Euroceftaz

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT EUROCEFTAZ (EUROCEFTAZ)

Composition:

Active substances: ceftazidime, tazobactam;

One vial contains ceftazidime sodium equivalent to anhydrous ceftazidime 1000 mg and tazobactam sodium equivalent to tazobactam 125 mg.

Pharmaceutical form. Powder for injection.

Main physicochemical properties: white or almost white crystalline powder.

Pharmacotherapeutic group. Antibacterial agents for systemic use. Cephalosporins. Ceftazidime, combinations. ATC code J01D D54.

Pharmacological Properties

Pharmacodynamics

Ceftriaxone is a third-generation cephalosporin antibiotic intended for parenteral administration. It exerts a bactericidal effect against many Gram-positive and Gram-negative bacteria.

Ceftriaxone is resistant to the action of beta-lactamases. It is also active against strains resistant to other cephalosporins.

Highly sensitive strains include: Streptococcus viridans, Streptococcus pneumoniae, Staphylococcus aureus, S. epidermidis, Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus ducreyi, Yersinia pestis, Borrelia burgdorferi, Treponema pallidum, Serratia marcescens, Peptostreptococcus spp., Proteus mirabilis, Proteus vulgaris.

Enterobacteriaceae species (Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Morganella morganii, Klebsiella spp., Enterobacter spp., Providencia spp.) are also sensitive to ceftriaxone, except for strains producing beta-lactamases.

Ceftriaxone is not effective against Acinetobacter spp., P. aeruginosa, Campylobacter jejuni, Bacteroides fragilis, Clostridium difficile, Listeria monocytogenes, Enterococcus faecalis, and methicillin-resistant staphylococci.

Mycoplasmas, mycobacteria, and chlamydiae are resistant to cephalosporins.

Tazobactam, a sulfone derivative of triazolylmethylpenicillanic acid, is an inhibitor of many beta-lactamases, including plasmid and chromosomal enzymes that commonly cause resistance to penicillins and cephalosporins, including third-generation cephalosporins. Tazobactam has only minimal antibacterial activity. The presence of tazobactam in the combined preparation Euroceftriaz is designed to enhance and broaden the antimicrobial spectrum of ceftriaxone, including coverage of bacteria producing beta-lactamases that are typically insensitive to ceftriaxone and other beta-lactam antibiotics.

Pharmacokinetics

Ceftriaxone is well absorbed after intramuscular administration and achieves high serum concentrations. The bioavailability of the drug is 100%.

Ceftriaxone rapidly penetrates into tissue fluids and is characterized by a high volume of distribution in most body tissues and fluids. In children with meningitis, ceftriaxone penetrates into the cerebrospinal fluid during inflammation of the meninges, achieving concentrations in cerebrospinal fluid amounting to 17% of plasma concentrations. In adult patients, 2–24 hours after a single 50 mg/kg dose, ceftriaxone concentrations in cerebrospinal fluid exceed the minimum inhibitory concentration for the most common causative agents of meningitis.

Due to its prolonged elimination half-life (averaging 8 hours, and twice as long in patients aged 75 years and older), ceftriaxone concentrations 24 hours after administration remain higher than the minimum inhibitory concentration for most microorganisms causing various infections.

Approximately 50–60% of administered ceftriaxone is excreted unchanged by the kidneys in urine, and the remainder via the liver. Ceftriaxone appears to reduce the elimination rate of tazobactam.

Clinical characteristics.

Indications.

Treatment of infections caused by microorganisms sensitive to the components of the drug:

• respiratory tract infections, especially pneumonia, as well as infections of the ear, nose and throat (ENT) organs;
• intra-abdominal infections (peritonitis, infections of the biliary tract and gastrointestinal tract);
• urinary tract infections;
• genital infections, including gonorrhea;
• sepsis;
• infections of bones, joints, soft tissues, skin, as well as wound infections;
• infections in immunocompromised patients;
• meningitis;
• disseminated Lyme borreliosis (early and late stages of the disease).

Preoperative prophylaxis of infections during surgical procedures on the gastrointestinal tract, biliary tract, urinary tract, and during gynecological procedures, but only in cases of potential or known contamination.

When prescribing Euroceftriaxone, official recommendations on antibiotic therapy must be followed, including recommendations on prevention of antibiotic resistance.

Contraindications.

Hypersensitivity to ceftriaxone or to any other cephalosporin. History of severe hypersensitivity reactions (e.g., anaphylactic reactions) to any other type of beta-lactam antibacterial agents (penicillins, monobactams, and carbapenems).

