Clindamycin-M capsules 0.15 g blister No. 10

Instructions for use Clindamycin-M capsules 0.15 g blister No. 10

Composition

active ingredient: clindamycin;

1 capsule contains clindamycin hydrochloride equivalent to clindamycin 0.15 g (150 mg);

excipients: calcium stearate, lactose monohydrate, colloidal anhydrous silicon dioxide, sodium methylparaben (E 219), sodium propylparaben (E 217), gelatin, titanium dioxide (E 171), tartrazine (E 102), erythrosine (E 127), brilliant blue, amaranth (E 123).

Dosage form

Capsules.

Main physicochemical properties: hard gelatin capsules with a pink cap and body; capsule contents are white powder.

Pharmacotherapeutic group

Antibacterials for systemic use. Lincosamides. Clindamycin. ATX code J01F F01.

Pharmacological properties

Pharmacodynamics.

Mechanism of action. The mechanism of action of clindamycin is based on the inhibition of protein biosynthesis by binding to the 50S subunit of the bacterial ribosome, resulting in a bacteriostatic effect in most cases.

Pharmacokinetic/pharmacodynamic relationship: Efficacy will depend significantly on the time during which the level of the substance exceeds the minimum inhibitory concentration (MIC) for the causative pathogen.

Mechanism of resistance. The mechanisms underlying the development of resistance to clindamycin may be as follows. Resistance in staphylococci and streptococci will mainly result from increased incorporation of methyl groups into 23S rRNA (so-called constitutive MLSB resistance), which greatly reduces the binding affinity of clindamycin to the ribosome. Most methicillin-resistant S. aureus (MRSA) strains have a constitutive MLSB phenotype and are therefore clindamycin resistant. Therefore, infections caused by macrolide-resistant staphylococci should not be treated with clindamycin even when demonstrated in vitro susceptibility because of the risk of selection during treatment of mutant strains with constitutive MLSB resistance.

Strains with constitutive MLSB resistance demonstrate complete cross-resistance between clindamycin and lincomycin, macrolides (e.g. azithromycin, clarithromycin, erythromycin, roxithromycin, spiramycin), and streptogramin B.

Pharmacokinetics.

Absorption, distribution and protein binding.

The difference between the clindamycin derivatives used is only in the time of absorption and cleavage of the esters. After that, clindamycin is present in the body as a free base (active form). Its esters should be considered precursors of the drug.

After oral administration, clindamycin hydrochloride and clindamycin 2-palmitate hydrochloride are rapidly and almost completely absorbed from the gastrointestinal tract. Simultaneous food intake slightly slows down absorption. When administered in the fasting state, maximum serum concentrations are reached after approximately 45-60 minutes, and when administered after a meal - after approximately 2 hours. After oral administration of a single dose of 150 mg or 300 mg, the concentrations are 1.9 to 3.9 μg/ml and 2.8 to 3.4 μg/ml, respectively (fasting state).

The binding of clindamycin to plasma proteins depends on its concentration and ranges from 60% to 94% within the therapeutic range.

Clindamycin readily penetrates tissues, crosses the placental barrier and is excreted in breast milk. Diffusion into the subarachnoid space is insufficient even in meningeal inflammation. High concentrations are achieved in bone tissue.

Biotransformation and excretion.

Clindamycin is primarily metabolized in the liver. Some metabolites are microbiologically active. Drugs that act as inducers of hepatic enzymes reduce the average retention time of clindamycin in the body.

Clindamycin is excreted approximately 2/3 in the feces and 1/3 in the urine.

The serum half-life of clindamycin is approximately 3 hours in adults and approximately 2 hours in children. The half-life is prolonged in patients with impaired renal function and moderate to severe hepatic impairment.

Clindamycin is not removed by dialysis.

