Loraxone (Powder) Instructions for Use

Marketing Authorization Holder

Exir Pharmaceutical, Co. (Iran)

ATC Code

J01DD04 (Ceftriaxone)

Active Substance

Ceftriaxone (Rec.INN registered by WHO)

Dosage Forms

	Loraxone	Powder for solution for intravenous and intramuscular administration 1 g: vial 1 pc. in a set with solvent or without it, vial 12 pcs.
		Powder for solution for intravenous and intramuscular administration 500 mg: vial 1 pc. in a set with solvent or without it, vial 12 pcs.

Dosage Form, Packaging, and Composition

Powder for solution for intravenous and intramuscular administration crystalline, from white to white with a yellowish tint.

Solvent water for injections – 5 ml.

Vials with a volume of 10 ml (1) in a set with a solvent (amp. 1 pc.) or without it – cardboard packs.
Vials with a volume of 10 ml (12) – cardboard packs.

Powder for solution for intravenous and intramuscular administration crystalline, from white to white with a yellowish tint.

Solvent water for injections – 10 ml.

Vials with a volume of 10 ml (1) in a set with a solvent (amp. 1 pc.) or without it – cardboard packs.
Vials with a volume of 10 ml (12) – cardboard packs.

Clinical-Pharmacological Group

Third generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

Cephalosporin antibiotic of the third generation for parenteral use. It has a bactericidal effect by inhibiting the synthesis of the cell membrane. In vitro, it suppresses the growth of most gram-positive and gram-negative microorganisms. Ceftriaxone is resistant to beta-lactamases (both penicillinases and cephalosporinases) produced by most gram-positive and gram-negative bacteria.

The drug is active against gram-positive microorganisms Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus group A (Streptococcus pyogenes), Streptococcus agalactiae, Streptococcus viridans, Streptococcus bovis; gram-negative microorganisms Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis, Citrobacter spp., Enterobacter spp. (some strains are resistant), Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp. (including Klebsiella pneumoniae), Moraxella spp., Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa (some strains are resistant), Salmonella spp. (including Salmonella typhi), Serratia spp. (including Serratia marcescens), Shigella spp., Vibrio spp. (including Vibrio cholerae), Yersinia spp. (including Yersinia enterocolitica).

Many strains of the listed microorganisms, which persistently multiply in the presence of other antibiotics (for example, penicillins, first-generation cephalosporins and aminoglycosides), are sensitive to ceftriaxone. Treponema pallidum is sensitive to ceftriaxone both in vitro and in animal experiments. According to clinical data, good efficacy of ceftriaxone was noted in primary and secondary syphilis.

The drug is also active against anaerobic microorganisms Bacteroides spp. (including some strains of Bacteroides fragilis), Clostridium spp. (including Clostridium difficile), Fusobacterium spp. (except Fusobacterium mostiferum, Fusobacterium varium), Peptococcus spp., Peptostreptococcus spp.

Some strains of Bacteroides spp. (for example, Bacteroides fragilis) that produce beta-lactamase are resistant to ceftriaxone. To determine the sensitivity of microorganisms, it is necessary to use discs containing Ceftriaxone, since it has been shown that in vitro certain strains of pathogens may be resistant to classical cephalosporins.

The drug is also resistant to Staphylococcus spp. (methicillin-resistant strains); most strains of enterococci (for example, Streptococcus faecalis).

Pharmacokinetics

Absorption

The AUC values after IV and IM administration coincide. This means that the bioavailability of ceftriaxone with IM administration is 100%.

Distribution

When administered parenterally, Ceftriaxone penetrates well into tissues and body fluids.

After IV administration, Ceftriaxone rapidly diffuses into the interstitial fluid, where the bactericidal effect persists for 24 hours.

Ceftriaxone reversibly binds to albumin and this binding is inversely proportional to the concentration: for example, when the drug concentration in blood serum is less than 100 mg/L, the binding of ceftriaxone to proteins is 95%, and at a concentration of 300 mg/L – only 85%. Due to the lower albumin content in the interstitial fluid, the concentration of ceftriaxone in it is higher than in the blood serum.

Elimination

In healthy adult subjects, T_1/2 is about 8 hours.

In adults, 50-60% of ceftriaxone is excreted unchanged in the urine, and 40-50% is also excreted unchanged in the bile. Under the influence of intestinal flora, Ceftriaxone is converted into an inactive metabolite.

In newborns, T_1/2 is up to 8 days, in elderly people over 75 years old, the average T_1/2 is approximately 2 times longer.

In newborns, approximately 70% of the administered dose is excreted by the kidneys.

Pharmacokinetics in special clinical cases

In renal failure or liver pathology in adults, the pharmacokinetics of ceftriaxone hardly changes, T_1/2 increases slightly. If renal function is impaired, excretion with bile increases, and if there is liver pathology, then the excretion of ceftriaxone by the kidneys increases.

