Clindamycin J (Solution) Instructions for Use

Marketing Authorization Holder

Jodas Expoim, LLC (Russia)

Manufactured By

Jodas Expoim, Pvt. Ltd. (India)

ATC Code

J01FF01 (Clindamycin)

Active Substance

Clindamycin (Rec.INN registered by WHO)

Dosage Form

Clindamycin J

Solution for intravenous and intramuscular administration 150 mg/1 ml: amp. 2 ml or 4 ml 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular administration transparent, colorless or with a slight yellowish tint.

Excipients: benzyl alcohol – 9 mg, disodium edetate – 0.5 mg, water for injections – up to 1 ml.

2 ml – vials (5) – cardboard packs.
4 ml – vials (5) – cardboard packs.
2 ml – glass vials (5) – plastic trays (1) – cardboard packs.
4 ml – glass vials (5) – plastic trays (1) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic of the lincosamide group

Pharmacotherapeutic Group

Antibiotic-lincosamide

Pharmacological Action

An antibiotic of the lincosamide group. It binds to the 50S ribosomal subunit and inhibits protein synthesis in bacterial cells by disrupting the protein chain elongation process. Clindamycin is capable of inhibiting the aminoacyl-tRNA binding process and the translocation reaction that occurs after the attachment of an amino acid molecule to the ribosome. Depending on the sensitivity of the microorganism and the concentration of the drug, Clindamycin can act bacteriostatically (predominantly) or bactericidally (in high concentrations).

Clindamycin is active against aerobic gram-positive bacteria – Staphylococcus aureus (methicillin-susceptible isolates), coagulase-negative staphylococci (methicillin-susceptible isolates), Streptococcus pneumoniae (penicillin-susceptible isolates); β-hemolytic streptococci group A, B, C, G; Streptococcus viridans, Corynebacterium spp.; aerobic gram-negative bacteria – Chlamydia trachomatis; anaerobic gram-positive microorganisms – Actinomyces spp., Clostridium spp. (except Clostridium difficile), Eggerthella (Eubacterium) spp., Peptococcus spp., Peptostreptococcus spp. (Finegoldia magna, Micromonas micros), Propionibacterium acnes; anaerobic gram-negative microorganisms – Bacteroides spp., Fusobacterium spp., Gardnerella vaginalis, Prevotella spp.; fungi – Pneumocystis jirovecii; protozoa – Toxoplasma gondii, Plasmodium falciparum.

The following microorganisms are usually resistant to clindamycin: Enterococcus spp., Listeria monocytogenes, Escherichia coli, Klebsiella spp., methicillin-resistant strains of Staphylococcus aureus, most gram-negative aerobic bacteria (including Enterobacteriaceae spp.), Neisseria gonorrhoeae, Neisseria meningitidis, Pseudomonas aeruginosa, Clostridium difficile, Haemophilus influenzae, Mycoplasma pneumoniae, Ureaplasma urealyticum, as well as fungi (including yeasts) and viruses.

Pharmacokinetics

After intramuscular administration at a dose of 600 mg, the C_max in plasma averages 9 µg/ml and is reached within 1-3 hours; after intravenous infusion at a dose of 300 mg over 10 minutes or 600 mg over 20 minutes, the C_max is 7 µg/ml and 10 µg/ml, respectively, reached by the end of clindamycin administration. Serum concentrations of clindamycin exceed the MIC for most susceptible microorganisms for at least 6 hours after administration at recommended doses.

40-90% of the administered clindamycin binds to plasma proteins in the body. Clindamycin easily penetrates into most body tissues and fluids, does not penetrate the intact blood-brain barrier (with inflammation of the meninges, permeability increases slightly). The concentration of clindamycin in bone tissue reaches approximately 40% (20-75%) of its concentration in blood serum. In breast milk, the concentration of clindamycin is 50-100% of its concentration in blood serum, in synovial fluid – 50%, in sputum – 30-75%, in peritoneal fluid – 50%, in fetal blood – 40%, in pus – 30%, in pleural fluid – 50-90% of the concentration in blood serum.

