Loraxim

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LORAXIM (Loraxime®)

Composition:

Active substance: cefotaxime;

Each vial contains sodium cefotaxime equivalent to cefotaxime 500 mg or 1000 mg.

Dosage form. Powder for solution for injection.

Main physicochemical properties: crystalline powder, from almost white to light yellow.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Other β-lactam antibiotics. Third-generation cephalosporins. Cefotaxime.

ATC code J01D D01.

Pharmacological Properties

Pharmacodynamics

Cefotaxime is a semi-synthetic third-generation cephalosporin antibiotic intended for parenteral administration. It exerts a bactericidal effect and has a broad spectrum of activity.

Sensitive to the drug are: Streptococcus (except group D), including Streptococcus pneumoniae; Staphylococcus aureus, including penicillinase-producing and non-producing strains; Bacillus subtilis and mycoides; Neisseria gonorrhoeae (penicillinase-producing and non-producing strains); Neisseria meningitidis; other Neisseria species; Escherichia coli; Klebsiella spp., including Klebsiella pneumoniae; Enterobacter spp. (some strains are resistant); Serratia spp.; Proteus (indole-positive and indole-negative species); Salmonella; Citrobacter spp.; Providencia; Shigella; Yersinia; Haemophilus influenzae and parainfluenzae (penicillinase-producing and non-producing strains, including ampicillin-resistant strains); Bordetella pertussis; Moraxella; Aeromonas hydrophila; Veillonella; Clostridium perfringens; Eubacterium; Propionibacterium; Fusobacterium; Bacteroides spp.; and Morganella.

Variable sensitivity to the drug is observed in: Pseudomonas aeruginosa; Acinetobacter; Helicobacter pylori; Bacteroides fragilis; and Clostridium difficile.

Resistant to the drug are: Streptococcus group D, Listeria, and methicillin-resistant staphylococci.

Pharmacokinetics

Absorption. Five minutes after a single intravenous administration of 1 g of cefotaxime, its serum concentration reaches 100 µg/mL. After intramuscular administration of the same dose, maximum blood concentration is achieved within 0.5 hours and amounts to 24 µg/mL. Bactericidal plasma concentration persists for up to 12 hours.

Distribution. Plasma protein binding averages 25–40%. Cefotaxime penetrates well into tissues and biological fluids of the body. It reaches effective concentrations in pleural, peritoneal, and synovial fluids. It crosses the blood-brain barrier and undergoes biotransformation to form an active metabolite.

Elimination. Approximately 60–70% of the administered dose is excreted unchanged in urine, and the remainder is excreted as metabolites. A portion is also excreted in bile. The elimination half-life is about 1 hour after intravenous administration and 1–1.5 hours after intramuscular administration. In patients with renal impairment and in elderly patients, the elimination half-life increases approximately twofold. In newborns, the half-life ranges from 0.75 to 1.5 hours, and in premature infants, from 1.4 to 6.4 hours.

Clinical characteristics.

Indications.

Infections caused by microorganisms sensitive to the drug:

• infections of the ear, nose, and throat organs (angina, otitis);
• respiratory tract infections (bronchitis, pneumonia, pleuritis, abscess);
• urinary tract infections;
• septicemia, bacteremia;
• intra-abdominal infections (including peritonitis);
• skin and soft tissue infections;
• bone and joint infections;
• meningitis (except listerial) and other central nervous system infections.

Prophylaxis of infections following gastrointestinal tract surgery, urological, and obstetric-gynecological operations.

Contraindications.

Hypersensitivity to cephalosporin antibiotics and other β-lactam antibiotics, hypersensitivity to lidocaine (for intramuscular administration); bleeding, enterocolitis in medical history (especially ulcerative colitis).

AV block without an implanted cardiac pacemaker, severe heart failure.

Interaction with other medicinal products and other types of interactions.

When used concomitantly with nephrotoxic agents (e.g., aminoglycosides) and potent diuretics (e.g., ethacrynic acid, furosemide), colistin, polymyxin, the risk of developing renal failure increases.

During treatment with cefotaxime, the effectiveness of oral contraceptives may be reduced; therefore, additional contraceptive measures should be used during this period. Cefotaxime should not be used together with bacteriostatic antibiotics (e.g., tetracyclines, erythromycin, chloramphenicol) due to the possibility of an antagonistic effect.