In newborns and children with inflammation of the meninges, Ceftriaxone penetrates into the cerebrospinal fluid, and in the case of bacterial meningitis, an average of 17% of the drug concentration in the blood serum diffuses into the cerebrospinal fluid, which is approximately 4 times more than with aseptic meningitis. 24 hours after IV administration of ceftriaxone at a dose of 50-100 mg/kg body weight, the concentration in the cerebrospinal fluid exceeds 1.4 mg/L.

In adult patients with meningitis, 2-25 hours after administration of ceftriaxone at a dose of 50 mg/kg body weight, the concentration of ceftriaxone many times exceeded the MIC required to suppress the pathogens causing meningitis.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug

• Sepsis;
• Meningitis;
• Abdominal infections (peritonitis, inflammatory diseases of the gastrointestinal tract, biliary tract);
• Bone and joint infections;
• Skin infections;
• Kidney and urinary tract infections;
• Respiratory tract infections (including pneumonia);
• ENT infections;
• Genital infections (including gonorrhea);
• Infections in patients with reduced immunity.

Prevention of infections in the postoperative period.

ICD codes

Dosage Regimen

The drug is administered intramuscularly and intravenously.

For adults and children over 12 years of age, the average daily dose is 1-2 g once a day (every 24 hours). In severe cases or in infections caused by moderately sensitive pathogens, the single daily dose may be increased to 4 g.

For newborns when the drug is administered once a day, the following doses are recommended: under 2 weeks of age – 20-50 mg/kg/day (a dose of 50 mg/kg body weight is not recommended to be exceeded due to the immature enzyme system of newborns).

For infants and children under 12 years of age, the daily dose is 20-75 mg/kg; for children weighing 50 kg or more, the drug is prescribed in doses intended for adults. A dose of more than 50 mg/kg body weight should be prescribed as an intravenous infusion for at least 30 minutes.

The duration of therapy depends on the course of the disease.

For bacterial meningitis in children (including newborns), the initial dose is 100 mg/kg body weight once a day, the maximum dose is 4 g/day. Once the pathogenic microorganism has been isolated and its sensitivity determined, the dose must be reduced accordingly. The best results were achieved with the following therapy durations:

For treatment of gonorrhea caused by both penicillinase-producing and non-penicillinase-producing strains, the recommended dose is 250 mg as a single intramuscular injection.

For the purpose of prevention in the pre- and postoperative period before infected or presumably infected surgical interventions, depending on the risk of infection, a single administration of ceftriaxone at a dose of 1-2 g is recommended 30-90 minutes before surgery.

In patients with impaired renal function with a creatinine clearance of more than 10 ml/min, provided liver function is normal, there is no need to reduce the dose of ceftriaxone. In severe renal failure (creatinine clearance less than 10 ml/min), it is necessary that the daily dose of ceftriaxone does not exceed 2 g.

In patients with impaired liver function, provided renal function is preserved, it is also not necessary to reduce the dose of ceftriaxone. In cases of simultaneous presence of severe liver and kidney pathology, the concentration of ceftriaxone in the blood serum must be regularly monitored. In patients on hemodialysis, there is no need to change the dose of the drug after this procedure.

Rules for preparation of solutions and administration of the drug

For intramuscular administration, 1 g of the drug must be diluted in 3.5 ml of 1% lidocaine solution and injected deep into the gluteal muscle; it is recommended to inject no more than 1 g of the drug into one buttock. Lidocaine solution should never be administered intravenously!

For intravenous injection, 1 g of the drug must be diluted in 10 ml of sterile distilled water and administered intravenously slowly over 2-4 minutes.

For intravenous infusion, 2 g of powder must be diluted in approximately 40 ml of a calcium-free solution, for example: in 0.9% sodium chloride solution, in 5% dextrose solution, in 10% dextrose solution, 5% fructose solution.

The duration of intravenous infusion is at least 30 minutes.

Adverse Reactions

From the digestive system nausea, vomiting, diarrhea or constipation, flatulence, abdominal pain, taste disturbance, stomatitis, glossitis, pseudomembranous enterocolitis, impaired liver function (increased activity of hepatic transaminases; rarely – alkaline phosphatase or bilirubin, cholestatic jaundice), dysbacteriosis.

From the hematopoietic system leukopenia, neutropenia, granulocytopenia, lymphopenia, thrombocytosis, thrombocytopenia, hemolytic anemia, hypocoagulation, decreased concentration of plasma coagulation factors (II, VII, IX, X), prolonged prothrombin time.

From the urinary system impaired renal function (azotemia, increased blood urea, hypercreatininemia, glucosuria, cylindruria, hematuria, oliguria, anuria).

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

Allergic reactions urticaria, chills or fever, rash, itching; rarely – bronchospasm, eosinophilia, polymorphic exudative erythema (including Stevens-Johnson syndrome), serum sickness, angioedema, anaphylactic shock.

