Ortocid (Powder) Instructions for Use

Marketing Authorization Holder

Kraspharma, PJSC (Russia)

ATC Code

J01XA02 (Teicoplanin)

Active Substance

Teicoplanin (Rec.INN registered by WHO)

Dosage Forms

	Ortocid	Powder for preparation of solution for intravenous, intramuscular administration and oral administration 200 mg: vial 1 or 10 pcs. or vial 1 or 5 pcs. in a set with solvent 3 ml or 5 ml amp. 1 or 5 pcs.
		Powder for preparation of solution for intravenous, intramuscular administration and oral administration 400 mg: vial 1 or 10 pcs. or vial 1 or 5 pcs. in a set with solvent 3 ml or 5 ml amp. 1 or 5 pcs.

Dosage Form, Packaging, and Composition

Powder for preparation of solution for intravenous and intramuscular administration and oral administration white with a brownish tint.

Solvent composition: water for injections – 3 ml or 5 ml.

200 mg – vials of colorless glass (1) – cardboard packs.
200 mg – vials of colorless glass (10) – cardboard boxes.
200 mg – vials of colorless glass (50) – cardboard boxes (for hospitals).
200 mg – vials of colorless glass (1) (1-50 pcs.) – cardboard boxes (for hospitals).
200 mg – vials of colorless glass (1) (in a set with solvent 3 ml amp.) – contour cell packaging (1) – cardboard packs.
200 mg – vials of colorless glass (1) (in a set with solvent 5 ml amp.) – contour cell packaging (1) – cardboard packs.
200 mg – vials of colorless glass (5) (in a set with solvent 3 ml amp. 5 pcs.) – contour cell packaging (1) – cardboard packs.
200 mg – vials of colorless glass (5) (in a set with solvent 5 ml amp. 5 pcs.) – contour cell packaging (1) – cardboard packs.

Powder for preparation of solution for intravenous and intramuscular administration and oral administration white with a brownish tint.

Solvent composition: water for injections – 3 ml or 5 ml.

400 mg – vials of colorless glass (1) – cardboard packs.
400 mg – vials of colorless glass (10) – cardboard boxes.
400 mg – vials of colorless glass (50) – cardboard boxes (for hospitals).
400 mg – vials of colorless glass (1) (1-50 pcs.) – cardboard boxes (for hospitals).
400 mg – vials of colorless glass (1) (in a set with solvent 3 ml amp.) – contour cell packaging (1) – cardboard packs.
400 mg – vials of colorless glass (1) (in a set with solvent 5 ml amp.) – contour cell packaging (1) – cardboard packs.
400 mg – vials of colorless glass (5) (in a set with solvent 3 ml amp. 5 pcs.) – contour cell packaging (1) – cardboard packs.
400 mg – vials of colorless glass (5) (in a set with solvent 5 ml amp. 5 pcs.) – contour cell packaging (1) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic of the glycopeptide group

Pharmacotherapeutic Group

Antibiotic-glycopeptide

Pharmacological Action

An antibiotic of glycopeptide structure. In vitro, it exhibits bactericidal activity against anaerobic and aerobic gram-positive microorganisms. Teicoplanin inhibits the growth of microorganisms sensitive to it by inhibiting the biosynthesis of the microbial cell wall at sites different from those in the microbial cell wall affected by beta-lactam antibiotics.

Active againstStaphylococcus spp. (including strains resistant to methicillin and other beta-lactam antibiotics), Streptococcus spp., Enterococcus spp., Listeria monocytogenes, Micrococcus spp, Corynebacterium spp. of group J/K and gram-positive anaerobes, including Clostridium difficile, Peptococcus spp.

In vitro, synergism was demonstrated regarding the bactericidal action on Staphylococcus aureus when combining teicoplanin with aminoglycosides or imipenem. In vitro, an additive effect and synergism against Staphylococcus aureus was shown by the combination of teicoplanin with rifampicin. Synergism of teicoplanin with ciprofloxacin was observed against Staphylococcus epidermidis.

