Sumakin: A combination bactericidal medicine

2021-06-26 04:17 AM

Antibacterial medicine (systemic) Sumakin is a bactericidal effect against bacteria sensitive to amoxicillin, the combination of amoxicillin with sulbactam helps prevent amoxicillin from being destroyed by beta-lactamases.

Producer

Mekophar.

Ingredient

Sumakin 625 Each tablet: Amoxicillin 500mg, sulbactam 125mg.

Sumakin 750 Each tablet: Amoxicillin 500mg, sulbactam 250mg.

Sumakin 1000 Each tablet: Amoxicillin 500mg, sulbactam 500mg.

Sumakin 1g Each tablet: Amoxicillin 875mg, sulbactam 125mg.

Sumakin 250/250 Each pack: Amoxicillin 250mg, sulbactam 250mg.

Sumakin 250/125 Each pack: Amoxicillin 250mg, sulbactam 125mg.

Sumakin 500/125 Each pack: Amoxicillin 500mg, sulbactam 125mg.

Pharmacodynamic

Pharmacotherapeutic group: antibacterial drugs (systemic route).

ATC code: J01CR02.

Sumakin is a bactericidal effect against bacteria sensitive to amoxicillin, the combination of amoxicillin with sulbactam helps prevent amoxicillin from being destroyed by beta-lactamases.

The bactericidal effect of amoxicillin is similar to that of other antibiotics of the beta-lactam or penicillin group: inhibition of protein biosynthesis of the bacterial cell wall, leading to the destruction of bacteria. The drug has a bactericidal effect during the division of susceptible bacteria. Its effect is dependent on its ability to find and bind to penicillin-binding proteins (PBPs) found in the inner layer of the bacterial cell wall. Penicillin-binding proteins, including transpeptidases, carboxypeptidases, and endopeptidases, enzymes are involved in the late stages of cell wall formation and in the reorganization of the cell wall during development and division. Penicillin binds to and inactivates the PBPs, causing the bacterial cell wall to weaken and eventually be destroyed.
 
Amoxicillin, a beta-lactam semi-synthetic antibiotic, has broad-spectrum bactericidal activity against a wide range of gram-positive and gram-negative bacteria, both aerobic and anaerobic. However, its sensitivity is reduced by beta-lactamase enzymes, so the susceptibility spectrum of the drug usually does not include strains of bacteria capable of producing beta-lactamases.

Sulbactam, a potent competitive, irreversible beta-lactamase inhibitor, showed intrinsically limited bactericidal activity with the exception of Neisseriaceae and Acinetobacter. However, it has an irreversible inhibitory effect on various beta-lactamases found in strains of bacteria resistant to penicillins and cephalosporins. Therefore, sulbactam may restore the bactericidal effect of amoxicillin against resistant bacteria due to its ability to produce beta-lactamase enzymes. In particular, it can exhibit beta-lactamase inhibitory action, which is the cause of resistant strains of bacteria that can be converted and have a very good clinical response. Sulbactam did not alter the effects of amoxicillin on susceptible strains. The presence of sulbactam in the composition of Sumakin enhances the effect of amoxicillin against drug-resistant strains of bacteria when treated with amoxicillin alone or in combination with other beta-lactam antibiotics.

This combination synergistically increases the effect and broadens the antibacterial spectrum of amoxicillin against beta-lactamase-producing strains:

Sensitive bacteria

Gram-positive aerobic bacteria: Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus faecalis (intestinal cocci), Streptococcus viridans, Staphylococcus aureus (including beta-lactamase-producing strains), Staphylococcus epidermidis (hemolytic, non-penicillinase-producing staphylococcus). ), Staphylococcus saprophyticus, Streptococci groups A, B, C and G, Streptococci viridans and some strains of Enterococci, Corynebacterium diptheriae, Listeria monocytogenes, Bacillus anthracis, Erysipelothrix rhusiopathiae, a few strains of Nocardia (although most are resistant).

Gram-negative aerobic bacteria: Neisseria gonorrhoeae, and N. gonorrhoeae (non-penicillinase producing), Haemophilus influenzae and some strains of H. Parainfluenzae and H. Ducreyi, some strains of Enterobacteriaceae, Proteus mirabilis, Salmonella and Shigella, P. vulgaris, Enterobacter aerogenes, Citrobacter freundii, Vibrio cholerae, Helicobacter pylori, Bordetella pertussis, Acinobacillus, Pasteurella multocida, Gardnerella vaginalis (Haemophilus vaginalis), Moraxella catarrhalis (Brahamella catarrhalis) non-beta-lactamase, strains of Acineitobacter, Procolilisteus, E. Klebsiella strains including Klebsiella pneumoniae.

