Active ingredients: Ceftriaxone
Ceftriaxone Sandoz 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use
Ceftriaxone Sandoz 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use
Ceftriaxone Sandoz 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use
The package inserts of Ceftriaxone - Generic Drug are available for pack sizes: - Ceftriaxone Sandoz 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use, Ceftriaxone Sandoz 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use, Ceftriaxone Sandoz 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use
- Ceftriaxone Sandoz 1 g / 10 ml powder and solvent for solution for injection for intravenous use
- Ceftriaxone Sandoz 2 g powder for solution for infusion
Why is Ceftriaxone used - Generic Drug? What is it for?
Ceftriaxone Sandoz contains the active substance ceftriaxone which is an antibiotic that is given to adults and children (including newborns). It works by killing the bacteria that cause infections. It belongs to a group of medicines called cephalosporins.
Ceftriaxone Sandoz is used to treat infections:
- of the brain (meningitis).
- of the lungs.
- of the middle ear.
- of the abdomen and abdominal wall (peritonitis).
- of the urinary tract and kidneys.
- of bones and joints.
- skin or soft tissue.
- some blood.
- of the heart.
It can be administered:
- to treat specific sexually transmitted infections (gonorrhea and syphilis).
- to treat patients with low white blood cell counts (neutropenia) who have fever due to bacterial infection.
- to treat chest infections in adults with chronic bronchitis.
- to treat Lyme disease (caused by tick bites) in adults and children, including infants from 15 days of age.
- to prevent infections during surgery.
Contraindications When Ceftriaxone - Generic Drug should not be used
You should not be given Ceftriaxone Sandoz if:
- you are allergic to ceftriaxone or any of the other ingredients of this medicine (listed in section 6).
- have had a sudden or severe allergic reaction to penicillin or similar antibiotics (such as cephalosporins, penicillins, monobactams and carbapenems). Possible signs include a sudden swelling of the throat or face, which can make it difficult to breathe or swallow, a sudden swelling of the hands, feet and ankles, and a severe rash that develops rapidly.
- you are allergic to lidocaine and Ceftriaxone Sandoz must be given to you by injection into a muscle.
Ceftriaxone Sandoz should not be given to children in the following cases:
- the baby is premature.
- the baby is a newborn (up to 28 days old) and has some blood problems or jaundice (yellowing of the skin or the whites of the eye) or has to be given a product that contains calcium through a vein.
Precautions for use What you need to know before taking Ceftriaxone - Generic Drug
Talk to your doctor, pharmacist or nurse before you are given Ceftriaxone Sandoz if:
- have recently received or are about to receive products containing calcium.
- have recently had problems with diarrhea after taking an antibiotic. Have had bowel problems, especially colitis (inflammation of the bowel).
- suffer from liver or kidney problems.
- have gallstones or kidney stones.
- have other diseases, for example haemolytic anemia (a reduction in red blood cells which can make the skin pale yellow and cause weakness or breathlessness).
- follows a low sodium diet.
If you are due to have a blood or urine test
If you are given Ceftriaxone Sandoz for a long time, you may need to have regular blood tests. Ceftriaxone Sandoz can affect the results of urine tests for sugar and a blood test known as a Coombs test. If you are about to be tested:
- tell the person who takes the sample that you have been given Ceftriaxone Sandoz.
Children
Talk to your doctor, pharmacist or nurse before giving your child Ceftriaxone Sandoz if:
- the child has recently received or is about to receive a product that contains calcium through a vein.
Interactions Which drugs or foods can modify the effect of Ceftriaxone - Generic Drug
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.
In particular, tell your doctor or pharmacist if you are taking any of the following medicines:
- a type of antibiotic called aminoglycoside.
- an antibiotic called chloramphenicol (used to treat infections, particularly eye infections).
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
Your doctor will evaluate the benefits of Ceftriaxone Sandoz treatment for you and the possible risks to your baby.
Driving and using machines
Ceftriaxone Sandoz can cause dizziness. If you feel dizzy, do not drive or use any tools or machines. Contact your doctor if you experience these symptoms.
Dose, Method and Time of Administration How to use Ceftriaxone - Generic Drug: Posology
Ceftriaxone Sandoz is usually given by a doctor or nurse as an injection given directly into a muscle. Ceftriaxone Sandoz will be prepared by a doctor, pharmacist or nurse and will not be mixed with or given to you at the same time as calcium-containing injections.
Usual dose
Your doctor will decide which dose of Ceftriaxone is right for you. The dose will depend on the severity and type of infection, any concomitant treatment with other antibiotics, your weight and age, how well your kidneys and liver are functioning. The number of days or weeks you will receive Ceftriaxone Sandoz will depend on the type of infection you have.
Adults, the elderly and children aged 12 years and over with a body weight of 50 kilograms (kg) or more:
- 1 to 2 g once a day depending on the severity and type of infection. If you have a severe infection, your doctor will give you a higher dose (up to 4 g per day). If your daily dose is more than 2 g, you can take it as a single dose once a day or as two divided doses.
