Zetamax

Zetamax is the first representative of the category of macrolide antibiotics.

Indications of the zetamax

It is indicated for elimination of severe and moderately severe infectious processes, which are provoked by bacterial strains with high sensitivity relative to azithromycin:

• chronic form of nonspecific bronchitis at the stage of exacerbation;
• acute stage of bacterial sinusitis;
• ambulatory pneumonia;
• tonsillitis or pharyngitis, provoked by streptococcus pyogenic.

[1]

Release form

Produced in powder form, in vials of 2 g. One package contains 1 bottle of medicine. In the kit there can be a special lid with a dispenser - to determine the amount of water added.

[2], [3]

Pharmacodynamics

The active component of the drug, azithromycin - is the first representative of the category of macrolide antibiotics, which are called azalides. It is different from erythromycin in its chemical composition. Its formation occurs by the introduction of a lactone ring of erythromycin type A nitrogen atom.

The mechanism of action of the active component consists in inhibiting the binding process of the bacterial protein - by synthesis with the 50S subunit of the ribosome, as well as inhibiting peptide translocation. In this case, the substance does not affect the binding of polynucleotides.

Pharmacokinetics

The drug has a prolonged effect, which allows it to provide a full-fledged antibacterial course after ingestion of a single dosage of drugs. Thanks to the information that was obtained after the testing of pharmacokinetics (with the participation of volunteers), it became known that the peak of serum concentration and AUC (in comparison with standard drugs with immediate release properties) it reaches immediately on the day of single administration of granules with azithromycin.

The relative bioavailability index of the drug is 83%, and the peak of the serum concentration of the substance reaches later by almost 2.5 hours.

With the use of the drug along with food, volunteers who took 2 grams of medicine immediately after a meal that contained a large amount of fats showed an increase in plasma peak and AUC levels by 115%, and 23%, respectively. With the use of drugs by volunteers after taking regular food, the peak of plasma indicators increased by 119%, while the AUC indices remained unchanged.

According to clinical tests, it can be concluded that azithromycin powder has better tolerability in the case of fasting.

Synthesis with plasma protein depends on the level of concentration and decreases by 51% in the case of 0.02 μg / ml, as well as by 7% in the case of 2 μg / ml. The distribution of matter occurs inside all tissues, the equilibrium state of the distribution volume is 31.1 l / kg.

Tissue values of azithromycin exceed its level in serum with plasma. The extensive distribution of drugs across tissues can provoke its drug activity. The antimicrobial effect of the component depends on the pH. It is likely that it is weakened by a decrease in this indicator.

The main part of the active substance is excreted with bile, in unmodified form.

Serum azithromycin values after a single dose (2 g) were reduced in accordance with the polyphase model, and the final half-life is 59 hours. Such a prolonged period of final half-life is most likely associated with an expanded distributional volume.

Biliary excretion (as a rule, unchanged) is considered the main way of excretion. For 7 days, about 6% of the dosage used can be detected as an unchanged substance in the urine.

[4]

Dosing and administration

It is recommended to drink the medicine on an empty stomach (at least 1 hour before meals or 2 hours after it).

In a bottle of powder, pour water (60 ml - 4 tablespoons or use a dispenser, if it is), then it should be closed and shaken. Next, you need to drink the contents of the tank, completely.

A single dose dosage for an adult is 2 g.

Use of the solution may cause vomiting. Therefore, if within 5 minutes after using the person started vomiting, you must take the medicine again.

Alternatively, it is possible to prescribe an alternative medicine if vomiting in the patient begins within 5-60 minutes after drug use - because at the moment there is too little information on the absorption of azithromycin.

At the onset of vomiting, after more than 1 hour after the use of the solution, the medicine is not needed again (under the condition of a properly functioning stomach in the patient).

Use of the zetamax during pregnancy

Tests that allow to reliably determine the possibility of using drugs in pregnant women have not been performed. In pregnancy, the prescription of this medicine is carried out only when it is not possible to use another medication.

There is no information on the ingestion of the substance into the mother's milk. It can be used during lactation only for vital indications, when there is no possibility of alternative therapy.

Contraindications

Among the contraindications: intolerance to erythromycin and azithromycin, and in addition to other ketolid antibiotics or macrolides, as well as other elements of drugs. Also, the medicine can not be administered to children.

Side effects of the zetamax

Basically (69% of all cases), the negative consequences of taking drugs were disorders in the work of the gastrointestinal tract - liquid stools and diarrhea, abdominal pains, and also vomiting along with nausea. Usually, these reactions were of moderate severity and passed after 2 days (68% of cases). In some cases, patients had vaginitis or an oral form of candidiasis. Among other side effects:

• disorder in the work of the National Assembly: most often - headaches; occasionally develops dysgeusia or dizziness;
• problems with hearing and balance: in single cases - vertigo;
• disorders in the work of the heart: from time to time heart rhythm can be felt;
• problems with the function of the gastrointestinal tract: in addition to the above, it can rarely occur constipation or gastritis, as well as dyspepsia;
• subcutaneous tissues, as well as skin: rarely a rash appears on the skin, hives develop in single cases;
• general disorders: occasionally there are pains in the sternum, asthenia can develop.

