Ceftriaxone 2 g powder for solution for injection/infusion - Summary of Product Characteristics (SmPC) (2023)

Each vial contains ceftriaxone sodium equivalent to 2 grams of ceftriaxone sodium.

Excipients with known effect

Each gram of ceftriaxone contains approximately 82 mg (3.6 mmol) of sodium.

A complete list of sponsors is provided in paragraph 6.1

Powder solution for injection or infusion (powder for injection/infusion).

White to pale yellow crystalline powder.

Ceftriaxone is indicated for the treatment of the following infections in adults and children, including term neonates (from birth):

bacterial meningitis

community-acquired pneumonia

nosocomial pneumonia

acute otitis media

intra-abdominal infection

Complicated urinary tract infections (including pyelonephritis)

bone and joint infections

Complicated skin and soft tissue infections

gonorrhea

syphilis

bacterial endocarditis

Ceftriaxone can be used for:

For the treatment of acute exacerbations of chronic obstructive pulmonary disease in adults

For the treatment of disseminated Lyme borreliosis (early (Stage II) and advanced (Stage III)) in adults and children, including neonates over 15 days of age.

For pre-operative prophylaxis of surgical site infections

Treatment of patients with fever and neutropenia due to suspected bacterial infection

For the treatment of patients with bacteremia associated or suspected to be related to any of the above infections

Ceftriaxone should be administered concomitantly with other antimicrobials if the potential range of pathogenic bacteria is beyond their range (see section 4.4).

Consideration should be given to official guidance on the appropriate use of antimicrobials.

dose

The dosage depends on the severity, sensitivity, site and type of infection, as well as the patient's age and liver and kidney function.

The recommended doses in the table below are generally recommended doses for these indications. In particularly severe cases, higher doses in the recommended range should be considered.

Adults and children over 12 years (≥50 kg)

* In case of documented bacteremia, consider the upper limit of the recommended dose range.

** Twice daily administration (12 doses every hour) may be considered if the daily dose is greater than 2 g.

Indications for adults and children over 12 years of age (≥ 50 kg) requiring special dosage:

acute otitis media

A single intramuscular injection of 1-2 g ceftriaxone is possible. Limited data suggest that ceftriaxone sodium 1-2 g daily intramuscularly for 3 days may be effective in patients with severe disease or treatment failure.

Preoperative prevention of surgical site infections

2 g as a single preoperative dose.

gonorrhea

A single intramuscular dose is 500 mg.

syphilis

The generally recommended dose is 500 mg-1 g once daily, increasing to 2 g once daily for 10-14 days for neurosyphilis. Dosing recommendations for syphilis (including neurosyphilis) are based on limited data. National or local guidelines should be considered.

Disseminated Lyme borreliosis (early [stage 2] and late [stage 3])

2 grams once a day for 14-21 days. The recommended duration of treatment varies and national or local guidelines should be taken into account.

A crowd of children

Neonates, infants and children aged 15 days to 12 years (< 50 years of age). Kilogram)

Children weighing more than 50 kg should take the usual adult dose.

* In case of documented bacteremia, consider the upper limit of the recommended dose range.

** Twice daily administration (12 doses every hour) may be considered if the daily dose is greater than 2 g.

Indications for neonates, infants and children aged 15 days to 12 years (< 50 kg) requiring a special dosing schedule:

acute otitis media

For the initial treatment of acute otitis media, a single intramuscular injection of ceftriaxone 50 mg/kg may be used. Limited data suggest that ceftriaxone sodium 50 mg/kg intramuscularly daily for 3 days may be effective in children who are seriously ill or who have failed initial treatment.

Preoperative prevention of surgical site infections

A single preoperative dose is 50-80 mg/kg.

syphilis

The generally recommended dose is 75-100 mg/kg (up to 4 g) once daily for 10-14 days. Dosing recommendations for syphilis (including neurosyphilis) are based on very limited data. National or local guidelines should be considered.

Disseminated Lyme borreliosis (early [stage 2] and late [stage 3])

50–80 mg/kg once daily for 14–21 days. The recommended duration of treatment varies and national or local guidelines should be taken into account.

Newborn 0-14 days

Ceftriaxone is contraindicated in premature infants up to and including 41 weeks of menstrual age (gestational age + chronological age).

* In case of documented bacteremia, consider the upper limit of the recommended dose range.