It is almost completely metabolized in the liver to form N-demethyl and sulfoxide active metabolites. T_1/2 in adults averages about 2.4 hours. About 10% of clindamycin is excreted unchanged by the kidneys, 3.6% by the intestines. The remaining amount is excreted as inactive metabolites, mainly with bile and feces. Clindamycin is not removed by hemodialysis and peritoneal dialysis.

In severe hepatic or renal insufficiency, T_1/2 is prolonged to 3-5 hours.

Indications

Severe infectious and inflammatory diseases caused by microorganisms sensitive to clindamycin: infections of the upper respiratory tract and ENT organs, including chronic sinusitis caused by anaerobic bacteria, otitis media (provided that antibacterial drugs active against aerobic gram-negative microorganisms are used simultaneously), recurrent pharyngotonsillitis; lower respiratory tract infections, including pneumonia, bronchitis, lung abscess, pleural empyema; scarlet fever; inflammatory diseases of the pelvic organs (endometritis, salpingitis, abscesses of the fallopian tubes and ovaries) and pelvic peritonitis (provided that antibacterial drugs active against aerobic gram-negative microorganisms are used simultaneously); skin and soft tissue infections, including infected wounds, abscesses, furunculosis, cellulitis (phlegmon), impetigo, acne, erysipelas; intra-abdominal infections, including peritonitis, abdominal abscesses (provided that antibacterial drugs active against aerobic gram-negative microorganisms are used simultaneously); oral cavity infections, including periodontal abscess and periodontitis; infectious diseases of bones and joints, including osteomyelitis and septic arthritis; septicemia; bacterial endocarditis; toxoplasmic encephalitis in patients with AIDS (in combination with pyrimethamine) in case of intolerance to standard therapy; pneumonia caused by Pneumocystis jirovecii in patients with AIDS (in combination with primaquine) in case of intolerance or resistance to standard therapy; malaria caused by Plasmodium falciparum, including with multidrug resistance (in combination with quinine).

The sensitivity of antibiotics in vitro varies by geographic region and over time, so local resistance information should be considered when choosing antibacterial therapy.

ICD codes

Dosage Regimen

Intravenous drip, intramuscular.

The recommended dose (provided that antibacterial drugs active against aerobic gram-negative microorganisms are used simultaneously): 2400-2700 mg/day, divided into 2, 3, or 4 equal doses. For infections caused by more therapy-sensitive pathogens: 1200-1800 mg/day, divided into 3 or 4 equal doses. The maximum daily dose is 4800 mg. In children aged 3 to 18 years, the dose is 20-40 mg/kg/day, divided into 3 or 4 equal doses.

Adverse Reactions

Infections and parasitic diseases common – pseudomembranous colitis; frequency unknown – vaginal infections.

From the hematopoietic system common – eosinophilia; frequency unknown – leukopenia, neutropenia, agranulocytosis, thrombocytopenia.

From the immune system very rare – anaphylactic shock; frequency unknown – anaphylactoid reactions, anaphylactic reaction, hypersensitivity reactions.

From the nervous system uncommon – taste perversion.

From the cardiovascular system common – thrombophlebitis; uncommon – decreased blood pressure; rare – respiratory and cardiac arrest (with too rapid intravenous administration of clindamycin).

From the digestive system common – abdominal pain, diarrhea, impaired liver function; uncommon – nausea, vomiting; very rare – colitis; frequency unknown – esophageal ulcer, esophagitis, jaundice.

From the skin and subcutaneous tissues common – maculopapular rash; uncommon – urticaria, erythema multiforme, skin itching; frequency unknown – toxic epidermal necrolysis, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), exfoliative and vesiculobullous dermatitis, generalized mild to moderate measles-like rash, acute generalized exanthematous pustulosis.

Other uncommon – with intravenous or intramuscular administration of clindamycin, soreness and abscess formation at the injection site may be observed; frequency unknown – local irritation.

There are reports of the possibility of the following adverse events during the use of clindamycin: impaired neuromuscular transmission, development of superinfection.

Contraindications

Hypersensitivity to clindamycin or lincomycin; children under 3 years of age; simultaneous use with erythromycin or chloramphenicol.

With caution history of gastrointestinal diseases (especially colitis), myasthenia gravis, severe hepatic and/or renal insufficiency, bronchial asthma, simultaneous use with peripheral muscle relaxants.