Ceftriaxone is contraindicated:

in preterm newborns aged ≤ 41 weeks postmenstrual age (gestational age + postnatal age)*;

in full-term newborns (aged ≤ 28 days):

• with hyperbilirubinemia, jaundice, hypoalbuminemia, or acidosis, since in such conditions bilirubin binding is likely impaired*;
• who require (or are expected to require) intravenous administration of calcium-containing drugs or infusions of calcium-containing solutions, due to the risk of precipitation of ceftriaxone calcium salt (see sections "Special precautions" and "Adverse reactions").

* In vitro studies have shown that ceftriaxone may displace bilirubin from its binding to serum albumin, potentially increasing the risk of bilirubin encephalopathy in these patients.

Before intramuscular administration of ceftriaxone, contraindications to lidocaine must be excluded if lidocaine is used as a solvent (see section "Dosage and administration"). Refer to the lidocaine instructions for medical use, especially contraindications.

Solutions of ceftriaxone containing lidocaine must never be administered intravenously.

Interaction with other medicinal products and other forms of interaction.

Under no circumstances should Euroceftriaxone be used with calcium-containing solutions (e.g., Ringer's solution). Calcium-containing solutions should not be administered within 48 hours after the last dose of ceftriaxone.

When high doses of Euroceftriaxone are used concomitantly with potent diuretics such as furosemide, no renal function impairment has been observed. There are no indications that Euroceftriaxone increases the nephrotoxicity of aminoglycosides. No disulfiram-like (antabuse-like) reactions have been observed after alcohol consumption immediately following ceftriaxone administration.

Ceftriaxone contains an N-methylthiotetrazole group, which may cause ethanol intolerance and bleeding, as seen with some other cephalosporins. Probenecid does not affect the excretion of Euroceftriaxone.

An antagonism between chloramphenicol and ceftriaxone has been reported.

Solvents containing calcium, such as Ringer's solution or Hartmann's solution, must not be used to dissolve Euroceftriaxone in vials or to dilute the reconstituted solution for intravenous administration, due to the risk of precipitation of ceftriaxone calcium salts. Precipitation of ceftriaxone calcium salts may also occur when Euroceftriaxone is mixed with calcium-containing solutions in the same intravenous infusion system. Euroceftriaxone must not be administered intravenously simultaneously with calcium-containing solutions, including prolonged infusions containing calcium (e.g., parenteral nutrition), via a Y-site system (see section "Dosage and administration"). However, in patients other than newborns, ceftriaxone and calcium-containing solutions may be administered sequentially, one after another, provided the infusion system is thoroughly flushed with a compatible fluid between infusions. In vitro studies using adult and neonatal cord plasma have shown that newborns are at increased risk of ceftriaxone calcium salt precipitation.

There are conflicting data regarding the potential for increased nephrotoxic effects of aminoglycosides when used concomitantly with cephalosporins. In such cases, clinical practice recommendations for monitoring aminoglycoside levels (and renal function) should be strictly followed.

According to literature data, ceftriaxone is incompatible with amikacin, vancomycin, fluconazole, and aminoglycosides.

Do not use solutions containing bicarbonates.

Bacteriostatic agents may interfere with the bactericidal action of cephalosporins.

Ceftriaxone may reduce the efficacy of hormonal oral contraceptives. Therefore, additional (non-hormonal) contraceptive methods are recommended during treatment and for 1 month after completion of therapy.

There are no reports of interaction between ceftriaxone and orally administered calcium-containing products, or between intramuscular ceftriaxone and calcium-containing products (intravenous or oral).

Ceftriaxone must not be mixed with solutions of other antimicrobial agents.

When cephalosporins and cyclosporine are used concomitantly, plasma levels and toxicity of the latter may increase.

Diclofenac enhances biliary excretion of the drug and reduces total urinary clearance.

Concomitant use of the drug with oral anticoagulants may potentiate the vitamin K antagonist effect and increase the risk of bleeding. Frequent monitoring of the international normalized ratio (INR) is recommended, and the dose of vitamin K antagonist should be appropriately adjusted both during and after ceftriaxone therapy.

Special precautions for use.

As with other cephalosporins, anaphylactic reactions with fatal outcomes have been reported during the use of Euroceftraz, even in patients without prior relevant history. Hypersensitivity reactions may also progress to Kounis syndrome, a serious allergic reaction that may lead to myocardial infarction (see section "Adverse reactions"). If allergic reactions occur, Euroceftraz should be discontinued immediately and appropriate therapy initiated. Ceftriaxone should be administered with caution in patients with hypersensitivity to penicillins due to possible cross-allergenicity.

