Amoxicillin Sandoz

General characteristics. Structure:

Active ingredients: Amoxicillin trihydrate of 0,574 g. It is equivalent to amoxicillin of 0,5 g.
Excipients: Magnesium stearate, поливидон, starch sodium glycollate, cellulose microcrystallic.
 
Structure of an obolochki:titan dioxide, talc, gipromelloza.

Pharmacological properties:

Pharmacokinetics. Absorption
Asolyutny bioavailability of amoxicillin depends on a dose and the mode of introduction and is ranging from 75 to 90%. In doses from 250 mg to 750 mg bioavailability (parameters: AUC and/or allocation with urine) is linearly proportional to a dose. In higher doses absorbability lower. Meal does not exert impact on absorption. Amoxicillin is acid resisting. At an oral single dose of 500 mg concentration of amoxicillin in blood makes 6-11 mg/l. After a single dose of 3 g of amoxicillin concentration in blood reaches 27 mg/l. The maximum concentration in plasma are observed in 1-2 hours after administration of drug.
 
Distribution
About 17% of amoxicillin are in the state connected with proteins of plasma. Therapeutic concentration of drug is quickly reached in plasma, lungs, a bronchial secret, liquid of a middle ear, bile and urine. Amoxicillin can get through the inflamed meninx into cerebrospinal liquid. Amoxicillin passes through a placenta and in a small amount it is found in breast milk.
 
Metabolism and removal
As the main place of removal of amoxicillin serve kidneys. About 60-80% of a peroral dose of amoxicillin are allocated within 6 hours after reception in not changed active form through kidneys and the small fraction is excreted in bile. About 7-25% of a dose are metabolized to inactive penitsillovy acid. Plasma elimination half-life at patients with not changed function of kidneys makes 1 - 1,5 hour. At patients with a heavy renal failure the elimination half-life varies from 5 to 20 hours. Substance gives in to a hemodialysis.

Amoxicillin represents the aminobenzylic penicillin possessing bactericidal action as a result of inhibition of synthesis of a bacterial cell wall.

Threshold MIC values for various sensitive organisms vary.

Enterobacteriaceae is considered to be sensitive at their inhibition amoxicillin in concentration of ≤8 mkg/ml of amoxicillin and resistant at concentration of ≥32 mkg/ml.

According to recommendations of NCCLS and when using NCCLS - the specified catarrholis methods M. (a β-laktamaz negative) and N. influenzae (a β-laktamaza negative) are regarded as ≤1 mkg/ml, sensitive at concentration, and resistant at ≥4 mkg/ml; Str. pneumoniae are considered sensitive at MIC of ≤2 mkg/ml and resistant at ≥8 mkg/ml.

Prevalence of resistant strains varies geographically therefore it is desirable to be guided by local information on resistance, especially at treatment of heavy infections. At such level of prevalence of resistant strains at which there is doubtful an expediency of use of drug at least at therapy of some infections, it is better to ask for the help the specialist.

Gram-positive aerobes:

• Bacillus anthracis.
• Corynebacterium spp. ^§
• Enterococcus faecalis. ^§
• Listeria monocytogenes.
• Streptococcus agalactiae.
• Streptococcus bovis.
• ^{Streptococcus pneumoniae #*} of 4.6-51.4%.
• Streptococcus pyogenes. ^#*
• Streptococcus viridans. ^§

Gram-negative aerobes:

• Brucella spp. ^#
• Escherichia coli ^* 46.7%.
• Haemophilus influenzae ^* 2-31.7% ^{of a}.
• Haemophilus para-influenzae ^* 15.3%.
• Neisseria gonorrhoeae ^§ 12-80% ^{of b}.
• Neisseria meningitidis. ^#
• Proteus mirabilis of 28%.
• Salmonella spp. ^§
• Shigella spp. ^§
• Vibrio cholerae.

Anaerobe bacterias:

• Bacteroides melaninogenicus. ^§
• Clostridium spp.
• Fusobacterium spp. ^§
• Peptostreptococci.