For combination therapy, cefotaxime solutions should not be mixed with aminoglycoside solutions; they must be administered separately.

Concomitant use of nifedipine increases cefotaxime bioavailability by 70%.

Probenecid blocks tubular secretion of cefotaxime and prolongs its elimination half-life.

Cefotaxime should not be used together with lidocaine:

• for intravenous administration;
• in children under 30 months of age;
• in patients with a history of hypersensitivity to lidocaine;
• in patients with heart block.

Special precautions.

The drug should be administered with caution in patients with renal or hepatic impairment and in those with a history of hypersensitivity to penicillins. In patients with renal dysfunction, the dose should be reduced according to the severity of renal insufficiency and pathogen sensitivity. During prolonged administration, renal function should be monitored and dysbiosis prevented. It is advisable to regularly monitor peripheral blood cell counts and liver function. A false-positive Coombs test may occur during treatment.

Anaphylactic reactions. Administration of cephalosporins requires careful assessment of allergic history (atopic diathesis, hypersensitivity reactions to β-lactam antibiotics). If a hypersensitivity reaction occurs, treatment should be discontinued. Cefotaxime is strictly contraindicated in patients with a history of immediate-type hypersensitivity reactions to cephalosporins. In case of any doubts, a physician must be present during the first dose administration due to the risk of anaphylactic reactions. Cross-allergenicity between cephalosporins and penicillins is well documented and occurs in 5–10% of cases. Cefotaxime should be used with extreme caution in patients with a history of penicillin allergy.

Pseudomembranous colitis. Pseudomembranous colitis, characterized by severe and persistent diarrhea, may develop within the first weeks of treatment. Diagnosis is confirmed by colonoscopy and/or histological examination. These complications are considered serious: the drug should be discontinued immediately and appropriate therapy initiated, including oral vancomycin or metronidazole. Concomitant use of cefotaxime with nephrotoxic drugs requires monitoring of renal function; treatment lasting more than 10 days requires blood count monitoring. Elderly and debilitated patients should receive vitamin K (to prevent hypocoagulation).

As with other broad-spectrum antibiotics, prolonged use may lead to overgrowth of resistant microorganisms, necessitating discontinuation of therapy. If superinfection occurs during treatment, appropriate antimicrobial therapy should be initiated. False-positive results in urine glucose testing by the reduction method may occur. To avoid this, an enzymatic test should be used.

Alcohol consumption is contraindicated during treatment due to possible disulfiram-like effects (facial flushing, epigastric and abdominal cramps, nausea, vomiting, headache, hypotension, tachycardia, dyspnea).

1 g of the powder for injection contains 2.2 mmol (50.5 mg) of sodium. The total sodium content at the maximum daily dose exceeds 8.7 mmol (200 mg). This should be taken into account in patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

The use of the drug during pregnancy is contraindicated.

Breastfeeding should be discontinued for the duration of treatment.

Ability to affect reaction speed when driving or operating machinery.

Due to the possibility of adverse reactions affecting the nervous system, driving or operating machinery should be avoided during treatment.

Administration and Dosage

The drug is intended for intravenous (bolus and infusion) and intramuscular administration.

For intravenous bolus injection, dissolve 1 g of powder in 8 mL of sterile water for injection. Administer slowly over 3–5 minutes.

For intravenous infusion, dissolve 1 g of powder in 50 mL of 0.9% sodium chloride solution or 5% glucose solution. The infusion should last 50–60 minutes.

For intramuscular injection, dissolve 1 g of powder in 4 mL of sterile water for injection or 1% lidocaine solution and inject deeply into the gluteal muscle.

The duration of treatment is determined individually by the physician.

For adults and children with body weight ≥50 kg, administer cefotaxime at a dose of 1 g every 12 hours. In severe cases, administer the drug at a dose of 1 g 3–4 times daily. The maximum daily dose is 12 g.

For uncomplicated infections, as well as urinary tract infections, administer intramuscularly or intravenously at a dose of 1 g every 12 hours.

For uncomplicated acute gonorrhea, administer 1 g intramuscularly once daily or intravenously.

For moderate infections, administer the drug at a dose of 1–2 g every 12 hours.