Cases of severe skin reactions (Stevens-Johnson syndrome or Lyell's syndrome/toxic epidermal necrolysis), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), which may be life-threatening or fatal, have been reported. However, the frequency of these events is unknown (see section "Adverse reactions").

Ceftriaxone may prolong prothrombin time. Therefore, prothrombin time should be monitored in suspected vitamin K deficiency.

Diarrhea associated with Clostridium difficile has been reported during treatment with nearly all antibacterial agents, including ceftriaxone, ranging from mild severity to fatal colitis. Antibacterial agents alter the normal flora of the colon, leading to overgrowth of Clostridium difficile. Clostridium difficile produces toxins A and B, which cause Clostridium difficile-associated diarrhea. Hyperproducing toxin strains of Clostridium difficile are associated with increased morbidity and mortality, as these infections may be resistant to antimicrobial therapy and may require colectomy. Clostridium difficile-associated diarrhea should be considered in all patients receiving antibiotics. A detailed medical history should be obtained, as Clostridium difficile-associated diarrhea may occur up to two months after completion of antibacterial therapy.

If Clostridium difficile-associated diarrhea is suspected or confirmed, antibiotics not active against Clostridium difficile should be discontinued. Appropriate fluid and electrolyte replacement, protein supplementation, antibiotic therapy active against Clostridium difficile, and surgical evaluation should be initiated as clinically indicated.

Prolonged use of Euroceftraz may lead to difficulties in controlling microorganisms resistant to the drug. Therefore, careful monitoring of patients is required. If superinfection occurs, appropriate measures should be taken.

After administration of ceftriaxone, usually at doses exceeding standard recommendations, shadows may be observed on ultrasound examination of the gallbladder, which may be misinterpreted as gallstones. These are precipitates of ceftriaxone calcium salt that disappear after completion or discontinuation of Euroceftraz therapy. Such changes rarely cause any symptoms. However, conservative management is recommended even in such cases. If these phenomena are accompanied by clinical symptoms, the decision to discontinue the drug should be made by the physician.

Isolated cases of pancreatitis have been reported in patients receiving ceftriaxone, possibly due to obstruction of the biliary tract. Most of these patients had risk factors for biliary stasis, such as prior treatment, severe illness, or total parenteral nutrition. The role of precipitates formed by Euroceftraz in the biliary tract in the development of pancreatitis cannot be excluded.

The safety and efficacy of ceftriaxone in neonates, infants, and children have been established for the doses described in the section "Dosage and administration". Studies have shown that ceftriaxone, like some other cephalosporins, may displace bilirubin from albumin binding sites in serum.

Ceftriaxone is contraindicated in premature and full-term neonates at risk of developing bilirubin encephalopathy (see section "Contraindications").

For patients with renal impairment but normal liver function, the dose of Euroceftraz does not need to be reduced. In renal insufficiency (creatinine clearance below 10 mL/min), the daily dose of ceftriaxone should not exceed 2 g.

In patients with impaired liver function but preserved renal function, dose adjustment of Euroceftraz is not required.

In cases of concomitant severe liver and kidney disease, serum concentrations of ceftriaxone should be monitored regularly. In patients undergoing hemodialysis, the dose of the drug does not need to be adjusted after the procedure.

Caution should be exercised when administering Euroceftraz to patients with renal insufficiency who are also receiving aminoglycosides and diuretics.

Cases of kidney stone formation have been reported, which resolved after discontinuation of ceftriaxone. If symptoms occur, ultrasound examination should be performed. The decision to use the drug in patients with a history of kidney stones or hypercalciuria should be made by the physician based on individual benefit-risk assessment.

In cases of severe renal and hepatic insufficiency, careful clinical monitoring of the safety and efficacy of the drug is recommended.

Ceftriaxone must not be mixed or administered simultaneously with calcium-containing solutions, even when administered through different infusion systems. Cases of precipitation in the lungs and kidneys, leading to fatal outcomes, have been reported with concurrent administration of ceftriaxone and calcium-containing products. Cases of intravascular precipitates have also been reported after concomitant use of ceftriaxone with intravenous calcium-containing solutions. Therefore, calcium-containing intravenous solutions must not be administered for at least 48 hours after the last dose of Euroceftraz (see section "Contraindications").