• Microorganisms, resistant to Amoxicillin
  • Gram-positive aerobes:
    • Staphylococcus (V-lactamazoproducing strains).
  • Gram-negative aerobes:
    • Acinetobacter spp.
    • Citrobacter spp.
    • Enterobacter spp.
    • Klebsiella spp.
    • Moraxella catarrholis ^*.
    • Proteus spp (indol positive).
    • Proteus vulgaris.
    • Providencia spp.
    • Pseudomonas spp.
    • Serratia spp.
  • Anaerobe bacterias:
    • Bacteroides fragilis.
  • Others:
    • Chlamydia Mycoplasma.
    • Rickettsia.

^{a -} products % β-lactamelements.

^{b -} penitsillinorezistentnost % (including intermediate resistance).

^# - There are no messages on emergence of β-laktzmazoprodutsiyushchy strains so far.

^§ - non-constant sensitivity; sensitivity cannot be predicted without carrying out tests for sensitivity

^* - clinical performance was shown for sensitive strains at use according to indications.

Bacteria can have resistance to amoxicillin (and, therefore, to ampicillin) as a result of products beta лактамаз, hydrolyzing aminopenicillin, changes penicillin - the connecting proteins, disturbance of permeability for drug or thanks to functioning of the special pompovy pumps extorting drug from a cell. At one microorganism there can be at the same time several mechanisms of resistance that explains existence of variable and unpredictable cross resistance to other beta lactams and antibacterial drugs from other groups.

Indications to use:

For peroral therapy of the following bacterial infections caused amoxicillin - sensitive gram-positive and gram-negative pathogens:

Upper respiratory tract infections, including infections of an ear, nose and throat:

Acute average otitis.
Acute sinusitis and bacterial pharyngitis.

Lower respiratory tract infections:

Exacerbation of chronic bronchitis.
 Community-acquired pneumonia .

Infections of lower parts of urinary ways: Cystitis.

Digestive tract infections: Bacterial enteritis. The combination therapy at the infections caused by anaerobic microorganisms can be required.

Prevention of an endocarditis at patients from risk group on development of an endocarditis - for example, when holding dental procedures.

Route of administration and doses:

Inside.
Therapy of infections
As a rule, therapy is recommended to be continued within 2-3 days after disappearance of symptoms. In case of an infection, caused by a β-hemolitic streptococcus, the full eradikation of a pathogen demands performing therapy not less than 10 days.

Parenteral therapy is shown at impossibility of carrying out peroral and at treatment of infections of heavy degree.
The adult (including patients of advanced age): Standard dose: the usual dose fluctuates from 750 mg to 3 g of amoxicillin a day in stages. It is in certain cases recommended to be limited to a dose of 1500 mg a day in stages.
Short course of therapy: uncomplicated infections of urinary tract: double administration of drug on 3 g on each introduction with an interval between doses of 10-12 hours.

To children up to 12 years: the daily dose for children makes 25 - 50 mg/kg/days in stages (at most 60 mg/kg/days) depending on the indication and disease severity.
To children with body weight higher than 40 kg: the adult dosage is recommended.

At a renal failure
At patients with a heavy renal failure the dose has to be lowered. At renal clearance less than 30 ml/min. are recommended increase in an interval between doses or reduction of the subsequent doses.

At a renal failure short courses of therapy of 3 g are contraindicated.
The adult (including patients of senile age):

  
Clearance of creatinine of ml/min.                     Dose                Interval between introductions  
        
> 30                                     Changes of a dose are not required     
                                                        10-30 500 mg                              of 12 h 
<                                                           10 500 mg                               of 24 h 

 

At a hemodialysis: 500 mg have to be entered after the end of a procedure.

To children with body weight less than 40 kg:

Clearance of creatinine of ml/min.                         Dose                     Interval between introductions  
> 30                                          Changes of a dose are not required     
10-30                                                          15 mg/kg                                of 12 h 
<10                                                            15 mg/kg                                of 24 h 

 

Prevention of an endocarditis by the Adult: for prevention of an endocarditis at the patients who are not under the general anesthesia it is necessary to enter 3 g of amoxicillin in 1 hour before operation and in need of 3 more g in 6 hours.
To children: administration of amoxicillin in a dose of 50 mg/kg is recommended.

For more detailed information and the description of categories of the patients entering into risk group on an endocarditis it is necessary to address the local official managements.

