Claforan^® (Powder) Instructions for Use

Marketing Authorization Holder

Amdipharm, Limited (Ireland)

Manufactured By

Pharmfirma Sotex, CJSC (Russia)

Or

Patheon UK, Limited (United Kingdom)

Contact Information

SANOFI

ATC Code

J01DD01 (Cefotaxime)

Active Substance

Cefotaxime (Rec.INN registered by WHO)

Dosage Form

Claforan®

Powder for solution for intravenous and intramuscular administration 1 g: vial. 1 pc.

Dosage Form, Packaging, and Composition

Powder for solution for intravenous and intramuscular administration white or yellowish-white, crystalline.

Colorless glass vials (1) – cardboard packs.

Clinical-Pharmacological Group

Third generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

Semi-synthetic antibiotic of the third generation cephalosporin group for parenteral administration.

It acts bactericidally. It has a broad spectrum of action. It is resistant to the action of most beta-lactamases.

Claforan^®is active against Aeromonas hydrophila, Bacillus subtilis, Bordetella pertussis, Borrelia burgdorferi, Moraxella (Branhamella) catarrhalis, Citrobacter diversus, Clostridium perfringens, Corynebacterium diphtheriae, Escherichia coli, Enterobacter spp. (susceptibility depends on epidemiological data and the level of resistance in each specific country), Erysipelothrix insidiosa, Eubacterium spp., Haemophilus spp. (including strains producing and not producing penicillinase, including ampicillin-resistant), Klebsiella pneumoniae, Klebsiella oxytoca, methicillin-susceptible strains of Staphylococcus spp. (including strains producing and not producing penicillinase), Morganella morganii, Neisseria gonorrhoeae (including strains producing and not producing penicillinase), Neisseria meningitidis, Propionibacterium spp., Proteus mirabilis, Proteus vulgaris, Providencia spp., Streptococcus spp. (including Streptococcus pneumoniae), Salmonella spp., Serratia spp. (susceptibility depends on epidemiological data and the level of resistance in each specific country), Shigella spp., Veillonella spp., Yersinia spp. (susceptibility depends on epidemiological data and the level of resistance in each specific country).

Resistant to the drug are Acinetobacter baumannii, Bacteroides fragilis, Clostridium difficile, Enterococcus spp., Listeria monocytogenes, methicillin-resistant strains of Staphylococcus spp., Pseudomonas aeruginosa, Pseudomonas cepacia, Stenotrophomonas maltophilia, gram-negative anaerobes.

Indications

Treatment of infectious and inflammatory diseases caused by microorganisms susceptible to the drug

• Respiratory tract infections;
• Urinary tract infections;
• Septicemia;
• Bacteremia;
• Endocarditis;
• Intra-abdominal infections (including peritonitis);
• CNS infections (including meningitis, except for listerial);
• Skin and soft tissue infections;
• Bone and joint infections.

Prevention of infectious complications after surgical operations on the gastrointestinal tract, urological and obstetric-gynecological operations.

ICD codes

Dosage Regimen

The drug is administered intramuscularly or intravenously (as a slow injection or infusion).

For adults with normal renal function in uncomplicated gonorrhea Claforan^® is prescribed intramuscularly at a dose of 0.5-1 g as a single dose.

For uncomplicated infections of moderate severity Claforan^® is administered intramuscularly or intravenously in a single dose of 1-2 g at intervals of 8-12 hours; the daily dose is 2-6 g.

For severe infections Claforan^® is administered intravenously in a single dose of 2 g, the interval between administrations is 6-8 hours; the daily dose is 6-8 g.

In cases where the infection is caused by insufficiently susceptible strains, the antibiotic susceptibility test is the only means of confirming the effectiveness of Claforan^®.

For adults with impaired renal function (GFR 10 ml/min and less) the single dose is reduced by half, the interval between administrations is not changed, and the daily dose is also reduced by half.

In cases where GFR cannot be measured, it can be calculated from the serum creatinine level using the Cockcroft formula for adults.

For men

Or

For women GFR (ml/min) = 0.85 × indicator for men.

