

- skin and soft tissue infections, infected burns;

- suppurative complications after surgical interventions and childbirth;

- a meningitis, an abscess of a brain;

- empyema of the pleura;

- otitis media.

ICD-10

I.A30-A49.A41.9   Septicemia, unspecified

VI.G00-G09.G00   Bacterial meningitis, not elsewhere classified

VI.G00-G09.G06.0   Intracranial abscess and granuloma

VIII.H65-H75.H66.9   Other otitis media, unspecified

X.J10-J18.J18   Pneumonia without clarification of the pathogen

XI.K65-K67.K65   Peritonitis

XI.K80-K87.K83.9   Disease of biliary tract, unspecified

XII.L00-L08.L08.9   Local infection of skin and subcutaneous tissue, unspecified

XIII.M00-M03.M00.9   Pyogenic arthritis, unspecified

XIII.M70-M79.M79.9   Soft tissue disorder, unspecified

XIII.M86-M90.M86.9   Osteomyelitis, unspecified

XIV.N30-N39.N39.0   Urinary tract infection without established localization

XIV.N40-N51.N41.9   Inflammatory disease of prostate, unspecified

XIV.N40-N51.N49   Inflammatory diseases of male genital organs, not elsewhere classified

XIV.N70-N77.N73.9   Inflammatory diseases of female pelvic organs, unspecified

XV.O60-O75.O75.3   Other infections during labor

XIX.T20-T32.T30   Thermal and chemical burns, unspecified

Contraindications:- bronchial asthma;

- severe chronic heart failure;

- eczema;

- nonspecific ulcerative colitis;

- Infectious mononucleosis;

- Hypersensitivity to carbenicillin and other penicillins.

Carefully:Severe renal dysfunction. Patients with renal insufficiency may need a dose reduction.

Patients taking anticoagulants. The drug may increase bleeding time.

Childhood.

Pregnancy and lactation:The FDA-B fetal action test did not reveal any risk to the fetus, and no controlled studies were conducted in pregnant women, or unwanted effects (other than fertility decline) were shown in animal experiments, but their results were not confirmed in controlled studies in women in the first trimester of pregnancy (and there is no evidence of risk in other trimesters). Passes through the placenta in low concentrations.

Lactation

Passes through the placenta and penetrates into breast milk (in low concentrations). Application is not recommended.

Dosing and Administration:Dosage is strictly individual. It determines the severity of the course of infection, the sensitivity of the pathogen, the age of the patient.

When administered intravenously to adults, a single dose is 50-80 mg / kg, the frequency of administration is 4-6 times a day, the interval between each administration is 4-6 hours; or 1-2 g every 6 h (depending on the etiology of the disease).

The duration of intravenous fluid administration is 3-4 minutes, intravenous infusion is 30-40 minutes. With the duration of intravenous infusion for more than 40 minutes, the necessary therapeutic concentration may not be achieved.

The maximum daily intake for adults is 40 g.

For children, the daily dose for intramuscular injection is 50-100 mg / kg, and for intravenous administration 250-500 mg / kg. Multiplicity of administration - every 6 hours. Duration of treatment is determined individually (up to 14 days).

If the excretory function of the kidneys is disturbed, doses of carbenicillin are reduced, and the intervals between administrations are increased.

With an indicator of residual nitrogen above 100 mg% or creatinine clearance less than 30 ml / min carbenicillin should be administered to adults intravenously, 2 g every 6-8 hours.

Application in elderly patients

Use in the elderly has not been systematically studied. In elderly people, the excretory function of the kidneys is often reduced. In this case, the doses of carbenicillin are reduced, and the intervals between administrations are increased. Due to age-related changes in the central nervous system, heart and vessels, kidneys, liver, correction and individual dose selection may be required.