Cross-resistance with antibiotics of other groups is generally not characteristic; however, Enterococcus spp. exhibits slight cross-resistance to teicoplanin and another glycopeptide – vancomycin.

Pharmacokinetics

After a single intramuscular administration of teicoplanin at a dose of 3-6 mg/kg, the bioavailability is about 90%.

After oral administration, Teicoplanin is not absorbed and, in the absence of gastrointestinal tract lesions, does not enter the systemic circulation; 40% of the orally administered dose is present in feces in a microbiologically active form. The study of the plasma concentration profile of teicoplanin in humans after intravenous administration at a dose of 3-6 mg/kg showed a biphasic distribution of teicoplanin (with a rapid distribution phase with a plasma T_1/2 of about 0.3 h, followed by a slower distribution phase with a plasma T_1/2 of about 3 h), after which a slow elimination of teicoplanin is observed with a terminal T_1/2 of approximately 150 h. Such a long T_1/2 allows the drug to be administered once daily.

With intravenous administration at a dose of 6 mg/kg body weight as a 30-minute infusion 3 times every 12 hours and then once daily (every 24 hours), the minimum plasma concentration of teicoplanin, amounting to 10 mg/l, could theoretically be achieved by day 4. The calculated maximum and minimum plasma concentrations at steady state, amounting to 64 mg/l and 16 mg/l, could be achieved by day 28 of treatment. Teicoplanin rapidly distributes into the skin (subcutaneous adipose tissue) and blister fluid, myocardium, lung tissue and pleural fluid, bone tissue and synovial fluid, but poorly penetrates into the cerebrospinal fluid. Weak affinity binding to plasma proteins is 90-95%. The V_d at steady state after intravenous administration of teicoplanin at a dose of 3-6 mg is 0.94-1.41 l/kg. The V_d in children does not significantly differ from that in adults.

After parenteral administration of teicoplanin, its metabolism is minimal (about 3%). 97% of the administered teicoplanin is excreted from the body unchanged. Approximately 80% of the administered dose is excreted by the kidneys. Renal clearance after intravenous administration of 3-6 mg/kg is 10.4-12.1 mg/h/kg. Total plasma clearance is 11.9-14.7 ml/h/kg.

Indications

Severe infections caused by susceptible gram-positive microorganisms, including in patients with allergies to penicillins and cephalosporins: endocarditis; septicemia; bone and joint infections; lower respiratory tract infections; skin and soft tissue infections; urinary tract infections; peritonitis occurring during continuous ambulatory peritoneal dialysis (CAPD).

Prophylaxis of infectious complications during dental and orthopedic surgeries when there is a risk of developing infections caused by gram-positive microorganisms.

For oral administration of the solution: pseudomembranous colitis caused by Clostridium difficile (associated with the use of antibacterial drugs).

ICD codes

Dosage Regimen

Administer intravenously as a slow bolus injection over 3-5 minutes, as an intravenous infusion over 30 minutes, or intramuscularly. For neonates, administer only as an intravenous infusion.

Reconstitute the 200 mg or 400 mg vial with the entire volume of the provided Water for Injections (3 ml or 5 ml) to form a solution. For intravenous infusion, further dilute the reconstituted solution in 100 ml of a compatible infusion fluid such as 0.9% Sodium Chloride or 5% Glucose.

For systemic Gram-positive infections in adults, administer a loading dose of 400 mg (6 mg/kg) intravenously every 12 hours for the first three doses. Subsequently, administer a maintenance dose of 400 mg (6 mg/kg) intravenously or intramuscularly once daily.

For severe infections like endocarditis or osteomyelitis, use a higher dosing regimen. Administer a loading dose of 12 mg/kg intravenously every 12 hours for three to five doses. Follow with a maintenance dose of 12 mg/kg intravenously or intramuscularly once daily.

For surgical prophylaxis, administer a single 400 mg intravenous dose approximately one hour before the procedure.

For oral administration to treat Clostridium difficile-associated enterocolitis, administer 100-200 mg (the contents of a 200 mg vial dissolved in 10-30 ml of water) orally twice daily for 7-14 days.

