Ampicillin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMPIcILLIN (AMPICILLIN)

Composition:

Active substance: ampicillin;

1 tablet contains ampicillin trihydrate equivalent to 250 mg of ampicillin;

Excipients: potato starch, talc, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white tablets, round-shaped, flat surface, with bevel and score line.

Pharmacotherapeutic group.

Beta-lactam antibiotics, penicillins. Broad-spectrum penicillins.

ATC code J01CA01.

Pharmacological Properties

Pharmacodynamics

Ampicillin trihydrate has a broad spectrum of antimicrobial activity. It is active against Gram-positive microorganisms (Streptococcus spp., including S. pneumoniae, Enterococcus spp., and others) and certain Gram-negative microorganisms (Neisseria meningitidis, N. gonorrhoeae, Escherichia coli, Shigella spp., Salmonella spp., Proteus spp., Bordetella pertussis, some strains of Haemophilus influenzae, and others). The drug is destroyed by penicillinase and therefore is ineffective against penicillinase-producing microbial strains (e.g., Staphylococcus spp.).

Pharmacokinetics

It is well absorbed after oral administration, penetrating into tissues and biological fluids of the body. The drug is not destroyed in the acidic environment of the stomach. After oral administration, maximum drug concentration in the blood is reached within 1.5–2 hours. The half-life (time required for the concentration of the drug in the blood to reduce by half) is 60–120 minutes. The drug is primarily excreted by the kidneys, resulting in high concentrations of unchanged antibiotic in urine. A significant amount is also excreted into bile. Within 6–8 hours, approximately 30% of the administered dose is excreted, and within 24 hours — approximately 60%. Ampicillin trihydrate does not accumulate with repeated administration, allowing its prolonged use in high doses.

Clinical characteristics.

Indications.

Infections caused by microorganisms sensitive to the drug:

• biliary system infections (cholangitis, cholecystitis);
• respiratory tract and ENT infections (pneumonia, bronchitis, lung abscess, sinusitis, pharyngitis, otitis, tonsillitis);
• meningitis;
• gastroenteritis caused by Shigella or Salmonella, typhoid fever and paratyphoid;
• bacterial endocarditis;
• urinary and genital system infections (pyelitis, pyelonephritis, cystitis, urethritis, gonorrhea);
• peritonitis;
• septicemia;
• skin and soft tissue infections.

Contraindications.

• Hypersensitivity to ampicillin and other β-lactam antibiotics (penicillins, cephalosporins, carbapenems), as well as to any excipients of the drug.
• Severe liver function impairment.
• Infectious mononucleosis.
• Leukemia.
• HIV infection.

Interaction with other medicinal products and other types of interactions.

Ampicillin enhances the effect of anticoagulants and aminoglycoside antibiotics, and reduces the efficacy of oral contraceptives. When ampicillin is used concomitantly with oral estrogen-containing medicinal products, their effectiveness is reduced due to diminished enterohepatic circulation of estrogens.

Probenecid and sulfinpyrazone reduce tubular secretion of ampicillin, thereby increasing the risk of its toxic effects.

Allopurinol increases the likelihood of skin rash.

High doses of ampicillin reduce plasma levels of atenolol; therefore, it is recommended to administer these drugs separately—atenolol should be taken first, followed by ampicillin.

Ampicillin reduces the clearance and increases the toxicity of methotrexate, and enhances digoxin absorption.
Concomitant use with chloroquine reduces ampicillin absorption.

When used with macrolides, paromomycin, tetracyclines, or chloramphenicol, the efficacy of both agents is reduced. Ampicillin may reduce the effect of sodium benzoate.

The efficacy of oral typhoid vaccine may be reduced when administered concurrently with ampicillin.

The drug is pharmaceutically incompatible with tetracyclines, chloramphenicol (chloromycetin), amphotericin, clindamycin, erythromycin, lincomycin, metronidazole, polymyxin B, acetylcysteine, chlorpromazine, hydralazine, dopamine, heparin, and metoclopramide.

Ampicillin may interfere with certain diagnostic tests, including urine glucose detection using copper sulfate; direct antiglobulin tests (Coombs test); and certain tests for proteins in urine or serum.

During ampicillin therapy, enzymatic glucose oxidase methods should be used for urine glucose testing.

At high urinary concentrations, ampicillin may cause false-positive results in chemical tests.

Special precautions for use

Prior to initiating therapy, it is necessary to rule out the presence of hypersensitivity to ampicillin and other β-lactam antibiotics in the patient.