Immune-mediated hemolytic anemia has been observed in patients receiving cephalosporins, including Euroceftraz. Cases of severe hemolytic anemia, including fatal cases, have been reported in adult and pediatric patients. If anemia develops during ceftriaxone therapy, hemolysis caused by ceftriaxone should be excluded, and the drug should be discontinued until the etiology of anemia is determined.

During prolonged treatment, blood counts should be monitored regularly.

In isolated cases, patients treated with Euroceftraz may show false-positive Coombs test results. Like other antibiotics, Euroceftraz may cause false-positive results in galactosemia testing. False-positive results may also occur in urine glucose testing; therefore, if glucosuria needs to be assessed during treatment, it should be determined by enzymatic methods only.

Encephalopathy

Encephalopathy has been reported during ceftriaxone use (see section "Adverse reactions"), particularly in elderly patients with severe renal insufficiency or central nervous system disorders. If ceftriaxone-associated encephalopathy is suspected (e.g., decreased level of consciousness, altered mental status, myoclonia, seizures), discontinuation of ceftriaxone should be considered.

Jarisch-Herxheimer reaction

At the beginning of ceftriaxone treatment, some patients with spirochetal infections may experience a Jarisch-Herxheimer reaction. This reaction is usually self-limiting, although symptomatic treatment may be required. Antibiotic therapy should not be discontinued if a Jarisch-Herxheimer reaction occurs.

Use during pregnancy or breastfeeding

There are no reliable data on the use of the combination of ceftriaxone with tazobactam in pregnant women. Therefore, the use of the drug during pregnancy is contraindicated.

Ceftriaxone passes into breast milk. The concentration of tazobactam in breast milk has not been studied. Therefore, the use of Euroceftraz during breastfeeding is contraindicated. If treatment is necessary, breastfeeding should be discontinued.

Fertility

Reproductive function studies have not shown evidence of adverse effects on male or female fertility.

Ability to affect reaction speed when driving vehicles or operating machinery

During ceftriaxone treatment, adverse reactions such as dizziness may occur, which may affect the ability to drive vehicles or operate complex machinery (see section "Adverse reactions"). Patients should exercise caution when driving or operating machinery.

Administration and Dosage

Euroceftraz injections are intended for intravenous or intramuscular administration only.

Adults and children aged 12 years and older: The usual dose is 1000/125 mg – 2000/250 mg of Euroceftraz once daily (every 24 hours). In severe infections or infections caused by pathogens with only moderate sensitivity to ceftriaxone, the daily dose may be increased up to 4000/500 mg. The daily dose must not exceed 4000 mg of ceftriaxone.

Children aged 2 to 12 years: 20–80 mg/kg body weight (calculated as ceftriaxone) once daily. The daily dose must not exceed 2000 mg of ceftriaxone.

Children with body weight above 50 kg should receive adult doses.

Intravenous doses of 50 mg/kg (calculated as ceftriaxone) or higher should be administered by infusion over at least 30 minutes.

Elderly patients

Dosage adjustment in elderly patients is not required.

Treatment duration

The duration of treatment depends on the course of the disease. As with other antibiotics, patients should continue receiving Euroceftraz for at least 48–72 hours after normalization of body temperature and laboratory results indicate absence of pathogens. Usually, the total duration of treatment is 4–14 days.

Combination therapy

A synergistic effect between ceftriaxone and aminoglycosides has been observed against many Gram-negative bacteria. Although increased efficacy of such combinations cannot always be predicted, it should be considered in life-threatening infections caused by Pseudomonas aeruginosa. Due to physical incompatibility between ceftriaxone and aminoglycosides, they should be administered separately at their recommended doses.

Dosing in special situations

Meningitis

In bacterial meningitis in children aged 2 to 12 years, treatment should be initiated at a dose of 100 mg/kg (based on ceftriaxone), but not exceeding 4000/500 mg once daily. Once the causative organism is identified and its sensitivity determined, the dose may be adjusted downward accordingly. Optimal treatment outcomes have been achieved with the following treatment durations:

Lyme borreliosis: Adults and children – 50 mg/kg of ceftriaxone (maximum daily dose: 2 g ceftriaxone) once daily for 14 days.

Gonorrhea

For treatment of gonorrhea (caused by penicillinase-producing or non-penicillinase-producing strains), a single intramuscular dose of 250 mg ceftriaxone is recommended.

