Sulfotaxim-Akos (Powder) Instructions for Use

Marketing Authorization Holder

Sintez PJSC (Russia)

ATC Code

J01DD51 (Cefotaxime and beta-lactamase inhibitor)

Active Substances

Sulbactam (Rec.INN registered by WHO)

Cefotaxime (Rec.INN registered by WHO)

Dosage Form

Sulfotaxim-Akos

Powder for solution for intravenous and intramuscular administration 1000 mg+500 mg: vial 1, 5, 10 or 50 pcs.

Dosage Form, Packaging, and Composition

Powder for preparation of solution for intravenous and intramuscular administration

1500 mg – vials – cardboard packs – By prescription
1500 mg – vials (10 pcs.) – cardboard packs – By prescription
1500 mg – vials (50 pcs.) – cardboard boxes – for hospitals

Clinical-Pharmacological Group

Third generation cephalosporin with beta-lactamase inhibitor

Pharmacotherapeutic Group

Systemic antibacterial agents; other beta-lactam antibacterial agents; third-generation cephalosporins

Pharmacological Action

Combined antibacterial agent.

Cefotaxime is a third-generation cephalosporin antibiotic for parenteral administration. It acts bactericidally by disrupting the synthesis of the microbial cell wall. It has a broad spectrum of antimicrobial activity.

Sulbactam does not possess clinically significant antibacterial activity (with the exception of the Neisseriaceae spp. family and Acinetobacter spp.). It is an irreversible inhibitor of most major beta-lactamases produced by microorganisms resistant to beta-lactam antibiotics.

The ability of sulbactam to prevent the destruction of penicillins and cephalosporins by resistant microorganisms has been confirmed in studies using resistant strains, against which Sulbactam exhibited pronounced synergy with penicillins and cephalosporins. Furthermore, Sulbactam interacts with some penicillin-binding proteins, therefore Cefotaxime + Sulbactam often has a more pronounced effect on susceptible strains than Cefotaxime alone.

The combination of cefotaxime and sulbactam is active against all microorganisms susceptible to cefotaxime. In addition, it exhibits synergy against various microorganisms.

Cefotaxime + Sulbactam is active against gram-positive and gram-negative microorganisms resistant to other antibiotics: Aeromonas hydrophila, Bacillus subtilis, Bordetella pertussis, Borrelia burgdorferi, Moraxella catarrhalis, Citrobacter diversus, Citrobacter freundii, Clostridium perfringens, Corynebacterium diphtheriae, Escherichia coli, Enterobacter spp., Erysipelothrix insidiosa, Eubacterium spp., Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Propionibacterium spp., Proteus mirabilis, Proteus vulgaris, Providencia spp., Staphylococcus spp., Streptococcus spp. (including Streptococcus pneumoniae), Salmonella spp., Shigella spp., Serratia spp., Veillonella spp., Yersinia spp., Pseudomonas spp. (except Pseudomonas cepacia, Pseudomonas aeruginosa).

Sensitivity depends on epidemiological data and the level of resistance in each specific country.

Resistant microorganisms Acinetobacter baumannii, Bacteroides fragilis, Clostridium difficile, Enterococcus spp., gram-negative anaerobes, Listeria monocytogenes, methicillin-resistant Staphylococcus spp., Pseudomonas cepacia, Pseudomonas aeruginosa, Stenotrophomonas maltophilia.

Pharmacokinetics

C_max of cefotaxime and sulbactam after IV administration in adults 5 minutes after 1.5 g of cefotaxime+Sulbactam (1 g cefotaxime and 0.5 g sulbactam) averaged 100 µg/ml and 20 µg/ml, respectively. C_max of cefotaxime and sulbactam after IM administration of 1.5 g of the drug averaged 20-30 µg/ml and 6-24 µg/ml, respectively.

Plasma protein binding of cefotaxime is 25-40%, sulbactam is about 38%. Bioavailability with IV administration is 100%, with IM administration is 90-95%. Therapeutic concentrations are achieved in most tissues (myocardium, bone, gallbladder, skin, soft tissues) and body fluids (synovial, pericardial, pleural, sputum, bile, urine, cerebrospinal fluid). V_d of cefotaxime is 0.25-0.39 l/kg, sulbactam is 0.29 l/kg. Sulbactam crosses the placental barrier. Cefotaxime crosses the placental barrier and is excreted in breast milk.

T_1/2 of cefotaxime is 1 hour with IV administration and 1-1.5 hours with IM administration. About 90% is excreted by the kidneys – 50% unchanged, the remainder as metabolites (15-25% as pharmacologically active desacetylcefotaxime and 20-25% as 2 inactive metabolites – M2 and M3). 10% of the administered dose is excreted via the intestines. T_1/2 of sulbactam averages about 1 hour. Approximately 84% of the sulbactam dose is excreted by the kidneys unchanged. No accumulation occurs in patients with normal renal function.

