Maxicin

Maxicin is an antibacterial agent of the newest category. It belongs to the group of 4th generation fluoroquinolones.

Indications Maxicina

It is indicated for the elimination of infections of bacterial origin and caused by microbes sensitive to drugs:

• in community-acquired pneumonia (this also includes types of the disease that are caused by strains of microbes that have multiple resistance to antibiotics);
• infections that affect the subcutaneous layer and skin and are complicated (this includes the infected form of diabetic foot syndrome);
• complicated infectious processes in the intra-abdominal region, including polymicrobial infections (including the process of abscess formation).

Release form

It is produced as a concentrate used in the manufacture of infusion solutions, in 20 ml vials. The vial also includes a solvent in a 100 ml container.

Pharmacodynamics

The mechanisms that promote resistance of microbes to inactivating substances (such as aminoglycosides with cephalosporins, as well as tetracyclines with penicillins and macrolides) do not affect the antibacterial properties of moxifloxacin. Cross-resistance between these antibiotics and moxifloxacin has not been detected. Plasmid-mediated resistance has not yet been detected either.

There is an opinion that the presence of the methoxy category in the C-8 value increases the activity and also reduces the selectivity of resistant mutant strains of microbes from the gram-positive group (compared to the C8-H category). At the C-7 value, an additional dicycloamine residue is observed, which prevents the active release of fluoroquinolones from the cells of pathogenic microorganisms - this is the mechanism for the development of resistance to fluoroquinolones.

In vitro tests have shown that resistance to moxifloxacin develops quite slowly. This is due to multiple mutations. An extremely low frequency of resistance is also observed (10-7–10-10). In the case of serial dilution of bacteria, only a slight increase in the MIC values of moxifloxacin is observed.

Cross-resistance has been identified among quinolones, but some anaerobes and gram-positive bacteria that are resistant to other quinolones are sensitive to moxifloxacin.

Pharmacokinetics

With a single infusion of 400 mg of the solution lasting 1 hour, the substance reaches its peak value at the end of the procedure and is approximately 4.1 mg/l. This corresponds to an increase in the drug indicator relative to its level during oral administration by an average of 26%.

The AUC value is 39 mg h/L and is only slightly higher than the same level after oral administration (35 mg h/L). The bioavailability of the drug is approximately 91%.

After multiple intravenous infusions of the drug (at a dosage of 400 mg) for 1 hour once a day, the minimum values, as well as the peak of the equilibrium plasma level, are located in the range of 4.1-5.9 and 0.43-0.84 mg/l, respectively. And at equilibrium values, the AUC of the drug in the dosing interval is approximately 30% higher than the value after the first dose.

The average equilibrium value reaches 4.4 mg/l, and this value is observed at the end of the infusion, which lasts 1 hour.

The active ingredient undergoes rapid distribution in the internal space of the body, outside the vessels. The medicinal level of AUC (the normal value is 6 kg h/l) is quite high at equilibrium values of the distribution volume (2 l/kg). The results revealed during in vitro and ex vivo testing showed values within 0.02-2 mg/l.

Synthesis with blood protein (usually albumin) reaches 45%, and this indicator is not affected by drug concentrations. Although this is a fairly low level, high peak values (10 MIC) have been detected for the free component.

Moxifloxacin has quite high values inside tissues (for example, in the lungs - alveolar macrophages and epithelial fluid), and also inside the paranasal sinuses (nasal polyps, ethmoid, and maxillary sinuses) and inflammatory foci, in which the total values exceed the obtained concentrations inside the plasma. Inside the intercellular fluid (in subcutaneous and muscle tissues, and also in saliva), the drug is found in high concentrations and in a free form that is not synthesized with protein. Along with this, large medicinal values can be observed inside the fluids and tissues of the peritoneum organs, as well as inside the female genital organs.

Peak levels, as well as the ratio of plasma and infusion site parameters, for individual target tissues show similar data for each route of administration after using a single dose of the drug (400 mg).

Biotransformation (phase 2) of moxifloxacin also occurs, after which it is excreted through the kidneys (in addition, with bile/faeces – unchanged or in the form of inactive elements M1 (sulfo compounds), as well as M2 (glucuronides)).

