Midecamycin

Pharmacological properties

midecamycin is a broad-spectrum macrolide antibiotic that is effective against gram-positive bacteria (staphylococci, streptococci, pneumococci, bacillus anthracis, corynebacterium diphtheriae and listeria monocytogenes), some gram-negative bacteria (bordetella pertusseris erypperblobella. bacteria (clostridium spp. and bacteroides spp.) and other bacteria such as mycoplasmas, ureaplasmas, chlamydia and legionella. midecamycin metabolites exhibit a similar, but less pronounced antibacterial effect.

Midecamycin inhibits the synthesis of RNA-dependent proteins in the stage of prolongation of the protein chain by reversible binding to the 50S subunit and inhibition of transpeptidation and / or translocation reactions. Due to the difference in the structure of ribosomes, binding to eukaryotic cells does not occur. Therefore, the toxicity of macrolides for human cells is low.

Mostly, midecamycin has a bacteriostatic effect. However, it can also be bactericidal depending on the type of bacterium, the concentration of the drug at the site of action, the size of the inoculum and the reproductive stage of the microorganism. In vitro activity decreases in an acidic environment. If the pH value in the environment of cultures of Staphylococcus aureus or Streptococcus pyogenes increases from 7.2 to 8.0, the minimum inhibitory ability of midecamycin is reduced by 2 times. If pH decreases, the situation reverses.

Midecamycin cumulates in human alveolar macrophages. Macrolides also cumulate in neutrophilic granulocytes. In vitro studies have shown that midecamycin also affects immune function. An increase in chemotaxis compared with erythromycin was found. In vivo, midecamycin stimulates the activity of natural killer cells. These studies indicate that midecamycin affects the immune system, which is important for the in vivo antibiotic effect of midecamycin.

Pharmacokinetics Midecamycin and myocamycin are rapidly and relatively well absorbed and reach C_max in blood serum 0.5–2.5 and 1.31–3.3 mcg / ml, respectively, for 1–2 hours. As food intake slightly reduces C_max, especially in children aged 4-16 years, it is recommended to take midecamycin before meals.

Midecamycin penetrates well into tissues, where it reaches higher concentrations than in blood (100%). High concentrations are achieved in the secretion of the bronchi, as well as in the skin. The volume of distribution of myocamycin is 228–329 liters.

47% of midecamycin and 3–29% of metabolites bind to blood proteins. Midecamycin acetate also passes into breast milk. After taking a dose of 1200 mg / day, 0.4–1.7 μg / ml of midecamycin acetate was detected in breast milk.

Midecamycin is mainly metabolized in the liver. It is mainly excreted in the bile and only about 5% in the urine.

Significant increase in C_max in serum, AUC and T_½ may be observed in patients with cirrhosis.

Indications

Respiratory and urogenital infections caused by mycoplasmas, legionella, chlamydia and ureaplasma urealyticum; infections of the respiratory tract, skin and soft tissues and other infections caused by bacteria sensitive to midecamycin and penicillin in patients with hypersensitivity to penicillins; enteritis caused by bacteria campylobacter spp .; treatment and prevention of diphtheria and pertussis.

Application

The drug should be taken before meals.

Suspension for oral administration intended for use in children.

Children with body weight less than 30 kg are prescribed 20–40 mg / kg body weight per day of suspension for oral administration, distributed in 3 doses; or 50 mg / kg of body weight per day, distributed over 2, and for severe infections - into 3 doses.

Dosing schedule for children (daily dose of 50 mg / kg body weight)

The duration of therapy is from 7 to 14 days. Treatment for chlamydial infection must be continued for 14 days.

Suspension preparation. To the contents of the bottle add 100 ml of boiled water and mix thoroughly. Shake the bottle thoroughly before each use.

Tablets. The drug is used before meals.

Adults and children weighing more than 30 kg: 1 tablet 400 mg 3 times a day. The maximum daily dose for adults is 1600 mg of medecamycin.

For children weighing less than 30 kg, a suspension for oral administration is used.

The course of therapy usually lasts 7-14 days. Treatment for chlamydial infection should be continued for 14 days.

Contraindications

Hypersensitivity to midecamycin or other components of the drug, severe liver dysfunction.

Side effects

On the part of the blood system and lymphatic system: single: eosinophilia.

From the gastrointestinal tract: infrequently: nausea, decreased appetite, vomiting, diarrhea and stomatitis; very rarely: pseudomembranous colitis, abdominal pain.

On the part of the skin and subcutaneous tissues: very rarely: skin rash, urticaria and pruritus, angioedema, Stevens-Johnson syndrome.

From the hepatobiliary system: very rarely: increased levels of hepatic transaminases and jaundice.

If severe side effects occur, treatment should be discontinued.

special instructions

With prolonged therapy, the activity of liver enzymes should be monitored, especially in patients with impaired liver function in the present or in the anamnesis.

Long-term use of the drug can lead to the development of superinfection. Persistent diarrhea can be a manifestation of pseudomembranous colitis.

Use during pregnancy and lactation. Midecamycin can only be prescribed if the expected benefit to the mother outweighs the likely risk to the fetus.

Since the drug passes into breast milk, breast-feeding must be stopped for the period of treatment with Macropen.

Children

Suspension for oral administration: used in children with body weight up to 30 kg.

Tablets: used in children weighing more than 30 kg.

The ability to influence the reaction rate when driving vehicles or while working with other mechanisms. There are no data on the influence of Macropen on the ability to drive vehicles and work with other mechanisms.

Interactions

Midecamycin is metabolized in the liver, where it can block the activity of the enzymes of the cytochrome p450 complex. unlike erythromycin, midecamycin and myocamycin does not bind to microsomal oxidases of liver cells and do not form stable complexes with cytochrome p450. as a result, they do not affect theophylline pharmacokinetics.

Caution is advised to use the drug in patients who are taking carbamazepine or cyclosporine in parallel and, if possible, control serum levels of the latter, due to the possibility of increasing serum cyclosporin levels and lengthening T_½ carbamazepine.

Ergot alkaloids are not recommended, as Macropen can reduce their metabolism in the liver and increase their concentration in blood plasma.

Caution is required with the simultaneous use of midecamycin with warfarin, since elimination of the latter may decrease, which increases the risk of bleeding.