Foraklav - instructions for use, dose, side effects, contraindications

1 bottle of Foreaklav 500 mg + 100 mg contains active ingredients: amoxicillin 500 mg (in the form of sodium salt 531.5 mg) and clavulanic acid 100 mg (in the form of potassium salt 119.7 mg);

1 bottle of Foreaklav 1000 mg + 200 mg contains active ingredients: amoxicillin 1000 mg (in the form of sodium salt 1063 mg) and clavulanic acid 200 mg (in the form of potassium salt 239.4 mg).

Description:

Powder from white to white with a yellowish hue of color.

Pharmacotherapeutic group:Antibiotic-penicillin semisynthetic + beta-lactamase inhibitor

ATX: & nbsp

J.01.C.R.02 Amoxicillin in combination with enzyme inhibitors

Pharmacodynamics:

Foraclav is a combination of amoxicillin-semisynthetic penicillin with a broad spectrum of antibacterial activity and clavulanic acid, an irreversible inhibitor of β-lactamases. Clavulanic acid forms a stable inactivated complex with these enzymes and provides stability of amoxicillin to the action of β-lactamases produced by microorganisms. Clavulanic acid, similar in structure to β-lactam antibiotics, has a weak intrinsic antibacterial activity.

Amoxicillin + clavulanic acid has a bactericidal effect in vivo on the following microorganisms:

Gram-positive aerobes:

Staphylococcus aureus (sensitive to methicillin) *

Streptococcus pneumoniae

Streptococcus pyogenes

Streptococcus agalactiae

Streptococcus spp. (other beta-hemolytic streptococci)

Gram-negative aerobes:

Haemophilus influenzae

Moraxella catarrhalis

Escherichia coli¹

Klebsiella pneumoniae¹

Amoxicillin + clavulanic acid has a bactericidal effect in vitro on the following microorganisms, however, the clinical significance of this action is still unknown:

Gram-positive aerobes:

Bacillis anthrasis

Enterococcus faecalis

Enterococcus jaecium¹

Gardnerella vaginalis

Corynebacterium spp.¹

Listeria monocytogenes

Nocardia asteroides

Streptococcus spp. groups viridans

Coagulase-negative staphylococci (sensitive to methicillin)

Staphylococcus saprophyticus

Gram-positive anaerobes:

Clostridium spp.

Peptococcus niger

Peptostreptococcus magnus

Peptostreptococcus micros Peptostreptococcus spp.

Gram-negative aerobes:

Bordet ella pertussis

Helicobacter pylori

Neisseria gonorrhoeae

Pasteurella multocida

Vibrio cholerae

Klebsiella oxytoca¹

Klebsiella spp.¹

Proteus mirabilis¹

Proteus vulgaris¹

Proteus spp.¹

Salmonella spp.¹

Shigella spp.¹

Gram-negative anaerobes:

Bacteroides fragilis

Bacteroides spp.

Capnocytophaga spp.

Eikenella corrodens

Fusobacterium nucleatum

Fusobacterium spp.

Porphyromonas spp.

Prevotella spp.

Other:

Borrelia burgdorferi

Treponema pallidum

Leptospira icterohaemorrhagiae

¹ - bacteria for which the acquired resistance to a combination of amoxicillin and clavulanic acid is likely

Microorganisms possessing natural resistance to a combination of amoxicillin and clavulanic acid:

Gram-negative aerobes:

Acinetobacler spp.

Citrobacler freundii

Enterobacter spp.

Hqfitia ctlvei

Legionella pneumophila

Morganella morganii

Providencia spp.

Pseudomonas spp.

Serralia spp.

Stenotrophomonas maltophilia

Yersinia enlerocolitica.

Other:

Chlamydia pneumoniae,

Chlamydia psittaci,

Chlamydia spp.,

Coxiella burnetii,

Mycoplasma spp.

