Lincomycin-Darnitsa solution for injection 30% ampoule 1 ml No. 10

Instructions Lincomycin-Darnitsa solution for injection 30% ampoule 1 ml No. 10

Composition

active ingredient: lincomycin;

1 ml of solution contains lincomycin hydrochloride equivalent to 300 mg of anhydrous lincomycin;

Excipients: disodium edetate, sodium hydroxide, water for injections.

Dosage form

Solution for injection.

Main physicochemical properties: transparent, colorless or slightly yellowish liquid with a slight specific odor.

Pharmacotherapeutic group

Antibacterials for systemic use. Lincosamides. Lincomycin. ATX code J01F F02.

Pharmacological properties

Pharmacodynamics

Lincomycin is an antibiotic of the lincosamide group, a product of the vital activity of Streptomyces lincolniensis. It inhibits protein synthesis in bacteria due to reversibly binding to the 50S subunit of ribosomes, disrupting the formation of peptide bonds.

Depending on the sensitivity of microorganisms and the concentration of the antibiotic, lincomycin can exhibit both bacteriostatic and bactericidal effects. The spectrum of activity in vitro includes a number of pathogens:

Susceptible microorganisms (minimum inhibitory concentration (MIC) ≤ 2 μg/ml):

anaerobic gram-positive bacteria that do not form spores, including Propionibacterium spp., Eubacterim spp., and Actinomyces spp.; anaerobic and microaerophilic gram-positive cocci, including Peptococcus spp., Peptostreptococcus spp., and microaerophilic streptococci; aerobic gram-positive microorganisms, including staphylococci, streptococci (except S. faecalis), and pneumococci.

Microorganisms with moderate sensitivity (MIC is 2–4 μg/mL):

anaerobic gram-negative, non-spore-forming bacteria, including Bacteroides spp., Fusobacterium spp.; anaerobic gram-positive, spore-forming bacteria, including Clostridium spp.

Resistant microorganisms or microorganisms with low susceptibility (MIC ≥ 8 μg/mL), including Streptococcus faecalis, Neisseria, most strains of Haemophilus influenzae, Pseudomonas and other gram-negative microorganisms.

Although Shigella bacteria are resistant in vitro to lincomycin (MIC is approximately 200–400 μg/ml), lincomycin is effective in this disease due to the very high levels of lincomycin achieved in the intestine (approximately 3000–7000 μg/g of feces).

Cross-resistance between clindamycin and lincomycin has been reported. Resistance is most often due to methylation of specific nucleosides in the 23S subunit of the 50S ribosomal RNA, which may confer cross-resistance to macrolides and streptogramins B (MLSB phenotype). Macrolide-resistant isolates of these organisms should be tested for inducible resistance to lincomycin/clindamycin by the D-test or another acceptable method. There are currently no criteria for interpreting lincomycin susceptibility test results.

Pharmacokinetics

Absorption: A single intramuscular dose of 600 mg produces a mean maximum serum level of 11.6 μg/mL after 1 hour and maintains therapeutic levels for 17–20 hours against most susceptible gram-positive organisms.

A 2-hour intravenous infusion of 600 mg lincomycin achieves a mean maximum serum concentration of 15.9 μg/mL and maintains therapeutic levels for 14 hours for most susceptible Gram-positive microorganisms.

Distribution: Based on direct and indirect evidence, it has been established that binding to blood proteins decreases with increasing serum concentration (saturable binding to plasma proteins).

In fetal blood, peritoneal and pleural fluids, concentrations of 25–50% of the blood level can be reached, in breast milk this figure is 50–100%, in bone tissue – about 40% and in surrounding soft tissues – 75%.

However, lincomycin penetrates slowly into the cerebrospinal fluid (1–18% of the blood level); in meningitis, the level in the cerebrospinal fluid reaches 40% of the blood level.

Elimination. A significant part of the drug is metabolized, metabolism occurs mainly in the liver. Normally, the serum half-life is 5.4 ± 1 h. However, this period may be prolonged in cases of impaired liver and/or kidney function. In this regard, it is necessary to reduce the frequency of administration of lincomycin in patients with impaired liver or kidney function.