Newborns, infants and children from 15 days to 12 years of age with a body weight of less than 50 kg:
- 50-80 mg Ceftriaxone Sandoz once daily for each kg of the child's body weight depending on the severity and type of infection. If you have a severe infection, your doctor will prescribe a higher dose starting from 100 mg for each kg of your body weight up to a maximum of 4 g per day. If your daily dose is more than 2 g, you can take it as a dose single once daily or as two separate doses.
- Children with a body weight of 50 kg or more should be given the usual adult dose.
Infants (0-14 days old)
- 20-50 mg Ceftriaxone Sandoz once daily for each kg of the baby's body weight depending on the severity and type of infection.
- The maximum daily dose should not exceed 50 mg for each kg of the infant's body weight.
People with liver and kidney problems
You may be given a different dose than the usual one. Your doctor will decide how much Ceftriaxone Sandoz you will need and will monitor you closely, depending on the severity of your liver and kidney disease.
Overdose What to do if you have taken an overdose of Ceftriaxone - Generic Drug
If you take more Ceftriaxone Sandoz than you should
If you are accidentally given more Ceftriaxone Sandoz than your prescribed dose, contact your doctor or the nearest hospital immediately.
If you forget to take Ceftriaxone Sandoz
If you miss an injection, you should receive it as soon as possible. However, if it is almost time for your next scheduled injection, skip the missed injection. Do not take a double dose (two injections together) to make up for a forgotten dose.
If you stop taking Ceftriaxone Sandoz
Do not stop taking Ceftriaxone Sandoz unless your doctor tells you to. If you have any further questions on the use of this medicine, ask your doctor or nurse.
Side Effects What are the side effects of Ceftriaxone - Generic Drug
Like all medicines, this medicine can cause side effects, although not everybody gets them.
You may experience the following side effects with this medicine:
Serious allergic reactions (not known, frequency cannot be estimated from the available data)
If you have a severe allergic reaction, contact your doctor immediately.
The signs could include:
- sudden swelling of the face, throat, lips or mouth. This can make breathing or swallowing difficult.
- sudden swelling of the hands, feet and ankles.
Severe rash (not known, frequency cannot be estimated from the available data)
If you get a severe rash, contact your doctor immediately.
- The signs may include a severe rash that develops rapidly, with blistering or peeling of the skin and possibly blistering in the mouth.
Other possible side effects:
Common (may affect up to 1 in 10 people)
- Abnormalities of white blood cells (such as decreased white blood cells and increased eosinophils) and platelets (decreased thrombocytes).
- Loose stools or diarrhea.
- Changes in the results of blood tests for liver function.
- Rash.
Uncommon (may affect up to 1 in 100 people)
- Fungal infections (for example, thrush).
- Decrease in the number of white blood cells (granulocytopenia).
- Reduction in the number of red blood cells (anemia).
- Blood clotting problems. The signs include easy bruising, pain and swelling of the joints.
- Headache.
- Dizziness
- Nausea or vomiting.
- Itching
- Pain or burning sensation along the vein where Ceftriaxone Sandoz was given. Pain where the injection was given.
- Fever.
- Abnormal values in kidney function tests (increase in blood creatinine).
Rare (may affect up to 1 in 1,000 people)
- Inflammation of the large intestine (colon). Signs include diarrhea, often with blood and mucus, stomach pain and fever.
- Difficulty in breathing (bronchospasm).
- Skin rash with hives (hives) which may cover a large area of the body, associated with itching and swelling.
- Blood or sugar in the urine.
- Edema (accumulation of fluids).
- Chills.
Not known (frequency cannot be estimated from the available data)
- Secondary infections that may not respond to the prescribed antibiotic.
- Form of anemia characterized by the destruction of red blood cells (haemolytic anemia).
- Severe decrease in the number of white blood cells (agranulocytosis).
- Convulsions.
- Dizziness.
- Inflammation of the pancreas (pancreatitis). The signs include severe pain in the stomach, which extends to the back.
- Inflammation of the oral mucosa (stomatitis).
- Inflammation of the tongue (glossitis). The signs include swelling, redness and irritation of the tongue.
- Problems with the gallbladder which can cause pain, nausea and vomiting.
- A neurological condition that can develop in infants with severe jaundice (nuclear jaundice).
- Kidney problems caused by calcium-ceftriaxone deposits. You may experience pain when you urinate, or the amount of urine produced may decrease.
- A false positive Coombs test (a test to detect blood problems).
- A false positive result for galactosemia (an abnormal buildup of the sugar galactose).
- Ceftriaxone Sandoz can interfere with some types of blood glucose tests; check with your doctor.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https: // www. aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and bottle after EXP.
