Amoctam

Description

White or almost white powder with a yellowish tinge.
Pharmacotherapeutic group: semi-synthetic antibiotic penicillin + beta-lactamase inhibitor.
ATC Code: J01CR02

Pharmacological properties
Pharmacodynamics

Amoctam is a combined preparation with a bactericidal effect against microorganisms sensitive to amoxicillin, including strains that produce beta-lactamases.

Amoxicillin is a semi-synthetic penicillin with a broad spectrum of activity from the aminopenicillin group; it inhibits the synthesis of proteins in the cell wall of pathogenic microorganisms.

Sulbactam is an irreversible inhibitor of beta-lactamases; expands the spectrum of activity of amoxicillin against resistant strains, the resistance of which develops under the influence of beta-lactamases; does not change the activity of amoxicillin against susceptible strains; binding to some penicillin-binding proteins of bacteria, it exhibits synergism when used simultaneously with beta-lactam antibiotics. It is stable in aqueous solution, has independent antibacterial activity against Neisseria gonorrhoeae and Acinetobacter spp. and is resistant to the action of most plasmid beta-lactamases.

Amoxicillin is active against the following microorganisms (including strains producing beta-lactamases):
Aerobic gram-positive bacteria: Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pyogenes, Streptococcus anthracis, Streptococcus pneumoniae, Streptococcus of viridans group, Enterococcus faeca1is, Corynebacterium spp., Listeria monocytogenes.

Anaerobic gram-positive bacteria: Clostridium spp., Peptococcus spp., Peptostreptococcus spp.

Aerobic gram-negative bacteria: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella spp., Salmonella spp., Shigella spp., Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidis, Neisseria gonorrhoeae, Moraxella catarrhalis, Haemophilus influenzae, Yersinia multocida, Campylobacter jejuni, Acinetobacter spp. (including Acinetobacter baumannii), Helicobacter pylori.
Anaerobic gram-negative bacteria: Bacteroides spp., including Bacteroides fragilis.

Pharmacokinetics
Amoxicillin

20% plasma protein binding. Amoxicillin is distributed in most tissues and body fluids, crosses the placental barrier and is found in breast milk. Elimination half-life is 1 h.
It is excreted mainly by the kidneys (glomerular filtration and tubular secretion) – 70-80% and with bile – 5-10%.
Sulbactam
Plasma protein bond is 40%. Elimination half-life is 1 h. Sulbactam has no effect on the pharmacokinetics of amoxicillin. Sulbactam is excreted almost completely unchanged by the kidneys (75-85%). Sulbactam does not cross the placental barrier.

Indications
Infectious and inflammatory diseases caused by microorganism strains sensitive to amoxicillin:
– infections of the upper respiratory tract and ENT organs (acute and chronic sinusitis, acute and chronic otitis media, retropharyngeal abscess, tonsillitis, pharyngitis);
– lower respiratory tract infections (acute bronchitis with bacterial superinfection, chronic bronchitis, pneumonia);
– infections of the biliary tract (cholecystitis, cholangitis);
– intestinal infections (salmonellosis);
– infections of the genitourinary system and pelvic organs (pyelonephritis, pyelitis, cystitis, urethritis, prostatitis, cervicitis, salpingitis, adnexitis, tubo-ovarian abscess, endometritis, bacterial vaginitis, postpartum sepsis, pelvioperitonitis, gonorrhea);
– infections of the skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses, abscess, phlegmon, wound infection);
– prevention of infectious and inflammatory diseases in surgery.

Contraindications
Hypersensitivity to amoxicillin, sulbactam, other components of the drug and penicillins; severe immediate hypersensitivity reactions (eg, anaphylaxis) to other beta-lactam antibiotics (eg, cephalosporins, carbapenems, monobactams); infectious mononucleosis (including with the appearance of a measles-like rash); ulcerative colitis; Crohn’s disease; herpesvirus infection.
Simultaneous intake of allopurinol (in the presence of allergic skin reactions when using penicillins).
History of colitis associated with the use of penicillins.

