Pharmacological properties
Pharmacodynamics. Ampicillin has a wide spectrum of antibacterial (bactericidal) action. Active against gram-positive microorganisms (staphylococcus spp., except for strains that produce penicillinase; streptococcus spp., including s. pneumoniae; corynebacterium diphtheriae, bacillus anthracis, clostridium spp., most enterococci) and gram-negative (escherichia coli, shigella spp., salmonella spp., neisseria meningitidis, n. gonorrhoeae, proteus mirabilis, some strains of klebsiella pneumoniae, haemophilus influenzae) microorganisms.
The drug is destroyed by penicillinase and therefore does not act on penicillinase-producing strains of bacteria. The drug inhibits peptidoglycan polymerase and transpeptidase, prevents the formation of peptide bonds and disrupts the late stages of cell wall synthesis of dividing microorganisms. The resulting membrane defects reduce the osmotic resistance of the bacterial cell, which leads to its death (lysis).
Pharmacokinetics. When administered in / m or in / in high concentrations in the blood. C max in the blood is detected after 15 minutes after in / in administration and after 0.5-1 hour after in / m. When administered in / m 0.5-1 g of ampicillin with an interval between doses of 4-6 hours in the blood, a therapeutic concentration is maintained.
It penetrates well into tissues and body fluids, is found in therapeutic concentrations in pleural, peritoneal and synovial fluid. In bile, it can be found in concentrations 4-100 times higher than in blood. Relatively little (10-30%) binds to plasma proteins. It does not penetrate the blood-brain barrier. It is almost not biotransformed. It is excreted mainly by the kidneys, partly with bile, in breastfeeding women it penetrates into milk. Within 12 hours, 45-70% of the administered dose is excreted in the urine. In case of impaired renal excretory function, the level of the drug in the blood increases and its excretion slows down. With creatinine clearance of 10 ml/min, the level of the antibiotic in the blood can be 10 times higher than in patients with normal renal function. T ½ is prolonged from 1-2 h normally to 10-12 h. Ampicillin does not accumulate when administered repeatedly, which makes it possible to use it in high doses and for a long time.
Indication
Sepsis, septic endocarditis, meningitis, respiratory tract infections (pneumonia, chronic bronchitis, lung abscess); urinary and biliary tract infections (pyelitis, pyelonephritis, cystitis, cholangitis, cholecystitis); skin and soft tissue infections and diseases caused by microorganisms sensitive to the action of antibiotics (caused by beta-hemolytic streptococcus group A or coagulase-positive staphylococcus sensitive to penicillin); sanitation of typhoid carriers (carriers of salmonella typhi and paratyphi).
Application
The dose of the drug and the duration of treatment are set individually, depending on the severity of the disease, the location of the infection and the sensitivity of the pathogen to the drug. A skin test for increased sensitivity to the antibiotic is mandatory. The drug is administered intramuscularly or intravenously (drip or jet).
The recommended dose for adults is 250-500 mg 4 times a day, daily - up to 1-3 g. In severe infections, the daily dose may be increased to ≥10 g.
Newborns are prescribed the drug in a daily dose of 20-40 mg/kg of body weight, children of other age groups - 50-100 mg/kg. In severe cases of infection, these doses can be doubled. The daily dose is administered in 4-6 doses with an interval of 4-6 hours.
For meningitis in children: at the age of up to 1 month, a daily dose of 100-500 mg/kg is prescribed, at the age of 1 month and older - a daily dose of 200-300 mg/kg in 6-8 injections. The daily dose is administered in 4-6 doses.
The duration of treatment is 7-14 days or more. Ampicillin treatment should be continued for at least 48-72 hours after normalization of body temperature and disappearance of symptoms of the disease. In infections caused by hemolytic streptococcus, the duration of treatment should be at least 10 days.
Solution for i / m administration is prepared immediately before use, adding 5 ml of sterile water for injection to the contents of the vial. For i / v jet administration, a single dose of the drug (no more than 2 g) is dissolved in 5-10 ml of water for injection or 0.9% sodium chloride solution and administered slowly over 3-5 minutes (administration in a dose of 1-2 g is carried out over 10-15 minutes). With a single dose exceeding 2 g, the drug is administered i / v drip. For i / v drip administration, a single dose of the drug (2-4 g) is dissolved in a small volume of water for injection (7.5-15 ml, respectively), then the resulting antibiotic solution is added to 125-250 ml of 0.9% sodium chloride solution or 5-10% glucose solution and administered at a rate of 60-80 drops per minute. When administered intravenously to children, a 5-10% glucose solution is used as a solvent. The solutions should be used immediately after preparation.