For patients on hemodialysis, 1-2 g/day is prescribed depending on the severity of the infection. On the day of dialysis, Claforan^® is administered after the end of the procedure.

For prematurely born infants (up to 1 week of life) the daily dose of Claforan^® is 50-100 mg/kg intravenously, divided into 2 administrations at 12-hour intervals. For prematurely born infants (1-4 weeks of life) the daily dose of Claforan^® is 75-150 mg/kg intravenously, divided into 3 administrations at 8-hour intervals.

For children with body weight under 50 kg the daily dose of Claforan^® is 50-100 mg/kg, administered intravenously or intramuscularly at intervals of 6-8 hours. The daily dose should never exceed 2 g. For severe infections, including meningitis, it is possible to double the daily dose.

For children with body weight of 50 kg and more the drug is prescribed in the same dose as for adults.

Intramuscular administration of the drug with 1% lidocaine solution is strictly contraindicated for children under 2.5 years of age.

For the prevention of postoperative infections before surgery during induction anesthesia, the drug is administered intramuscularly or intravenously at a dose of 1 g with repeated administration 6-12 hours after surgery.

During cesarean section at the moment of clamping the umbilical vein, Claforan^® is administered intravenously at a dose of 1 g, then – after 6-12 hours, 1 g of Claforan^® is re-administered intramuscularly or intravenously.

The duration of treatment is set individually.

Rules for preparation of injection solutions

For preparation of solution for intramuscular administration, the powder should be dissolved with sterile water for injections in an amount of 4 ml for 1 g and 10 ml – for 2 g. A 1% lidocaine solution can be used as a solvent for intramuscular administration. When using lidocaine as a solvent, intravenous administration of Claforan^® is strictly contraindicated.

For preparation of solution for intravenous administration 1 g or 2 g of powder is dissolved in 40-100 ml of sterile water for injections or infusion solution. The injection is carried out slowly over 3-5 minutes, due to the possible development of life-threatening arrhythmias, when administering cefotaxime through a central venous catheter. The following solutions can be used for infusions (cefotaxime concentration 1 g/250 ml): water for injections, 0.9% sodium chloride solution, 5% dextrose (glucose) solution, Ringer’s solution, sodium lactate solution, as well as solutions of hemaccel, ionosteril, macrodex 6%, reomacrodex 12%, tutofusin B.

Aseptic conditions must be ensured when dissolving the dry substance for injection and preparing solutions for injection, especially if the diluted drug is not administered immediately.

Adverse Reactions

Allergic reactions angioedema, bronchospasm, rash, skin redness, urticaria; very rarely – anaphylactic shock, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

From the digestive system possible – nausea, vomiting, abdominal pain, increased activity of liver enzymes (ALT, AST, LDH, GGT, ALP) and/or bilirubin, diarrhea (diarrhea may be a symptom of enterocolitis, which in some cases is accompanied by the appearance of blood in the stool. A special form of enterocolitis is pseudomembranous colitis).

From the urinary system deterioration of renal function (increase in creatinine level), especially with combined use with aminoglycosides; very rarely – interstitial nephritis.

From the hematopoietic system neutropenia; rarely – agranulocytosis, eosinophilia, thrombocytopenia; in isolated cases – hemolytic anemia.

From the CNS encephalopathy (when the drug is administered in high doses), especially in patients with renal failure.

From the cardiovascular system in isolated cases – arrhythmias (with bolus administration through a central venous catheter).

Other weakness, fever, superinfection.

Local reactions inflammation at the injection site.

During treatment of borreliosis Jarisch-Herxheimer reaction (during the first days of treatment), skin rash, itching, fever, leukopenia, increased liver enzyme levels, difficulty breathing and joint discomfort.

Contraindications

• Hypersensitivity to cephalosporins.

When using lidocaine as a solvent, the following contraindications should be considered (for intramuscular administration of Claforan^®)

• Intracardiac blocks without an established pacemaker;
• Severe heart failure;
• Intravenous administration;
• Children under 2.5 years of age (for intramuscular administration);
• Hypersensitivity to lidocaine or another amide-type local anesthetic.

