Zetamax

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

Indications Zetamax

It is indicated for the treatment of severe and moderately severe infectious processes caused by bacterial strains with high sensitivity to azithromycin:

• chronic form of non-specific bronchitis in the acute stage;
• acute stage of bacterial sinusitis;
• outpatient pneumonia;
• tonsillitis or pharyngitis caused by Streptococcus pyogenes.

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Release form

It is available in powder form, in 2 g bottles. One package contains 1 bottle of medicine. The kit may include a special cap with a dispenser - to determine the volume of water added.

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Pharmacodynamics

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

The mechanism of action of the active component consists in inhibition of the process of protein binding of bacteria - by means of synthesis with the 50S subunit of the ribosome, as well as preventing peptide translocation. At the same time, the substance does not affect the binding of polynucleotides.

Pharmacokinetics

The drug has a prolonged effect, which allows it to provide a full antibacterial course after oral administration of a single dose of the drug. Thanks to the information that was obtained after testing the 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 a single dose of granules with azithromycin.

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

When taking the drug with food - volunteers who took 2 g of the drug immediately after a meal containing a large amount of fats experienced an increase in the peak plasma parameters and AUC level by 115% and 23%, respectively. When volunteers took the drug after eating a normal meal, the peak plasma parameters increased by 119%, but the AUC parameters remained unchanged.

Based on clinical testing data, it can be concluded that azithromycin powder is better tolerated when taken on an empty stomach.

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

Tissue indices of azithromycin exceed its level in serum and plasma. Extensive distribution of the drug in tissues can provoke its medicinal activity. The antimicrobial action of the component depends on pH indices. It is likely that it weakens with a decrease in this index.

The main part of the active substance is excreted in bile, unchanged.

Serum azithromycin concentrations after a single dose (2 g) declined in a polyphasic pattern, with a terminal half-life of 59 hours. This prolonged terminal half-life is likely related to an extended volume of distribution.

Biliary excretion of the drug (usually unchanged) is considered the main route of excretion. Over a period of 7 days, approximately 6% of the dose taken can be found as unchanged substance in the urine.

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Dosing and administration

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

You need to pour water into the bottle with the powder (60 ml - 4 tablespoons or use a dispenser, if there is one), then close it and shake it. Then you need to drink the contents of the container completely.

A single dose of the medicine for an adult is 2 g.

The use of the solution may provoke vomiting. Therefore, if a person starts vomiting within 5 minutes after use, the medicine must be taken again.

It is also possible to prescribe an alternative drug if the patient begins to vomit within 5-60 minutes after taking the drug, because at the moment there is too little information about the absorption of azithromycin.

If vomiting occurs more than 1 hour after taking the solution, there is no need to re-use the medicine (provided the patient has a properly functioning stomach).

Use Zetamax during pregnancy

Tests that allow to reliably determine the possibility of using the drug in pregnant women have not been performed. During pregnancy, this drug is prescribed only if it is impossible to use another drug.

There is no information about the substance getting into breast milk. It is allowed to use during lactation only for vital indications, when there is no possibility of alternative therapy.

Contraindications

Contraindications include: intolerance to erythromycin and azithromycin, as well as other ketolide antibiotics or macrolides, as well as other elements of the drug. The drug should not be prescribed to children.

Side effects Zetamax

In most cases (69% of all cases), the negative consequences of taking the drug were gastrointestinal disorders - loose stools and diarrhea, abdominal pain, and vomiting with nausea. Usually, these reactions were moderate and passed after 2 days (68% of cases). In some cases, patients experienced vaginitis or oral candidiasis. Among other side effects:

• Disorders in the functioning of the nervous system: most often headaches; occasionally dysgeusia or dizziness develops;
• problems with hearing and balance: in isolated cases – vertigo;
• heart problems: heart rhythm may occasionally be felt;
• problems with the gastrointestinal tract: in addition to those described above, constipation or gastritis, as well as dyspeptic symptoms, may rarely occur;
• subcutaneous tissues, as well as skin: rarely a rash appears on the skin, in isolated cases urticaria develops;
• General disorders: chest pain occasionally appears, asthenia may develop.