Prophylaxis of surgical infections

For prophylaxis of postoperative infections in surgery, a single dose of 1–2 g ceftriaxone (Euroceftraz) should be administered 30–90 minutes before the start of surgery, depending on the degree of infection risk. For procedures on the colon and rectum, simultaneous (but separate) administration of Euroceftraz and one of the 5-nitroimidazoles (e.g., ornidazole) is well established.

Renal and hepatic impairment

In patients with impaired liver function, dose reduction is not necessary if kidney function remains normal. Only in cases of preterminal renal insufficiency (creatinine clearance less than 20 ml/min) should the daily dose of ceftriaxone not exceed 2 g. Patients undergoing hemodialysis do not require additional doses after dialysis. However, serum concentrations of ceftriaxone should be monitored for possible dose adjustment, as elimination may be reduced in such patients. The daily dose of Euroceftraz in patients undergoing hemodialysis should not exceed 2 g (based on ceftriaxone).

Preparation of solutions

Prepare solutions immediately before use.

Intramuscular injection

For intramuscular injection, dissolve 1 g in 3.5 ml of 1% lidocaine solution; administer deeply into the gluteal muscle. It is recommended not to inject more than 1 g into a single buttock. Prior to lidocaine use, perform a skin sensitivity test. Solutions containing lidocaine must not be administered intravenously.

Intravenous injection

For intravenous injection, dissolve 1 g of Euroceftraz in 10 ml of sterile water for injection; administer slowly intravenously over 2–4 minutes.

Intravenous infusion

Intravenous infusion should last at least 30 minutes. To prepare the infusion solution, dissolve 2 g of Euroceftraz in 40 ml of one of the following calcium-free infusion solutions: 0.9% sodium chloride, 0.45% sodium chloride + 2.5% glucose, 5% glucose, 10% glucose, 6% dextran in 5% glucose solution, 6–10% hydroxyethyl starch, water for injection. Due to possible incompatibility, solutions containing ceftriaxone and tazobactam must not be mixed with solutions containing other antibiotics, either during preparation or administration.

Solvents containing calcium, such as Ringer's solution or Hartmann's solution, must not be used to reconstitute Euroceftraz in vials or to dilute the reconstituted solution for intravenous administration, due to the risk of precipitation of calcium-ceftriaxone salts. Precipitation of calcium-ceftriaxone salts may also occur when Euroceftraz is mixed with calcium-containing solutions in the same intravenous infusion system. Euroceftraz must not be administered intravenously simultaneously with calcium-containing solutions, including prolonged infusions containing calcium, such as parenteral nutrition (see section "Interaction with other medicinal products and other forms of interaction").

Children

To be used in children aged 2 years and older.

Overdose

In case of overdose, nausea, vomiting, and diarrhea may occur. Overdose of cephalosporin antibiotics may lead to symptoms of cerebral irritation, potentially resulting in seizures. In case of overdose, hemodialysis or peritoneal dialysis will not significantly reduce drug concentrations. There is no specific antidote. Treatment of overdose is symptomatic.

Side effects

Euroceftriaxone is usually well tolerated. The following adverse reactions may occur during its use.

Infections and infestations:
Candidiasis, common – genital fungal infections, secondary fungal infections and infections caused by resistant microorganisms, pseudomembranous colitis, superinfections.

Blood and lymphatic system disorders:
Common – eosinophilia, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, prolonged prothrombin time; uncommon – increased serum creatinine levels; very rare – coagulation disorders. Very rare cases of agranulocytosis (<500/mm³) have been observed, mostly after administration of a cumulative dose of 20 g or more. Blood counts should be monitored regularly during prolonged therapy. A slight prolongation of prothrombin time has been reported.

Gastrointestinal disorders:
Common – diarrhea, nausea, vomiting, stomatitis, glossitis; uncommon – pancreatitis, possibly due to biliary tract obstruction (most of these patients had risk factors for biliary stasis such as prior treatment, severe illness, or total parenteral nutrition; precipitation caused by Euroceftriaxone in the biliary tract cannot be excluded as a contributing factor in pancreatitis); very rare – pseudomembranous enterocolitis.

Hepatobiliary disorders:
Very common – pseudolithiasis of the gallbladder, precipitates of calcium salt of ceftriaxone in the gallbladder with corresponding symptoms in children, reversible cholelithiasis in children (these events were rarely observed in children); common – increased serum levels of liver enzymes (AST, ALT, alkaline phosphatase); frequency not known – kernicterus, hepatitis (usually reversible upon discontinuation of ceftriaxone), cholestatic hepatitis (see section "Special precautions").

