Lincomycin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LINCOMYCIN (LINCOMYCIN)

Composition:

Active substance: lincomycin;

1 capsule contains lincomycin hydrochloride, calculated as lincomycin, 250 mg;

Excipients: colloidal anhydrous silicon dioxide, calcium stearate, microcrystalline cellulose.

Capsule shell composition: titanium dioxide (E 171), gelatin.

Pharmaceutical form. Capsules.

Main physicochemical properties: hard gelatin capsules, size 0, with white body and cap.

The capsule contents – a white or almost white powder.

Pharmacotherapeutic group.

Antibacterial agents for systemic use. Macrolides, lincosamides and streptogramins. Lincosamides.

ATC code J01F F02.

Pharmacological properties.

Pharmacodynamics.

Sensitivity

Depending on the susceptibility of the microorganism and the concentration of the antibiotic, lincomycin may exert either bactericidal or bacteriostatic effects.

The table below shows minimal inhibitory concentration (MIC) values obtained from literature sources. The prevalence of resistance may vary over time and depending on the region.

* - lincomycin is inactive against H. influenzae, enterococci, and species of the genus Neisseria (see section "Indications").

An in vitro phenomenon of cross-resistance of dissociated type has been observed between clindamycin and lincomycin on one side, and macrolide antibiotics (erythromycin, clarithromycin, azithromycin) on the other. There is absolute cross-resistance between lincomycin and clindamycin. Rapid development of resistance has not been observed in in vitro and in vivo studies. In staphylococci, resistance to lincomycin or clindamycin develops gradually in vitro. Studies indicate the absence of common antigenic properties between lincomycin and penicillins.

Pharmacokinetics.

Absorption

When administered orally on an empty stomach, 25–30% of the drug is absorbed. After oral administration of 500 mg of lincomycin, the maximum serum concentration is approximately 3 µg/mL, reached within 2–4 hours after administration. If lincomycin is taken with food, this value decreases by approximately 50%. After oral administration, therapeutic concentrations of the drug in the blood are maintained for 6–8 hours against the most susceptible Gram-positive pathogens.

Distribution

Based on published studies, it has been established that the binding of the drug to plasma proteins is saturable, meaning the percentage of bound drug decreases as the drug concentration in serum increases.

Concentrations of the drug in fetal blood, peritoneal, and pleural fluids may reach 25–50% of blood levels; in breast milk — 50–100%; in bone tissue — approximately 40%; and in soft tissues — 75% of blood concentrations.

At the same time, lincomycin penetrates slowly into cerebrospinal fluid (1–18% of blood concentration). During meningitis, an increase in drug levels up to approximately 40% compared to blood concentration has been observed.

Elimination

A relatively large portion of the drug metabolism occurs primarily in the liver. Normally, the elimination half-life from serum is 5.4 ± 1 hour. In cases of impaired liver and/or kidney function, this period may be prolonged; therefore, in patients with impaired liver and/or kidney function, a reduced dosing frequency of lincomycin should be considered.

After a single oral dose of 500 mg, urinary excretion of microbiologically active form ranges from 1–31% (on average, 4%), and fecal excretion up to 33%.

Given that drug concentrations in bile may exceed blood levels by up to 10 times, biliary excretion is undoubtedly an important route of drug elimination from the body following oral administration.

Residual amounts of the drug are excreted as metabolites that are microbiologically inactive. Hemodialysis and peritoneal dialysis procedures do not affect the elimination of lincomycin from the blood.

Clinical characteristics.

Indications.

Lincomycin is indicated for the treatment of infections caused by strains of gram-positive aerobic microorganisms sensitive to lincomycin, such as streptococci, pneumococci, and staphylococci, or by anaerobic bacteria sensitive to the drug:

1. Infections of the upper respiratory tract: chronic sinusitis caused by anaerobic strains. Lincomycin may be used to treat selected cases of suppurative otitis media or as an adjunctive therapy together with an antibiotic effective against aerobic gram-negative pathogens. Infections caused by H. influenzae are not an indication for the use of this drug (see section "Pharmacodynamics").
2. Infections of the lower respiratory tract, including infectious exacerbations of chronic bronchitis and infectious pneumonia.
3. Skin and soft tissue infections caused by susceptible microorganisms, in cases where penicillin-group antibiotics are not indicated.
4. Bone and joint infections, including osteomyelitis and septic arthritis.
5. Septicemia and endocarditis. In individual cases of septicemia and/or endocarditis due to pathogens sensitive to lincomycin, a pronounced response to lincomycin therapy has been observed. However, bactericidal agents are preferred for the treatment of such infections.

Contraindications.