In people with normal values for various tests, during clinical testing of the drug, a noticeable deviation was observed, which had no causal connection with the drug being tested:

• lymphatic and hematopoietic systems: occasionally neutro- or leukopenia developed;
• laboratory tests: most often, the level of leukocytes decreased, the number of bicarbonates in the blood decreased, and the number of eosinophils increased. Less often, an increase in such indicators as the level of bilirubin, creatinine, and urea, as well as the activity of ALT and AST, and in addition, a change in the potassium indicators in the blood were observed. Subsequent observations showed that such changes are reversible.

Overdose

The data obtained as a result of clinical studies allow us to conclude that overdose of the drug causes reactions similar to side effects from taking the drug in the required dosages. General treatment measures are necessary to eliminate negative manifestations - supportive and symptomatic therapy.

Interactions with other drugs

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

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

When combined with cetirizine, no significant changes in the QT interval were observed, as well as a pronounced pharmacokinetic interaction between them at steady-state values of both drugs.

In patients with HIV, dideoxynosine in combination with azithromycin had no effect on the pharmacokinetic properties of the drug at steady-state levels of didanosine (compared to using placebo).

Concomitant administration with digoxin should be done with caution, as there is a possibility of increasing plasma digoxin levels.

Combination of the drug with zidovudine results in a weak effect on the pharmacokinetic properties or excretion of the latter in urine (along with its glucuronide decay product). It is also noted that when azithromycin is administered, the index of clinically active decay product (phosphorylated zidovudine) increases inside blood mononuclear cells. However, it was not possible to identify the medicinal significance of this fact.

Azithromycin has little interaction with the hepatic hemoprotein P450 system. 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 means of the hemoprotein-metabolite complex.

Combination with indole alkaloid derivatives is not recommended, since the simultaneous use of these drugs can theoretically cause ergotism.

Pharmacokinetic testing was also conducted when azithromycin was combined with the following drugs metabolized by hemoprotein P450:

• atorvastatin - when combined with this drug, its plasma levels did not change (data from the analysis of inhibition of HMG-CoA reductase);
• carbamazepine - when combined with azithromycin, its (as well as its active breakdown product) plasma parameters remain unchanged;
• cimetidine - if this substance is taken 2 hours before taking azithromycin, the pharmacokinetics of the latter remains unchanged;
• Oral anticoagulants (such as coumarin) - when administered to volunteers, azithromycin had no effect on the anticoagulant properties of warfarin. There is evidence of an increased anticoagulant effect when azithromycin is combined with coumarin-type drugs. Therefore, although no link has been established between these drugs, frequent monitoring of prothrombin time is required when these drugs are used together;
• cyclosporine - as a result of simultaneous use with this substance, the peak concentration and AUC values increased - within 0-5 for cyclosporine. Therefore, it is necessary to combine these drugs with caution. If joint administration is necessary, it is necessary to monitor the indicators during therapy and adjust the dosages in accordance with them;
• efavirenz - no significant changes in their pharmacokinetics were observed when these substances were combined;
• the combination of azithromycin with fluconazole does not change the properties of the latter. AUC and half-life of azithromycin also do not change in the case of a combination with fluconazole, but at the same time a decrease in its plasma indicators (by 18%) was still 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 case of combination with nelfinavir, the steady-state serum levels of azithromycin increase. When these drugs are used simultaneously, there is no need to adjust the dosage of azithromycin, but careful monitoring of the possible development of side effects of azithromycin is a necessary condition;
• concomitant administration with rifabutin does not affect serum levels of these substances, but neutropenia sometimes develops as a result of such a combination. It is believed that this disorder is caused by the use of rifabutin, but no connection has been established between the concomitant administration of drugs and the development of this side effect;
• no significant changes in peak concentration and AUC were detected when the drug was combined with sildenafil, as well as interactions of the drug with terfenadine, as well as with the substances theophylline and triazolam;
• In case of combined use with trimethoprim or sulfamethoxazole, no significant effect on their peak, excretion and AUC values was noted. Serum azithromycin level also remained unchanged.

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Storage conditions

The medicine should be stored in a tightly sealed package. Maximum temperature – 30°С.

Shelf life

Zetamax is suitable for use for 3 years from the date of release of the drug. After diluting the suspension, the prepared solution can be used within 12 hours.