Pharmacokinetics:

Amoxicillin and clavulanic acid in combination with ns influence the pharmacokinetics of each other friend. Maximum plasma concentration after bolus intravenous injection Amoxicillin + clavulanic acid (1000 mg + 200 mg) is 105 μg / ml for amoxicillin and 28 μg / ml for clavulanic acid, with administration of 500 mg amoxicillin and 100 mg clavulanic acid 32 μg / ml and 10 μg / ml, respectively.

Therapeutic concentrations of amoxicillin and clavulanic acid are detectable in various fluids and tissues of the body (including the abdominal cavity, fat and muscle tissues and interstitial fluid, skin, lungs and pleural fluid, gallstones bladder, synovial and peritoneal fluid, bile and pus). Both components are characterized by low binding to plasma proteins (13-20%). Amoxicillin penetrates into breast milk, clavulanic acid also penetrates into breast milk in trace concentrations. With the exception of the possibility of developing sensitization, diarrhea or candidiasis of the mucous membranes of the oral cavity, no other negative influences Amoxicillin and clavulanic acid on the health of infants fed breast milk. Amoxicillin and clavulanic acid penetrate the placental barrier. However, there was no adverse effect on the fetus. Approximately 60-70% amoxicillin and 40-65% of clavulanic acid are excreted by the kidneys unchanged in the first 6 hours after a single bolus injection of 1000 mg / 200 mg. 10-25% of the initial the dose of amoxicillin is excreted by the kidneys in the form of inactive penicillic acid.

Clavulanic acid in the human body is subject to intensive metabolism and is excreted by the kidneys, intestines and with exhaled air. The half-life (T1/2) amoxicillin (dose 1000 mg) is 0.9 hours, clavulanic acid (200 mg dose) - 0,9 hours. T1/2 with the administration of 500 mg of amoxicillin and 100 mg of clavulanic acid - 1 hour for both components. In patients with severe renal insufficiency T1/2 increases to 7.5 h for amoxicillin and up to 4.5 h for clavulanic acid. Both components are removed by hemodialysis and minor amounts - by peritoneal dialysis.

Indications:

Bacterial infections caused by microorganisms sensitive to amoxicillin / clavulanic acid:

- Infections of ENT organs, incl. tonsillitis, sinusitis, otitis media.

- Infections of the lower respiratory tract, incl. exacerbation of chronic bronchitis, lobar pneumonia and bronchopneumonia.

- Urinary tract infections (including cystitis, urethritis, pyelonephritis), infections of female genital organs, gonorrhea.

- Infections of the skin and soft tissues.

- Infections of bones and joints, incl. osteomyelitis, if necessary, long-term therapy is possible.

- Other infectious diseases: septic abortion, postpartum sepsis, septicemia, peritonitis, intra-abdominal sepsis, postoperative infections.

Prevention of postoperative infections during surgical interventions on the gastrointestinal tract, pelvic organs, head and neck, heart, kidneys, bile ducts, as well as when implanting artificial joints.

The sensitivity of bacteria to the combination of amoxicillin and clavulanic acid varies depending on the region and over time. Wherever possible, local sensitivity data should be taken into account.

Contraindications:

- Hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, other beta-lactam antibiotics, incl.to penicillins and cephalosporins in the anamnesis;

- Infectious mononucleosis;

- previous episodes of jaundice or impaired liver function with amoxicillin / clavulanic acid in history.

Carefully:

- impaired renal function (creatinine clearance <30 mL / min);

- abnormal liver function.

Pregnancy and lactation:

Pregnancy

Parenteral administration of a combination of amoxicillin and clavulanic acid did not reveal teratogenic effects. In women with premature rupture of membranes, it was found that preventive therapy with this combination may be associated with an increased risk of developing necrotizing enterocolitis in newborns. The drug is not recommended for use during pregnancy, except when the benefit to the mother exceeds the potential risk to the fetus.