Other headache, dizziness, nosebleeds, candidiasis, superinfection.

Contraindications

• First trimester of pregnancy;
• Hypersensitivity to cephalosporins and penicillins.

The drug should be prescribed with caution for hyperbilirubinemia in newborns, to premature infants, in renal failure, in hepatic failure, ulcerative colitis, enteritis or colitis associated with the use of antibacterial drugs, in the second and third trimesters of pregnancy, during lactation (breastfeeding).

Use in Pregnancy and Lactation

The drug is contraindicated for use in the first trimester of pregnancy. The drug should be used with caution in the second and third trimesters of pregnancy.

If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

In patients with impaired liver function, provided renal function is preserved, there is no need to reduce the dose of ceftriaxone. In cases of simultaneous presence of severe liver and kidney pathology, the concentration of ceftriaxone in the blood serum must be regularly monitored.

Use in Renal Impairment

In patients with impaired renal function with a creatinine clearance of more than 10 ml/min, provided liver function is normal, there is no need to reduce the dose of ceftriaxone. In severe renal failure (creatinine clearance less than 10 ml/min), it is necessary that the daily dose of ceftriaxone does not exceed 2 g. In cases of simultaneous presence of severe liver and kidney pathology, the concentration of ceftriaxone in the blood serum must be regularly monitored. In patients on hemodialysis, there is no need to change the dose of the drug after this procedure.

Pediatric Use

For adults and children over 12 years of age, the average daily dose is 1-2 g once a day (every 24 hours). In severe cases or for infections caused by moderately sensitive pathogens, the single daily dose may be increased to 4 g.

For newborns when the drug is administered once a day, the following doses are recommended: under 2 weeks of age – 20-50 mg/kg/day (a dose of 50 mg/kg body weight is not recommended to be exceeded due to the immature enzyme system of newborns).

For infants and children under 12 years of age, the daily dose is 20-75 mg/kg; for children with a body weight of 50 kg or more, the drug is prescribed in doses intended for adults. A dose of more than 50 mg/kg body weight should be administered as an intravenous infusion over at least 30 minutes.

In vitro studies have shown that, like other cephalosporin antibiotics, Ceftriaxone is capable of displacing bilirubin bound to serum albumin.

Therefore, in newborns with hyperbilirubinemia and especially in premature newborns, the use of ceftriaxone requires even greater caution.

Special Precautions

In cases of simultaneous severe renal and hepatic impairment, the plasma concentration of the drug should be monitored regularly.

In patients undergoing hemodialysis, the plasma concentration of ceftriaxone should be monitored, as a decrease in its elimination rate is possible in such cases.

During long-term treatment, peripheral blood counts, liver and kidney function parameters should be monitored regularly.

In rare cases, ultrasound of the gallbladder reveals shadows that disappear after discontinuation of the drug (even if this phenomenon is accompanied by pain in the right hypochondrium, continuation of antibiotic prescription and symptomatic treatment are recommended).

During treatment, the consumption of alcohol (ethanol) is contraindicated, as disulfiram-like effects are possible (facial flushing, abdominal spasms, nausea, vomiting, headache, decreased blood pressure, tachycardia, shortness of breath).

Despite a detailed medical history, which is a rule for other cephalosporin antibiotics as well, the possibility of anaphylactic shock cannot be excluded, which requires immediate therapy (first, epinephrine is administered intravenously, then glucocorticosteroids).

Elderly and debilitated patients may require vitamin K administration during treatment.

Use in Pediatrics

In vitro studies have shown that, like other cephalosporin antibiotics, Ceftriaxone is capable of displacing bilirubin bound to serum albumin.

Therefore, in newborns with hyperbilirubinemia and especially in premature newborns, the use of ceftriaxone requires even greater caution.

Overdose

Symptoms: possible intensification of side effects.

Treatment: symptomatic therapy is performed. Excessively high plasma concentrations of ceftriaxone cannot be reduced by hemodialysis or peritoneal dialysis.

Drug Interactions

There is synergism between ceftriaxone and aminoglycosides regarding their effect on many gram-negative bacteria. Although the enhancement of the effect of such combinations cannot be predicted in advance, their joint administration is justified in cases of severe and life-threatening infections (for example, those caused by Pseudomonas aeruginosa).

Ceftriaxone is incompatible with ethanol.

NSAIDs and other platelet aggregation inhibitors increase the likelihood of bleeding.

With simultaneous use with “loop” diuretics and other nephrotoxic drugs, the risk of nephrotoxicity increases.

Pharmaceutical Interaction

Due to physical incompatibility of ceftriaxone and aminoglycosides, they must be administered separately in recommended doses.

It should not be mixed in the same infusion vial or in the same syringe with another antibiotic.

Storage Conditions

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

Shelf Life

The shelf life is 2 years.

Freshly prepared solutions of ceftriaxone are physically and chemically stable for 6 hours at room temperature.

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.