In chronic renal failure in elderly patients over 80 years of age, T_1/2 of cefotaxime increases to 2.5 hours. T_1/2 in children is 0.75-1.5 hours, in newborns, including premature infants, children is 1.4-6.4 hours. In patients with end-stage renal disease, a significant prolongation of T_1/2 of sulbactam was detected (averaging 6.9 and 9.7 hours in various studies). Hemodialysis caused significant changes in T_1/2, total clearance and V_d of sulbactam.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to the combination of cefotaxime with sulbactam: CNS infections (including meningitis, except for listerial), lower respiratory tract and ENT infections, urinary tract infections, bone, joint, skin and soft tissue infections including infected wounds and burns), pelvic organ infections, gonorrhea, peritonitis, sepsis, intra-abdominal infections, endocarditis, Lyme disease (borreliosis), infections against the background of immunodeficiency.

Prevention of infections after surgical operations (including urological, obstetric-gynecological, gastrointestinal).

ICD codes

Dosage Regimen

IV (bolus, drip) and IM. The dose, method and frequency of administration should be determined by the severity of the infection, the sensitivity of the pathogen and the patient’s condition.

Treatment can be started before receiving the results of the susceptibility test.

The dose and frequency of administration are set individually, depending on the indications, age, severity of the infection.

In renal failure, adjustment of the dosage regimen is required depending on CC.

Adverse Reactions

From the nervous system seizures, headache, dizziness, encephalopathy (impaired consciousness, movement disorders).

From the urinary system decreased renal function/hypercreatininemia, especially with combined use with aminoglycosides, acute renal failure, interstitial nephritis.

From the digestive system nausea, vomiting, diarrhea or constipation, flatulence, abdominal pain, increased activity of liver transaminases (ALT, AST, LDH, GGT, ALP) and/or bilirubin concentration, pseudomembranous colitis, hepatitis (sometimes with jaundice). These deviations in laboratory parameters (which can also be explained by the presence of infection) rarely exceed the ULN by 2 times and indicate liver damage, manifested by cholestasis and often asymptomatic.

From the hematopoietic organs leukopenia, eosinophilia, thrombocytopenia, bone marrow failure, pancytopenia, neutropenia, agranulocytosis, hemolytic anemia.

From the cardiovascular system : arrhythmias (due to rapid bolus injection into a central vein).

From the immune system urticaria, anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock, Jarisch-Herxheimer reaction.

From the skin: rash, skin itching, multiforme erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), acute generalized exanthematous pustulosis.

Local reactions fever, phlebitis/thrombophlebitis, inflammatory reactions at the injection site, pain and infiltrate at the IM injection site.

Other superinfection (in particular, candidal vaginitis, candidiasis of the oral mucosa).

Contraindications

Hypersensitivity to sulbactam, cefotaxime, other cephalosporins.

With caution

In patients with a history of allergy to penicillins (risk of developing cross-allergic reactions), simultaneous use with aminoglycosides, chronic renal failure, neonatal period (for IV administration).

Use in Pregnancy and Lactation

Cefotaxime and Sulbactam cross the placental barrier. Studies conducted in animals have not revealed teratogenic or fetotoxic effects. However, the safety of use during pregnancy in humans has not been established, so this combination should not be used during pregnancy. Cefotaxime is excreted in human breast milk. If it is necessary to use during lactation, breastfeeding should be discontinued.

Special Precautions

The use of cephalosporins requires collection of an allergic history (allergic diathesis, hypersensitivity reactions to beta-lactam antibiotics). If an allergic reaction occurs, the drug should be discontinued. Patients who have had a history of allergic reactions to penicillins may have increased sensitivity to cephalosporins (in 5-10% of cases). Anaphylactic reactions developing in this situation can be serious or even fatal. In patients with a history of allergy to penicillins, the drug should be used with caution. The condition should be carefully monitored during the first administration of the drug due to the possible anaphylactic reaction. If the first symptoms and signs of anaphylactic shock appear, the administration of the drug should be stopped immediately and adequate therapy should be prescribed.

During the administration of this combination or after the end of treatment, pseudomembranous colitis may occur, manifested by severe prolonged diarrhea, including with blood. In this case, administration is stopped, adequate therapy is prescribed, including vancomycin or metronidazole orally. The appointment of drugs that inhibit intestinal peristalsis is contraindicated.

In renal failure, the dose should be adjusted depending on CC.

Caution should be exercised with simultaneous use with aminoglycosides. Renal function should be monitored in all cases of combined use with aminoglycosides, other nephrotoxic drugs in elderly patients or with renal failure.

During treatment for more than 10 days, monitoring of the number of blood cells is necessary. If these indicators deviate from the norm, the combination should be discontinued.

During treatment, a false-positive Coombs test and a false-positive urine glucose reaction may be obtained (it is recommended to use glucose oxidase methods for determining plasma glucose concentration).

Effect on ability to drive vehicles and mechanisms

In case of development of such a side effect as dizziness, the ability to concentrate and react may be impaired. In such cases, patients should refrain from driving vehicles and mechanisms.

Drug Interactions

The likelihood of kidney damage increases with simultaneous administration with aminoglycosides, polymyxin B and “loop” diuretics.

Drugs that block tubular secretion increase the plasma concentrations of the combination and slow down the excretion of the components.

Probenecid delays excretion and increases the concentration of cephalosporins in blood plasma.

Pharmaceutically incompatible with solutions of other antibiotics in the same syringe or dropper.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.