Hypersensitivity to the active substance or to any other component of the drug, or to clindamycin. Meningitis.

Interaction with other medicinal products and other forms of interactions.

Possible potentiation of the effect of drugs belonging to the class of neuromuscular blocking agents (see section "Special precautions for use").

Concomitant oral administration of kaolin-pectin mixtures delays absorption of lincomycin by 90%. Therefore, to avoid such interaction, these mixtures should be taken at least 2 hours before or 3–4 hours after administration of lincomycin.

In vitro, antagonistic interactions between lincomycin and erythromycin, as well as macrolide compounds with chemical structures related to erythromycin, have been observed. Because of the potential clinical significance of this interaction, these two medicinal products should not be prescribed simultaneously.

Lincomycin may affect the results of blood alkaline phosphatase level determination. As a result, laboratory tests may show falsely elevated enzyme levels.

Cases of cross-resistance between lincomycin and clindamycin have been reported.

Special precautions.

Microbiological studies should be conducted to identify causative pathogens and their sensitivity to lincomycin.

The efficacy of lincomycin has been demonstrated in the treatment of staphylococcal infections resistant to other antibiotics but sensitive to lincomycin. However, lincomycin-resistant strains of staphylococci have been identified; therefore, during therapy with Lincomycin, bacterial cultures and sensitivity testing of pathogens should be performed. When macrolides are used, partial but not complete cross-resistance may occur. If clinically indicated, the drug may be used concomitantly with other antibacterial agents.

To reduce the rate of emergence of drug-resistant bacteria and preserve the effectiveness of lincomycin and other antibacterial agents, Lincomycin should be used only for the treatment or prevention of infections that are proven or highly likely to be caused by susceptible bacteria. When results of bacterial cultures and sensitivity testing are available, they should be taken into account when selecting or modifying antibacterial therapy. In the absence of such data, empirical choice of therapy may be influenced by local epidemiological data and regional patterns of susceptibility.

Lincomycin is not indicated for the treatment of minor bacterial infections or viral infections. Prescribing Lincomycin in the absence of confirmed or highly suspected bacterial infection is unlikely to benefit the patient and increases the risk of developing drug-resistant bacteria.

Due to the risk of pseudomembranous colitis, before deciding on the use of lincomycin, the physician should evaluate the nature of the infection and consider the appropriateness of less toxic alternative agents (e.g., erythromycin).

Diarrhea associated with Clostridium difficile has been reported with the use of nearly all antibacterial agents, including lincomycin.

The severity of symptoms may range from mild diarrhea to fatal colitis. Antibacterial agents alter the normal gut flora, leading to overgrowth of C. difficile, which produces toxins A and B. C. difficile-associated diarrhea may present as mild watery diarrhea but can progress to severe persistent diarrhea, leukocytosis, fever, intense abdominal cramps, mucus, or blood in the stool.

In cases of mild pseudomembranous colitis, discontinuation of the drug is usually sufficient. For moderate to severe cases, treatment should include fluid and electrolyte replacement, protein supplementation, and administration of antibacterial agents effective against C. difficile in colitis.

Treatment should be initiated immediately upon diagnosis of pseudomembranous colitis. Diagnosis is usually based on clinical symptoms, but endoscopic findings or detection of C. difficile and its toxins in the patient's stool may also be used to confirm the diagnosis.

Without treatment, patients may develop potentially fatal complications such as peritonitis, shock, or toxic megacolon.

C. difficile-associated diarrhea occurs more frequently and tends to be more severe in debilitated patients and elderly individuals. Increased morbidity and mortality may also be associated with C. difficile strains capable of producing higher levels of toxins.

C. difficile-associated diarrhea should be considered in patients who develop diarrhea following antibiotic use. A careful medical history should be obtained, as onset of C. difficile-associated diarrhea has been reported even up to 2 months after completion of antibacterial therapy.

Lincomycin should be administered with caution in patients with a history of gastrointestinal disorders, particularly colitis.

Lincomycin should not be used to treat meningitis, as drug levels in cerebrospinal fluid are insufficient.

During prolonged treatment, liver and kidney function and blood parameters should be monitored regularly.

Use of lincomycin may lead to overgrowth of nonsusceptible organisms, including fungal organisms such as yeasts. If superinfection occurs, appropriate measures should be taken according to the clinical situation. If patients with pre-existing fungal infections require treatment with Lincomycin, concomitant antifungal therapy should be administered.

Lincomycin should be used with caution in patients with a history of bronchial asthma or severe allergies.

Surgical procedures, when indicated, should be performed in conjunction with antibiotic therapy.