After intramuscular administration of 600 mg, the excretion of bacteriologically active drug in the urine is 1.8–24.8% (average – 17.3%), and in feces – 4–14%. After intravenous administration of 600 mg within 2 hours, the excretion of bacteriologically active drug in the urine is 4.9–30.3% (average – 13.8%). The rest of the drug is excreted in the form of bacteriologically inactive metabolites. Hemodialysis and peritoneal dialysis do not affect the excretion of lincomycin from the blood.

Indication

Use for the treatment of severe infections caused by lincomycin-sensitive strains of streptococci, pneumococci, and staphylococci.

This medicine should be used in patients with a penicillin allergy or other patients for whom, in the opinion of the physician, the use of penicillin is inappropriate.

Contraindication

Lincomycin is contraindicated in patients with a history of hypersensitivity to lincomycin, clindamycin, or any other component of the drug.

Meningitis.

Interaction with other medicinal products and other types of interactions

Antagonism has been demonstrated between lincomycin and erythromycin in vitro. It is not recommended to administer these two drugs together due to the potential for clinically significant interactions.

Lincomycin has neuromuscular blocking properties that may potentiate the effects of other neuromuscular blocking agents; lincomycin should be administered with caution to patients receiving such drugs.

Application features

Lincomycin should not be administered intravenously as a bolus of undiluted medicinal product. Intravenously, the medicinal product may only be administered by drip infusion over a period of at least 1 hour (see section "Method of administration and dosage").

Prescribing Lincomycin-Darnitsa in the absence of a confirmed or highly suspected bacterial infection is unlikely to be beneficial to the patient and increases the risk of developing bacteria resistant to the drug.

To prevent the development of aseptic necrosis, intramuscular injections should be administered deep into the muscle.

Antibiotics are often associated with diarrhea, which usually resolves after antibiotic therapy is discontinued. Occasionally, after starting antibiotic therapy, patients may experience watery or bloody stools, with or without abdominal cramps and fever, and may occur 2 or more months after the last dose of the antibiotic. In such cases, the patient should seek medical attention as soon as possible.

Certain infections may require incision and drainage or other indicated procedures in addition to antibiotic therapy.

Microbiological studies should be performed to identify the pathogens and their sensitivity to lincomycin.

Necessary surgical procedures should be performed in combination with antibiotic therapy.

The effectiveness of lincomycin for the treatment of staphylococcal infections resistant to other antibiotics and sensitive to lincomycin has been demonstrated. Lincomycin-resistant staphylococcal strains have been identified, therefore, in combination with Lincomycin-Darnitsa therapy, bacteriological cultures and sensitivity testing of pathogens are necessary. In the case of macrolides, partial, but not complete, cross-resistance is possible. If indicated, the drug can be used simultaneously with other antibacterial agents.

The use of lincomycin for the treatment of minor bacterial infections and viral infections is not indicated.

In order to reduce the rate of emergence of drug-resistant bacteria and to maintain the effectiveness of lincomycin and other antibacterial drugs, Lincomycin-Darnitsa should be used only for the treatment or prevention of infections that are proven or very likely to be caused by susceptible bacteria. If the results of bacteriological cultures and susceptibility testing are available, they should be taken into account when selecting or changing antibacterial therapy. In the absence of such data, empirical selection of therapy should be made taking into account local epidemiological data and local characteristics of susceptibility patterns.

Risk of colitis

Due to the risk of pseudomembranous colitis associated with the use of antibacterial agents, before deciding to use lincomycin, the physician should analyze the nature of the infection and evaluate the possibility of using less toxic alternative drugs (e.g., erythromycin).

The drug should be used with caution in patients with gastrointestinal diseases, including colitis.

Treatment with antibacterial drugs disrupts the normal flora of the large intestine and can lead to overgrowth of clostridia. Studies have shown that a toxin produced by Clostridium difficile is the main cause of antibiotic-associated colitis. Pseudomembranous colitis should be treated immediately after the initial diagnosis. In cases of mild pseudomembranous colitis, it is usually sufficient to stop taking the drug. In cases of moderate to severe severity, treatment should include the administration of electrolyte solutions, proteins and the appointment of antibacterial drugs effective against Clostridium difficile in colitis.