The maximum daily dose should not exceed 50 mg/kg.

Indications for newborns 0-14 days requiring a specific dosing schedule:

acute otitis media

For the initial treatment of acute otitis media, a single intramuscular injection of ceftriaxone 50 mg/kg may be used.

Preoperative prevention of surgical site infections

20-50 mg/kg as a single preoperative dose.

syphilis

The generally recommended dose is 50 mg/kg once daily for 10-14 days. Dosing recommendations for syphilis (including neurosyphilis) are based on very limited data. National or local guidelines should be considered.

duration of treatment

The duration of treatment varies depending on the course of the disease. As with general antibiotic therapy, ceftriaxone should be continued for 48 to 72 hours after resolution of fever or evidence of bacterial eradication.

elderly

If renal and hepatic function are satisfactory, the recommended adult dose does not need to be adjusted.

Patients with liver dysfunction

Available data do not suggest that mild or moderate hepatic impairment requires dose adjustment, provided that renal function is not impaired.

There are no data from studies in patients with severe hepatic impairment (see section 5.2).

Patients with renal failure:

There is no need to reduce the dose of ceftriaxone in patients with renal impairment unless there is hepatic impairment. Only in the case of end-stage renal disease (creatinine clearance <10 ml/min) the dose of ceftriaxone should not exceed 2 g per day.

Hemodialysis patients do not require additional booster doses after haemodialysis. Ceftriaxone cannot be removed by peritoneal or haemodialysis. Due to safety and efficacy, close clinical monitoring is recommended.

Patients with severe hepatic and renal insufficiency

In patients with severe renal and hepatic impairment, close clinical monitoring is recommended to ensure safety and efficacy.

Method of administration

intramuscular administration

Dissolve 2 g of ceftriaxone in 7.0 ml of 1% lidocaine solution for injection BP. The solution should be administered by deep intramuscular injection. Intramuscular injection should be injected into a relatively large muscle and the injection volume per site should not exceed 1 g.

Doses greater than 1 g should be divided over several injection sites.

As the solvent used is lidocaine, the resulting solution should never be administered intravenously (see section 4.3). The information in the Summary of Product Characteristics of lidocaine should be taken into account.

intravenous administration

Ceftriaxone can be administered by intravenous infusion over at least 30 minutes (preferred route) or by slow intravenous injection over 5 minutes. Intermittent intravenous injections should be administered over 5 minutes, preferably into larger veins. The intravenous dose for infants and children under 12 years of age is 50 mg/kg. and more and should be infused. In neonates, the intravenous dose should be administered over 60 minutes to reduce the potential risk of bilirubin encephalopathy (see sections 4.3 and 4.4). Intramuscular injection should be considered if intravenous administration is not possible or appropriate for the patient. If the dose is more than 2 grams, an intravenous injection should be used.

Ceftriaxone is contraindicated in neonates (≤28 days) who require (or may require) intravenous calcium-containing solutions, including continuous calcium-containing infusions such as parenteral nutrition, due to the risk of ceftriaxone calcium precipitation. See section 4.3).

Calcium-containing diluents (such as Ringer's solution or Hartmann's solution) should not be used to reconstitute ceftriaxone vials or to further dilute reconstituted vials for intravenous administration as a precipitate may form. Precipitation of ceftriaxone with calcium may also occur when ceftriaxone is mixed with calcium-containing solutions in the same intravenous line. Therefore, ceftriaxone and calcium-containing solutions should not be mixed or co-administered (see sections 4.3, 4.4 and 6.2).

For pre-operative prophylaxis of surgical site infections, ceftriaxone should be administered 30-90 minutes prior to surgery.

For instructions on reconstituting the medicinal product before administration, see section 6.6.

Hypersensitivity to ceftriaxone or any other cephalosporin.

History of severe hypersensitivity (e.g. anaphylaxis) to any other type of beta-lactam antibiotic (penicillins, monobactams and carbapenems).

Contraindications to the use of ceftriaxone are:

• Premature infants less than 41 weeks postmenarche (gestational age + chronological age)*

• Newborn rituals (under 28 days of age):

- People with hyperbilirubinaemia, jaundice, hypoalbuminemia or acidosis, as bilirubin conjugation may be impaired in these conditions*

- If intravenous calcium treatment or infusions containing calcium are required (or expected) due to the risk of precipitation of ceftriaxone calcium salt (see sections 4.4, 4.8 and 6.2).)