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Ceftriaxone Sandoz contains
Ceftriaxone Sandoz 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use
one vial of powder contains:
active ingredient: ceftriaxone disodium 3.5 H2O 298.2 mg equal to ceftriaxone 250 mg; u
The solvent vial contains: 1% aqueous solution of lidocaine.
Ceftriaxone Sandoz 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use
one vial of powder contains:
active ingredient: ceftriaxone disodium 3.5 H2O 596.5 mg equal to ceftriaxone 500 mg;
one solvent vial contains: 1% aqueous solution of lidocaine.
Ceftriaxone Sandoz 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use
one vial of powder contains:
active ingredient: ceftriaxone disodium 3.5 H2O 1.193 g equal to ceftriaxone 1 g;
one solvent vial contains: 1% aqueous solution of lidocaine.
What Ceftriaxone Sandoz looks like and contents of the pack
Ceftriaxone Sandoz 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use:
1 vial of powder + 1 vial of 2 ml solvent.
Ceftriaxone Sandoz 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use:
1 vial of powder + 1 vial of 2 ml solvent.
Ceftriaxone Sandoz 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use:
1 vial of powder + 1 vial of 3.5 ml solvent.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
CEFTRIAXONE SANDOZ
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
CEFTRIAXONE SANDOZ 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use: one bottle of powder contains:
Active ingredient: disodium ceftriaxone 3.5 H20 298.2 mg equal to ceftriaxone 250 mg;
CEFTRIAXONE SANDOZ 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use
one bottle of powder contains:
Active ingredient: ceftriaxone disodium 3.5 H2O 596.5 mg equal to ceftriaxone 500 mg;
CEFTRIAXONE SANDOZ 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use
one bottle of powder contains:
Active ingredient: ceftriaxone disodium 3.5 H2O 1.193 g equal to ceftriaxone 1 g;
CEFTRIAXONE SANDOZ 1 g / 10 ml powder and solvent for solution for injection for intravenous use.
one bottle of powder contains:
Active ingredient: ceftriaxone disodium 3.5 H2O 1.193 g equal to ceftriaxone 1 g;
CEFTRIAXONE SANDOZ 2 g powder for solution for infusion
one bottle contains:
Active ingredient: disodium ceftriaxone 3.5 H2O 2.386 g equal to ceftriaxone 2 g.
For the full list of excipients, see 6.1.
03.0 PHARMACEUTICAL FORM
Powder and solvent for solution for injection.
Powder for solution for infusion.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Of elective and specific use in serious bacterial infections of ascertained or presumed origin from "difficult" Gram-negative or from mixed flora with the presence of Gram-negative resistant to the most common antibiotics.
In particular, the product is indicated, in the aforementioned infections, in defied and / or immunosuppressed patients. Prophylaxis of surgical infections.
04.2 Posology and method of administration
Calcium-containing diluents (e.g. Ringer's or Hartmann's solution) should not be used to reconstitute ceftriaxone vials or to further dilute reconstituted vials for i.v. administration, as a precipitate may form. Precipitation of ceftriaxone with calcium can also occur when ceftriaxone is mixed with calcium-containing solutions in the same IV administration line.
Therefore, ceftriaxone and calcium-containing solutions should not be mixed together or administered simultaneously (see sections 4.3, 4.4 and 6.2).
General dosage schedule
Adults and children over 12 years: the recommended dose is 1g of CEFTRIAXONE SANDOZ once a day (every 24 hours). In severe cases or in infections caused by moderately sensitive microorganisms, the dose can reach 4 g administered in a single solution.
Infants (up to 2 weeks): the daily dose is 20-50 mg / kg of body weight once administered; due to the immaturity of their enzymatic systems, it should not exceed 50 mg / kg (see section 4.4).
Children (3 weeks to 12 years): the daily dose can vary between 20 and 80 mg / kg. For intravenous doses equal to or greater than 50 mg / kg it is recommended to use a perfusion lasting at least 30 minutes.
For children weighing more than 50 kg the adult dosage should be used.
Senior citizens: the dosage regimen for adults does not require changes in the case of elderly patients.
The duration of therapy depends on the course of the infection.
Like all antibiotic-based therapies, in general the administration of CEFTRIAXONE SANDOZ should be continued for a minimum of 48-72 hours after the breakdown or after the demonstration of complete bacterial eradication.
Prophylaxis of surgical infections
For the prevention of post-operative infections, 1 g i.m. or 1-2 g i.v. in a single dose will be administered, in relation to the type and risk of contamination of the intervention, one hour before the intervention.
Dosage in particular conditions
Kidney failure | and: in subjects with creatinine clearance greater than 10 ml / min the posology remains unchanged. In case of creatinine clearance of 10 ml / min or less, up to a maximum of 2 g once daily can be administered.
Hepatic insufficiency: normal dosage.
Associated renal and hepatic insufficiency: check plasma concentrations of ceftriaxone.