Indication

Acute and chronic bacterial infections caused by clindamycin-sensitive pathogens, including:

bone and joint infections;

ear, nose and throat infections;

infections of the teeth and jaw area;

lower respiratory tract infections;

pelvic and abdominal infections;

infections of the female genital organs;

skin and soft tissue infections;

scarlet fever.

In severe clinical conditions, treatment should initially be carried out with drugs containing clindamycin, which are slowly injected into the blood vessel (via infusion).

Contraindication

Clindamycin-M should not be used in patients with sensitivity to clindamycin, lincomycin, or any other component of the drug.

Clindamycin-M is not suitable for the treatment of meningitis because the concentration of the antibiotic achieved in the cerebrospinal fluid is too low.

Typically, a dosage form such as capsules is not suitable for use in children under 6 years of age.

Interaction with other medicinal products and other types of interactions

If possible, Clindamycin-M should not be combined with erythromycin, as an antagonistic effect on antibacterial activity has been observed in vitro.

Pathogenic microorganisms demonstrate cross-resistance to clindamycin and lincomycin.

Since the drug Clindamycin-M has the property of blocking neuromuscular transmission, it can enhance the effect of muscle relaxants (e.g. ether, tubocurarine, pancuronium halide). This can lead to unexpected life-threatening situations during operations. Therefore, Clindamycin-M should be used with caution in patients receiving the above-mentioned drugs.

The reliability of the contraceptive effect of oral contraceptives is questionable when used concomitantly with Clindamycin-M. Therefore, other methods of contraception should be used in addition during treatment with Clindamycin-M.

Vitamin K Antagonists: Elevated coagulation parameters (prothrombin time/international normalized ratio) and/or bleeding have been observed in patients receiving clindamycin in combination with vitamin K antagonists (e.g. warfarin, acenocoumarol and fluindione). Therefore, coagulation parameters should be monitored in such patients.

Application features

Clindamycin-M should be used with caution in the following categories of patients:

with impaired liver function;

with disorders of neuromuscular transmission (myasthenia gravis, Parkinson's disease);

with a history of gastrointestinal diseases (for example, inflammation of the colon);

with atopy;

with allergies and asthma.

Note: Clindamycin-M should not be used in patients with acute respiratory infections if they are caused by viruses. Clindamycin-M is not suitable for the treatment of meningitis because the antibiotic concentrations achieved in the cerebrospinal fluid are too low.

Severe hypersensitivity reactions have been reported in patients treated with clindamycin, including serious skin reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. If a hypersensitivity reaction or serious skin reaction occurs, clindamycin should be discontinued and appropriate treatment should be initiated (see Contraindications and Adverse Reactions).

During long-term treatment (more than 10 days), clinical blood tests and liver and kidney function should be checked regularly.

Long-term and repeated use of the drug Clindamycin-M may lead to the development of superinfection or colonization of the skin and mucous membranes with resistant microorganisms or yeast fungi.

Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis. Antibacterial therapy disrupts the normal flora of the colon, leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD and are the primary cause of “antibiotic-associated colitis.” Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections may be refractory to antimicrobial therapy and require colectomy.

The possibility of CDAD should be considered in all patients with antibiotic-associated diarrhea. A careful history should be taken, as CDAD has been reported to develop up to two months after the use of antibacterial agents. Progression to colitis, including pseudomembranous colitis, may occur, and the severity of the condition may range from mild to fatal.

If antibiotic-associated diarrhea or antibiotic-associated colitis is diagnosed or suspected, antibacterial agents, including clindamycin, should be discontinued and appropriate therapeutic measures initiated. Medicinal products that inhibit peristalsis are contraindicated in this situation.

In cases of moderate to severe pseudomembranous colitis, consideration should be given to fluid and electrolyte management, protein supplementation, and the use of antibacterial agents clinically effective for the treatment of Clostridium difficile colitis.

If therapy is continued, liver and kidney function tests should be performed.