* In vitro studies have shown that ceftriaxone may displace bilirubin from serum albumin binding sites, which may result in a risk of bilirubin encephalopathy in these patients.

If lidocaine solution is used as the solvent, lidocaine should be excluded prior to intramuscular injection of ceftriaxone (see section 4.4). See the Lidocaine Summary of Product Characteristics, especially Contraindications.

Ceftriaxone solution containing lidocaine should never be administered intravenously.

hypersensitivity reaction

As with all beta-lactam antimicrobials, serious and sometimes fatal allergic reactions have been reported (see section 4.8). If a severe allergic reaction occurs, treatment with ceftriaxone should be discontinued immediately and appropriate emergency measures instituted. Before initiating treatment, the patient should be checked for a history of serious hypersensitivity reactions to ceftriaxone, other cephalosporins or any other type of beta-lactam agent. Ceftriaxone should be used with caution in patients with a history of non-severe hypersensitivity to other beta-lactams.

Serious cutaneous adverse reactions (Stevens-Johnson syndrome or Lyell's syndrome/toxic epidermal necrolysis) and drug reactions with eosinophilia and systemic symptoms (DRESS) have been reported in association with ceftriaxone treatment. )) may be life-threatening or fatal. However, the frequency of these events is unknown (see section 4.8).

Jarisch-Herxheimer reaction (JHR)

Some patients infected with spirochetes may develop the Jarisch-Herxheimer reaction (JHR) soon after starting treatment with ceftriaxone. JHR is usually a self-limiting disease or can be treated with symptomatic treatment. Antibiotic treatment should not be stopped if such a reaction occurs.

INTERACTIONS WITH PRODUCTS CONTAINING CALCIUM

Fatal reactions to ceftriaxone calcium deposits in the lungs and kidneys have been reported in premature and full-term infants less than 1 month of age. At least one of these patients was receiving ceftriaxone and calcium through different intravenous lines at different times. In the available scientific data, there are no confirmed reports of intravascular deposits in patients treated with ceftriaxone and calcium-containing solutions or other calcium-containing products, except in neonates.in vitroStudies have shown that neonates are at an increased risk of ceftriaxone calcium precipitation compared to other age groups.

In patients of all ages, ceftriaxone should not be mixed or co-administered with any calcium-containing intravenous fluid, even through another infusion line or infusion site. However, for patients older than 28 days of age, ceftriaxone and a calcium-containing solution may be administered continuously if the infusion line is used at a different site or if the infusion line is changed between infusions or flushed thoroughly with saline to avoid precipitation. For patients requiring continuous infusion of calcium-containing total parenteral nutrition (TPN) solutions, healthcare professionals may consider alternative antimicrobial therapies that do not pose a similar risk of precipitation. If ceftriaxone is deemed necessary in a patient requiring continuous nutrition, TPN solution and ceftriaxone may be administered simultaneously, albeit through separate infusion lines at different sites. Alternatively, the infusion of the TPN solution may be interrupted during the ceftriaxone infusion and flush the infusion line between the solutions (see sections 4.3, 4.8, 5.2 and 6.2).

A crowd of children

The safety and efficacy of ceftriaxone in neonates, infants and children have been established at the doses described in "Dasimetry and administration" (see section 4.2). Studies have shown that ceftriaxone, like some other cephalosporins, can replace bilirubin in serum albumin.

Ceftriaxone is contraindicated in premature and full-term infants at risk of developing bilirubin encephalopathy (see section 4.3).

Immune-mediated hemolytic anemia

Immune-mediated haemolytic anemia has been observed in patients receiving cephalosporins, including ceftriaxone (see section 4.8). Cases of severe haemolytic anemia, including fatalities, have been reported during treatment with ceftriaxone in adults and children.

Diagnosis of cephalosporins if the patient develops anemia while taking ceftriaxone-Associated anemia should be considered and ceftriaxone discontinued until the underlying cause is identified.

long-term treatment

Periodic complete blood counts should be performed during long-term treatment.

Colitis/insensitive microbial overgrowth

Antibiotic-associated colitis and pseudomembranous colitis have been reported with use of nearly all antimicrobial agents, including ceftriaxone, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who develop diarrhea during or after ceftriaxone administration (see section 4.8). Ceftriaxone should be discontinued and specific treatment institutedClostridium difficileshould be taken into account. Do not take drugs that inhibit peristalsis.