Premature: maximum dose 50 mg / kg once daily
Method of administration
From a microbiological point of view the product should be used immediately after reconstitution. If not used immediately, in-use storage conditions and periods prior to use are the responsibility of the user. The chemical and physical stability of the medicinal product after reconstitution has been demonstrated for 24 hours between + 2 ° C and + 8 ° C and for 6 hours for the product stored at a temperature below 25 ° C.
They can vary in color from pale yellow to amber depending on the concentration and storage period; this characteristic has no influence on the efficacy or tolerability of the drug.
Solution for intramuscular use
To perform the intramuscular injection, dissolve CEFTRIAXONE SANDOZ im with the appropriate solvent (1% lidocaine solution) which is 2 ml for CEFTRIAXONE SANDOZ 250 mg and 500 mg, and 3.5 ml for CEFTRIAXONE SANDOZ 1 g: inject deeply the extemporaneous solution thus obtained in the buttock, alternating the buttocks in subsequent injections.
The lidocaine solution should not be administered intravenously.
Solution for intravenous use
To carry out the i.v. injection, dissolve CEFTRIAXONE SANDOZ with the appropriate solvent (water for injections) which is 10 ml for CEFTRIAXONE SANDOZ 1 g, and inject directly into a vein in 2-4 minutes.
Solution for infusion
To carry out intravenous perfusion, dissolve CEFTRIAXONE SANDOZ at the rate of 2 g in 40 ml of perfusion liquid free of calcium ions (physiological solution, 5% or 10% glucose solution, 5% levulose solution, dextran glucose solution at 6%).
The perfusion will last for at least 30 minutes.
CEFTRIAXONE SANDOZ solutions should not be mixed in solutions containing other antimicrobial drugs or with diluting solutions other than those listed above due to possible incompatibility.
04.3 Contraindications
CEFTRIAXONE SANDOZ is contraindicated in patients with known hypersensitivity to beta-lactam antibiotics. Hypersensitivity to cephalosporins or to any of the excipients. In patients hypersensitive to penicillin, the possibility of cross-allergic reactions should be considered.
In pregnant women and in very early childhood, the product should be administered in cases of real need and under the direct supervision of the doctor.
Hyperbilirubinemic infants and preterm infants should not be treated with ceftriaxone. Studies in vitro have shown that ceftriaxone can displace bilirubin from its binding sites to plasma albumin and bilirubin encephalopathy may develop in these patients.
Treatment with calcium, due to the risk of precipitation of calcium salts-ceftriaxone in term births (see sections 4.4, 4.5 and 4.8)
Ceftriaxone is also contraindicated in:
premature babies up to a corrected age of 41 weeks (weeks of gestation + weeks of life);
full-term infants (up to 28 days of age):
with jaundice or the presence of hypoalbuminemia or acidosis, as these are conditions in which bilirubin could be altered;
if they were to request (or are thought to require) an i.v. with calcium, or with calcium-containing infusions, due to the risk of precipitation of ceftriaxone with calcium (see sections 4.4, 4.8 and 6.2).
When lidocaine is used frequently, contraindications should be ruled out before administering the intramuscular injection of ceftriaxone.
04.4 Special warnings and appropriate precautions for use
As with other cephalosporins, anaphylactic shock cannot be excluded, even in the presence of an accurate patient history.
Each gram of CEFTRIAXONE SANDOZ contains 3.6x mmol of sodium. To be taken into consideration in patients on a low sodium diet.
Diarrhea associated with Clostridium difficile (CDAD), the severity of which can range from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, causing the overgrowth of C. difficult.
C. difficultproduces toxins A and B, which contribute to the development of CDAD. The strains of C. difficult hypertoxin producers cause increased morbidity and mortality, as these infections may be refractory to antimicrobial therapy and may require colectomy. CDAD should be considered in all patients who develop diarrhea after antibiotic use. A careful medical history is required, as cases of CDAD have been reported to occur more than two months after administration of antibacterial agents.
If CDAD is suspected or confirmed, it may be necessary to stop using antibiotics not directly in opposition to C. difficult. Depending on the clinical indications, adequate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficult and surgical evaluation.
As with other antibacterial agents, superinfections with non-sensitive microorganisms may occur.
Shadows were found on ultrasound scans of the gallbladder that were mistaken for gallstones, usually following administration of higher than the standard recommended doses. However, these shadows are precipitates of calcium-ceftriaxone, which disappear upon termination or discontinuation of therapy with Ceftriaxone SANDOZ. These findings have rarely been associated with symptoms. In symptomatic cases, non-surgical conservative management is recommended. In symptomatic cases, discontinuation of CEFTRIAXONE SANDOZ treatment should be at the discretion of the physician.