During treatment, regular monitoring of kidney and liver function, as well as peripheral blood parameters, is required. Serious and sometimes fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving beta-lactam antibiotics. Although anaphylaxis occurs more frequently following parenteral administration, it has also occurred in patients taking oral penicillins. These reactions are more likely to occur in individuals with a history of hypersensitivity to beta-lactams. The drug should be administered with desensitizing agents in patients with bronchial asthma, hay fever, or other allergic conditions. If signs of anaphylactic shock occur, emergency measures must be taken immediately to reverse this condition.

Toxic effects on the central nervous system may occur when high doses are used in patients with impaired renal function.

The drug should be discontinued if skin rash develops. Ampicillin should be avoided in infectious mononucleosis and/or acute or chronic lymphocytic leukemia.

Patients with lymphocytic leukemia have an increased risk of developing skin rash.

Prolonged or repeated use may lead to rapid overgrowth of resistant microorganisms, such as Candida or Pseudomonas, and development of superinfections.

Use during pregnancy or breastfeeding

Teratogenic effects of ampicillin have not been observed. However, ampicillin should be used during pregnancy 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 with this drug.

Ability to influence the speed of reactions when driving or operating machinery

During treatment with this drug, some patients may experience adverse reactions affecting the central nervous system (see section "Adverse reactions"). Therefore, caution should be exercised when driving or engaging in other potentially hazardous activities requiring increased attention and rapid psychomotor reaction speed.

Dosage and Administration.

The drug should be used as prescribed by a physician. Ampicillin should be administered orally 30 minutes before or 2 hours after meals. The duration of ampicillin treatment is determined individually (from 5 days to 3 weeks or more), depending on the characteristics of the disease, patient's age, therapeutic efficacy, and renal function. After disappearance of clinical symptoms of the disease, ampicillin should still be continued for additional 2–3 days.

The recommended standard single dose for adults and children aged 14 years and older is 250–1000 mg every 6 hours. The dosing regimen should be established by a physician.

Urinary tract infections: 500 mg every 8 hours.

Typhoid fever and paratyphoid: 1000–2000 mg every 6 hours. In acute cases – for 2 weeks; in chronic carriers – 4–12 weeks.

Uncomplicated gonorrhea: single dose of 2000 mg of ampicillin in combination with 1000 mg of probenecid. A repeat treatment course is recommended in women.

Respiratory tract and ENT infections: 250 mg every 6 hours.

Pneumonia: 500 mg every 6 hours.

For children aged 6 years and older, the drug should be administered at a daily dose of 100 mg/kg body weight. The daily dose should be divided into 4–6 doses.

Patients with severe renal impairment (creatinine clearance less than 10 mL/min) require dosage regimen adjustment: either the dose should be reduced or the dosing interval prolonged.

Children.

This dosage form of ampicillin should not be used in children under 6 years of age.

Overdose.

In case of overdose, toxic effects on the central nervous system (dizziness, headache), dyspeptic symptoms (nausea, vomiting, diarrhea), and allergic reactions such as skin rash may occur. If symptoms of overdose occur, the drug should be discontinued immediately, and symptomatic treatment initiated as needed: gastric lavage, activated charcoal, saline laxatives, correction of water-electrolyte balance, hemodialysis. In case of allergic reactions, antihistamines and desensitizing agents are indicated.

Adverse reactions.

Immune system disorders: allergic reactions, including rashes (urticarial, maculopapular), pruritus, hyperemia, urticaria, rhinitis, conjunctivitis, fever, joint pain, eosinophilia, exfoliative dermatitis, purpura, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, Quincke's edema, anaphylaxis, anaphylactic shock.

Gastrointestinal disorders: nausea, vomiting, diarrhea, taste alterations, abdominal pain, stomatitis, glossitis, dry mouth, intestinal dysbiosis, gastritis, enterocolitis, hemorrhagic colitis. During treatment or within several weeks after completion of antibiotic therapy, there is a risk of developing pseudomembranous colitis.

Hepatic and hepatobiliary disorders: hepatitis, cholestatic jaundice.

Central and peripheral nervous system disorders: tremor, seizures, headache, neuropathy may occur when high doses are used in patients with renal impairment.

Laboratory abnormalities: mild increases in the activity of liver transaminases, lactate dehydrogenase, alkaline phosphatase, creatinine; pseudopositive results in non-enzymatic glucosuria tests and Coombs' test.

Other: reversible hematopoietic disturbances (leukopenia, thrombocytopenia, hemolytic anemia, agranulocytosis), interstitial nephritis, superinfection, candidiasis. When administering Ampicillin to patients with bacteremia (sepsis), a bacteriolysis reaction (Jarisch-Herxheimer reaction) may occur.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua/.

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach and sight of children.

Packaging. 250 mg tablets, 10 tablets per blister; 1 or 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and place of business.

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.