As with other antimicrobials, superinfection may occur in non-susceptible organisms.

Severe renal failure and liver failure

In severe renal and hepatic impairment, close clinical monitoring is recommended to ensure safety and efficacy (see section 4.2).

Interference with serological tests

May interfere with the Coombs test as ceftriaxone may cause false positive test results. Ceftriaxone may also cause false positive results in galactosemia tests (see section 4.8).

Non-enzymatic methods used to measure urine glucose may give false positive results. Urine glucose determination during treatment with ceftriaxone should be performed enzymatically (see section 4.8).

The presence of ceftriaxone may falsely lower the blood glucose estimates obtained by some blood glucose monitoring systems. Please refer to the manual for each system. Alternative test methods should be used if necessary.

sodium

This medicinal product contains 165 mg sodium per 2 g vial, equivalent to 8.3% of the World Health Organization's recommended maximum daily intake of 2 g sodium for adults.

Antibacterial spectrum

Ceftriaxone has a limited spectrum of antimicrobial activity and may not be suitable as a single agent for the treatment of certain types of infections unless a causative agent has been identified (see section 4.2). For multimicrobial infections, additional antibiotic therapy should be considered if suspected pathogens include ceftriaxone-resistant organisms.

Using lidocaine

When using lidocaine solution as a solvent,Ceftriaxone solution is for intramuscular injection only. Contraindications, warnings and other relevant information regarding lidocaine detailed in the Summary of Product Characteristics of lidocaine should be considered before use (see section 4.3). Lidocaine solution should never be administered intravenously.

Cholelithiasis

If shadows appear on the sonogram, the possibility of ceftriaxone calcium precipitation should be considered. Turbidities mistaking for gallstones were found on ultrasonography of the gallbladder and were more frequently observed at ceftriaxone doses of 1 g/day and above. Particular attention should be paid to the pediatric population. This precipitate disappeared after discontinuation of ceftriaxone treatment. Ceftriaxone calcium precipitation is rarely associated with symptoms. In symptomatic cases, conservative non-surgical treatment is recommended and physicians should consider discontinuing ceftriaxone based on a benefit-risk assessment (see section 4.8).

A brave attitude

Cases of pancreatitis, possibly due to biliary obstruction, have been reported in patients receiving ceftriaxone (see section 4.8). Most patients had cholestasis and sludge risk factors such as cholestasis and sludge. Before main treatment, severe disease and total parenteral nutrition. Initiators or cofactors of ceftriaxone-related cholestasis cannot be ruled out.

kidney stones

Cases of nephrolithiasis have been reported which resolved upon discontinuation of ceftriaxone (see section 4.8). In symptomatic cases, ultrasound should be performed. Physicians should consider use in patients with a history of kidney stones or hypercalciuria based on a thorough risk-benefit assessment.

encephalopathy

Cases of encephalopathy have been reported with ceftriaxone (see section 4.8), especially in elderly patients with severe renal impairment (see section 4.2) or central nervous system disease. In case of suspected ceftriaxone-related encephalopathy (eg

Calcium-containing diluents, such as Ringer's solution or Hartmann's solution, should not be used to reconstitute ceftriaxone vials or to further dilute reconstituted vials for intravenous administration as a precipitate may form.

Precipitation of ceftriaxone with calcium may also occur when ceftriaxone is mixed with calcium-containing solutions in the same intravenous line.

Ceftriaxone should not be administered concomitantly with calcium-containing intravenous solutions, including continuous calcium-containing infusions, e.g. by site Y parenteral nutrition. rinsed with a suitable fluid.

in vitroStudies using umbilical cord plasma from adults and neonates have shown an increased risk of neonatal ceftriaxone calcium precipitation (see sections 4.2, 4.3, 4.4, 4.8 and 6.2).

Concomitant use with oral anticoagulants may increase the effect of antivitamin K and the risk of bleeding. Frequent monitoring of the International Normalized Ratio (INR) during and after treatment with ceftriaxone is recommended, and the dose of antivitamin K medicinal products adjusted accordingly (see section 4.8).

There is conflicting evidence that aminoglycosides may increase nephrotoxicity when co-administered with cephalosporins. In such cases, aminoglycoside levels (and renal function) recommended in clinical practice should be closely monitored.

become onein vitroAntagonism studies have been observed with concomitant use of chloramphenicol and ceftriaxone. The clinical significance of this finding is unclear.