Lactation

The drug can be used during breastfeeding. With the exception of the possibility of developing sensitization, diarrhea, or candidiasis of the oral mucosa associated with the penetration of trace amounts of active substances of this preparation into breast milk, no other adverse effects were observed in infants fed breastfeeding.In case of adverse effects in infants who are breastfeeding, it is necessary to stop it.

Dosing and Administration:

Intravenously.

The dose depends on the severity of the infection, age, body weight and function of the patient's nights.

Doses are given in terms of the content of amoxicillin / clavulanic acid. The minimum course of antibiotic therapy should be 5 days. The maximum duration of therapy can be 14 days, after which its effectiveness and tolerability should be assessed.

Adults and children over 12 years of age and weighing more than 40 kg

Infections of mild to moderate severity: 1000 mg / 200 mg every 8 hours.

Severe infections: 1000 mg / 200 mg every 4-6 hours.

Prophylaxis in surgery

Surgical interventions of less than 1 h: 1000 mg / 200 mg during the initial anesthesia.

Surgical interventions of more than 1 h: 1000 mg / 200 mg during the initial anesthesia and then to 4 doses of 1000 mg / 200 mg for 24 hours.

Patients with impaired function of night

Dose adjustment is based on the maximum recommended dose of amoxicillin and on the values of creatinine clearance (CK).

CK> 30 ml / min	Correction of the dose is not required.
KK 10-30 ml / min	The initial dose is 1000 mg / 200 mg and then 500 mg / 100 mg twice a day.
CK <10 ml / min	The initial dose is 1000 mg / 200 mg and then 500 mg / 100 mg every 24 hours.

Patients on hemodialysis

Dose adjustment is based on the maximum recommended dose of amoxicillin. The initial dose is 1000 mg / 200 mg, then 500 mg / 100 mg every 24 hours and an additional 500 mg / 100 mg at the end of the hemodialysis session.

Patients with impaired hepatic function

Treat with caution; regularly monitor liver function.

At present, there is insufficient data to correct the dose in such patients.

Elderly patients

Correction of the dose is not required.

Children

For children weighing less than 40 kg, the dose is calculated depending on the body weight.

Less than 3 months with a body weight of less than 4 kg (25 mg / 5 mg) / kg every 12 hours.

Less than 3 months with a body weight of more than 4 kg (25 mg / 5 mg) / kg every 8 hours.

In children younger than 3 months, the drug is administered only slowly infusion for 30-40 minutes.

From 3 months to 12 years with a body weight of less than 40 kg

(25 mg / 5 mg) kg every 6-8 hours depending on the severity of the infection

Children with dysfunction of night

Correction of the dose is based on the maximum recommended dose of amoxicillin

CK> 30 ml / min	Correction of the dose is not required.
KK 10-30 ml / min	(25 mg / 5 mg) / kg 2 times a day.
CK <10 ml / min	(25 mg / 5 mg) / kg every 24 hours.

Children on hemodialysis

Correction of the dosing regimen is based on the maximum recommended dose of amoxicillin - (25 mg / 5 mg) / kg every 24 hours and additionally (12.5 mg / 2.5 mg) / kg at the end of the hemodialysis session (to compensate for the decrease in concentration of amoxicillin and clavulanic acid in blood plasma) and further (25 mg / 5 mg) / kg per day.

Children with impaired liver function

Treat with caution; regularly monitor liver function. At present, there is insufficient data to correct the dose in such patients.

Preparation of solutions for intravenous injection.

Dissolve the contents of the vial in water for injection - 600 mg (500 mg + 100 mg) in 10 ml of water for injection or 1.2 g (1000 mg + 200 mg) - in 20 ml of water for injection.

Intravenous injection slowly for 3-4 minutes.

The resulting solution should be introduced within 20 minutes after dilution. Preparation of solutions for intravenous infusion. For infusion introduction of Foraklav preparation, further dilution is necessary: prepared solutions containing 600 mg (500 mg + 100 mg) or 1.2 g (1000 mg + 200 mg) of the preparation,should be diluted in 50 ml or 100 ml of the infusion solution, respectively: sodium chloride solution 0.9%, sodium lactate solution for intravenous administration, Ringer's lactate solution according to Hartman, calcium chloride and sodium chloride solution for intravenous administration.