Clindamycin treatment is sometimes an alternative in cases of penicillin allergy (hypersensitivity to penicillin). Cross-allergy between clindamycin and penicillin is not known and is not expected to occur due to the structural differences between these substances. However, anaphylactic reactions (hypersensitivity) to clindamycin have been reported in isolated cases in individuals who are already allergic to penicillin. This should be considered when using clindamycin to treat patients with penicillin allergy.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Clindamycin-M contains 121 mg of lactose monohydrate per 1 capsule. When using the drug according to the instructions, the patient receives up to 484 mg of lactose monohydrate. This corresponds to the total amount of lactose contained in 4 capsules of the drug Clindamycin-M. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not use Clindamycin-M.

Excipients: tartrazine (E 102), amaranth (E 123), sodium methylparaben (E 219), sodium propylparaben (E 217), which are part of the capsule shell, may cause allergic reactions (possibly delayed).

Use during pregnancy or breastfeeding

Use during pregnancy.

A large study of pregnant women exposed to clindamycin during the first trimester of pregnancy (approximately 650 infants) did not show an increased incidence of birth defects. However, there is insufficient evidence to support the safety of clindamycin use during pregnancy.

The results of experimental studies in animals do not suggest direct or indirect harmful effects on the course of pregnancy, embryonal/fetal development, the course of childbirth or postnatal development.

Clindamycin crosses the placenta. It is assumed that therapeutic, effective concentrations are achieved in the fetus. When using the drug during pregnancy, the benefits and possible risks associated with treatment should be carefully weighed.

Use during breastfeeding.

Clindamycin passes into breast milk. Therefore, in breast-fed infants, the development of sensitization, diarrhea and colonization of the mucous membranes with yeast fungi cannot be excluded. Due to the risk of serious adverse reactions in breast-fed infants, clindamycin should not be used by breastfeeding women.

Reproductive function.

Animal studies have not shown any evidence of impaired reproductive function. There are no data on the effects of clindamycin on human reproductive function.

Ability to influence reaction speed when driving vehicles or other mechanisms

Clindamycin has minor or moderate influence on the ability to drive and use machines. Some side effects (including dizziness, drowsiness, see section "Adverse reactions") may affect the ability to concentrate and react; therefore, they may affect the ability to drive and use machines.

Method of administration and doses

Clindamycin-M should be taken with sufficient fluid (at least 1 large glass of water) to avoid possible irritation of the esophagus.

If an infection caused by β-hemolytic streptococcus is suspected or if there are signs of β-hemolytic streptococcus, treatment should be carried out for at least 10 days.

Adults.

Depending on the location and severity of the infection, adults and children aged 14 and over should take 4–12 capsules per day (equivalent to 0.6–1.8 g of clindamycin).

The daily dose is divided into 4 doses.

To provide higher doses, there are also medicines with a higher content of the active substance.

Liver disease. In patients with moderate to severe liver disease, the half-life of clindamycin is prolonged. Usually, if Clindamycin-M is administered every 8 hours, no dose reduction is necessary. However, patients with severe hepatic impairment should be monitored for clindamycin plasma levels. Depending on the results obtained, a dose reduction or prolongation of the dosing intervals may be necessary.

Renal disease. The elimination half-life of clindamycin is prolonged in renal disease; however, no dose reduction is necessary in mild to moderate renal impairment. However, plasma clindamycin levels should be monitored in patients with severe renal impairment or anuria. Depending on the results of these measurements, a reduction in dose or, alternatively, an extension of the dosing interval to 8 or even 12 hours may be necessary.

Hemodialysis: Clindamycin is not removed by hemodialysis. Therefore, no additional dose is required before or after hemodialysis.

Children.

This dosage form should be used in children over 6 years of age.

Depending on the location and severity of the infection, children under 14 years of age should use 8–25 mg of clindamycin per kilogram of body weight per day, see table.

Table.

The daily dose is divided into 3-4 separate doses. As a rule, 4 doses are preferred.