CEFTRIAXONE SANDOZ is eliminated for about 56% in the urine and for the remaining 44% in the bile in microbiologically active form. It is mainly present in the faeces in an inactive form. In case of impaired renal function it is eliminated at a higher level via the biliary route, with the faeces. Since the half-life is only slightly increased in this circumstance, a reduction in the CEFTRIAXONE SANDOZ dosage is not necessary in most cases, provided that liver function is normal. Only in the presence of very severe renal insufficiency (creatinine clearance ≤ 10 ml / min) the maintenance dose every 24 hours should be reduced to half the usual dose.
Like other cephalosporins, it has been shown that ceftriaxone can partially interfere with the binding sites of bilirubin with plasma albumin. Third generation cephalosporins, like other beta-lactamines, can induce microbial resistance and this occurrence is greater towards opportunistic organisms. especially Enterobacteriaceae and Pseudomonas, in immunosuppressed subjects and probably, by associating more beta-lactamines with each other.
As with any antibiotic therapy, regular checks of the blood count should be carried out in the case of prolonged treatments.
In extremely rare cases, in patients treated with high doses, ultrasound of the gallbladder has revealed findings that can be interpreted as thickening of the bile. This condition promptly regressed upon interruption or termination of therapy. Even if these findings are symptomatic, purely conservative treatment is recommended.
Positive Coombs tests (sometimes false) have been reported during treatment with cephalosporins.
Before starting therapy with CEFTRIAXONE SANDOZ, a careful investigation should be carried out to establish whether the patient has in the past manifested hypersensitivity phenomena to cephalosporins, penicillins and other drugs.
The product should be administered with caution in patients allergic to penicillin as cases of cross-hypersensitivity between penicillins and cephalosporins have been described. Due to the immaturity of organ functions, premature babies should not be treated with doses of Ceftriaxone Sandoz above 50 mg / kg / day.
As for the other antibiotics, prolonged use can favor the development of resistant bacteria and in case of superinfection it is necessary to adopt the most appropriate measures.
Acute hypersensitivity reactions may require the use of adrenaline and other emergency measures. Preparations containing lidocaine should not be administered intravenously and to patients allergic to this local anesthetic. If there are signs of infection, the responsible organism should be isolated. and appropriate therapy, based on sensitivity tests, should be adopted.
Analyzes on samples collected before the start of therapy should be carried out to determine the susceptibility of the responsible organism to ceftriaxone. Therapy with CEFTRIAXONE SANDOZ can however be started pending the results of these analyzes; and treatment should still be, if appropriate. , subsequently modified according to the results of the analyzes. Before using CEFTRIAXONE SANDOZ in combination with other antibiotics, the instructions for use of the other drugs should be carefully read to know any contraindications, warnings, precautions and unwanted reactions.
Renal function should be carefully monitored.
Pseudomembranous colitis has been reported following the use of cephalosporins (or other broad spectrum antibiotics); it is important to consider this diagnosis in patients who experience diarrhea after antibiotic use.
Interactions with calcium-containing products
Cases of fatal reactions with calcium-ceftriaxone precipitates in lungs and kidneys in preterm and full-term infants less than 1 month have been reported. At least one of them had received ceftriaxone and calcium at different times and through different intravenous lines. Among the available scientific data, there are no reports of confirmed intravascular precipitation in patients other than neonates treated with ceftriaxone and calcium-containing solutions or any other calcium-containing products. Studies in vitro showed that infants have an increased risk of calcium-ceftriaxone precipitation compared to other age groups.
In patients of any age, CEFTRIAXONE SANDOZ must not be mixed or administered simultaneously with any calcium-containing intravenous solution, even via different infusion lines or at different infusion sites. However, in patients over 28 days of age, ceftriaxone and calcium-containing solutions can be administered sequentially, one after the other, provided that infusion lines are used at different sites or if, between infusions, the Infusion lines are replaced or thoroughly flushed with physiological saline to avoid precipitation. In patients requiring continuous infusion with calcium-containing TPN solutions, healthcare professionals may consider using alternative antibacterial treatments, which do not carry such a risk of precipitation. If the use of ceftriaxone is considered necessary in patients requiring continuous feeding, the solutions for TPN and ceftriaxone can be administered simultaneously, provided that through different infusion lines and at different sites. Alternatively, the infusion of TPN solution may be stopped for the ceftriaxone infusion period, observing the provision to flush the infusion lines between each administration (see sections 4.3, 4.8, 5.2 and 6.2).
Cases of pancreatitis, possibly due to biliary obstruction, have been observed rarely in patients treated with Ceftriaxone. Most patients had risk factors for biliary stasis and biliary sludge, for example, prior to main therapy, severe disease, and total parenteral nutrition. The triggering or concomitant role of CEFTRIAXONE SANDOZ-related biliary precipitation cannot be excluded.
In cases of severe renal and hepatic insufficiency, the dosage should be reduced according to the recommendations given.