Side effects:

The adverse events presented below are listed according to the frequency of occurrence. The frequency is distributed as follows: Often (>1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely (> 1/10000 and <1/1000), rarely (<1/10000, including individual cases).

Allergic reactions

Infrequent - skin rash, itching, hives; rarely erythema multiforme; very rarely - angioedema, anaphylactic reactions, a syndrome similar to serum sickness, allergic vasculitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

Co side of the hematopoietic and lymphatic system

Rarely, reversible leukopenia (including neutropenia) and thrombocytopenia; very rarely - reversible agranulocytosis and hemolytic anemia, prolongation of prothrombin time and bleeding time, eosinophilia, thrombocytosis, anemia.

From the nervous system

Infrequent - dizziness, headache; very rarely - convulsions (in patients with impaired renal function when taking high doses of the drug), insomnia, agitation, anxiety, behavior change.

From the digestive system

Often - diarrhea; infrequently - nausea, vomiting, indigestion; very rarely - antibiotic-associated colitis (including pseudomembranous and hemorrhagic).

From the liver and biliary tract

Infrequent - moderate increase in activity of aspartate aminotransferase (ACT) and alanine aminotransferase (ALT); very rarely - hepatitis and cholestatic jaundice (noted in patients receiving penicillin antibiotics and cephalosporins), increased activity of alkaline phosphatase and / or bilirubin concentration.

Undesirable reactions from the liver occur mainly in men and in elderly patients and can be associated with long-term therapy; usually occur during or soon after the end of treatment, but in some patients they develop only a few weeks after the end of treatment. Usually, unwanted reactions from the liver are reversible.Undesirable phenomena from the liver can be severe up to death in some cases. In almost all cases, these were patients with severe previous illnesses or potentially hepatotoxic drugs.

From the side of the kidneys and urinary tract

Very rarely - interstitial nephritis, crystalluria.

Superinfections

Often - candidiasis of the skin and mucous membranes.

Local Reactions

Rarely, thrombophlebitis at the injection site.

Overdose:

Symptoms: disorders of the gastrointestinal tract and violations of water-electrolyte balance, convulsions. Crystalluria, caused by the use of amoxicillin, in some cases led to renal failure.

Treatment: symptomatic. Both substances are removed from the bloodstream by hemodialysis.

In the presence of high concentrations of amoxicillin in urine, it can precipitate in urinary catheters at room temperature. It is necessary to regularly check the patency of such catheters.

Interaction:

Probenecid reduces tubular secretion of amoxicillin, which can lead to an increase and maintenance of amoxicillin concentration in the blood (but not clavulanic acid). The simultaneous use of the drug Foraclav and probenecid is not recommended.

The simultaneous use of allopurinol and amoxicillin may increase the risk of skin allergic reactions.

Penicillins can slow the excretion of methotrexate from the body by inhibiting its tubular secretion, so the simultaneous use of the drug Foraklav and methotrexate may increase the toxicity of methotrexate.

The drug may reduce the effectiveness of oral hormonal contraceptives, which should be prevented by patients using oral hormonal contraceptives as a method of contraception.

In the literature, rare cases of an increase in the international normalized ratio (INR) in patients with simultaneous use of acenocoumarol or warfarin and amoxicillin are described. If it is necessary to simultaneously use Foraklav with indirect anticoagulants, prothrombin time or INR should be carefully monitored during treatment and when the Foreaklav preparation is withdrawn, correction of the dose of indirect anticoagulants may be required.

In patients taking mycophenolate mofegil,after the start of the combination of amoxicillin with clavulanic acid, a decrease in the concentration of the active metabolite, mycophenolic acid, was observed, until the next dose of the drug was taken approximately 50%. Changes in this concentration can not accurately reflect the overall changes in the exposure of mycofepolic acid.