Features of use:

Use at a renal failure
At patients with a renal failure amoxicillin removal delay is possible that depending on degree of insufficiency reduction of a daily dose of drug can demand.

With care it is necessary to apply at children, premature and newborn: it is necessary to monitorirovat functions of kidneys, a liver and hematologic indicators .

Before therapy by amoxicillin it is important to make sure of absence in the anamnesis of reactions of hypersensitivity to the penicillin and cephalosporins capable to cause cross allergic reaction (10-15%).

There are messages on development heavy, sometimes from the death, reactions of hypersensitivity (anaphylactoid) against the background of therapy by penicillin. These reactions are more often noted at the people having in the anamnesis hypersensitivity to beta lactams.

In the presence of heavy frustration from digestive tract with diarrhea and vomiting it is not necessary to apply Amoksitsillin Sandoz as these states can reduce its absorbability. Purpose of a parenteral form of amoxicillin is recommended to such patients.

At development of heavy persistent diarrhea it is necessary to consider probability of pseudomembranous colitis (in most cases the caused Clostridium difficile).

Prolonged use of amoxicillin in certain cases can lead to growth of bacteria and mushrooms, insensitive to it. In this regard patients have to monitorirovatsya attentively on development of superinfection.

The acute anaphylaxis and other heavy manifestations of allergic reactions after oral administration of amoxicillin meet seldom. At emergence of such reaction carrying out a complex of urgent actions is necessary: in/in introduction of Epinephrinum , then antihistaminic drugs, compensation of volume and introduction of glyukortikoid. Patients need careful observation and other therapeutic procedures if necessary (an artificial respiration, oxygen).

Presence of amoxicillin at high concentration at urine can cause drug precipitation in an uric catheter therefore catheters need to be checked periodically.

At use of amoxicillin in high doses for the purpose of a minimizirovaniye of risk of an amoksitsillinovy crystalluria it is important to watch adequacy of consumption and removal of liquid.

The artificial diuresis leads to decrease in concentration of amoxicillin in blood as a result of acceleration of its removal.

Diarrhea can promote deterioration in absorbability and reduction of efficiency of medicines.

When determining availability of glucose in urine against the background of therapy amoxicillin recommends to use enzymatic glyukozoksidantny methods. When using chemical methods high concentration of amoxicillin in urine can be the cause of frequent false positive results of a research.

Amoxicillin can reduce concentration of estriol in urine at pregnant women.

In high concentration amoxicillin can reduce glycemia indicators.

Amoxicillin can influence results of proteinaceous researches when using the colorimetric analysis.

Side effects:

Side effects are classified as follows:
- Often: 10%, or are more rare, but 1% is more often.
- Infrequently: 1%, or is more rare, but 0.1% are more often.
- Seldom: 0.1 the % or is more rare, but 0.01% are more often.
- Very seldom, including isolated cases: 0.01 the % or is more rare.
Infections and infection
Infrequently - prolonged and repeated use of medicine can lead to development of superinfection and colonization of resistant microorganisms or mushrooms, for example, to oral and vaginal candidiasis.
 
Disturbances from system of blood and lymphatic system
Seldom - an eosinophilia and hemolitic anemia.

Very seldom - isolated cases of a leukopenia, granulocytopenia, thrombocytopenia, a pancytopenia, anemia, a miyelosupressiya, agranulocytosis, lengthening of a bleeding time and prothrombin time are registered . All changes were reversible at the therapy termination.
 
Disturbances from immune system
Seldom - throat hypostasis, a serum disease, an allergic vasculitis, an anaphylaxis and an acute anaphylaxis in rare instances.
 
Neurologic disturbances
Seldom - reactions from TsNS meet seldom and include hyperkinesias, dizziness and spasms. Spasms can be observed at patients with a renal failure or at the patients receiving high doses of drug.
 
Gastrointestinal frustration
Often - a sensation of discomfort, nausea, vomiting , appetite loss, a meteorism, the liquefied chair, diarrhea, enantema (in particular on mucous a mouth), dryness in a mouth, disturbance of flavoring perception. As a rule, the listed effects are characterized by easy severity and often disappear in process of continuation of therapy or very quickly after its termination. It is possible to reduce the frequency of these complications by means of reception of amoxicillin together with food.