The safety and efficacy of CEFTRIAXONE SANDOZ in neonates, infants and children have been established for the dosages described in sectionDosage and administration. Clinical studies have shown that ceftriaxone, like some other cephalosporins, can remove bilirubin from serum albumin.
CEFTRIAXONE SANDOZ should not be used in neonates (particularly premature infants) at risk of developing bilirubin encephalopathy.
During prolonged treatment complete blood counts should be performed at regular intervals.
If lidocaine is used as a diluent, ceftriaxone solutions should only be administered by intramuscular injection.
04.5 Interactions with other medicinal products and other forms of interaction
The concomitant administration of high doses of Ceftriaxone Sandoz with high-activity diuretics (eg furosemide) in high doses has not shown up to now disturbances in renal function. There is no evidence that CEFTRIAXONE SANDOZ increases the renal toxicity of aminoglycosides. The ingestion of alcohol following the administration of CEFTRIAXONE SANDOZ does not give effects similar to those of disulfiram; ceftriaxone, in fact, does not contain the N-methylthiotetrazole group believed to be responsible for both the possible intolerance to alcohol and the haemorrhagic manifestations occurring with other cephalosporins. Elimination of CEFTRIAXONE SANDOZ is not affected by probenecid.
In a studio in vitro antagonistic effects have been observed with the combination of chloramphenicol and ceftriaxone.
It has been demonstrated in experimental conditions synergism of action between CEFTRIAXONE SANDOZ and aminoglycosides against many Gram-negative germs. The enhancement of the activity of these associations, although not always predictable, must be taken into consideration in all those serious infections, resistant to other treatments, due to organisms such as Pseudomonas aeruginosa. Due to physical incompatibilities, the two drugs must be administered separately at the recommended doses.
Ceftriaxone Sandoz must not be added to solutions containing calcium, such as Hartman and Ringer solutions (see sections 4.3, 4.4 and 4.8).
Do not use calcium-containing diluents, such as Ringer's solution or Hartmann's solution, to reconstitute CEFTRIAXONE SANDOZ ampoules or to further dilute a reconstituted vial for i.v. administration, as precipitate may form. Precipitation of calcium-ceftriaxone can also occur when Ceftriaxone is mixed with calcium-containing solutions in the same IV administration line.CEFTRIAXONE SANDOZ should not be administered concomitantly with calcium-containing intravenous solutions, including continuous calcium-containing infusions, such as those used for parenteral nutrition through a Y-line. However, in patients other than neonates, CEFTRIAXONE SANDOZ and calcium-containing solutions may be administered sequentially, one after the other, as long as the lines are thoroughly rinsed with a compatible liquid between one infusion and another. in vitro performed with adult plasma and neonatal plasma from the umbilical cord have shown that neonates have an increased risk of calcium-ceftriaxone precipitation.
Based on literature reports, ceftriaxone is incompatible with amsacrine, vancomycin, fluconazole and aminoglycosides.
In rare cases, the Coombs test may produce false positives in patients treated with CEFTRIAXONE SANDOZ.
CEFTRIAXONE SANDOZ, like other antibiotics, can cause false positives in tests for galactosemia.
Likewise, non-enzymatic methods for the determination of glucose in urine can produce false positive results. For this reason, the determination of glucose levels in the urine during therapy with CEFTRIAXONE SANDOZ must be carried out enzymatically.
Ceftriaxone may impair the efficacy of hormonal oral contraceptives. It is therefore advisable to use additional (non-hormonal) contraceptive measures during treatment and in the month following treatment.
04.6 Pregnancy and lactation
Ceftriaxone crosses the placental barrier. Its safety during human pregnancy has not been established. Reproduction studies in animals have shown no evidence of embryotoxicity, foetotoxicity or teratogenicity, nor adverse effects on male or female fertility, parturition or perinatal and postnatal development. In primates, no embryotoxicity or teratogenicity was observed.
Low concentrations of ceftriaxone are excreted in human breast milk. Therefore, caution should be exercised when CEFTRIAXONE SANDOZ is administered to breastfeeding women.
In pregnant women, during lactation and in very early childhood, the product should be administered in cases of real need and under the direct supervision of the doctor.
04.7 Effects on ability to drive and use machines
As Ceftriaxone Sandoz sometimes induces dizziness, the ability to drive and use machines may be impaired.
04.8 Undesirable effects
Side effects are usually mild and of short duration.
Systemic side effects
Gastrointestinal disorders (about 2% of cases): loose stools or diarrhea, nausea, vomiting, stomatitis and glossitis, rarely thickening of the bile.
Haematological alterations (about 2%): eosinophilia, leukopenia, granulocytopenia, haemolytic anemia, thrombocytopenia. Frequency not known: Cases of agranulocytosis have been reported, most of them after 10 days of treatment and after total doses of 20 g or more.
Skin reactions (about 1%): rash, allergic dermatitis, itching, urticaria, edema. Frequency not known: Cases of severe cutaneous adverse reactions (erythema multiforme, Stevens-Johnson syndrome or Lyell's syndrome / toxic epidermal necrolysis) have been reported.