Lincomycin has been shown to block neuromuscular transmission of impulses and thus may potentiate the effects of other neuromuscular blocking agents. Therefore, lincomycin should be used with caution in patients receiving such drugs.

Lincomycin should be used with caution in patients with atopy.

Lincomycin should be used with caution in patients with severe renal and/or hepatic impairment associated with severe metabolic disturbances. Dosage adjustments should be made for such patients (see section "Dosage and administration"). When high doses are used in these patients, serum lincomycin levels should be monitored, as the elimination half-life of the drug may be prolonged by 2–3 times in these patient groups.

Use during pregnancy or breastfeeding.

Lincomycin can cross the placental barrier in humans. Cord serum concentrations reach approximately 25% of maternal serum concentrations. Significant accumulation of the drug in amniotic fluid does not occur. Controlled studies on the use of lincomycin in pregnant women have not been conducted. In 302 children born to women who received lincomycin treatment at various stages of pregnancy, no increase in the frequency of congenital anomalies or growth retardation was observed compared to the control group during the first 7 years of life.

Lincomycin should not be used during pregnancy unless clearly needed. Lincomycin has been detected in human breast milk at concentrations ranging from 0.5 to 2.4 mcg/mL. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the therapy for the mother.

Ability to affect reaction speed when driving or operating machinery.

No significant effect on reaction speed during driving or operating machinery has been reported; however, isolated cases of dizziness have been observed.

Dosage and Administration.

Dosage and route of administration should be determined based on the severity of infection, patient's condition, and bacterial pathogen sensitivity. The duration of treatment is determined individually by a physician.

The drug should preferably be taken 1–2 hours before or 1–2 hours after meals. Hard capsules must be taken with sufficient amount of water.

Adults

500 mg 3–4 times daily.

Children (aged 6 years and older)

30–60 mg/kg/day, divided into 3–4 equal doses.

Patients with impaired renal and/or hepatic function

If lincomycin must be used in patients with severe renal and/or hepatic impairment, the appropriate dose is 25–30% of the dose recommended for patients with normal renal/liver function.

Children.

This medicinal product (capsules) is not recommended for children under 6 years of age.

Overdose.

In case of overdose, gastrointestinal disturbances may occur, including abdominal pain, nausea, vomiting, and diarrhea.

To treat overdose, vomiting should be induced or, if indicated, gastric lavage should be performed. There is no known specific antidote.

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

Adverse Reactions

Gastrointestinal system: abdominal pain, nausea, vomiting, and antibiotic-associated diarrhea (see section "Special precautions for use"), esophagitis, glossitis, stomatitis, anal pruritus. Nearly all antibiotics, including penicillins, cephalosporins, and lincosamides, may cause severe diarrhea (sometimes preceded by a latent period), colitis, including pseudomembranous colitis, due to toxins produced by C. difficile. If diarrhea develops during treatment, the drug should be discontinued gradually. Colitis may also develop 2–3 weeks after completion of therapy. Avoid using drugs that suppress intestinal peristalsis.

Hematological system: cases of neutropenia, leukopenia, agranulocytosis, and thrombocytopenic purpura have been reported. Rare cases of aplastic anemia and pancytopenia have also been described, in which a causal role of lincomycin cannot be excluded.

Immune system: hypersensitivity reactions, including angioneurotic edema, serum sickness, anaphylaxis; some of these reactions were observed in patients with hypersensitivity to penicillin. Rare cases of erythema multiforme, sometimes resembling Stevens–Johnson syndrome, have been associated with the use of lincomycin.

Severe anaphylactoid reactions require immediate intensive treatment with epinephrine, oxygen therapy, and intravenous administration of corticosteroids. If indicated, airway patency should also be restored, including by intubation if necessary.

Skin and mucous membranes: pruritus, skin rashes, urticaria, vaginitis, and rare cases of exfoliative and vesiculobullous dermatitis have been reported.

Liver: jaundice and changes in liver function tests (including elevated serum transaminase levels) have been observed during lincomycin therapy.

Kidneys: although a direct link between lincomycin and kidney damage has not been established, renal function impairment has been observed in individual cases, as indicated by azotemia, oliguria, and/or proteinuria.

Ear and vestibular system: tinnitus and vertigo have been reported in individual cases.

Use of lincomycin may lead to overgrowth of non-susceptible organisms, including yeast fungi.

Shelf life. 4 years.

Storage conditions. In the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 capsules per blister, 3 blisters per carton.

Prescription status. Prescription only.

Manufacturer/Applicant. JSC "Kyivmedpreparat".

Address of manufacturer and location of its business activity / address of applicant and/or applicant's representative. 139 Saksaganskogo Street, Kyiv, 01032, Ukraine.