Use in children

Intramuscularly at 50-100 mg / kg / day, intravenously drip 250-500 mg / kg / day. Multiplicity of administration: every 6 hours. Intramuscular or intravenous infants with a body weight of up to 2 kg - 75 mg / kg every 12 hours during the first week of life, then 75 mg / kg every 8 hours, newborns weighing 2 kg and more - 75 mg / kg every 8 hours during the first week, then - 75 mg / kg every 6 hours. Apply only under the supervision of a qualified pediatrician.

Side effects:Allergic reactions: urticaria, erythema, Quincke's edema, rhinitis, conjunctivitis, rarely anaphylactic shock, arthralgia, eosinophilia.

From the side of the hematopoiesis system: thrombocytopenia, leukopenia, neutropenia.

From the digestive system: transient increase in the level of hepatic transaminases in the blood, colitis, caused by C. difficile.

From the coagulation system of the blood: hemorrhagic syndrome (with impaired renal excretory function).

From the side of water-electrolyte exchange: hyponatremia or hypokalemia (when administered in high doses).

Effects due to chemotherapeutic action: possible development of superinfection caused by carbenicillin resistant microorganisms, vaginal candidiasis.

Local reactions: soreness at the injection site (with intramuscular injection); aseptic phlebitis (with intravenous administration).

Overdose:There were no cases of overdose.

The goals of therapy with a possible overdose are maintenance of vital functions, rapid administration of symptomatic therapy. The drug can be removed from the body by hemodialysis.

Interaction:Aminoglycosides - significant mutual inactivation, the interval between administrations should be at least 1 hour, injected into different parts of the body.

Methotrexate is a decrease in the clearance of methotrexate due to the competition of drugs for tubular secretion, an increase in its toxicity.

Probenecid - a decrease in the tubular secretion of carbenicillin, an increase in its concentration in the blood and the risk of toxic effects. This is used when prolonged maintenance of high concentrations is necessary.

Anticoagulants (coumarin or indanedione derivatives, heparin), thrombolytic agents - risk of bleeding. Joint use is not recommended.

Non-steroidal anti-inflammatory drugs (especially acetylsalicylic acid), diflunisal in high doses, salicylates, drugs that inhibit platelet aggregation, sulfinpyrazone - the risk of hypoprothrombinemia, ulcerative gastrointestinal lesions, bleeding. Joint use is not recommended.

Special instructions:Antisignagic penicillin. It is active against gram-negative microorganisms, Pseudomonas aeruginosa (development of resistance is noted).

Used in the treatment of severe infectious diseases, mainly in combination antibiotic therapy, urinary tract infections, nosocomial infections.

In clinical practice in the treatment of patients with severe infectious lesions is often used in combination therapy, especially in combination with aminoglycosides. Nevertheless, nowadays monotherapy with modern β-lactams - ureidopenicillins, carbapenems, etc., is more justified.

Inhalation use of antibacterial agents (including carbenicillin) with the use of a nebulizer for the purpose of influencing chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis gives a positive effect in the form of an improvement function of external respiration, reducing the frequency of exacerbations of the disease against a background of development of undesirable drug reactions that is more rare than with systemic application of antibacterial agents.

In the treatment of sepsis, combined therapy with aminoglycosides (including in combination with carbenicillin) is not recommended, due to the high risk of unwanted reactions, primarily nephrotoxicity. The monotherapy with modern β-lactams of a wide spectrum of action (carbapenems, cephalosporins of the third generation, etc.) is justified, since it has no less clinical effect and significantly less leads to manifestations of toxicity.

The use of carbenicillin leads to the frequent occurrence of adverse drug reactions: bleeding, neutropenia.

Do not administer intramuscularly more than 2 g of the drug in one place.

During the treatment period, the drug requires constant monitoring of thromboplastin time, prothrombin time with intravenous administration of the drug in patients receiving long-term therapy, or with renal failure. The drug suppresses the aggregation of platelets.

Cross-resistance with cephalosporins is possible.

Carbenicillin can be injected into the joint cavity, intrapleural, used for inhalation, for rinsing cavities.

Instructions
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