Claforan, 1 g

Pharmgroup:

Cephalosporin antibiotic.

Pharmic action:

Claforan is a semi-synthetic antibiotic of the group of cephalosporins of generation III for parenteral use. Cefotaxime acts bactericidally. It is also resistant to the action of most B-lactamases.

The following are usually sensitive to the drug: Aeromonas hydrophila; Bacillus subtilis; Bordetella pertussis; Borrelia burgdorferi; Moraxella (Branhamella) catarrhalis; Citrobacter diversus; Clostridium perfringens; Corynebacterium diphtheriae; Escherichia coli; Enterobacter spp. (sensitivity depends on epidemiological data and on the level of resistance in each particular country); Erysipelothrix insidiosa; Eubacterium; Haemophilus penicillin- and nonpenicillin-forming strains, including ampi-R; Klebsiella pneumoniae; Klebsiella oxytoca; Methi-S-Staphylococcus, including penicillin- and nonpenicillin-derived strains; Morganella morganii; Neisseria gonorrhoeae, including penicillin- and nonpenicillin-derived strains; Neisseria meningitidis; Propionibacterium; Proteus mirabilis, vulgaris; Providencia; Streptococcus pneumoniae, Salmonella; Seratia spp. (sensitivity depends on epidemiological data and on the level of resistance in each country); Shigella, Streptococcus spp.; Veillonella; Yersinia (sensitivity depends on epidemiological data and on the level of resistance in each country).

The following are resistant to Claforan drug: Acinetobacter baumannii, Bacteroides fragilis; Clostridium difficile; Enterococcus; Gram-negative anaerobes; Listeria monocytogenes, Methi-R staphylococcus; Pseudomonas aeruginosa, Pseudomonas cepacia; Stenotrophomonas maltophilia.
Pharmacokinetics: In adults – 5 minutes after a single IV administration of 1 g of cefotaxime the concentration in blood plasma is 100 µg/ml. After intravenous administration of cefotaxime in the same dose the maximum concentration in plasma is detected after 0.5 hours and is 20 to 30 mcg/ml.

The T1/2 of Claforan is 1 h when administered intravenously and 1-1.5 h when administered intravenously.

The binding to plasma proteins (predominantly albumins) is on average 25-40%.

About 90% of the administered dose is excreted in the urine: 50% unchanged and about 20% as the metabolite deacetylcephotaxime.

The T1/2 of cefotaxime is increased up to 2.5 h in the elderly (over 80 years).

In adults with impaired renal function, the volume of distribution does not change and the T1/2 does not exceed 2.5 h, even in the last stages of renal failure.

In children, neonates and preterm infants, plasma cefotaxime levels and volume of distribution are similar to those in adults receiving the same dose of the drug in mg/kg. The T1/2 of cefotaxime is 0.75 to 1.5 h.

In neonates and preterm infants, plasma levels of cefotaxime and volume of distribution are similar to those in children. The average T1/2 of cefotaxime is 1.4 to 6.4 h.

Indications

Cefotaxime is for the treatment of infections caused by microorganisms sensitive to the drug.

Active ingredient

Composition

One vial contains 1 g of sterile cefotaxime powder, which corresponds to 1.048 g of cefotaxime sodium salt.

How to take, the dosage

Cefotaxime is given intramuscularly or intravenously (as a slow injection or infusion).

Dosage in adults with normal renal function:

In uncomplicated gonorrhea, the single dose is 0.5-1 g and is given intravenously once.

In uncomplicated infections of moderate severity, cefotaxime is administered in a single dose of 1-2 g w/o or w/o, 8-12 hours later, so the daily dose ranges from 2 g to 6 g.

In severe infections, the single dose is 2 g and is administered by IV after 6-8 hours, so the daily dose varies from 6 to 8 g.

In cases where the infection is caused by insufficiently sensitive strains, an antibiotic sensitivity test is the only means of confirming the efficacy of cefotaxime.

Dosage in adults with impaired renal function:

In cases where creatinine level is less than 10 ml/min, half the single dose is used. The interval of administration remains unchanged (see above).

Accordingly, the daily dose will also be halved. In cases where creatinine clearance cannot be measured, it can be calculated from serum creatinine using the Cockroft formula for adults:

For men:

orClcr (ml/min) = Weight (kg) x (140 – age )

72 x creatinine (mg/%)

Clcr (ml/min) = Weight (kg) x (140 – age)

0.814 x creatinine (mmol/L)

For women:

Clcr (ml/min) = 0.85 x rate in men

For patients on hemodialysis: 1-2 g per day, depending on severity of infection. On the day of dialysis, cefotaxime is administered after dialysis has ended.

In preterm infants (before 1 week of life) the daily dose of the drug is 50-100 mg/kg and is administered by IV at 12-hour intervals.

In preterm children (1-4 weeks of life) the daily dose of the drug is 75-150 mg/kg and is administered by IV at 8-hour intervals.

In children with a body weight of up to 50 kg the daily dose of the drug is 50-100 mg/kg and is administered by IV or IV/m at 6-8 h intervals.

Note: The daily dose should never exceed 2 g. In severe infections such as meningitis, the daily dose may be doubled. I/m injection with 1% lidocaine is strictly contraindicated in children under 2.5 years of age.

In children with a body weight of 50 kg or more the drug is prescribed in the same dose as in adults.