Skin and subcutaneous tissue disorders:
Common – rash, allergic dermatitis, pruritus, urticaria, edema, exanthema, angioedema; very rare – exudative multiform erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) (see section "Special precautions").

Renal and urinary disorders:
Uncommon – increased blood urea and creatinine levels, oliguria, hematuria, glucosuria; very rare – cylindruria, interstitial nephritis, renal stone formation, primarily in children aged 3 years and older who received high daily doses (≥80 mg/kg/day), or cumulative doses exceeding 10 g, and who had additional risk factors (limited fluid intake, bed rest). Renal stone formation may be asymptomatic or clinically apparent and may lead to renal failure, which resolves after discontinuation of ceftriaxone therapy.

Nervous system disorders:
Headache and dizziness, tremor, seizures, rarely – encephalopathy.

Cardiac disorders:
Increased or decreased blood pressure, palpitations. Kounis syndrome with frequency "not known".

Respiratory, thoracic and mediastinal disorders:
Dyspnea, bronchospasm.

Immune system disorders:
Anaphylactic or anaphylactoid reactions, anaphylactic shock, hypersensitivity.

Ear and labyrinth disorders:
Vertigo.

General disorders:
Uncommon – headache and dizziness, chills, rigors, serum sickness, edema, epistaxis, weakness.

Local reactions:
With intravenous administration – phlebitis, pain, induration along the vein; inflammatory reactions of the vein wall have been observed in isolated cases. These can be avoided by slow injection (2–4 minutes).

Intramuscular injection without lidocaine is painful.

Impact on laboratory test results:

Increased serum creatinine levels. In isolated cases, false-positive Coombs test results may occur during treatment with Euroceftriaxone. Like other antibiotics, Euroceftriaxone may cause false-positive results in galactosemia testing. False-positive results may also occur in urine glucose testing; therefore, if glucose in urine needs to be assessed during treatment, it should be determined only by enzymatic methods.

Diarrhea following ceftriaxone use may be associated with Clostridium difficile. Adequate fluid and electrolyte replacement should be administered as needed (see section "Special precautions").

Precipitates of calcium ceftriaxone salt.

Rare cases of severe adverse reactions, sometimes fatal, have been reported in preterm and full-term neonates (age <28 days) who received intravenous ceftriaxone and calcium-containing products. Post-mortem examinations revealed precipitates of calcium ceftriaxone salt in the lungs and kidneys. The high risk of precipitate formation in neonates is due to their small blood volume and longer elimination half-life of ceftriaxone compared to adults (see sections "Contraindications", "Special precautions").

Cases of renal precipitate formation have been reported, primarily in children aged 3 years and older receiving high daily doses (≥80 mg/kg/day), or cumulative doses exceeding 10 g, and who had additional risk factors (limited fluid intake, bed rest). The risk of precipitate formation increases in immobilized patients or those with dehydration. Renal precipitates may be asymptomatic or clinically evident and may lead to renal failure, which resolves after discontinuation of ceftriaxone.

Cases of gallbladder precipitates of calcium ceftriaxone salt have been reported, primarily in patients receiving doses higher than the standard recommended dose. In children, prospective studies have shown variable incidence of precipitate formation with intravenous administration, reaching over 30% in some studies. The incidence appears lower with slow infusion (over 20–30 minutes). Precipitate formation is usually asymptomatic, but in rare cases may present with clinical symptoms such as pain, nausea, and vomiting. Symptomatic treatment is recommended in such cases. Precipitates typically resolve after discontinuation of ceftriaxone (see section "Special precautions").

Reporting suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk ratio of the medicine. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua

Shelf life: 3 years.

Storage conditions: Store at temperatures not exceeding 25°C. Keep out of reach of children.

Incompatibilities:

The product must not be added to infusion solutions containing calcium, such as Hartmann’s or Ringer’s solutions, including parenteral nutrition solutions, due to the risk of precipitate formation. Calcium-containing solutions should not be administered within 48 hours after the last dose of ceftriaxone. The product is incompatible with amikacin, vancomycin, fluconazole, aminoglycosides, and other antibiotics.

Do not mix with solvents other than those specified in the section "Dosage and administration".

Packaging: 1 vial per cardboard box.

Prescription status: Prescription only.

Manufacturer: Swiss Parenterals Ltd.

Manufacturer's address and location of operations:
Unit II, Plot 402, 412-414 Kerala Industrial Estate, GIDC, Near Bavla, Ahmedabad, Gujarat, 382220, India.