Overdose

No symptoms of overdose have been observed so far. Gastric lavage is indicated if necessary. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the blood serum. A specific antidote is unknown.

Side effects

The adverse reactions listed below have been identified during clinical trials and during post-marketing surveillance. Within each category, adverse reactions are presented by frequency and clinical significance.

Adverse reactions are classified according to frequency as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (frequency cannot be estimated from the available data). Adverse reactions are listed within each category in order of decreasing seriousness.

Infections and invasions.

Common: pseudomembranous colitis*

Frequency not known: Clostridium difficile colitis*, vaginal infections

From the blood and lymphatic system.

Common: agranulocytosis*, neutropenia*, thrombocytopenia*, leukopenia*, eosinophilia

From the immune system.

Rare: drug fever.

Very rare: anaphylactic reaction*.

Frequency unknown: anaphylactic shock*, anaphylactoid reaction*, hypersensitivity*.

From the nervous system.

Uncommon: taste distortion, neuromuscular blockade.

Frequency unknown: dizziness, drowsiness, headache.

From the gastrointestinal tract.

Very common: esophageal irritation, oesophagitis*, stomatitis, soft stools, diarrhoea, abdominal pain, vomiting, nausea.

Frequency not known: esophageal ulcer*

Hepatobiliary disorders.

Very rare: transient hepatitis with cholestatic jaundice

Frequency unknown: jaundice*.

On the skin and subcutaneous tissue.

Common: maculopapular rash, crusted rash*, urticaria.

Rare: toxic epidermal necrolysis, Stevens-Johnson syndrome*, Lyell syndrome, angioedema/angioedema*, exfoliative dermatitis*, bullous dermatitis*, erythema multiforme, pruritus, vaginitis.

Very rare: rash, blistering, hypersensitivity reactions.

Frequency not known: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)*, acute generalized exanthematous pustulosis*.

Musculoskeletal and connective tissue disorders.

Very rare: polyarthritis.

From the kidneys and urinary tract.

Renal dysfunction in the form of azotemia, oliguria and/or proteinuria.

Frequency unknown: acute kidney injury: (see section "Special warnings and precautions for use").

Laboratory test results.

Common: Abnormal biochemical liver function tests.

* Adverse reactions identified during post-marketing use of the medicinal product (see section "Special warnings and precautions for use").

Adverse reactions of antibiotics (class effect).

Often, pseudomembranous enterocolitis may develop when using the drug Clindamycin-M. Immediately after determining (diagnosing) pseudomembranous enterocolitis, the doctor should consider discontinuing the use of the drug Clindamycin-M and initiating appropriate treatment (use of specific antibiotics/chemotherapeutic agents with clinically proven efficacy). Drugs that inhibit peristalsis are contraindicated.

The use of clindamycin may lead to overgrowth of other intestinal microorganisms, including fungi.

Sometimes allergic reactions occur even after the first use. Very rarely, severe acute allergic reactions, such as anaphylactic shock, occur. In such cases, the use of Clindamycin-M should be discontinued immediately and appropriate emergency measures should be taken (e.g., antihistamines, corticosteroids, sympathomimetics, and, if necessary, artificial ventilation).

Reporting of suspected adverse reactions. Once a medicinal product has been authorised, it is very important to report suspected adverse reactions. This allows the benefit-risk balance of the medicinal product to be monitored. Physicians should report any suspected adverse reactions as required by law.

Expiration date

2 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 ºС.

Keep out of reach of children.

Incompatibility

Due to the existence of antagonism between clindamycin and erythromycin, their simultaneous use is not recommended. It should not be used together with ampicillin, diphenylhydantoin, barbiturates, aminophylline, calcium gluconate and magnesium sulfate.

Packaging

10 capsules in a blister; 1 blister in a cardboard pack.

Vacation category

According to the recipe.

Producer

Location of the manufacturer and its business address

Ukraine, 19100, Cherkasy region, Monastyryshche, Zavodska st., 8.