Zivox

Zyvox is a new generation antibiotic. It contains an artificial component of linezolid, which belongs to the category of oxazolidinones.

Indications of the zivoksa

It is indicated for the elimination of infectious pathologies caused by microbes that are sensitive to linezolid. In the case of diseases that are provoked by gram-negative microorganisms, it is required to resort to combined treatment with various antibacterial drugs.

Zyvox is used for:

• hospital / out-of-hospital forms of pneumonia;
• infectious processes inside the skin with its appendages (proceeding against the background of complications);
• infectious processes inside the skin with appendages (without complications), among which are caused by streptococcus pyogenic, and in addition to methicillin-sensitive types of staphylococcus aureus;
• infectious processes caused by enterococci (among them also strains resistant to vancomycin).

Release form

It is produced in tablet form (in one blister 10 tablets) or in the form of a parenteral solution (the volume of packets with infusions is 300 ml). The package contains 1 blister plate or 10 packets with infusion.

Pharmacodynamics

Testing the drug in vitro has shown that it is active against a variety of microbial species, among which both forming and not forming a protective membrane.

The mechanism of drug exposure is related to the fact that it can selectively block protein synthesis inside microbial cells, disrupting the processes of translation occurring in the ribosomes of bacteria.

During the testing, it was possible to identify resistance against linezolid in such microbes: influenza rod, pseudomonas, moraxella cataris, and also enterobacteria and Neisseria species.

In the case of a cross randomly selected (placebo-controlled) test, it was found that the active substance had no particular effect on the QT interval.

Pharmacokinetics

Absorption of the active ingredient from the gastrointestinal tract is quite high, and the bioavailability index reaches 100%. The lowest and peak concentrations of the substance, as well as the period of their achievement (depending on the dosage and form of drugs):

• single use of 400 mg (in a tablet) - a peak value of 8.1 μg / ml (with a possible deviation of up to 1.83), reaching a period of: 1.52 hours (with a deviation of up to 1.01);
• 400 mg (tablet) with a regimen of 1 every 12 hours - a peak level of 11 μg / ml (with a deviation of up to 4.37), a minimum level of 3.08 μg / ml (deviation to 2.25), a period of achievement: 1 , 12 hours (with a deviation of up to 0.47);
• a single dose of 600 mg (in a tablet) - a peak value of 12.7 μg / ml (with a deviation of up to 3.96), a period of achievement: 1.28 hours (with a possible deviation of 0.66);
• 600 mg (tablet) with a dosage regimen of 1 every 12 hours - a peak value of 21.2 μg / ml (with a possible deviation of up to 5.78), a minimum level of 6.15 μg / ml (with a deviation of up to 2.94), the period of achievement: 1.03 hours (deviation 0.62);
• single injection IM 600 mg - peak level 12.9 μg / ml (with possible deviation up to 1.6), period reaching 0.5 hours (with a deviation of up to 0.1);
• in / m administration of 600 mg of medication every 12 hours - a peak level of 15.1 μg / ml (with a possible deviation of up to 2.52), a minimum of 3.68 μg / ml (deviation up to 2.36), a period of achievement : 0.51 hours (with a deviation of up to 0.03).

It should be taken into account that with a large amount of fat in food, the peak level of the substance (after oral intake) is lowered by 17%. At the same time, the period of reaching this indicator is also extended, up to 2.2 hours.

Linezolid is well distributed inside the tissues, about 31% of the component is bound inside the serum. The average index of the distribution volume is 40-50 liters.

Metabolism of the active component is realized with the formation of 2 basic inactive derivatives. One of them is formed by means of an enzymatic pathway, and the second one is on the contrary non-enzymatic. The tests showed that during the metabolism of linezolid, the hemoprotein P450 participates minimally.

Removal of drugs is mainly carried out through the kidneys (65%). About 30% of the substance is excreted unchanged, and another 50% in the form of derivatives. The average index of the kidney cleansing rate is approximately 40 ml / minute (similar figures indicate net tubular reabsorption). Approximately 10% of the substance is excreted through the intestines in the form of derivatives.

Dosing and administration

Use the drug in 2 ways - parenterally or orally. If the parenteral method was used at the initial stage of the treatment, the patient is allowed to be transferred to the oral route with a similar dosage. Its dimensions are appointed by the attending physician.

To eliminate hospital / extrahospital pneumonia, and in addition to this complicated form of infectious processes in the appendages and skin, 600 mg of the drug are required 2 times a day. This course lasts for 10-14 days.

In the treatment of pathologies caused by Enterococcus fecium, it is usually required to take 600 mg of the drug 2 times a day. The therapeutic course continues for 14-28 days.

When treating uncomplicated infectious processes in the appendages and skin, a dosage of 400-600 mg of LS is required 2 times a day. The treatment course lasts for 10-14 days.

During therapy, it is very important to strictly observe 12-hour intervals between procedures for using drugs. Each 12 hours is allowed to use no more than 600 mg of the drug.

There is no information on the safety of the drug over a period of more than 28 days.