For severe infections (e.g., meningitis), administer 2 g intravenously every 6–8 hours.

For children with body weight <50 kg, the recommended dose is 50–100 mg/kg/day, divided into 3–4 intramuscular or intravenous doses. In severe infections (including meningitis), increase the daily dose to 100–200 mg/kg and administer 4–6 times daily intravenously or intramuscularly.

For premature infants and children under 1 week of age, the daily dose is 50 mg/kg, divided into 2 equal doses, administered intravenously.

For children aged 1–4 weeks, the daily dose is 50–100 mg/kg, divided into 3 equal doses, administered intravenously.

For prophylaxis of infections before surgical procedures, administer a single dose of 1 g of cefotaxime at the time of anesthesia induction. If necessary, repeat the dose after 6–12 hours.

In patients with impaired renal function, the dose should be reduced. When creatinine clearance is ≤10 mL/min, the daily dose should be halved.

Children.

Cefotaxime should not be administered intramuscularly in children under 2.5 years of age.

Overdose.

Symptoms: Possible fever, leukopenia, thrombocytopenia, acute hemolytic anemia, skin, gastrointestinal and hepatic reactions, dyspnea, renal failure, stomatitis, anorexia, temporary hearing loss, disorientation, encephalopathy (especially in patients with renal failure). In isolated cases, seizures and exacerbation of adverse effects may occur.

Treatment. There is no specific antidote. Serum cefotaxime levels can be reduced by hemodialysis or peritoneal dialysis. Symptomatic therapy should be administered as needed.

In case of anaphylactic shock, appropriate emergency measures should be initiated immediately. If signs of hypersensitivity reaction occur (skin rash, urticaria, headache, nausea, loss of consciousness), administration of cefotaxime should be discontinued. In case of severe hypersensitivity or anaphylactic reaction, appropriate therapy should be initiated (administration of epinephrine and/or glucocorticoids). Additional measures may be required depending on the clinical condition, such as artificial ventilation, administration of histamine receptor antagonists. In case of circulatory failure, resuscitation measures should be implemented.

Adverse reactions.

Gastrointestinal system: nausea, vomiting, diarrhea, flatulence, abdominal pain, dysbiosis; rarely – stomatitis, glossitis, pseudomembranous colitis.

Allergic reactions: hyperemia, rash, skin itching, urticaria, bronchospasm, erythema multiforme exudativum, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exanthema, anaphylactic reactions, angioneurotic edema; rarely – anaphylactic shock.

Hepatobiliary system: hepatitis, acute liver failure, impaired liver function, jaundice, cholestasis.

Biochemical parameters: increased levels of liver transaminases, lactate dehydrogenase, alkaline phosphatase, and bilirubin; increased concentrations of blood urea nitrogen and creatinine; positive Coombs test.

Peripheral blood: granulocytopenia, neutropenia, transient leukopenia, thrombocytopenia, agranulocytosis, anisocytosis, eosinophilia, hypoprothrombinemia, hemolytic anemia, hypocoagulation.

Central nervous system: headache, dizziness, seizures, reversible encephalopathy, increased fatigue, weakness.

Local reactions at the injection site: pain and infiltration at the site of intramuscular injection, pain along the vein, tissue inflammation, phlebitis.

Effects due to biological activity: possible development of superinfection (including candidiasis, vaginitis).

Other: hemorrhages and bleeding, autoimmune hemolytic anemia, interstitial nephritis, arrhythmia (with rapid intravenous bolus administration).

When treating infections caused by spirochetes, a Jarisch-Herxheimer-like reaction may occur, which can lead to fever, chills, headache, and joint pain.

Shelf life. 3 years.

Storage conditions. Store at a temperature not exceeding 30 °C in the original packaging. Keep out of reach of children.

Incompatibility.

The solution of this drug is incompatible with solutions of aminoglycosides in the same syringe or infusion. Use only the diluents specified in the section "Administration and dosage."

Packaging. 1 vial per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Exir Pharmaceutical Company, Iran.

Exir Pharmaceutical Company, Iran.

Manufacturer's address and location of business activity.

2nd km Ring Road, Boroujerd 69189, Iran.

2nd km Ring Road, Boroujerd 69189, Iran.