With caution
Severe hepatic failure, diseases of the gastrointestinal tract, chronic renal failure (CRF), old age (due to possible renal failure).

Use during pregnancy and breastfeeding
The usage during pregnancy is possible only if the potential benefit for the mother outweighs the potential risk to the fetus. If the use the drug during lactation is necessary, breastfeeding should be stopped.

Dosage and administration
The dosage regimen should be set individually depending on the severity of the course and localization of the infection, the sensitivity of the pathogen. Treatment should be continued for at least another 2-3 days after the disappearance of the clinical symptoms of the disease, but no more than 14 days.
When treating infections caused by beta-haemolytic streptococcus, the drug is recommended to be used for at least 10 days.
The drug is injected deeply intramuscularly, intravenous bolus or intravenous infusion.

Doses equivalent to amoxicillin:
The usual recommended dose for adults and children over 12 years old: 1.0 g is administered 2-3 times a day;
For the prevention of postoperative infections during operations lasting less than 1 hour during induction anesthesia, the drug is administered intravenously at a dose of 1.0 g.
For longer operations — 1.0 g every 6 hours during the day. If the risk of infection is high, the administration can be continued for several days.
For children from 6 to 12 years old: 500 mg 3 times a day;
For children from 2 to 6 years old: 250 mg 3 times a day;
For children below 2 years old: 40-60 mg/kg 2-3 times a day;
In severe infections, the daily dose of the drug (equivalent to amoxicillin) can be increased to 100 mg/kg/day, especially those caused by gram-negative pathogens.

Patients with impaired renal function:
The dosing schedule is changed depending on the creatinine clearance (CC).
When CC is more than 30 ml/min, changes in the dosage regimen are not required; when CC is 10-30 ml/min, treatment begins with IV injection of 1.0 g, then 500 mg IV 2 times a day; with CC less than 10 ml/min – 1.0 g, then 500 mg/day intravenously once a day.
Hemodialysis reduces the plasma concentration, and therefore, during and at the end of dialysis, an additional 500 mg of the drug is injected IV.
In children with chronic renal failure, the usual single doses are used, increasing the intervals between doses, as indicated for adults.

Solutions preparation method:
For IM administration, 5 ml of water for injection should be added to the contents of the vial (500 mg + 250 mg or 1000 mg + 500 mg).
Use freshly prepared solutions.
For IV administration, a single dose of the drug should be dissolved in 0.9% NaCl solution or 5% dextrose (glucose) solution in a volume of 10 ml (for intravenous jet injection) to 100-200 ml (for IV invasive administration).
For IV infusion, dilution with lactated Ringer’s solution is acceptable.
When diluted with lactated Ringer’s solution, the solution should be prepared in 2 stages: first, use sterile water for injection, then the resulting solution should be diluted with a solution of lactated Ringer’s solution.
With IV injection, the prepared solution is administered slowly.
With IV infusion, the prepared solution is administered slowly dripping over 15-60 minutes.

Adverse effects
Immune system disorders: Quincke’s edema, respiratory disorders, anaphylactic shock.
Skin and subcutaneous tissue disorders: urticaria, exudative erythema multiforme, exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalised exanthematous pustulosis (AGEP).
Gastrointestinal disorders: nausea, vomiting, diarrhea, dyspepsia, pain in the epigastric region, pseudomembranous colitis.
Hepatobiliary disorders: increased activity of “hepatic” transaminases, cholestatic jaundice, hepatitis.
Blood and lymphatic system: anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis.
Nervous system disorders: hyperactivity, agitation, anxiety, insomnia, confusion, behavior change.
General disorders and disorders at the injection site: burning and pain at the injection site, in some cases – phlebitis at the intravenous injection site.

Overdose
Symptoms: gastrointestinal disorders (nausea, vomiting, diarrhea) and water-electrolyte balance.
In case of an overdose, it is recommended to stop the drug administration.
A small number of reports have dealt with cases of interstitial nephritis with oliguric renal failure due to an overdose of amoxicillin. Such drug-induced kidney injury is reversible: renal function is restored after stopping the drug administration.
Treatment: symptomatic. In severe cases — hemodialysis.