People who had normal indices of various analyzes had a noticeable deviation during clinical drug testing, which did not have any cause for a connection with the tested drug:

• lymphatic and hematopoietic systems: occasionally neutrophilic or leukopenia developed;
• laboratory testing: most often the level of leukocytes decreased, the number of bicarbonates decreased in blood and eosinophils increased. Less frequent increase in such indicators as the level of bilirubin, creatinine and urea, as well as the activity of ALT and ASAT, and in addition the change in blood potassium levels. Subsequent observations have shown that such changes are reversible.

Overdose

The information obtained as a result of clinical studies suggests that when an overdose of the drug develops reactions similar to the side effects of taking drugs at the required dosages. To eliminate negative manifestations, general therapeutic measures are needed - supportive and symptomatic therapy.

Interactions with other drugs

Caution should be exercised when combined with drugs that can extend the QT interval (such as cyclophosphamide with haloperidol, and quinidine and ketoconazole with terfenadine and lithium).

Antacids - in the case of combination with a magadrite in a single dose of 20 ml, the degree and rate of absorption of the active component of Zetamax will not change. All other tests of interaction with azithromycin were performed on drugs with immediate release, and also had comparable AUC values (dosage ranges ranged from 500 to 1200 mg).

When combined with cetirizine, there were no significant changes in the QT interval, as well as pronounced pharmacokinetic interaction between them at equilibrium values of both drugs.

In patients with HIV, dideoxynosine in combination with azithromycin had no effect on the pharmacokinetic properties of drugs with equilibrium didanosine (compared with placebo).

Combined admission with digoxin should be carried out cautiously, since there is a possibility of an increase in plasma digoxin.

Combination of the drug with zidovudine leads to a weak effect on the pharmacokinetic properties or excretion of the latter (along with its glucuronide product degradation). It is also noted that with the introduction of azithromycin, the clinically active decay product (phosphorylated zidovudine) increases within the blood mononuclear cells. At the same time, it was not possible to reveal the medicinal value of this fact.

Azithromycin interacts little with the liver system of the hemoprotein P450. There is evidence that the drug does not affect the properties of erythromycin, as well as other macrolides. Azithromycin does not induce or inactivate hemoprotein P450 by the hemoprotein metabolite complex.

Combine with the derivatives of indole alkaloids is not recommended, since the simultaneous use of these drugs in theory can cause ergotism.

Also, pharmacokinetics were tested with a combination of azithromycin with the following drugs metabolized by hemoprotein P450:

• atorvastatin - when combined with this drug, its indices in plasma did not change (data of the slowdown analysis of GMK-CoA reductase);
• carbamazepine - when combined with azithromycin it (as well as its active decay product) plasma indices remain unchanged;
• cimetidine - in the case of the use of this substance 2 hours before the use of azithromycin, the pharmacokinetics of the latter remains unchanged;
• anticoagulants for oral administration (such as coumarin) - when consumed by volunteers, azithromycin had no effect on the anticoagulant properties of warfarin. There is evidence of an increase in anticoagulant effects when azithromycin is combined with drugs such as coumarin. Therefore, although it was not possible to establish a link between these drugs, it is often necessary to monitor prothrombin time in the case of combined use of the above medicines;
• Cyclosporine - as a result of concomitant use with this substance, the peak concentration and AUC increased in the range 0-5 for cyclosporine. Therefore, it is necessary to combine the data of drugs with caution. If a joint appointment is necessary, during the therapy it is required to monitor the indicators and adjust the dosages in accordance with them;
• efavirenz - with the combination of these substances, there were no noticeable changes in their pharmacokinetics;
• The combination of azithromycin with fluconazole does not change the properties of the latter. AUC and the half-life of azithromycin also do not change in the case of a compound with fluconazole, but nevertheless a decrease in its plasma indices (by 18%) was observed, although this change did not have a clinical effect on the body;
• when the drug is combined with methylprednisolone, indinavir, and midazolam, the pharmacokinetic properties of the above substances remain unchanged;
• in the case of combination with nelfinavir, the equilibrium serum azithromycin values increase. With the simultaneous use of these drugs, you do not need to adjust the dosage of azithromycin, but a prerequisite is careful monitoring of the possible development of side effects of azithromycin;
• combined with rifabutin does not affect the serum levels of these substances, but as a result of this combination, neutropenia sometimes develops. It is believed that this disorder is caused by the use of rifabutin, but the relationship between the combined administration of medications and the development of this adverse reaction has not been established;
• there were no significant changes in the peak concentration and AUC in the combination of the drug with sildenafil, as well as with drug interactions with terfenadine, as well as with theophylline and triazolam;
• in the case of concomitant use with trimethoprim or sulfamethoxazole, no significant effect on the indices of their peak, excretion and AUC was observed. Serum azithromycin was also unchanged.

[5]

Storage conditions

The medicine should be stored in tightly sealed packaging. The maximum temperature is 30 ° C.

Shelf life

Zetamax is suitable for use for 3 years after the release of the medicine. After dilution of the suspension, the finished solution can be used for 12 hours.