At development of heavy persistent diarrhea it is necessary to consider a possibility of very rare complication, pseudomembranous colitis . Prescription of medicines, suppressing a peristaltics is contraindicated.

Very seldom - emergence of black coloring of language.
 
Disturbances from a liver and bile-excreting system
Infrequently - tranzitorny increase in level in average degree of liver enzymes.

Seldom - cases of hepatitis and cholestatic jaundice .
 
Disturbances of skin and hypodermic fatty tissue
Often - skin reactions in the form of a dieback, an itch, a small tortoiseshell; the typical korepodobny dieback appears for 5-11 day from the beginning of therapy. Immediate development of a small tortoiseshell demonstrates allergic reaction to amoxicillin and demands the therapy termination.

Seldom - a Quincke's disease (Quincke's edema), an exudative multiformny erythema, acute generalized pustulous rashes, Stephens-Johnson's syndrome, a toxic epidermal necrolysis, violent and exfoliative dermatitis.
 
Disturbances of kidneys 
Seldom - acute intersticial nephrite.
 
General frustration
Seldom - development of medicinal fever.

Interaction with other medicines:

Combined use is not recommended
Combined use with Allopyrinolum can lead to development of allergic skin reactions.

Increase in absorbability of digoxin against the background of therapy by the drug Amoxicillin Sandoz is possible.

Combined use of amoxicillin and anticoagulants, such as coumarin, can increase probability of bleedings in connection with lengthening of a prothrombin time . At purpose of anticoagulants together with Amoxicillin Sandoz is required monitoring of homeostatic indicators.

Probenetsid suppresses removal of amoxicillin through kidneys, and leads to increase in concentration of amoxicillin in bile and blood.

There is a probability of antagonism of effect of amoxicillin at co-administration of bacteriostatic drugs: macroleads, tetracyclines, streptocides and chloramphenicol .

Combined use of a methotrexate and amoxicillin can increase degree of metotreksatovy toxicity, it is possible as a result of competitive inhibition of tubular renal secretion of a methotrexate amoxicillin.
 
It is necessary to apply with care
Oral hormonal contraceptives: use of amoxicillin can lead to tranzitorny reduction of concentration of estrogen and progesterone in blood and to reduce efficiency of contraceptives. In this regard it is recommended for the period of treatment by amoxicillin in addition to use other non-hormonal methods of contraception.

Contraindications:

Use at pregnancy and feeding by a breast

Use of amoxicillin during pregnancy and breastfeeding is possible only if the estimated advantage for mother exceeds potential risk for a fruit and the baby.

Drug is emitted in breast milk and in rare instances can lead to development of diarrhea and/or fungal colonization of a mucous membrane in newborns. It is also important to consider a possibility of a sensitization of the newborn to a beta laktamnym to antibiotics.

In need of purpose of drug in the period of a lactation it is necessary to stop breastfeeding. 
- Hypersensitivity to penicillin.
- Simultaneous use with a beta laktamnymi antibiotics, such as cephalosporins, karbopenema (a possibility of a cross allergy).

With care:
- Allergic diathesis.
- Asthma.
- Renal failure.
- At children, premature and newborn.
- Viral infections.
- Acute lymphoblastoid leukosis.
- An infectious mononucleosis (in connection with the increased risk of erythematic rash on skin).

Overdose:

Symptoms: Amoxicillin usually does not cause acute toxic effects, even at accidental reception of high doses. The overdose can be shown by symptoms of gastrointestinal frustration, disturbance of water and electrolytic balance. At patients with a heavy renal failure the overdose by high doses of amoxicillin can be followed by signs of nephrotoxicity and a crystalluria.

Treatment: the specific antidote of amoxicillin does not exist. Therapy includes administration of absorbent carbon (there are no indications for a gastric lavage, as a rule) or symptomatic measures. Special attention should be paid water electrolytically to balance. Use of a hemodialysis is possible.

Storage conditions:

To store at a temperature not above 25 °C. Period of validity 4 years. To store in places unavailable to children. Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

In 1 blister of 12 tablets. In a cardboard pack 1 blister.