Zyvox

Zyvox is a new generation antibiotic. It contains the artificial component linezolid, which is included in the category of oxazolidinones.

Indications Zyvox

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 necessary to resort to combined treatment with various antibacterial drugs.

Zyvox is used for:

• hospital/community-acquired forms of pneumonia;
• infectious processes within the skin and its appendages (occurring against the background of complications);
• infectious processes inside the skin with appendages (without complications), including those caused by Streptococcus pyogenes, and also by methicillin-sensitive types of Staphylococcus aureus;
• infectious processes caused by enterococci (including strains resistant to vancomycin).

Release form

It is available in tablet form (10 tablets in one blister) or as a parenteral solution (infusion bags volume – 300 ml). The package contains 1 blister plate or 10 infusion bags.

Pharmacodynamics

In vitro testing of the drug has shown that it is active against a wide range of microbes, including those that form and those that do not form a protective membrane.

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

During the testing process, resistance to linezolid was detected in the following microbes: influenza bacillus, pseudomonas, Moraxella catarrhalis, as well as enterobacteria and Neisseria species.

In a randomized, placebo-controlled crossover study, the active substance was found to have no significant effect on the QT interval.

Pharmacokinetics

The absorption of the active ingredient from the gastrointestinal tract is quite high, and the bioavailability rate 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 the drug):

• single use of 400 mg (in a tablet) - peak value 8.1 mcg/ml (with a possible deviation of up to 1.83), period of achievement: 1.52 hours (with a deviation of up to 1.01);
• 400 mg (in a tablet) with a regimen of taking 1 time every 12 hours - peak level 11 mcg/ml (with a deviation of up to 4.37), minimum level 3.08 mcg/ml (deviation up to 2.25), period of achievement: 1.12 hours (with a deviation of up to 0.47);
• single dose of 600 mg (in tablet) – peak value 12.7 mcg/ml (with a deviation of up to 3.96), period of achievement: 1.28 hours (with a possible deviation of 0.66);
• 600 mg (in a tablet) at a dosing regimen of 1 time every 12 hours - peak value 21.2 mcg/ml (with a possible deviation of up to 5.78), minimum level 6.15 mcg/ml (with a deviation of up to 2.94), period of achievement: 1.03 hours (deviation 0.62);
• single intramuscular injection of 600 mg - peak level 12.9 mcg/ml (with a possible deviation of up to 1.6), period of reaching 0.5 hours (with a deviation of up to 0.1);
• intramuscular administration of 600 mg of the drug every 12 hours - peak level 15.1 mcg/ml (with a possible deviation of up to 2.52), minimum level 3.68 mcg/ml (deviation up to 2.36), period of achievement: 0.51 hours (with a deviation of up to 0.03).

It is necessary to take into account that with a large amount of fat in food, the peak level of the substance (after oral administration) decreases by 17%. At the same time, the period of reaching this indicator also increases – up to 2.2 hours.

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

The active component is metabolized with the formation of two main inactive derivatives. One of them is formed by the enzymatic pathway, and the second, on the contrary, is non-enzymatic. Testing has shown that hemoprotein P450 is minimally involved in the process of linezolid metabolism.

The drug is excreted mainly through the kidneys (65%). About 30% of the substance is excreted unchanged, and another 50% in the form of derivatives. The average renal clearance rate is about 40 ml/minute (such figures indicate pure tubular reabsorption). About 10% of the substance is excreted through the intestines in the form of derivatives.

Dosing and administration

The medicine can be used in 2 ways - parenterally or orally. If the parenteral method was used at the initial stage of treatment, the patient is allowed to switch to the oral method with a similar dosage. Its size is prescribed by the attending physician.

To eliminate hospital/community-acquired pneumonia, and in addition complicated forms of infectious processes in the appendages and skin, 600 mg of the drug is required 2 times a day. This course lasts for 10-14 days.

In the process of treating pathologies caused by enterococci faecium, it is usually necessary to take 600 mg of the drug 2 times a day. The treatment course lasts for 14-28 days.

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

During therapy, it is very important to strictly observe 12-hour intervals between drug administration procedures. No more than 600 mg of the drug is allowed to be used every 12 hours.

There is no information on the safety of using the drug for periods longer than 28 days.