Clavulanic acid can lead to nonspecific binding of immunoglobulin G and albumin with a cell membrane of erythrocytes, which can lead to a false positive reaction with a Coombs sample.

Pharmaceutical incompatibility

The preparation of Foraclav should not be mixed in one vial or syringe with blood preparations, other protein liquids, such as protein hydrolysates, and with intravenous lipid emulsions, aminoglycosides (decrease in aminoglycoside activity).

Solution of the drug Foraclav should not be mixed with solutions of dextrose, dextran or sodium bicarbonate.

Special instructions:

Before starting treatment with the drug, you need to collect a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins or other allergens.

Serious, and sometimes lethal, hypersensitivity reactions (anaphylactic reactions) to penicillins are described. The risk of occurrence of such reactions is highest in patients who have a history of hypersensitivity reactions to penicillins. In case of an allergic reaction, it is necessary to stop treatment with the drug and begin the appropriate alternative therapy. Serious anaphylactic reactions should be immediately taken appropriate measures (epinephrine). Oxygen therapy, intravenous glucocorticosteroids, and airway patency, including intubation, may also be required.

It is necessary to avoid the use of the drug Foraklav in case of suspected infectious mononucleosis, since in patients with this disease amoxicillin can cause a skinlike skin rash, which makes it difficult to diagnose the disease. Long-term treatment with the drug may lead to excessive reproduction of insensitive microorganisms.

Cases of pseudomembranous colitis occur when antibacterial drugs are used, the severity of which can range from mild to life-threatening.Therefore, it is important to consider the possibility of developing pseudomembranous colitis in patients with diarrhea during or after using antibacterial drugs. If the diarrhea is long and has a pronounced character, treatment should be discontinued, and the patient should be examined. Contraindicated use of drugs that inhibit intestinal peristalsis.

If it is necessary to simultaneously use the drug with indirect anticoagulants prothrombin time or INR should be carefully monitored, with the appointment or cancellation of the drug may require correction of the dose of indirect anticoagulants.

In patients with impaired renal function, the dosage regimen is adjusted in accordance with the degree of impairment (see section "Method of administration and dose").

In patients with reduced diuresis, crystalluria is very rare. During the administration of high doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain an adequate diuresis to reduce the likelihood of amoxicillin crystals.

If it is necessary to use high doses of Foraclav, patients on a diet low in salt should take into account the presence of sodium ion in the preparation.

During prolonged therapy with the drug it is recommended to periodically evaluate the function of the kidneys, liver and hematopoiesis.

The high content of amoxicillin in the urine can lead to false positive results in the determination of glucose in the urine (for example, the Benedict test, Feeling's test). In this case, it is recommended to use a glucose oxidant method for determining the concentration of glucose in the urine.

Effect on the ability to drive transp. cf. and fur:

Given the possibility of developing dizziness, as a side effect of the central nervous system in the treatment of the drug, care should be taken when working with mechanisms and driving vehicles.

Form release / dosage:

Powder for the preparation of a solution for intravenous administration of 500 mg + 100 mg, 1000 mg + 200 mg.

Packaging:For 500 mg of amoxicillin and 100 mg of clavulanic acid or 1000 mg of amoxicillin and 200 mg of clavulanic acid in a bottle of neutral colorless glass of hydrolytic class III with a capacity of 10 ml or 20 ml, corked with a rubber stopper under running-in with an aluminum cap (type Flip ofl). 1 bottle together with the instruction but applied to a cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002923

Date of registration:20.03.2015

The owner of the registration certificate:FORTYUN MED, LTD FORTYUN MED, LTD Russia

Manufacturer: & nbsp

SANJIVANI PARANTERAL, Limited India

Information update date: & nbsp20.03.2015

Illustrated instructions

Instructions

Foraclav (Foraklav)