Other rare side effects: headache, dizziness and dizziness, symptomatic precipitation of calcium-ceftriaxone salt in the gallbladder, increased liver enzymes, glycosuria, haematuria, oliguria, increased serum creatinine, genital mycosis, fever, chills and anaphylactic or anaphylactoid reactions, for example bronchospasm.
Ceftriaxone must not be mixed or administered concomitantly with calcium-containing solutions or products, even through different infusion lines.
Rarely, serious, and in some cases fatal, adverse reactions have been reported in preterm and full-term neonates (intravenous age. post mortem precipitation of calcium-ceftriaxone salt.
The high risk of precipitation in neonates is due to their reduced plasma volume and the longer half-life of ceftriaxone compared to adults (see sections 4.3, 4.4 and 5.2).
Superinfections caused by microorganisms not sensitive to ceftriaxone (candida, fungi or other resistant microorganisms) may develop. A rare side effect caused by infection with Clostridium difficile being treated with CEFTRIAXONE SANDOZ is pseudomembranous colitis. Therefore, in patients who present with diarrhea following the use of an antibacterial agent it is necessary to consider the possibility of developing this pathology.
Very rare cases of renal precipitation have been reported, particularly in children over 3 years of age who had been treated with high daily doses (e.g. ≥80 mg / kg / day) or with total doses greater than 10 grams and who they had high risk factors (e.g. fluid restrictions, bed confinement, etc.). The risk of precipitate formation increases in dehydrated or immobilized patients. This event may be symptomatic or asymptomatic, may result in renal failure and anuria and is reversible upon discontinuation of Ceftriaxone Sandoz.
Precipitation of calcium ceftriaxone salts in the gallbladder has been observed, predominantly in patients treated with doses above the recommended standard. In children, prospective studies have shown a variable incidence of precipitation with intravenous administration, which in some studies was greater than 30%. The incidence appears to be lower with slow infusion (20-30 minutes). effect is generally asymptomatic, but in rare cases the precipitations have been accompanied by clinical symptoms, such as pain, nausea and vomiting. In these cases symptomatic treatment is recommended. The precipitations are generally reversible after discontinuation of ceftriaxone.
Isolated cases of pancreatitis have been reported.
Bleeding disorders have been reported as very rare side effects.
Local side effects
In rare cases, after i.v. phlebitic reactions occurred. These can be minimized by giving a slow injection (2-4 minutes).
The intramuscular injection without lidocaine solution is painful.
Hypersensitivity reactions may occur in predisposed subjects.
Influence on diagnostic tests
Coombs' test may rarely produce false positive results in patients treated with Ceftriaxone Sandoz. Like other antibiotics, Ceftriaxone Sandoz can produce false positive results in tests for galactosemia.
Likewise, non-enzymatic methods for the determination of glucose in urine can produce false positive results. For this reason, the determination of glucose levels in the urine during therapy with CEFTRIAXONE SANDOZ must be carried out enzymatically.
04.9 Overdose
In the event of an overdose, nausea, vomiting and diarrhea may occur. Concentrations of ceftriaxone cannot be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Treatment is symptomatic.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antibacterial for systemic use.
ATC code: J01DD04
Ceftriaxone exerts its antibacterial action by blocking specific bacterial enzymes (PBPs) responsible for the synthesis of the cell wall.
Ceftriaxone occurs in the form of yellowish crystals, easily soluble in water, relatively soluble in methanol and poorly soluble in ethanol; the pH of a 12% solution varies between 6.0 and 8.0. The pKa values are between 2.0 and 4.5.
The 1 g pack contains 82.91 mg of sodium.
Ceftriaxone is an antibiotic derived from cephalosporanic acid, characterized by a metoximinic residue which gives it stability against bacterial beta-lactamases, as well as by a triazine function responsible for its pharmacokinetic properties. It has a very broad spectrum of action in vitro. on Gram + and Gram - aerobes, and is endowed with a bactericidal activity which is expressed at concentrations lower than 0.1 mcg / ml for most sensitive bacteria.
In clinical use it is indicated only in serious infections (see section 4.2) due to the following Gram negative germs: Enterobacter, Serratia marcescens, Citrobacter, Pseudomonas aeruginosa. Ceftriaxone also shows good activity against anaerobic bacteria. in the long half-life, it allows to obtain, with a single daily administration, antibiotic concentrations higher than the minimum inhibitory concentration.
In vitro sensitivity test
The sensitivity of Gram-positive and Gram-negative pathogens to CEFTRIAXONE SANDOZ can be evaluated both by the diffusion test with discs and by the dilution method in the usual culture media. In any case, it is recommended to use discs containing ceftriaxone, as some sensitive bacterial strains when evaluated with a specific ceftriaxone disc, are resistant when evaluated with standard discs for the cephalosporin class.