[ 1 ]

Use Zyvox during pregnancy

The drug's effect on human fertility, as well as the course of pregnancy and fetal development, has not been studied. Animal tests have shown reproductive toxicity, suggesting that there is a potential danger to humans. Pregnant women should be prescribed the drug only under the supervision of their doctor, and if the patient has strict indications.

Animal testing has shown that linezolid can pass into breast milk. Since there is a danger to the child, it is not recommended to use the drug during lactation. If the drug must be taken, breastfeeding should be discontinued for the duration of treatment.

Contraindications

Among the contraindications of the drug:

• the patient's intolerance to the active component of the drug, as well as other antibiotics included in this category;
• patients during the period of use of MAO inhibitors, and in addition for 2 weeks after completion of the treatment course using them;
• children under 12 years of age.

If the patient has problems with liver function, the drug is prescribed only after assessing the benefits and all possible risks, and only under the supervision of a doctor.

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

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

Side effects Zyvox

During clinical trials, the most frequently reported adverse effects of the drug were headaches, nausea, candidiasis, and bowel disorders. Due to adverse reactions, 3% of those treated had to discontinue the drug.

As a result of using Zivox, patients may experience the following negative effects:

• infectious processes: candidiasis in the vagina or oral cavity, vaginitis, fungi, and also colitis (sometimes in pseudomembranous form);
• hematopoietic system: development of neutro-, thrombocyto-, pancyto- and leukopenia, and in addition to this, eosinophilia or myelosuppression, as well as anemia (sometimes in the sideroblastic form);
• metabolic processes: lactic acidemia or hyponatremia;
• CNS organs: the appearance of a metallic taste in the mouth, sleep disorders, convulsions, paresthesia, dizziness, and along with this the development of hypoesthesia or serotonin intoxication. In addition, tinnitus may occur, optic neuropathy may develop (in this case, symptoms such as disorders or loss of vision and distortion of color perception) or peripheral neuropathy appear;
• cardiovascular system organs: development of thrombophlebitis, phlebitis or arrhythmia, and in addition, increased blood pressure and microstroke;
• Gastrointestinal organs: the appearance of vomiting, abdominal pain (local or general), dyspeptic symptoms, and in addition, dryness of the oral mucosa and a change in the shade of the tongue and tooth enamel. Also the development of glossitis or gastritis, and in addition, pancreatitis or stomatitis;
• hepatobiliary system: increased values of ALT, AST, and along with this, alkaline phosphatase, development of hyperbilirubinemia and changes in the level of liver tests;
• urinary system organs: renal failure, development of polyuria, hyperuricemia, and hypercreatininemia;
• analysis data: increased LDH, lipase with amylase, and also sugar and creatine phosphokinase; decreased albumin, and along with this total protein; in addition, changes in potassium with calcium and sodium with bicarbonate. In some cases, a decrease in sugar (under normal nutrition conditions), an increase in the reticulocyte index and a change in the chloride index were observed;
• others: development of hyperhidrosis;
• allergic manifestations: development of dermatitis, urticaria, alopecia, Quincke's edema, and anaphylaxis; in addition, bullous rash and itching may occur;
• specific phenomena after parenteral administration: the appearance of hyperthermia or a feeling of thirst, a state of fever or fatigue, as well as pain at the injection site.

Interactions with other drugs

The combined use of the drug with dopaminergic, vasoconstrictor and sympathomimetic (direct and indirect) drugs may cause an increase in blood pressure.

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

During treatment with Zivox, it is recommended to limit the consumption of products containing a lot of tyramine (while taking the medicine, it is advisable to eat no more than 100 mg of tyramine). Taking large doses of tyramine together with linezolid can provoke a vasoconstrictive effect. During the therapy, it is necessary to consume mature cheeses, yeast extracts and fermented soy products in limited quantities, as well as drink non-distilled alcoholic beverages.

The active substance of the drug non-selectively suppresses MAO (reversible effect). Although the dosages used during therapy with Zivox do not have a significant medicinal effect on MAO, the combined use of these drugs is not recommended.

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

Potent inducers of the CYP3 A4 element may reduce linezolid exposure.

[ 2 ], [ 3 ]

Storage conditions

The medicine is kept in a place inaccessible to children, under standard conditions. Temperature indicators are no more than 25°C. An opened package with a medicinal solution must be used immediately.

[ 4 ]

Shelf life

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