Фузиданат®

General characteristics. Structure:

Active ingredient: 500 mg of sodium of a fuzidat.
Excipients однйо ampoules with buffered solution: эдетат dinatrium, dinatrium dihydrophosphate, citric acid monohydrate, water for injections
 
Antimicrobic low toxic connection, active against gram-positive cocci steady against Methicillinum (Oxacillinum) and rezistenstny gram-positive activators.

Pharmacological properties:

Pharmacodynamics. Fuzidovy acid concerns to group of Fusidinums, antimicrobic connections which work as inhibitors of synthesis of protein in a bacterial cell. Blocking elongation of a factor of G, they prevent its linkng with ribosomes and guanozintrifosfaty that interrupts release of the energy necessary for synthesis of protein and leads to death of a bacterial cell.
 
Фузиданат® has high activity against stafilokokk, including Staphylococcus aureus, Staphylococcus epidermidis, including strains, Neisseria meningitidis, steady against Methicillinum (Oxacillinum), Neisseria gonorrhoeae, Haemophilus spp., Moraxella spp. and Corynebacterium spp. In concentration of 0,03-0,12 mkg/ml inhibits almost all strains of Staphylococcus aureus. Is less active concerning Streptococcus spp., including Streptococcus pneumoniae, Salmonella spp is not active concerning Escherichia coli., Proteus spp., other gram-negative bacteria, protozoa and mushrooms.
 
For Fuzidanata® there is no cross resistance; affects the strains of stafilokokk steady against other antibiotics. Фузиданат® it is characterized by a hypotoxicity. It is applied when other antibiotics are contraindicated, for example, in the presence of an allergy to penicillin and other antibiotics, and also at a renal failure.

Pharmacokinetics. After single infusions in a dose of 500 mg within more than 2 hours the maximum concentration of sodium of a fuzidat in blood serum makes 52 mkg/ml. At repeated infusions each 8 hours within 2-3 days drug cumulation is observed, at the same time the maximum concentration of sodium of a fuzidat in blood serum reaches 60-120 mkg/ml.
 
Elimination half-life about 10-15 hours. Communication with proteins (albumine) more than 95%. It is well distributed in fabrics with low and high blood supply. The high bactericidal concentration exceeding the minimum inhibiting concentration for stafilokokk (0.03-0,16 mkg/ml) are created in skin and hypodermic cellulose, cartilaginous and connecting tissue, tissues of heart, lungs, a liver, kidneys, bones, synovial fluid, eye tissues, purulent separated, a phlegm, sequesters, strupa, in contents of abscesses, including brain abscesses. Фузиданат® it is metabolized in a liver. It is removed preferential with bile through intestines, to a lesser extent - kidneys. Gets through a placenta and in small amounts - into breast milk.

Indications to use:

Bacterial infections, caused by microorganisms, sensitive to Fuzidanat®: pneumonia, abscess of lungs, a pleura empyema, a bacterial endocarditis, sepsis, a mucoviscidosis, osteomyelitis, infections of skin and soft tissues (the pyoderma, a wound fever infected burns).

Route of administration and doses:

Фузиданат® enter intravenously kapelno. An average dose for adults with body weight more than 50 kg - 500 mg 3 times a day. An average dose for children and adults with body weight less than 50 kg - 6-7 mg/kg 3 times a day.

It is not required from the patients with a renal failure and also who are on a hemodialysis of dose adjustment.

The recommended duration of a course of treatment – 3-6 days, with the subsequent transition to reception of peroral forms of fuzidovy acid.

Rules of preparation of solution and introduction. Solution is prepared by ex tempore by dissolution of 500 mg of the powder Fuzidanat® in 10 ml of the enclosed buffered solution, and then the received solution 5% of solution of a dextrose or other compatible solution for infusions dissolve in 500 ml 0.9% of solution of sodium of chloride.