Anaerobic bacteria: Bacteroides strains including B. fragilis, Actinomyces, Arachnia, Bifidobacterium, Clostridium tetani, C. Perfringens, Eubacterium, Lactobacillus, Peptococccus, PeptoStreptococcus and Propionibacterium, Fusobacterium.

Spirochetes: Treponema pallidum, Borelia burgdoferi cause Lyme disease.

Moderately sensitive bacteria

Gram-positive aerobic bacteria: Enterococcus faecium.

Drug-resistant bacteria

Gram-positive aerobic bacteria: staphylococcus (Staphylococcus aureus).

Gram-negative aerobic bacteria: Acinobacter alcaligenes, Moraxella catarrhalis producing beta-lactamases, Campylobacter, Citrobacter freundii, Citrobacter koseri, Enterobacter, Klebsiella oxytoca, Klebsiella pneumoniae, Legionella, Morganella morganii, Proteus rettgeri, Proteus Pneumonia, Providencia, Serra vulgaris, Providencia, Yersinia enterocolitica.

Anaerobic bacteria: Bacteroides fragilis.

Other bacteria: Mycobacterium, Mycoplasma, Rickettsia.

Complete cross-resistance usually occurs between amoxicillin and ampicillin.

Pharmacokinetics

The amount of amoxicillin absorbed after oral administration is approximately 80% and is not affected by food. Mean peak serum concentrations are reached approximately 1-2 hours after oral administration. In subjects with normal renal function, the mean serum half-life is approximately 1 hour. Amoxicillin is distributed in most body tissues and biological fluids, therapeutic concentrations are achieved in bronchial secretions, nasal sinus and amniotic fluid, saliva, body fluids, cerebrospinal fluid, and exudates. membranes and middle ear. Approximately 20% of the drug is bound to plasma proteins.

The drug is excreted mainly in the urine as active (70-80%) and into bile (5-10%). Amoxicillin crosses the placental barrier and is excreted in breast milk.

When sulbactam is administered parenterally, bioavailability of the drug is almost 100%, however, if administered orally, absorption from the gastrointestinal tract is incomplete. To improve absorption, several prodrugs have been synthesized, among which sulbactam pivoxil has the best absorption.

The pharmacokinetics of sulbactam is similar to that of amoxicillin and, when administered concomitantly, there are no pharmacokinetic interactions between the drugs.

Peak serum concentrations of sulbactam are also achieved at the same time as amoxicillin and peak values ​​are also dose dependent.

The plasma protein binding is approximately 40%. It is also mainly excreted in the urine as unchanged (75-85%).

The half-life of the drug in serum is approximately 1 hour, in patients with severe renal impairment, excretion of the drug is slowed down.

The drug also crosses the placental barrier and is excreted in breast milk.

Indications and uses

Treatment of infections caused by susceptible bacteria:

Infections of the mouth and respiratory tract: otitis media, sinusitis, tonsillitis, pharyngitis, laryngitis, tracheitis, pneumonia, bronchitis,... (especially in severe or recurrent cases broadcast).

Intra-abdominal infections, gynecological infections.

Urinary tract infections: especially in cases of recurrent or complicated cystitis.

Skin and soft tissue infections: lymphatic vasculitis, cellulitis, open wounds or tissue loss, dental and oral abscesses caused by Staphylococcus aureus.

Mixed infections caused by amoxicillin-susceptible organisms and by amoxicillin-susceptible beta-lactamase-producing organisms in combination with sulbactam can be treated with Sumakin alone without the need for additional therapy. use any other antibiotic preparations.

Appropriate microbiological tests (isolation and susceptibility testing) should therefore be performed prior to initiation of treatment to determine the causative organism and its susceptibility to Sumakin.

Treatment should be initiated prior to the availability of bacteriological results if there is reason to suspect an infection caused by beta-lactamase-producing organisms. Once the results of the bacteriological examination are available, the necessary treatment regimen can be adjusted.

Dosage and Administration

Usual dose for adults and children from 12 years of age: 1 tablet (SUMAKIN 1000 or SUMAKIN 750) every 8 hours or every 12 hours (SUMAKIN 1g), or 1-2 tablets twice a day (SUMAKIN 625); or 2-4 packs x 2 times/day (SUMAKIN 250/250) or x 2-3 times/day (SUMAKIN 250/125); or 1-2 packs x 2-3 times/day (SUMAKIN 500/125).