Use in Pregnancy and Lactation

The safety of using cefotaxime during human pregnancy has not been studied. Cefotaxime crosses the placental barrier, so the drug should not be prescribed during pregnancy.

Cefotaxime passes into breast milk, so if it is necessary to use Claforan^® during lactation, breastfeeding should be discontinued.

In experimental studies on animals, no teratogenic effect of the drug was detected.

Pediatric Use

For children with body weight of 50 kg and more the drug is prescribed in the same dose as for adults.

Intramuscular administration of the drug with 1% lidocaine solution is strictly contraindicated for children under 2.5 years of age.

Special Precautions

Before prescribing Claforan^®, it is necessary to collect an allergic history, especially regarding indications of allergic diathesis, hypersensitivity reactions to beta-lactam antibiotics. Cross-allergy between penicillins and cephalosporins is known, which occurs in 5-10% of cases. In patients with a history of allergic reactions to penicillin, the drug should be used with extreme caution.

The use of Claforan^® is strictly contraindicated in patients with a history of immediate-type hypersensitivity reactions to cephalosporins. In case of any doubts, the presence of a physician during the first administration of the drug is mandatory due to the possible anaphylactic reaction.

If hypersensitivity reactions occur, the drug should be discontinued.

During the first weeks of treatment, pseudomembranous colitis may occur, manifested by severe, prolonged diarrhea. The diagnosis is confirmed by colonoscopy and/or histological examination. This complication is considered very serious. Claforan^® should be discontinued immediately and adequate therapy should be prescribed (including oral vancomycin or metronidazole).

With simultaneous use of Claforan^® and potentially nephrotoxic drugs (aminoglycoside antibiotics, diuretics), renal function should be monitored (due to the risk of nephrotoxic action).

Patients who require sodium intake restriction should take into account the sodium content in cefotaxime sodium salt (48.2 mg/g).

During treatment, a false-positive Coombs test may appear.

During treatment, it is recommended to use glucose oxidase methods for determining blood glucose levels, due to the development of false-positive results when using non-specific reagents.

The rate of drug administration should be controlled.

Control of laboratory parameters

If the duration of treatment with the drug exceeds 10 days, it is necessary to monitor the peripheral blood picture. In case of neutropenia development, treatment should be discontinued.

Overdose

Symptoms when using beta-lactam antibiotics, including Cefotaxime, in high doses, there is a risk of developing reversible encephalopathy.

Treatment if necessary, symptomatic therapy is carried out. There is no specific antidote.

Drug Interactions

With simultaneous use with Claforan^®, probenecid delays excretion and increases plasma concentrations of cefotaxime.

With simultaneous use, Claforan^® may potentiate the nephrotoxic effect of drugs that have a nephrotoxic effect.

Pharmaceutical interaction

Claforan^® solution is incompatible with solutions of other antibiotics (including aminoglycosides) in the same syringe or infusion solution.

Storage Conditions

The drug should be stored in a light-protected place, out of reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

The solution for intramuscular injections, prepared using water for injections or 0.5% or 1% lidocaine hydrochloride solution, is chemically stable for 8 hours (at room temperature not exceeding 25°C (77°F)) or for 24 hours (when stored in a light-protected place at a temperature from 2°C (35.6°F) to 8°C (46.4°F)).

The solution for injection or infusion prepared using water for injections is chemically stable for 12 hours (at room temperature not exceeding 25°C (77°F)) or for 24 hours (when stored in a light-protected place at a temperature from 2°C (35.6°F) to 8°C (46.4°F)).

A pale yellow tint of the solution does not indicate a reduction in the antibiotic’s activity.

The solution for infusion prepared using infusion solutions is chemically stable for 8 hours after dilution in Haemaccel, Ionosteril, or Tutofusin solutions and for 6 hours after dilution in a 10% dextrose (glucose) solution, Macrodex, or Reomacrodex.

Dispensing Status

The drug is dispensed by prescription.

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.