Adults with body weight have less than 50 kg and children one dose there correspond 6-7 ml of the received solution on 1 kg of body weight. Fuzidanat® solution is entered intravenously kapelno directly into large veins or through a catheter in the central veins. Rate of administering adults - 60-80 caps/min., at children have 10-15 caps/min. Introduction duration through a catheter in the central vein makes more than 2 hours; in a superficial vein - not less than 6 hours. After the end of infusion it is struyno necessary in/in to enter 30-50 ml of 0.9% of solution of sodium of chloride or 5% of solution of a dextrose.

The mix Fuzidanat® with buffered solution cannot be entered without further cultivation, this solution can be used only once, the remains of unused solution should be destroyed.

The prepared Fuzidanat® solution for infusions keeps stability within 24 hours at the room temperature.

Features of use:

Фузиданат® it is impossible to enter intramusculary or subcutaneously.

If in a combination with Fuzidanata® other antibiotic for parenteral administration is appointed, then solutions are entered separately.

It is not recommended to appoint Fuzidanat® to the patients receiving the drugs inhibiting CYP3A4.

In the course of treatment it is necessary to control function of a liver, especially at the patients who are at the same time receiving hepatotoxic drugs with liver diseases, with obstruction of biliary tract or at a combination to the drugs having a way of removal, identical with fuzidovy acid, for example, with lincomycin and rifampicin. If during therapy by Fuzidanat the hyperbilirubinemia with jaundice or without it develops, and also activity of liver enzymes increases (transaminases, an alkaline phosphatase), drug should be cancelled. Increase in activity of "hepatic" enzymes and jaundice are usually quickly reversible after drug withdrawal. Jaundice is more often observed in cases of bystry intravenous administration or exceeding of a dose.

As Fuzidanat® competitively inhibits linkng of bilirubin with protein, it should be applied with care at patients with disturbance of transport and metabolism of bilirubin. Kernicterus cases at newborns were not observed, however, it is necessary to appoint drug with care the newborn with jaundice, acidosis, premature, and also the newborn with other serious illness.

Side reactions from bodies of a hemopoiesis concern, mainly, a white sprout of a hemopoiesis and are observed at prolonged use of drug, usually more than 15 days, and at its cancellation are exposed to involution.

The risk of development of an acute renal failure usually is available for patients with jaundice in the presence of the contributing factors.

In rare instances at the combined use with inhibitors reductase 3-trigidroksi-3-methylglutaryl-coenzyme A as a result of a rabdomioliz in a blood plasma raises kreatinfosfokinaza level, muscular weakness and a mialgiya therefore such patients have to be under careful observation are observed.

At the heavy infections demanding long antibacterial therapy, Fuzidanat® can be appointed in combination with other anti-staphylococcal antibiotics, for example, penitsillazoustoychivy penicillin, ampicillin, Methicillinum, kloksatsilliny. flukloksatsilliny, cephalosporins, erythromycin, rifampicin, lincomycin therefore the additive or sinergidny effect is reached.

At bystry infusional introduction of Fuzidanat® causes a spasm of veins, thrombophlebitis and hemolysis of erythrocytes.

1 ml of Fuzidanata® solution contains 3,1 mmol of sodium and 1,1 mmol of phosphate.

Фузиданат® does not influence ability of the patient to control of vehicles and performance of other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Frequency of occurrence of side effects at use of fuzidovy acid for infusions made 3:10000 courses of treatment. Side effects are listed in decreasing order of frequency.

Local reactions: thrombophlebitis, spasm of veins.

Digestive tract: nausea, diarrhea, abdominal pains, vomiting.

General symptoms: indisposition, fatigue, adynamy, drowsiness, anorexia.

Skin and soft tissues: rash (erythematic, makulo-papular, pustular), itch, urticaria.

Gepatobiliarny system: increase in concentration of bilirubin, alkaline phosphatase, transaminases, jaundice, hepatonephric syndrome.

Bodies of a hemopoiesis: a leukopenia, thrombocytopenia, a pancytopenia, anemia, hemolysis of erythrocytes (at bystry introduction).