In vitro experiments and also in phase 1 clinical trials did not reveal any metabolic interactions in terms of pharmacokinetic parameters with other drugs that participate in the phase 1 biotransformation process using enzymes of the hemoprotein P450 system.

Regardless of the route of administration, the degradation products (M1 with M2) are observed in plasma in values lower than the unchanged element. In preclinical tests, both of these components were tested in comparable amounts, as a result of which a possible impact on the tolerability and safety of the drug was excluded.

The half-life is approximately 12 hours. The average level of total clearance when using 400 mg of the drug is in the range of 179-246 ml/minute. Clearance in the kidneys is approximately 24-53 ml/minute, from which it can be concluded that partial reabsorption of the drug occurs in the body - from the kidneys through the tubules.

Concomitant administration of probenecid with ranitidine does not result in changes in renal clearance values of the drug.

Dosing and administration

For adults, the recommended dose is 400 mg once daily for any type of infection. The recommended dosage should not be exceeded.

The duration of the therapeutic course is prescribed in accordance with the severity of the pathology, as well as the effectiveness of the drug.

At the beginning of therapy, it is necessary to use the drug in infusion form, but later, if there are appropriate indications, it is allowed to be prescribed in the form of tablets for oral administration.

Community-acquired pneumonia is treated using a stepwise method (first intravenous infusions, then oral tablets), the total duration of which is 1-2 weeks.

When eliminating complicated infectious processes in the subcutaneous layer and skin, a step-by-step method is also used with a total course duration of 1-3 weeks.

In complicated infections in the intra-abdominal region, stepwise treatment continues for 5-14 days.

It is prohibited to exceed the above-mentioned periods of therapeutic courses.

The data obtained as a result of clinical tests showed that the duration of the course using tablets and infusion solution of the drug reached a maximum of 21 days (during the elimination of infections in the subcutaneous layer and skin).

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Use Maxicina during pregnancy

Maxicin should not be prescribed to pregnant women.

Contraindications

Among the contraindications:

• a person has an intolerance to any substance in the composition of the drug, or other antibiotics included in the category of quinolones;
• breastfeeding period;
• children, as well as adolescents who are at an age of intensive growth.

Side effects Maxicina

Using the solution may cause the following side effects:

• vomiting with nausea, as well as diarrhea (this may be a symptom of pseudomembranous colitis) and the development of hyperbilirubinemia;
• dizziness with headaches, a feeling of anxiety or a general state of depression, severe fatigue, psychomotor agitation, development of psychosis, as well as sleep disorders;
• allergic manifestations – itchy skin with rash, facial swelling (or swelling of the vocal cords), as well as the development of photosensitivity;
• development of eosinophilia or agranulocytosis, as well as leukopenia or thrombocytopenia and an increase in the activity of AST and ALT elements;
• the appearance of nephrotic syndrome, rarely – acute renal failure;
• development of tachycardia, arthralgia or myalgia, decreased blood pressure and visual impairment.

Interactions with other drugs

No significant drug interactions have been demonstrated with substances such as probenecid, atenolol, theophylline with itraconazole, as well as ranitidine, glibenclamide, calcium supplements, and morphine with oral contraceptives and digoxin. When combining Maxicin with the above drugs, no dosage adjustments are required.

Combination with warfarin does not change the pharmacokinetics of Maxicin, as well as the PT and other characteristics of blood coagulation.

Changes in the INR indicator - cases of increased anticoagulant activity have been observed in people who combined antibiotics (including moxifloxacin) with anticoagulants. Risk factors include age and health status, as well as infectious pathologies (with concomitant inflammation). Although clinical tests did not reveal any interactions between the drug and warfarin, people using combined treatment with these drugs need to monitor the INR and adjust the dose of the anticoagulant taken orally if necessary.

The pharmacokinetic properties of digoxin are slightly altered by moxifloxacin. Multiple doses of moxifloxacin in volunteers resulted in an increase in peak digoxin levels (approximately 30% at steady state) but no effect on AUC.

In case of intravenous infusion of the solution, the simultaneous use of activated carbon only slightly reduces the AUC value (by approximately 20%).

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Storage conditions

The solution is kept in a place protected from the sun and moisture, at a temperature of no more than 25°C.

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Shelf life

Maxicin can be used for a period of 2 years from the date of manufacture of the medicine.