Children under 12 years old (using oral powder): 75-100 mg of amoxicillin/kg, divided 2-3 times/day.

Patients with renal impairment: use as directed by the physician or reduce the dose according to the creatinine clearance (calculated according to the amoxicillin content).

10mL/min < Clcr < 30 mL/min: 500 mg every 12 hours.

Clcr < 10 mL/min: 500 mg every 24 hours.

Hemodialysis patients: 500 mg every 24 hours and an additional dose after dialysis.

Use caution

Hypersensitivity reactions

Before initiating treatment with amoxicillin/sulbactam, a careful history of allergy to penicillins, cephalosporins, sulbactam or other beta-lactams should be carefully investigated.

Serious and sometimes fatal hypersensitivity reactions (including anaphylaxis and serious skin reactions) may occur in patients treated with penicillin therapy. These reactions are more likely to occur in individuals with a history of allergy to penicillins, beta-lactam antibiotics, and allergic individuals. If an allergic reaction occurs, discontinue amoxicillin/sulbactam therapy and institute appropriate alternative therapy.

Non-susceptible bacteria

Amoxicillin is not suitable for the treatment of certain types of infections unless the pathogen has been documented and is known to be susceptible or it is highly likely that the pathogen would be suitable for treatment with amoxicillin. This especially applies when considering the treatment of patients with urinary tract infections and serious infections of the ears, nose, and throat.

Convulsions

Convulsions may occur in patients with impaired renal function or in patients receiving high doses or in patients with risk factors (eg, history of convulsions, being treated for epilepsy, or meningitis).

Amoxicillin/sulbactam should be avoided if a rash is suspected due to the presence of infectious mononucleosis following amoxicillin/sulbactam use.

The Jarisch-Herxheimer reaction

Following treatment of Lyme disease with amoxicillin, a Jarisch-Herxheimer reaction may occur. It results directly from the bactericidal activities of amoxicillin on the bacterium that causes Lyme disease, the spirochetes Borrelia burgdorferi. Patients should be made aware that this is a common and often self-limiting outcome of antibiotic treatment for Lyme disease.

Superinfection

Patients treated with Sumakin may develop superinfections with fungi or other pathogenic bacteria (mainly Pseudomonas or Candida). If superinfection occurs, discontinue use and institute appropriate therapeutic measures.

Prolonged use of amoxicillin/sulbactam can sometimes lead to the overgrowth of non-susceptible organisms.

Antibiotic-associated colitis has been reported with most antibacterial agents and can range in severity from mild to life-threatening. Therefore, it is important to consider the diagnosis in patients who develop diarrhea during or after antibiotic use. If antibiotic-associated colitis occurs, immediately discontinue amoxicillin/sulbactam, consult a physician, and initiate appropriate treatment. In this case, antimotility drugs are contraindicated.

Prolonged treatment

Must periodically check hematology, liver and kidney function during the course of treatment. Elevations of liver enzymes (mainly glutamic-oxalacetic transaminases) and changes in blood count have been reported.

Anticoagulants

Prothrombin time prolongation has rarely occurred in patients treated with amoxicillin. Regular testing is recommended when co-administered with anticoagulants. If necessary, the anticoagulant dose can be adjusted to maintain the desired level of anticoagulation.

Stones - urine

In patients receiving parenteral therapy, urolithiasis has rarely occurred in patients with oligouria. When taking high doses of amoxicillin, fluid intake should be maintained to minimize amoxicillin-induced urinary stones. In patients with bladder catheterization, regular checks should be made to avoid precipitating tubal occlusion.

Diagnostic tests

High concentrations of amoxicillin in serum and urine have a certain influence on laboratory results. Due to the high concentration of amoxicillin in the urine, it is common to cause false-positive results for chemical reactions. During amoxicillin therapy, urine glucose testing should be performed using the enzyme glucose oxidase method.

Amoxicillin can falsify oestriol test results in pregnant women. A slight decrease in the relationship between estriol and estrone concentrations and serum estradiol levels. Supportive contraception should be used in female patients taking estrogen or progestin contraceptive therapy.

Caution with the elderly and children.

Use caution when driving or operating machinery.

Overdose

To date, there have been no reports of overdoses of amoxicillin-sulbactam.

Contraindications

Patients with a history of allergy to penicillins or to cephalosporins, or to sulbactam, or to any of the excipients. The patient has a history of gastrointestinal disease. Infections with mononucleosis. Herpes virus infection, being treated with allopurinol.