Urinary system: renal failure.

Immune system: allergic reactions, anaphylactic reactions.

Interaction with other medicines:

Pharmaceutical it is incompatible with Kanamycinum, gentamycin, Vancomycinum, karbenitsilliny, with solutions of amino acids, with donor (whole) blood, with the infusion solutions containing lipids with solutions for peritoneal dialysis, with concentrated (> 20%) solutions of a dextrose and calcium - the containing medicines.
 
Fuzidanat® solution is compatible to the following infusion solutions:
- 0,9% chloride sodium solution for intravenous infusions (1-2 mg/ml);
- 5% dextrose solution for intravenous infusions (1-2 mg/ml);
- Solution Ringer lactate (1 mg/ml);
- Lactate sodium solution for intravenous infusions (1 mg/ml);
- 0,18% solution of sodium of chloride and 4% dextrose solution for intravenous infusions (1 mg/ml);
- 0.3% solution of potassium of chloride and 5% dextrose solution for intravenous infusions (1mg/ml).
 
At co-administration of Fuzidanat®s drugs which metabolism is connected with system of CYP ZA4 cytochrome, perhaps mutual inhibition of metabolism. At a combination of Fuzidanat® to inhibitors reductase 3-trigidroksi-3-methylglutaryl-coenzyme A such as statines, raises concentration in a blood plasma of both drugs. At simultaneous use with Fuzidanatom® concentration in a blood plasma of cyclosporine, coumarin anticoagulants derivatives increase (correction of a dose at use together with Fuzidanatom® is necessary, and also at its cancellation), inhibitors of HIV proteases (a ritonavir and a sakvinavir). Interaction with lincomycin and rifampicin as they have a way of removal, identical with fuzidovy acid, is possible.
 
At a combination to glycopeptides, ftorkhinolona antagonism of action is observed.
 
At simultaneous use of fuzidovy acid with other anti-staphylococcal antibiotics, for example, penitsillazoustoychivy penicillin, ampicillin, Methicillinum, kloksatsilliny. flukloksatsilliny, cephalosporins, erythromycin, rifampicin, lincomycin, it is observed the additive or sinergidny effects.

Contraindications:

Intramuscular or hypodermic introduction apreshcheno!
 
Hypersensitivity to any of drug components, the III trimester of pregnancy.

With care: at an abnormal liver function, obstruction of biliary tract, disturbance of transport and metabolism of bilirubin, existence of jaundice, during treatment by hepatotoxic drugs, at a combination to lincomycin and rifampicin, at newborns with jaundice, acidosis, and also at premature or newborn with other serious illness.

Fuzidovy acid gets through a placental barrier. B pilot studies is established that drug has no teratogenic effect.

In I and II trimesters of Fuzidanat® apply in cases when the estimated advantage for mother exceeds potential risk for a fruit. As fuzidovy acid is capable to replace bilirubin in connection with albumine, it is necessary to avoid its use in the III trimester of pregnancy because of possible development of a kernicterus in newborns.

The clinical importance of detection of fuzidovy acid in insignificant quantities in breast milk is not known therefore in the period of a lactation it is necessary to apply with care.

Overdose:

Cases of overdose of fuzidovy acid are unknown. Probable symptoms of acute overdose: gastrointestinal frustration, changes from a liver (change of biochemical indicators, jaundice).
Treatment: symptomatic and maintenance therapy. The hemodialysis is not effective.

Storage conditions:

List B. To store at a temperature not above 25 °C, in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Фузиданат® powder for preparation of solution for infusions of 500 mg in a bottle from transparent glass with a rubber bung and a metal cap with a plastic covering.

Sterile buffered solution of 10 ml in a bottle of 12 ml from transparent glass with a rubber bung and a metal cap with a plastic covering.

1 bottle with the powder Fuzidanata® and 1 bottle with sterile buffered solution together with the application instruction is placed in a pack from a cardboard.