Clostridium difficile-associated diarrhea (CDAD) has been associated with the use of nearly all antibacterial drugs, including lincomycin, and has ranged in severity from mild diarrhea to fatal colitis. Antibacterial drug treatment disrupts the normal flora of the large intestine, leading to overgrowth of Clostridium difficile.

Clostridium difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of Clostridium difficile cause increased morbidity and mortality, as the infection may be refractory to antibacterial therapy and require colectomy. CDAD should be considered in patients who develop diarrhea after taking antibiotics. A detailed history is also necessary, as cases of CDAD have been reported 2 months after the administration of antibacterial drugs.

In cases of suspected or confirmed CDAD, current non-Clostridium difficile antibacterial therapy should be discontinued. Fluid and electrolyte management, protein supplementation, Clostridium difficile antibacterial therapy, and surgical evaluation should be initiated as clinically indicated.

Allergy

Lincomycin-Darnitsa should be used with caution in patients with a history of severe bronchial asthma or severe allergies, or those with atopy.

Hypersensitivity

Serious hypersensitivity reactions, including anaphylactic reactions and severe cutaneous adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis and erythema multiforme, have been reported with the use of lincomycin. In the event of an allergic reaction to lincomycin, treatment should be discontinued and appropriate therapy should be initiated (see section 4.8).

Meningitis

Although lincomycin penetrates the cerebrospinal fluid (CSF), the level of lincomycin in the CSF may be insufficient to treat meningitis, so the drug should not be prescribed in such cases.

Superinfections

The use of lincomycin may result in overgrowth of non-susceptible organisms, particularly yeasts. In the event of superinfections, appropriate measures should be taken as indicated by the clinical situation. If patients with pre-existing fungal infections require treatment with lincomycin, concomitant antifungal therapy should be administered.

In patients with severe renal impairment, the serum half-life of lincomycin may be prolonged compared to patients with normal renal function. In patients with hepatic impairment, the serum half-life may be doubled compared to patients with normal hepatic function.

Patients with severe renal and/or hepatic impairment should be dosed with caution and serum lincomycin levels should be monitored during high-dose therapy.

During long-term treatment, it is necessary to periodically perform liver and kidney function tests, as well as blood tests.

Application to the elderly

Experience to date suggests that a subgroup of elderly patients with serious medical conditions are more likely to develop diarrhoea. If the drug is prescribed to this group of patients, it is necessary to carefully monitor changes in bowel frequency.

Pediatric use

Low birth weight and premature infants are more prone to developing toxicity.

Important information about excipients

This medicine contains sodium compounds, therefore patients on a controlled sodium diet should be careful when using it.

Ability to influence reaction speed when driving vehicles or other mechanisms

No particular effect on the reaction speed when driving or using other mechanisms was noted, but isolated cases of dizziness were reported.

Use during pregnancy or breastfeeding

There are no studies of the teratogenic potential of lincomycin in animals and no adequate and well-controlled studies of the effects of lincomycin on pregnant women. Lincomycin should not be used during pregnancy unless clearly necessary.

Lincomycin has been reported to be present in human breast milk at concentrations ranging from 0.5 to 2.4 μg/mL. Because of the potential for serious adverse reactions in breastfed infants from lincomycin, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the benefit of the drug to the mother.

Method of administration and doses

Lincomycin should not be administered intravenously as a bolus of undiluted medicinal product. Intravenously, the medicinal product may only be administered by drip infusion over a period of at least 1 hour.

If severe diarrhea develops during therapy, the use of this antibacterial agent should be discontinued.

Adults

Intramuscular injection

The usual dose is:

600 mg intramuscularly every 24 hours.

Severe infections: 600 mg intramuscularly every 12 hours (or more frequently), as determined by the severity of the infection.

Intravenous administration

The usual dose is:

600 mg to 1 g every 8–12 hours.

In severe infections, these doses may be increased.

In life-threatening conditions, the daily dose for intravenous administration may be up to 8 g.

Children (from 1 month of age)

10 mg/kg per day as 1 injection.

Severe infections: 10 mg/kg every 12 hours or more frequently.

Intravenous injections

10 to 20 mg/kg per day, depending on the severity of the infection, may be administered in several doses according to the described dilution and infusion rate rules.

Dosage for patients with impaired liver or kidney function.