[2], [3]

Use of the zivoksa during pregnancy

The effect of the drug on human fertility, but also the course of pregnancy and the development of the fetus, has not been studied. In animal tests, the drug demonstrated reproductive toxicity, from which it can be concluded that there is a potential danger to humans. Pregnant women should be prescribed medication solely under the supervision of the treating doctor, and also if the patient has strict testimony.

Animal testing has shown that linezolid is able to pass into breast milk. Since there is a danger to the child, it is not recommended to use drugs during lactation. If a medicine is needed, it is necessary to cancel breastfeeding for the period of treatment.

Contraindications

Among the contraindications of drugs:

• patient intolerance to the active ingredient of the drug, as well as other antibiotics that fall into this category;
• patients during the period of application of MAO inhibitors, and in addition, within 2 weeks after the completion of the treatment course with their use;
• children age less than 12 years.

If the patient has problems with hepatic function, the medicine is prescribed only after assessing the benefits and all possible risks, and also exclusively under the supervision of the doctor.

Particular caution is required if the patient has such abnormalities (and only if there is the possibility of constant monitoring of blood pressure):

• manic depression;
• uncontrolled increase in blood pressure;
• hyperthyroidism;
• pheochromocytoma;
• the presence of acute episodes of dizziness;
• recurrent schizophrenia.

Side effects of the zivoksa

In the course of clinical testing, headaches, nausea, candidiasis, as well as stool disorders were most often mentioned among the negative effects of drug use. Because of adverse reactions of 3% of those who treated, it was necessary to cancel the medication.

As a result of the application of Zyvox in patients can be observed such negative manifestations:

• infectious processes: candidiasis in the vagina or oral cavity, vaginitis, fungi, as well as colitis (sometimes in a pseudomembranous form);
• hematopoietic system: development of neutro-, thrombocyto-, pancito- and leukopenia, and in addition to eosinophilia or myelosuppression, as well as anemia (sometimes in sideroblastic form);
• metabolic processes: lactacidemia or hyponatremia;
• organs of the central nervous system: the appearance of metallic taste in the mouth, sleep disorders, convulsions, paresthesias, dizziness, and with it the development of hypoesthesia or serotonin intoxication. In addition, ringing in the ears may occur, optical neuropathy may develop (with signs such as disorders or loss of vision and distortion of color perception) or peripheral neuropathy;
• CAS organs: development of thrombophlebitis, phlebitis or arrhythmia, and in addition, increased pressure and microinsult;
• Gastrointestinal organs: the appearance of vomiting, abdominal pain (local or general), dyspeptic phenomena, and also dryness of the oral mucosa and a change in the shade of the tongue and enamel of the teeth. Also the development of glossitis or gastritis, and in addition to this pancreatitis or stomatitis;
• hepatobiliary system: increase in ALT, AST, and AL together with it, development of hyperbilirubinemia and changes in the level of hepatic samples;
• organs of the urinary system: renal failure, development of polyuria, hyperuricemia, and hypercreatininaemia;
• data analysis: an increase in LDH, lipase with amylase, and in addition, sugar and creatine phosphokinase; a decrease in albumin, and at the same time a total protein; In addition, the change in the values of potassium with calcium and sodium with bicarbonate. In some cases, there was a decrease in sugar levels (under normal diet conditions), an increase in the reticulocyte count and a change in the chloride index;
• others: development of hyperhidrosis;
• allergic manifestations: the development of dermatitis, urticaria, alopecia, Quincke edema, as well as anaphylaxis; In addition, bullous rash and itching may occur;
• specific phenomena after parenteral administration: the appearance of hyperthermia or thirst, the state of fever or fatigue, as well as painful sensations at the site of administration.

[1]

Interactions with other drugs

Combined use of the drug with dopaminergic, vasoconstrictive and sympathomimetic (direct and indirect) drugs can cause an increase in blood pressure.

In the case of simultaneous use with serotonergic drugs, the development of serotonin intoxication is possible. Therefore, such combination of drugs is not recommended, except for situations when both of them are necessary for the patient according to the indications. In this case, the treating physician will need to carefully monitor the patient's condition and, in case of intoxication develop, decide on the abolition of one of the drugs, taking into account all the risks and the high probability of withdrawal syndrome when stopping the use of serotonergic medication.

During treatment with Zyvox it is recommended to limit the use of products containing a lot of tyramine (taking medicine, it is advisable to eat not more than 100 mg of tyramine). Taking large doses of tyramine together with linezolid can provoke vasoconstrictive action. During the period of therapy, you should eat a limited amount of mature cheeses, yeast extracts and fermented soy products, and drink non-distilled alcoholic beverages.

The active substance of the drug indiscriminately suppresses MAO (reversible effect). Although the dosages used during the period of Zyvox therapy do not have a significant drug effect on MAO, the combined use of these drugs is not recommended.

Linezolid does not affect the pharmacokinetic characteristics of drugs metabolized by the P450 element.

Powerful inductors of the element CYP3 A4 can reduce the exposure indices of linezolid.

[4], [5], [6], [7]

Storage conditions

The medicine is contained in a place inaccessible to the child, under standard conditions. Temperature indices - not more than 25 ° С. An open packet of medicinal solution must be used immediately.

[8], [9], [10]

Shelf life

Zyvox is suitable for use for 3 years from the date of manufacture of the medicine.

[11]