Use in pregnant and lactating women

Use caution in pregnant and lactating women as human studies have not been performed.

Pregnant

No toxicity to the fetus has been observed, however, Sumakin should only be used when the benefit of use has been assessed against the possible risk to the fetus.

Breastfeeding Women

Amoxicillin is excreted in breast milk. Although the risks have not been clearly established, when used by nursing mothers can cause sensitization, diarrhea, fungal infections, and skin rashes.

Interactive

Allopurinol: Concomitant use of allopurinol during treatment with amoxicillin may increase the likelihood of allergic skin reactions.

Probenecid: Concomitant use of probenecid is not recommended, as it reduces the tubular secretion of amoxicillin and sulbactam. Concomitant use of probenecid may lead to increased and prolonged blood levels of amoxicillin and sulbactam.

Chloramphenicol, macrolides, sulfonamides, and tetracyclines: Tetracyclines and other antibacterial agents may interfere with/antagonize the bactericidal action of penicillins.

Anticoagulants: Anticoagulants and penicillin antibiotics have been widely used in practice without reported interactions. However, in the literature, there are cases of increased international normalization in patients maintained on acenocoumarol or warfarin and for whom a course of amoxicillin was indicated. If concurrent therapy is required, careful monitoring of prothrombin time or international normalization is recommended by the addition or discontinuation of amoxicillin. Furthermore, if necessary, the dose of oral anticoagulants can be adjusted.

Methotrexate: Penicillins may decrease the excretion of methotrexate and sulbactam may increase the concentration/effect of methotrexate, thereby increasing the toxicity of the drug.

Typhoid vaccine: Typhoid vaccine is inactivated by antibacterial drugs. Sulbactam reduces the concentration/effectiveness of typhoid vaccine.

Subclinical: Amoxicillin may affect the total serum protein value or give a false positive reaction in the urine glucose test by color reaction. High levels of amoxicillin can lower blood glucose.

Incompatibility

Since there are no incompatibility studies, this drug should not be mixed with other drugs.

Side effects

Common, 1/100 ADR < 1/10

Digestive disorders: nausea, vomiting, diarrhea, dyspepsia, epigastric pain,...

Skin and subcutaneous tissue disorders: skin rash.

Uncommon, 1/1000 ADR < 1/100

Skin and subcutaneous tissue disorders: urticaria and pruritus.

Rare, 1/10000 ADR < 1/1000

Allergic reactions: urticaria, quince edema, maculopapularity, respiratory disorders, and, rarely, anaphylaxis.

Interstitial nephritis.

Hematologic reactions: anemia; disorders of platelets, white blood cells; eosinophilia; leukopenia, and agranulocytosis.

Liver: liver dysfunction.

Candida infection in the mouth or elsewhere is a manifestation of altered bacterial balance.

Neurological: hyperactivity, anxiety, insomnia, behavioral changes.

There are some cases of pseudomembranous enterocolitis.

Stevens-Johnson syndrome, erythema multiforme, and toxic epidermal necrolysis.

Very rare, < 1/10000

Infections and parasites: Candida skin and mucosal diseases.

Blood and lymphatic system disorders: reversible leukopenia (including severe leukopenia or agranulocytosis), reversible thrombocytopenia and hemolytic anemia, prolongation of bleeding time, and duration prothrombin time.

Immune system disorders: severe allergic reactions including epigastric edema, anaphylaxis, serum sickness, and hypersensitivity vasculitis.

Central nervous system disorders: hyperactivity, dizziness, and convulsions.

Gastrointestinal disorders: antibiotic-associated colitis including pseudomembranous colitis and hemorrhagic colitis, black hairy tongue.

Hepatobiliary system disorders: hepatitis and cholestatic jaundice; mean increase in AST and/or ALT.

Skin and subcutaneous tissue disorders: skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, generalized bullous and exfoliative dermatitis, acute generalized pustular rash (AGEP) and drug response to eosinophilia and systemic symptoms (DRESS).

Urinary system and kidney disorders: interstitial nephritis, urolithiasis.

Frequency unknown

Immune system disorders: Jarisch-Herxheimer reaction.

Instructions to handle ADR

If severe ADR occurs, Sumakin must be discontinued. For treatment see “Overdose”.

Preservation

Store in a dry place, protected from light, at a temperature not exceeding 30oC.

Presentation and packaging

Film-coated tablets: Box of 2 blisters x 7 tablets.

Oral powder: box of 12 packs x packs of 1.5g (Sumakin 250/250 and 250/125), a box of 12 packs x packs of 3g (Sumakin 500/125).