05.2 "Pharmacokinetic properties
Injected via i.m. or i.v. ceftriaxone rapidly diffuses from plasma to tissues, reaching plasma peaks of approximately 150 mcg / ml after 1 g i.v. and at 100 mcg / ml after 1 g i.m. The half-life is 6-11 hours in plasma and 10-11 hours in tissues.
Ceftriaxone easily diffuses into the following fluids or tissues: middle ear mucosa, middle ear fluid in children, nasal mucosa, tonsil, lung and bronchial secretion, pleural fluid, ascitic fluid, synovial fluid, spongy and compact bone tissue, fluid periprosthetic in bone tissue, skeletal muscle, myocardium, pericardium, adipose tissue, bile and gallbladder wall, cortical and medullary kidney, urine, prostate, uterus, ovary, tube, vagina.
It also penetrates through the blood brain barrier, reaching multiple concentrations of CMI for the bacteria most frequently isolated from the CSF of patients with inflamed meninges. The mean concentrations of distribution of Ceftriaxone following a single parenteral dose in these areas are shown in Table 1.
Table 1
The drug is not metabolized in the body and is therefore eliminated in active form by the kidney and liver in the amount of about 56% and 44% respectively. The renal elimination of ceftriaxone occurs by glomerular filtration, while the tubular secretion does not seem to have any relevance. . It is mainly present in the faeces in an inactive form.
Pharmacokinetics in particular clinical situations
In the first week of life, 80% of the dose is excreted in the urine; in the first month this value falls to levels similar to those in adults. In infants less than 8 days of age, the mean elimination half-life is usually two or three. times longer than that of young adults.
05.3 Preclinical safety data
Toxicological studies have shown a LD of 1840-3000 mg / kg (after i.v. administration) in rats.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Powder and solvent for solution for injection for intramuscular use:
the solvent vial contains lidocaine hydrochloride.
Powder and solvent for solution for injection for intravenous use:
the solvent vial contains water for injections.
06.2 Incompatibility
Solutions containing ceftriaxone should not be mixed with or added to other agents. In particular, diluents containing calcium (e.g. Ringer's solution or Hartmann's solution) should not be used to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for i.v. administration, as precipitate may form. Ceftriaxone must not be mixed or administered concomitantly with calcium-containing solutions (see sections 4.2, 4.3, 4.4 and 4.8).
06.3 Period of validity
Expiry of the unopened package correctly stored: 3 years.
From a microbiological point of view the product should be used immediately after reconstitution. If not used immediately, in-use storage conditions and periods prior to use are the responsibility of the user. The chemical and physical stability of the medicinal product after reconstitution has been demonstrated for 24 hours between + 2 ° C and + 8 ° C and for 6 hours for the product stored at a temperature below 25 ° C.
06.4 Special precautions for storage
No special storage precautions.
06.5 Nature of the immediate packaging and contents of the package
Glass bottle (plus any glass vial for reconstitution liquids) with pierceable rubber stopper, fixed with metal ring, and plastic cap. The bottle is enclosed in a cardboard box together with the package leaflet.
CEFTRIAXONE SANDOZ 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use:
1 bottle of powder + 1 solvent vial of 2 ml
CEFTRIAXONE SANDOZ 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use:
1 bottle of powder + 1 solvent vial of 2 ml
CEFTRIAXONE SANDOZ 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use:
1 bottle of powder + 1 solvent vial of 3.5 ml;
CEFTRIAXONE SANDOZ 1 g / 10 ml powder and solvent for solution for injection for intravenous use:
1 bottle of powder + 1 solvent vial of 10 ml
CEFTRIAXONE SANDOZ 2 g powder for solution for infusion:
1 bottle of powder
06.6 Instructions for use and handling
No special instructions.
Unused product and waste derived from this medicine must be disposed of in accordance with local legal requirements.
07.0 MARKETING AUTHORIZATION HOLDER
Sandoz Spa - Largo U. Boccioni, 1 - 21040 Origgio (VA)
08.0 MARKETING AUTHORIZATION NUMBER
CEFTRIAXONE SANDOZ 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use:
1 bottle of powder + 1 solvent vial AIC n ° 035902016
CEFTRIAXONE SANDOZ 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use:
1 bottle of powder + 1 solvent vial AIC n ° 035902028
CEFTRIAXONE SANDOZ 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use:
1 bottle of powder + 1 solvent vial AIC n ° 035902030
CEFTRIAXONE SANDOZ 1 g / 10 ml powder and solvent for solution for injection for intravenous use:
1 bottle of powder + 1 solvent vial AIC n ° 035902042
CEFTRIAXONE SANDOZ 2 g powder for solution for infusion:
1 bottle of AIC powder n ° 035902055
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
October 2004 / October 2009
10.0 DATE OF REVISION OF THE TEXT
June 2010