Interactions with other drugs
The Amoctam drug is incompatible with aminoglycosides, blood derivatives and protein lysis products, so they cannot be mixed in the same container.
Antibacterial antibiotics (including aminoglycosides, cephalosporins, cycloserine, vancomycin, rifampicin) have a synergistic effect; bacteriostatic antibiotics (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) have an antagonistic effect.
The use of probenecid can cause a decrease in renal tubular secretion, which leads to a prolonged increase in the plasma concentration of amoxicillin. The Amoctam drug slows down the excretion of methotrexate.
The Amoctam drug increases the effectiveness of indirect anticoagulants (monitoring of blood clotting parameters is necessary). Reduces the effectiveness of oral contraceptives. When used together with allopurinol, the risk of developing allergic skin reactions increases.

Special instructions
Before starting treatment with the drug, it is necessary to collect a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins or other substances that cause an allergic reaction of the patient. Serious and sometimes fatal hypersensitivity reactions (including anaphylactic and severe cutaneous adverse reactions) to penicillins have been described. The risk of such reactions is high in patients with a history of hypersensitivity reactions to penicillins. In the event of an allergic reaction, it is necessary to discontinue treatment with the drug and initiate appropriate alternative therapy.
Treatment of patients with bronchial asthma, eczema or hay fever should be carried out under the supervision of a physician.
Due to the high concentration of amoxicillin in the urine, it can be deposited on the walls of the catheter, therefore, it is necessary to periodically monitor the patency of the catheter.
Amoxicillin can reduce the concentration of total protein in the blood plasma. A false-positive result of reactions is possible during tests for urinary glucose by a colorimetric method, a reversible increase in prothrombin time.
With prolonged use of the drug, it is possible to increase the activity of “hepatic” transaminases.
Amoxicillin reduces the effectiveness of oral contraceptives. Therefore, women taking progestin-only and estrogenic contraceptives it is advised to use alternative or complementary methods of contraception.
With prolonged use of the drug, it is necessary to periodically monitor the functions of the kidneys, liver and general blood test.
A high concentration of amoxicillin helps to reduce the concentration of blood glucose.
Long-term use can lead to an increase in the number of insensitive pathogens. With prolonged use, it is possible to develop superinfection, candidiasis. Pseudomembranous colitis has been reported with almost all antibacterial agents, including amoxicillin, and can range in severity from mild to life-threatening. Therefore, it is important to consider the possibility of developing pseudomembranous colitis in patients with diarrhea during or after antibiotic use. If the diarrhea is prolonged or severe and the patient experiences abdominal cramps, treatment should be discontinued immediately, the patient should be examined and appropriate treatment initiated. The use of drugs that inhibit intestinal motility is contraindicated. The onset of generalized erythema with fever accompanied by pustules at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis (AGEP). This ADR requires discontinuation of treatment with amoxicillin and is a contraindication for its use in the future in any situation. In case of impaired renal function, correction of the dosage regimen of the drug is necessary, depending on the degree of renal failure.

Effects on the ability to drive and use machines
No data on the negative effect of the Amoctam drug in recommended doses on the ability to drive and use mechanisms is available.
However, given the likelihood of central nervous system disorders, care should be taken when engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Presentation
Powder for solution for infusion, 250 mg, 500 mg.
The drug quantity containing 250 or 500 mg of the active substance is placed in transparent glass vials of the 1st hydrolytic class with a capacity of 10 or 20 ml, hermetically sealed with rubber stoppers, crimped with aluminum caps or combined caps (aluminum caps with safety plastic caps).
1 vial with the drug and instructions for medical use are placed in a cardboard box.
For in-patient facilities:
From 10 to 50 vials with the drug with an equal number of instructions for medical use are placed in a cardboard box.

Storage conditions
In a dark place at a temperature below 25 °C.
Keep out of the reach of children.

Shelf life
3 years.
Do not use after expiry date.

Prescription status
Rx only.