Adjust the dosage for patients with renal impairment. For creatinine clearance 30-80 ml/min, administer the standard maintenance dose every 48 hours. For creatinine clearance 10-30 ml/min, administer the standard maintenance dose every 72 hours. For creatinine clearance less than 10 ml/min, administer the standard maintenance dose every one to two weeks, guided by serum concentration monitoring.

For children over 2 months, administer 10 mg/kg every 12 hours for three loading doses, followed by 10 mg/kg once daily. For neonates, administer a single 16 mg/kg loading dose on the first day, followed by 8 mg/kg once daily. Monitor serum concentrations in all pediatric patients, especially neonates.

Determine the exact dose based on the patient’s body weight for all indications and administration routes. Monitor trough serum teicoplanin concentrations; target levels are typically 10-20 mg/L for standard infections and 20-30 mg/L for severe, deep-seated infections like endocarditis.

Adverse Reactions

From the digestive system: nausea, vomiting, diarrhea.

From the hematopoietic system: agranulocytosis, leukopenia, neutropenia, thrombocytopenia, eosinophilia.

From the liver and biliary tract: increased activity of hepatic transaminases and/or alkaline phosphatase in blood serum.

From the urinary system: increased serum creatinine concentrations, renal failure.

From the nervous system: dizziness, headache, seizures with intravenous administration.

From the hearing organ and labyrinthine disorders: hearing loss, tinnitus and vestibular disorders.

Allergic reactions: rash, itching, fever, chills, bronchospasm, anaphylactic reactions, anaphylactic shock, urticaria, angioedema, rare reports of exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome.

Infusion reactions: erythema or “flushing” of the upper body.

Local reactions: erythema, pain at the injection site, thrombophlebitis, abscess at the intramuscular injection site.

Other: superinfection.

Contraindications

Hypersensitivity to teicoplanin.

With caution: patients with hypersensitivity to vancomycin (risk of cross-hypersensitivity); in patients with renal failure (dose regimen adjustment, monitoring of hearing status, hematological parameters, renal and liver function indicators is required); in patients undergoing long-term treatment (monitoring of hearing status, hematological parameters, renal and liver function indicators is required); with concurrent treatment with other ototoxic and nephrotoxic drugs: aminoglycosides, colistin, amphotericin B, cyclosporine, cisplatin, furosemide and ethacrynic acid.

Use in Pregnancy and Lactation

Should not be used during pregnancy or if pregnancy is suspected, except in cases where the potential benefit to the mother outweighs the possible harm to the fetus. Animal studies have not revealed teratogenic effects of teicoplanin.

It is not known whether Teicoplanin is excreted in human breast milk. If use during lactation is necessary, the issue of temporary discontinuation of breastfeeding should be decided.

Special Precautions

There have been reports of toxic effects on the hearing organ, hematological, hepatic and renal toxicity of teicoplanin. Therefore, hearing status, hematological parameters, and functional state of the liver and kidneys should be monitored, especially in patients with renal failure, in patients receiving long-term treatment with teicoplanin, and in patients simultaneously receiving treatment with other ototoxic and nephrotoxic drugs (aminoglycosides, colistin, amphotericin B, cyclosporine, cisplatin, furosemide and ethacrynic acid).

Superinfection: as with other antibiotics, the use of teicoplanin, especially if prolonged, may lead to overgrowth of microorganisms not susceptible to teicoplanin (bacteria or fungi); if superinfection develops during treatment, appropriate measures should be taken.

Effect on ability to drive vehicles and operate machinery

During the treatment period, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, because Teicoplanin may cause dizziness and other side effects that may affect these abilities.

Drug Interactions

When combined with nephrotoxic and ototoxic drugs (streptomycin, neomycin, kanamycin, gentamicin, amikacin, tobramycin, cephaloridine, colistin, amphotericin B, cyclosporine, cisplatin, furosemide, ethacrynic acid), an increased risk of developing side effects is possible with simultaneous or sequential use of teicoplanin.

Teicoplanin is pharmaceutically incompatible with aminoglycosides.

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.