Contraindication
Hypersensitivity to ampicillin and other β-lactam antibiotics (penicillins, cephalosporins, carbapenems); severe liver and kidney dysfunction; infectious mononucleosis; leukemia; HIV infections; gastrointestinal diseases/colitis associated with the use of antibiotics.
Side effects
On the part of the immune system: allergic reactions, including rash, itching, redness, urticaria, rhinitis, conjunctivitis, fever, joint pain, eosinophilia, exfoliative dermatitis, purpura, exudative erythema multiforme, Stevens-Johnson syndrome, Quincke's edema, anaphylactic shock.
From the hepatobiliary system: hepatitis, cholestatic jaundice.
From the side of the central nervous system and peripheral nervous system: when using the drug in high doses in patients with renal failure, dizziness, headache, tremor, convulsions, neuropathy are possible.
Local reactions: including swelling, itching, hyperemia at the injection site.
Laboratory indicators: increased activity of hepatic transaminases, LDH, LF, creatinine, pseudopositive results of non-enzymatic glucosuric tests and Coombs' reaction.
Other: reversible disorders of hematopoiesis (leukopenia, thrombocytopenia, hemolytic anemia, agranulocytosis), interstitial nephritis, superinfection, candidiasis. When using Ampicillin in patients with bacteremia (sepsis), a bacteriolysis reaction (Jarish-Herxheimer reaction) is possible.
Special instructions
During treatment, systematic monitoring of kidney, liver and peripheral blood function is necessary. In patients with renal insufficiency, the dose of the drug should be reduced; in patients with severe renal insufficiency (creatinine clearance 10 ml/min), the drug should be administered in half the dose at 12-hour intervals.
It should be used with caution in the treatment of sick children if the mother has a history of hypersensitivity to penicillins.
For asthma, hay fever, and other allergic diseases, the drug should be used while simultaneously prescribing desensitizing agents.
With prolonged treatment with the drug in weakened patients, the development of superinfection caused by microorganisms resistant to the drug is possible.
It is necessary to stop taking the drug if a skin rash occurs.
Patients with lymphocytic leukemia have an increased risk of developing a skin rash.
Use during pregnancy and breastfeeding. The teratogenic effect of Ampicillin has not been identified. However, the use of Ampicillin during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus.
Ampicillin passes into breast milk in low concentrations. Breastfeeding should be discontinued during treatment.
Children. Ampicillin is used in pediatric practice.
Ability to influence the reaction rate when driving vehicles or working with other mechanisms. During treatment, some patients may experience adverse reactions from the central nervous system (see Side effects), so caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.
Interactions
Ampicillin enhances the effect of anticoagulants, aminoglycoside antibiotics, reduces the effect of oral contraceptives. With the simultaneous use of ampicillin with oral estrogen-containing drugs, a decrease in their effectiveness is noted due to the weakening of the hepatic circulation of estrogen.
Probenecid reduces the tubular secretion of ampicillin, resulting in an increased risk of its toxic effects.
Allopurinol increases the likelihood of skin rash.
Ampicillin in high doses reduces the level of atenolol in the blood plasma, therefore it is recommended to use these drugs separately, first atenolol, and then ampicillin.
Ampicillin reduces the clearance and increases the toxicity of methotrexate, enhances the absorption of digoxin.
When ampicillin interacts with macrolides, paromomycin, tetracyclines, chloramphenicol, the effect of both drugs is reduced. Ampicillin may reduce the effect of sodium benzoate.
When used simultaneously with beta-blockers, the likelihood of anaphylactic reactions increases.
Overdose
In case of overdose, toxic effects on the central nervous system (dizziness, headache), dyspeptic phenomena (nausea, vomiting, loose stools), allergic reactions in the form of skin rash are possible. In case of symptoms of overdose, the drug should be immediately discontinued and, if necessary, symptomatic treatment should be carried out: gastric lavage, administration of activated charcoal, saline laxatives, correction of water and electrolyte balance, hemodialysis. In case of allergy, antihistamines and desensitizing agents are indicated.
Storage conditions
In the original packaging at a temperature not exceeding 25 °C.