There have been no reports of interactions between ceftriaxone and oral calcium products or between intramuscular ceftriaxone and calcium products (intravenous or oral).

The Coombs test may give false positive results in patients treated with ceftriaxone.

Like other antibiotics, ceftriaxone may cause false-positive test results for galactosemia.

Similarly, non-enzymatic methods of measuring urine glucose may give false positive results. Therefore, the determination of glucose in the urine during treatment with ceftriaxone should be carried out by an enzymatic method.

Renal impairment has not been observed following concomitant administration of high doses of ceftriaxone and strong diuretics such as furosemide.

Co-administration of probenecid did not reduce the elimination of ceftriaxone.

Pregnant

Ceftriaxone crosses the placental barrier. There are limited data from the use of ceftriaxone in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to embryonal/foetal, perinatal and postnatal development (see section 5.3). Ceftriaxone should only be used during pregnancy if the benefits outweigh the risks, especially during the first trimester.

breast-feeding

Ceftriaxone is excreted in breast milk in low concentrations, but therapeutic doses of ceftriaxone are not expected to affect the breastfed infant. However, the risk of diarrhea and fungal infections of the mucous membranes cannot be excluded. The possibility of sensitization should be considered. A decision should be made whether to discontinue breast-feeding or to discontinue/abstain from ceftriaxone therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

Reproduction studies have shown no adverse effects on male and female fertility.

The most common adverse reactions of ceftriaxone were eosinophilia, leucopenia, thrombocytopenia, diarrhoea, rash and elevated liver enzymes.

Data to determine the frequency of adverse reactions to ceftriaxone were obtained from clinical trials.

The following conventions have been used for frequency classification:

Very common (≥ 1/10)

Common (≥1/100 - <1/10)

Uncommon (≥ 1/1,000 - < 1/100)

Rare (≥ 1/10,000 - < 1/1,000)

Not known (cannot be estimated from the available data)

^oneBased on post-launch reports. As these reactions were reported voluntarily by a group of uncertain size, it was not possible to reliably estimate their frequency and therefore they are classified as unknown.

^AndSee section 4.4

Description of selected adverse reactions

infection and infection

Reports of diarrhea following ceftriaxone use may be associated with:Clostridium difficile. Appropriate fluid and electrolyte management should be implemented (see section 4.4).

Precipitation of ceftriaxone calcium salt

Rare, serious and even fatal adverse reactions have been reported in premature and full-term infants (< 28 days of age) treated with intravenous ceftriaxone and calcium. Precipitation of ceftriaxone calcium was observed in the lungs and kidneys post-mortem. Neonates have a lower blood volume and a longer half-life of ceftriaxone than adults and are therefore at greater risk of precipitation (see sections 4.3, 4.4 and 5.2).

Precipitation of ceftriaxone in the urine has been reported, mainly in children treated with high doses (e.g. ≥80 mg/kg/day or total dose >10 g) with moderate other risk factors (e.g. dehydration, stay at home). bed). This event may be asymptomatic or symptomatic and may result in ureteral obstruction and post-renal acute renal failure, but is usually reversible upon discontinuation of ceftriaxone (see section 4.4).

Precipitation of ceftriaxone calcium in the gall bladder has been observed, mainly in patients receiving therapeutic doses higher than the standard recommended dose. Prospective studies have shown a variable rate of precipitation in children after intravenous administration - more than 30% in some studies. Slow infusions (20–30 minutes) tend to be less frequent. This effect is usually asymptomatic, but in rare cases the precipitate is accompanied by clinical signs such as pain, nausea and vomiting. Symptomatic treatment is recommended in such cases. Precipitation is usually reversible upon discontinuation of ceftriaxone (see section 4.4).

Report suspected side effects

It is important to report suspected side effects after approval. It enables continuous monitoring of the benefit-risk balance of drugs. Healthcare professionals are asked to report any suspected side effects to the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card on Google Play or the Apple App Store.

Pharmacotherapeutic group: systemic antibiotics, third generation cephalosporins

Kod ATC: J01DD04

Mechanism

Ceftriaxone inhibits bacterial cell wall synthesis when bound to penicillin binding protein (PBP). This leads to disruption of the biosynthesis of the cell wall (peptidoglycan), which leads to the lysis and death of bacterial cells.

resist

Bacterial resistance to ceftriaxone may be due to one or more of the following mechanisms:

• β-lactamase hydrolysis, including extended spectrum β-lactamases (ESBL), carbapenemase and the Amp C enzyme, which can be induced or stably restored in some aerobic Gram-negative bacteria.