In patients with impaired hepatic or renal function, the serum half-life of lincomycin is increased, which is the basis for reducing the frequency of lincomycin administration. If lincomycin therapy is necessary in patients with significant renal impairment, the appropriate dose should be 25% to 30% of the dose recommended for patients with normal renal function.

The duration of treatment is determined individually.

Infections caused by β-hemolytic streptococcus.

Treatment should last at least 10 days.

Dilution and infusion rate

The dose for administration in the form of infusion is calculated as follows:

1 g of lincomycin is diluted in at least 100 ml of an appropriate dilution solution (0.9% sodium chloride solution), and the infusion duration should be at least 1 hour.

The indicated doses can be administered repeatedly, the frequency of administration is determined according to the need, while the daily dose should not exceed the maximum recommended dose of lincomycin, which is 8 g.

Note: Severe cardiovascular and respiratory reactions may occur if this drug is administered in higher than recommended concentrations and at higher rates.

Children

Lincomycin-Darnitsa should be used in children aged 1 month and older in recommended doses (see section “Method of administration and dosage”).

Overdose

In case of overdose, secondary gastrointestinal disorders may occur, including abdominal pain, nausea, vomiting and diarrhea. Severe cardiopulmonary reactions have been described after too rapid intravenous administration of undiluted high doses. Such reactions did not occur if the drug was diluted according to the recommendations.

Treatment of overdose is possible by gastric lavage or induction of vomiting. There is no specific antidote known.

Hemodialysis and peritoneal dialysis are ineffective in removing lincomycin from the blood.

Adverse reactions

From the side of the organs of hearing and vestibular apparatus: tinnitus, vertigo.

Gastrointestinal: glossitis, stomatitis, nausea, heartburn, vomiting, abdominal discomfort and pain, persistent diarrhea, colitis (including pseudomembranous colitis, Clostridium difficile-associated colitis), candidiasis, itching in the anus, decreased appetite.

Liver and biliary tract disorders: Jaundice and changes in liver function tests (especially increased serum transaminase levels) may also occur during lincomycin therapy.

Renal and urinary disorders: renal dysfunction (azotemia, oliguria, proteinuria), vaginitis.

From the nervous system: headache, dizziness.

Cardiovascular: episodes of hypotension have been reported after parenteral administration of the drug, especially when administered too rapidly. Rarely, episodes of depression of cardiac activity and respiratory function, tachycardia, dizziness, asthenia, skeletal muscle relaxation up to cardiopulmonary shock have also been observed after too rapid intravenous administration.

Blood and lymphatic system disorders: Neutropenia, leukopenia, agranulocytosis and thrombocytopenic purpura have been reported. There have been isolated reports of aplastic anemia and pancytopenia, in which the effect of lincomycin as the cause of the adverse reaction cannot be excluded.

Immune system disorders: Angioedema, serum sickness and anaphylactic shock, some of which have occurred in patients with penicillin hypersensitivity. Rare cases of erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis have also been reported in association with the administration of lincomycin.

In the event of acute severe hypersensitivity reactions, the use of adrenaline and other emergency medical measures may be required (if clinically indicated), including oxygen therapy, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway patency.

Skin and subcutaneous tissue disorders: itching, skin rash (vesicular, macular, roseola, punctate, urticarial, spotty), urticaria, vaginitis, rarely - exfoliative and vesiculobullous dermatitis.

The likelihood of these reactions can be minimized by administering the drug in the form of deep intramuscular injections and avoiding the use of indwelling intravenous catheters.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. It allows for continued monitoring of the benefit-risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Expiration date

2 years.

The expiration date determines the use of the medicine until the last day of the specified month.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 ° C. Do not freeze.

Keep out of reach of children.

Incompatibility

The drug is pharmaceutically incompatible with kanamycin, ampicillin, barbiturates, theophylline, calcium gluconate, heparin and magnesium sulfate.

Lincomycin is incompatible in the same syringe or dropper with kanamycin, novobiocin, or phenytoin.

Packaging

1 ml in an ampoule; 5 ampoules in a contour blister pack; 2 contour blister packs in a pack.

Vacation category

According to the recipe.

Producer

PrJSC "Pharmaceutical Company "Darnitsa".

Location of the manufacturer and its business address

Ukraine, 02093, Kyiv, Boryspilska St., 13.