In order to prevent the development of infections before surgery 1 g is usually administered v/m or intravenously with the beginning of anesthesia, with repeated administration 6-12 hours after surgery.

In a cesarean section, 1 g Claforan is administered intravenously at the time of umbilical vein clamping, then 1 g cefotaxime is re-injected intravenously or intravenously 6-12 hours later.

Method and duration of administration: For intravenous injection dissolve cefotaxime with sterile water for injections in an amount of 4 ml for 1 g and 10 ml for 2 g. For intravenous infusion 1 g or 2 g of the drug is dissolved in 40-100 ml of sterile water for injection or infusion solution. Injection of the solution should be carried out slowly over 3-5 minutes due to the possible development of life-threatening arrhythmias when administering cefotaxime through a central venous catheter.

If administered by injection, the contents of the bottle with cefotaxime may be dissolved in water for injection or in 1% lidocaine solution. In the case of lidocaine use it is strictly contraindicated to administer the drug intravenously.

The duration of the treatment course is determined individually.

Note: it is necessary to ensure aseptic conditions during dilution of the vial content and preparation of the solution (especially if the diluted cefotaxime is not administered immediately).

Interaction

Compatibility instructions: cefotaxime should not be mixed with other antibiotics, either in the same syringe or in the same infusion solution. This also applies to aminoglycosides.

The following solutions may be used for infusion (cefotaxime concentration 1 g/250 ml): water for injection, 0.9% sodium chloride solution, 5% dextrose, Ringer’s solution, sodium lactate, as well as: Gemaccel, Jonosteril, Macrodex 6%, Reomacrodex 12%, Tutofusin B.

Probenicide delays excretion and increases plasma concentrations of cephalosporins.

As with other cephalosporins, cefotaxime may potentiate the nephrotoxic effect of drugs with nephrotoxic effects.

A positive Coombs test may occur during therapy with cephalosporins.

The use of glucose oxidase methods of blood sugar determination is recommended because of the development of false-positive results when using nonspecific reagents.

Special Instructions

Anaphylactic reactions:

The administration of cephalosporins requires an allergic history (allergic diathesis, hypersensitivity reactions to β-lactam antibiotics);

If a patient develops a hypersensitivity reaction, treatment must be discontinued;

The use of cefotaxime is strictly contraindicated in patients with a history of immediate-type hypersensitivity reactions to cephalosporins. If there is any doubt, the presence of a physician during the first administration of the drug is mandatory due to a possible anaphylactic reaction.

Cross-allergy between cephalosporins and penicillins is known to occur in 5-10% of cases. In patients with a history of allergy to penicillins the drug is used with extreme caution.

Pseudomembranous colitis.

In the first weeks of treatment, pseudomembranous colitis may occur, manifesting as severe, prolonged diarrhea. The diagnosis is confirmed by colonoscopy and/or histological examination. This complication is considered very serious: the administration of Claforan is stopped immediately and adequate therapy including oral vancomycin or metronidazole is prescribed.

Contraindications

Side effects

Anaphylactic reactions: angioedema, bronchospasm, weakness, rarely – anaphylactic shock.

Skin reactions: rash, redness, urticaria. As in the case of other cephalosporins, the development of complications such as erythema multiforme, Stevens-Johnson syndrome, toxic skin necrosis is very rare.

Gastrointestinal reactions: nausea, vomiting, abdominal pain, diarrhea may occur. As with the prescription of other broad-spectrum antibiotics, 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 (see Special Precautions).

Liver reactions: increase of liver enzymes (ALT, ACT, LDH, gamma GT, ALT) and/or bilirubin.

Reactions in peripheral blood: neutropenia, rarely – agranulocytosis, eosinophilia, thrombocytopenia, single cases of hemolytic anemia.

Reactions of the renal system: worsening of renal function (increased creatinine level), especially in combination with aminoglycosides, very rare cases of interstitial nephritis have been reported.

CNS reactions: encephalopathy (in case of high doses), especially in patients with renal failure.

Cardiovascular reactions: single cases of arrhythmias, following bolus administration via central venous catheter (see “Method and duration of administration”).

Others: fever, inflammation at the injection site, superinfection.

In the treatment of borreliosis: Jarisch-Herxheimer reaction (during the first days of treatment), skin rash, itching, fever, leukopenia, increased liver enzymes, difficulty in breathing and joint discomfort.

In addition to the above, the rate of administration of the drug should be monitored (See “Dosage and administration”) and renal function should be controlled in all cases of combined administration of cefotaxime with aminoglycosides.

In patients requiring sodium restriction, the sodium content of cefotaxime sodium salt (48.2 mg/g) should be taken into account. If the duration of treatment is more than 10 days, the leukocyte count should be monitored and, in case of neutropenia, treatment should be discontinued.

Overdose

There is a risk of reversible encephalopathy when using high doses of β-lactam antibiotics, including cefotaxime. There is no specific antidote.

Pregnancy use

Cefotaxime penetrates into breast milk, therefore breastfeeding should be interrupted if it is necessary to prescribe the drug.

Cefotaxime penetrates through the placental barrier. Studies in animals have shown no teratogenic effect of the drug. However, the safety of cefotaxime use in human pregnancy has not been determined, so the drug should not be used during pregnancy.

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