• Penicillin binding protein has a reduced affinity for ceftriaxone.

• The outer membrane is impermeable to Gram-negative organisms.

• Leakage of bacteria from the pump.

Sensitivity test breakpoints

The Minimum Inhibitory Concentration (MIC) breakpoints established by the European Committee for Microbial Susceptibility Testing (EUCAST) are as follows:

one. Susceptibility was inferred from susceptibility to cefoxitin.

Si. Susceptibility is inferred from penicillin susceptibility.

Down. Isolates with ceftriaxone MICs above the sensitive cut-off point are rare and should be retested if detected and sent to a reference laboratory if confirmed.

Hi. The breakpoints apply to daily intravenous doses of 1 g x 1 and higher doses of at least 2 g x 1.

Clinical efficacy against specific pathogens

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. If necessary, specialist advice should be sought if local resistance is so widespread that the effectiveness of ceftriaxone sodium for at least some types of infection is questionable.

£ All methicillin-resistant staphylococci are resistant to ceftriaxone.

⁺Resistance > 50% in at least one area

^%ESBL-producing strains are persistently resistant

absorb

intramuscular administration

Following intramuscular injection, the mean peak plasma concentrations of ceftriaxone are approximately half those observed after intravenous administration of the same dose. Peak plasma concentrations after a single 1 g intramuscular injection are approximately 81 mg/l and are reached 2-3 hours after dosing.

The area under the plasma concentration-time curve after intramuscular administration was comparable to the area under the plasma concentration-time curve after an equal dose intravenously.

intravenous administration

Following intravenous bolus administration of 500 mg and 1 g ceftriaxone, the mean peak plasma concentrations of ceftriaxone were approximately 120 and 200 mg/L, respectively. Following intravenous infusions of ceftriaxone at doses of 500 mg, 1 g and 2 g, ceftriaxone plasma concentrations were approximately 80, 150 and 250 mg/l, respectively.

distribute

Ceftriaxone has a volume of distribution of 7-12 L. Concentrations well in excess of the minimum inhibitory concentrations for most relevant pathogens have been detected in tissues including lung, heart, biliary tract/liver, tonsils, middle ear and nasal mucosa, bone, spinal cord pleura, prostate and synovial fluid. Mean peak plasma concentration (C_maximum) observed after repeated dosing. In most cases, steady-state is reached within 48-72 hours, depending on the route of administration.

penetrate certain tissues

Ceftriaxone penetrates the meninges. Penetration is greater when the meninges are inflamed. The mean peak concentration of ceftriaxone in the cerebrospinal fluid of patients with bacterial meningitis has been reported to be as high as 25% of the plasma concentration compared to only 2% in patients without meningitis. Ceftriaxone reaches peak concentrations in the cerebrospinal fluid approximately 4-6 hours after intravenous administration. Ceftriaxone crosses the placental barrier and is excreted in breast milk in low concentrations (see section 4.6).

protein binding

Ceftriaxone binds reversibly to albumin. Plasma protein binding is approximately 95% at plasma concentrations below 100 mg/l. The binding is saturated and the bound fraction decreases with increasing concentration (up to 85% at a plasma concentration of 300 mg/l).

Biotransformation

Ceftriaxone is not systemically metabolised. But it will be converted into inactive metabolites by the intestinal flora.

eliminate

The plasma clearance of total ceftriaxone (conjugated and unconjugated) is 10-22 ml/min. Renal clearance is 5-12 ml/min. 50-60% of ceftriaxone is excreted unchanged in the urine, mainly by glomerular filtration, while 40-50% is excreted unchanged in the bile. The half-life of total ceftriaxone in adults is approximately 8 hours.

Patients with renal or hepatic impairment

In patients with renal or hepatic insufficiency, the pharmacokinetics of ceftriaxone are slightly altered and the half-life is slightly prolonged (less than 2-fold), even in patients with severe renal insufficiency.

The relatively small increase in half-life following renal injury may be explained by a compensatory increase in non-renal clearance due to reduced protein binding and a corresponding increase in non-renal clearance of total ceftriaxone.