Use in Pregnancy and Lactation

Clindamycin should not be used in the first trimester of pregnancy; in the second and third trimesters, the drug is used only if the intended benefit to the mother outweighs the potential risk to the fetus.

If it is necessary to prescribe during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Should be prescribed with caution in severe hepatic insufficiency.

Use in Renal Impairment

Should be prescribed with caution in severe renal insufficiency.

Pediatric Use

Contraindicated for use in children under 3 years of age.

Geriatric Use

No dose adjustment is required with normal (for this age) liver and kidney function.

Special Precautions

In case of development of a hypersensitivity reaction or a severe skin reaction, such as drug rash with eosinophilia and systemic symptoms (DRESS syndrome), Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis, treatment with clindamycin should be discontinued and appropriate therapy for these complications should be initiated.

Antibacterial drugs suppress the normal intestinal flora, which can promote the overgrowth of Clostridium difficile, producing toxins A and B, and lead to the development of Clostridium difficile-associated diarrhea. All cases of diarrhea in patients during antibiotic therapy should be considered suspicious for the development of Clostridium difficile-associated diarrhea. A thorough history is necessary in case of development of Clostridium difficile-associated diarrhea within 2 months after the prescription of antibacterial drugs. After diagnosis of pseudomembranous colitis, in mild cases, discontinuation of treatment and the use of ion-exchange resins (cholestyramine, colestipol) is sufficient; in moderate and severe cases, replacement of fluid, electrolyte, and protein losses and the prescription of an antibacterial drug effective against Clostridium difficile are indicated.

Drugs that reduce gastrointestinal motility should not be prescribed simultaneously with clindamycin.

Clindamycin should be used with caution in patients with a history of gastrointestinal diseases, especially colitis. Antibiotic-associated colitis and diarrhea occur more frequently and in a more severe form in debilitated patients and/or elderly patients.

With the use of all antibacterial agents, including Clindamycin, overgrowth of microorganisms not susceptible to this drug, especially yeast-like fungi, is possible. If superinfection develops, appropriate measures should be taken depending on the clinical situation.

Clindamycin should not be prescribed for the treatment of meningitis, as it poorly penetrates the blood-brain barrier.

When using the drug in high doses, monitoring of the plasma concentration of clindamycin is necessary. If treatment is carried out for a prolonged period, regular studies of liver and kidney function should be performed.

In patients with impaired liver and kidney function, no dose adjustment is required, since Clindamycin practically does not accumulate in the body if administered at 8-hour intervals. Patients with severe hepatic and/or renal insufficiency should be prescribed Clindamycin with caution and liver (liver enzymes) and kidney function should be monitored.

Drug Interactions

In vitro antagonism between clindamycin and erythromycin has been established. Since this antagonism may be clinically significant, these drugs should not be taken simultaneously.

With simultaneous use of clindamycin with chloramphenicol, a mutual weakening of the effect is noted due to the fact that chloramphenicol can displace Clindamycin from the bound state or prevent its binding to the 50S subunit of bacterial ribosomes.

It has been established that with intravenous administration, Clindamycin impairs neuromuscular transmission and, consequently, may enhance the effect of other neuromuscular blockers or peripherally acting muscle relaxants. Therefore, Clindamycin should be used with caution in patients receiving drugs from these groups, such as vecuronium bromide, rocuronium bromide, gentamicin, rapacuronium bromide (with magnesium), or pancuronium bromide.

A synergistic effect of other antibiotics when used with clindamycin on neuromuscular blocking agents has been described. In this regard, extreme caution should be exercised when using antibiotics together with muscle relaxants, as their synergistic effect when used together can cause deeper and more prolonged muscle relaxation and may delay recovery.

In patients receiving Clindamycin in combination with vitamin K antagonists (e.g., warfarin, acenocoumarol, and fluindione), an increase in parameters characterizing blood clotting ability (prothrombin time and INR) and/or bleeding was observed. In this regard, patients receiving treatment with vitamin K antagonists should undergo frequent monitoring of coagulation test results.

Clindamycin is pharmaceutically incompatible with ampicillin, phenytoin, barbiturates, aminophylline, calcium gluconate, magnesium sulfate, ceftriaxone, and ciprofloxacin.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.