In patients with hepatic impairment, the half-life of ceftriaxone is not prolonged due to a compensatory increase in renal clearance. This is also due to the observed paradoxical increase in total drug clearance as an increase in the free fraction of ceftriaxone in plasma where the increase in volume of distribution parallels total clearance.

elderly

In elderly people over 75 years of age, the mean elimination half-life is usually two to three times longer than in younger adults.

A crowd of children

The half-life of ceftriaxone is prolonged in neonates. From birth to 14 days of age, free ceftriaxone concentrations may still increase due to factors such as reduced glomerular filtration and altered protein binding. In children, the half-life is shorter than in neonates and adults.

Plasma clearance and volume of distribution of total ceftriaxone are greater in neonates, infants and children than in adults.

linear/non-linear

The pharmacokinetics of ceftriaxone are non-linear and, when based on total drug concentrations, all key pharmacokinetic parameters, with the exception of the elimination half-life, are dose dependent and increase less than proportionally with dose. The non-linearity is due to saturation of plasma protein binding and is therefore seen with total plasma ceftriaxone but not with free (unbound) ceftriaxone.

Pharmacokinetic/pharmacodynamic relationship

As with other β-lactams, the pharmacokinetic/pharmacodynamic index iLiveEfficacy is defined as the percentage of the dosing interval at which the unbound drug concentration remains above the Minimum Inhibitory Concentration (MIC) of ceftriaxone for each target species (i.e. %T > MIC).

According to literature reports, ceftriaxone is not compatible with amsacrine, vancomycin, fluconazole and aminoglycosides.

Solutions containing ceftriaxone should not be mixed or added to medicinal products other than those mentioned in section 6.6.

In particular, calcium-containing diluents (e.g. Ringer's solution, Hartmann's solution) should not be used to reconstitute ceftriaxone or to further dilute reconstituted vials as a precipitate may form.

Ceftriaxone should not be mixed or co-administered with calcium-containing solutions, including total parenteral nutrition (see sections 4.2, 4.3, 4.4 and 4.8).

If concomitant treatment with another antibiotic is planned, ceftriaxone should not be given in the same syringe or infusion.

Unopened - 3 years.

Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 24 or 25 hours^TenC and store at 2-8°C for four days. From a microbiological point of view, the product should be used immediately after opening. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. Normally, this time does not exceed 24 hours at 2-8°C, unless reconstituted under controlled and validated aseptic conditions.

Unopened: Do not store above 25°C. To hold The bottle is packed in an outer box.

After reconstitution: Store at 2-8°C, see section 6.3 for specific storage instructions.

Ceftriaxone is supplied in a 50 ml Type II clear glass injection bottle closed with a Type I uncoated/Omniflex rubber stopper and sealed with an aluminum/plastic stopper.

The bottles are supplied in boxes of 1 and 10.

Not all packages can be released.

vial 1g - intravenous concentration: about 100 mg/ml,

1 g vial - intravenous concentration: approximately 50 mg/ml

2 g vial - Intravenous or intravenous concentration: approximately 50 mg/ml

(More information can be found in chapter 4.2).

refactoring table

¹For intravenous injection, dissolve 1 g of ceftriaxone in 10 ml of water for injections. The injection should be given directly into a vein or through an intravenous line over 5 minutes.

²Doses greater than 1 g should be divided over several injection sites.

^#Approximate Usable Volume and Approximate Displacement Volume are provided for reconstitution with water for injection.

It is recommended to use freshly prepared solutions. See section 6.3 for storage conditions of reconstituted medicinal products.

Do not mix ceftriaxone in the same syringe with any medicine except Lidocaine 1% Injection BP (for intramuscular injection only).

*Ceftriaxone is compatible with several commonly used intravenous solutions, such as injection solutions. Sodium Chloride IV BP, 5% or 10% Dextrose IV BP, Sodium Chloride and Dextrose IV BP (0.45% NaCl and 2.5% Dextrose), Dextran 6% Dextrose IV BP-500%% Water injections and injections.

The reconstituted solution should be clear. Do not use if particles are present.

When reconstituted with water for injections (Ph Eur), ceftriaxone sodium forms a pale yellow to orange solution. Changes in the color intensity of freshly prepared solutions do not indicate changes in potency or safety.

For single use only. Any unused content is rejected.

Walkhart Ltd

Ash Road to the North

Rexam

Ultrafiltration LL13 9

Great Britain